MMM y PMC - Asociacion Medica de Puerto Rico

médico-científico de la asociación médica de puerto rico
Convenciòn
AMPR2013
www.asocmedpr.org
25 al 28 de julio de 2013
Embassy Suites Dorado del Mar
Año 2013 - Volumen 105 - Número 2
Los afiliados de MMM y PMC tienen mucho que decir.
BOLETIN
Médico Científico de la Asociación Médica de Puerto Rico
Año 2013 - Volumen 105 - Número 2
Contenido
Catalogado en Cumulative Index e Index Medicus Listed in Cumulative Index and Index Medicus
No. ISSN-0004-4849. Registrado en Latindex -Sistema Regional de Información en Línea para
Revistas Científicas de América Latina, el Caribe, España y Portugal
Mensaje del Presidente
5
Coaliciones en favor de los pacientes
Natalio Izquierdo Encarnación, MD
Original Article/Artículos Originales
Nedjibia Martínez
76 años, afiliada MMM desde 2003.
Elba I. López
59 años, afiliada PMC desde 2009.
Juan Vega
72 años, afiliado MMM desde 2006.
“Yo padecía de cáncer, pero con
mi plan siempre me he sentido
segura y tranquila.”
¡Yo le debo mi vida a MMM!
“Me encontraba sola en mi casa,
encerrada y deprimida, pero al
llegar a PMC y compartir en el
Members Club, no sólo me sirvió
de terapia, sino que además,
encontré una familia”.
“Yo estuve 14 días en el hospital,
me hicieron un “bypass” grande en
la pierna izquierda y en mi proceso
de recuperación mi plan siempre
estuvo ahí, apoyándome”.
Por eso, de este plan,
¡nadie me mueve!
9
Neutropenia and Thrombocytopenia in very low
birth weight
Norma A. Claudio MD, Inés García MD, Lourdes García MD, Marta Valcárcel MD
15
Differences in prevalence of inflammatory bowel
disease in Puerto Rico between commercial
and government-sponsored managed health
care insured individuals
Roberto Vendrell MD, Heidi L. Venegas PhD, Cynthia M. Pérez PhD, Carlos Morel MSC,
Ruth V. Román MPH, Esther A. Torres MD
20
Embolización de tumores hipervasculares de la
base del craneo: Descripción de una serie de
casos y propuestas de un algoritmo terapéutico
Rafael Almeida Pereza, Héctor Espinosa-, García, Gabriel Alcalá-Cerra, Ginna de la Rosa Manjarréz, Fernando Orozco Gómez, Adalberto Rafael Mejía Barrios
28
Estudio de la exploración de conocimientos y actitudes en relación a la prevención y transmisión del dengue en Puerto Rico en el 2012
Ian Rivera Rodríguez, Augusto A. Puig Rivera, Raul H. Morales-Borges
36
Cervical Dysplasia and pre-term birth in San Juan City Hospital: A Cohort Retrospective
Study
Axel Torres MD, Edgardo Rivera Rosa MD,
Keimari Méndez MD, Ana Menéndez MD,
Josefina Romaguera MD
Case Reports / Reporte de Casos
39
Llame hoy a:
1-855-622-5605
1-877-522-0655
1-877-522-0656
(libre de cargos)
MMM TTY (audioimpedidos) PMC TTY (audioimpedidos)
Lunes a domingo, de 8:00 a.m. a 8:00 p.m.
Cardiac amyloidosis secondary to multiple
myeloma
Francisco Parrilla MD, Rafael E. Calderón MD,
Rafael Figueroa MD, Carmen Gurrea MD
ILUSTRACION DE PORTADA
Frank Astor, M.D.
Artropodos
Ilustración digital de cubierta realizada por Juan Laborde-Crocela y diseño gráfico de Alberto Ignacio González en la Oficina
de Informática de la AMPR. Impreso en los talleres gráficos digitales de la Asociación Médica de Puerto Rico
E-mail:galberto@asocmedpr.org
MMM Healthcare, Inc. (HMO) y PMC Medicare Choice, Inc. (HMO) son planes de salud con un contrato Medicare.
H4004 – PMC Medicare Choice H4003 – MMM Healthcare, Inc. Y0049_2013 4002 0087 2. File and use 06132013. Endosos pagados.
MP-PRD-PRI-604-060713-S
43
Hypersensitive Pneumonitis: A Case Report
Libertad I. Ruscalleda Reyes MD, Jesús
Román Vélez MD
47
The cardiology and endocrinology connection between amiodarone and thyrotoxicosis:
Case Report and Review of the Literature
Coromoto Palermo-Garófalo MD, José Hernán
Martínez MD, Frieda Silva MD, Eva González MD, Oberto Torres MD, Jannette Figueroa MD,
José González MD, María de Lourdes Miranda MD
54
Solid pseudopapillary pancreatic tumor as a
portal hypertension causal: The first reported
case in Puerto Rico
Daisy Torres MD, Carlos García-Gubern MD,
Maruja Santiago MD, Felipe Sánchez-Gaetán MD
59
Penetrating eye globe injury from trauma with a metallic nail: A case report
Juan C. Almodóvar-Mercado MD, Vanessa
López-Beauchamp MD
62
Ocular findings in patients with oculocutaneous albinism type IA with G47D tyrosinase gene
mutation in Puerto Rico: A case report
Ferdinand Rodríguez-Agramonte, Natalio J.
Izquierdo MD, Carmen Cadilla Phd
65
Mucormycosis of the vulva in an
immunocompromised pediatric patient
Makieri Colón MD, Josefina Romaguera MD,
Keimary Méndez MD, Denise Vilchez MD,
Edward J. Navas MD, José Pérez MS
Review Article/Artículo de Reseña
68
Overview of thyroid physiology: An essential for
understanding Familiar Euthyroid Multinodular
Goiter José Hernán Martínez MD, Coromoto
Palermo MD, Francisco Fernández
González MD, Iván Laboy MD
OFICINAS ADMINISTRATIVAS
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4
Asociación Médica de Puerto Rico
JUNTA DE DIRECTORES
Dr. Natalio Izquierdo Encarnación
Dra. Wanda G. Vélez Andújar
Dr. Raúl G. Castellanos Bran
Dr. Pedro J. Zayas Santos
Dra. Ilsa Figueroa Dra. Hilda Ocasio Maldonado
Dr. Raúl A. Yordán Rivera
Dr. Jaime M. Díaz Hernández
Dr. Arturo Arché Matta
Dr. Juan Rodríguez Del Valle
Dr. Gonzalo González Liboy
Dr. Rolance G. Chavier Roper
Dr. Ricardo Marrero Santiago
Dr. Rafael Fernández Feliberti
Dra. Mildred R. Arché
Dr. Salvador Torrós Romeu
Dra. Daisy Quirós
Presidente
Pres. Electo
Presidente Saliente
Tesorero
Secretaria
Vicepresidenta AMPR
Vicepresidente AMPR
Vicepresidente AMPR
Pres. Cámara Delegados
Vicepres. Cámara Delegados
Delegado AMA
Delegado AMA
Delegado Alt. AMA
Delegado Alterno AMA
Pres. Distrito Central
Pres. Distrito Este
Pres. Distrito Sur
JUNTA DE EDITORES
Objetivos
Humberto Lugo Vicente, MD, Presidente
Luis Izquierdo Mora, MD
Melvin Bonilla Félix, MD
Carlos González Oppenheimer, MD
Eduardo Santiago Delpin, MD
Francisco Joglar Pesquera, MD
Yocasta Brugal, MD
Juan Aranda Ramírez, MD
Francisco J. Muñiz Vázquez, MD
Walter Frontera, MD
Mario. R. García Palmieri, MD
Natalio Izquierdo Encarnación, MD
José Ginel Rodríguez, MD
La Asociación Médica de Puerto Rico es fundada
en el año de 1902, cuando por aquel entonces, el
insigne doctor Manuel Quevedo Báez ve la necesidad de aglutinar a la profesión médica puertorriqueña en un núcleo para la defensa de la colectividad
y así fomentar el contínuo progreso de la ciencia y
el arte de la medicina y el mejoramiento de la salud
del pueblo de Puerto Rico. Tras vencer incontables
dificultades e inconvenientes naturales de la época,
se celebró la asamblea constituyente el día 21 de
septiembre de 1902, en el salón de sesiones de la
Cámara de Delegados en la ciudad de San Juan.
Reserva de derechos
El “Boletín” se distribuye a los médicos y estudiantes de medicina de Puerto Rico y se publica en versión digital en
www.asocmedpr.org.
Todo anuncio que se publique en el Boletín de la Asociación Médica de Puerto Rico deberá cumplir con las normas
establecidas por la Asociación Médica de Puerto Rico y la Asociación Médica Americana.
La Asociación Médica de Puerto Rico no se hace responsable por los productos o servicios anunciados.
La publicación de los mismos no necesariamente implica el endoso de la Asociación Médica de Puerto Rico.
Todo anuncio para ser publicado debe reunir las normas establecidas por la publicación. Todo material debe entregarse listo para la imprenta y con sesenta días de anterioridad a su publicación.
La AMPR no se hará responsable por material y/o artículos que no cumplan con estos requisitos.
Todo artículo recibido y/o publicado está sujeto a las normas y reglamentos de la Asociación Médica de Puerto Rico.
Ningún artículo que haya sido previamente publicado será aceptado para esta publicación. La Asociación Médica de
Puerto Rico no se hace responsable por las opiniones expresadas o puntos de vista vertidos por los autores, a menos
que esta opinión esté claramente expresada y/o definida den tro del contexto del artículo.
Todos los derechos reservados. El Boletín está totalmente protegido por la ley de derechos del autor y ninguna persona o entidad puede reproducir total o parcialmente el material que aparezca publicado sin el permiso escrito de los
autores.
Mensaje del Presidente
Coaliciones en Favor de
los Pacientes
5
Natalio Izquierdo
Encarnación, MD
Realidades de la Población de Pacientes
Envejecientes en la Isla
La salud en la isla caribeña de Puerto Rico
sigue sin ser un derecho constitucional. Sin
embargo los gobiernos ven la salud como una
cuestión de justicia social y de derechos humanos. Los esfuerzos de los partidos políticos
tratan de lograr la equidad en el acceso a la
prestación de servicios y los beneficios mismos. Estos esfuerzos incluyen la restructuración y reinvención del Sistema de Salud, de
acuerdo a las necesidades cambiantes de la
población puertorriqueña.
En PR la población mayor de 65 años es de
15%, pero esta proporción va en aumento. La
población de pacientes de Medicare sigue creciendo. En la Isla el 71% de los pacientes se
ha acogido a un plan de “Medicare Advantage”
(MA). Es decir, tres de cada cuatro pacientes
se acogen a un MA probablemente por los
beneficios de salud dental, entre otros. Por tal
modalidad, el crecimiento de los planes de MA
en PR ha subido de 80,000 pacientes (en el
2004) a 600,000 pacientes (en el 2013).
Estos planes “Medicare Advantage” se conocen también como la “Parte C” de Medicare
y son ofrecidos por compañías aseguradoras
privadas. Estas compañías han sido previamente aprobadas por Medicare. El Plan MA
provee toda la cubierta hospitalaria (Medicare
Parte A) y la cubierta médica (Parte B). Los
planes MA proveen cubierta para algunos servicios extra, tales como cubierta dental.
La mayoría de los MA incluyen una cubierta
para medicamentos (Parte D), aunque estos
en PR están restringidos por formularios locales, además del tope de gastos de Medicare (que son alrededor de $2,000 anuales).
El gasto en medicamentos recetados a esta
población aumentó de 30 millones de dólares
a 60 millones para el año 2012. Es menester
hacer un esfuerzo, por proteger el programa
de MA. Se necesita mucha educación.
En PR, el 70% de los pacientes se acogen a un
plan de MA. Se dice que en PR la proporción
es invertida, al compararse con los ciudadanos americanos que viven en EU continental.
Por ejemplo, en el estado de Vermont, sólo 6%
de los pacientes se acogieron a planes de tipo
MA.
El sistema MA en PR da espacio a otra relación colaborativa entre el servicio de salud
pública del país y la industria privada, ya que
algunos pacientes médico-indigentes tienen la
llamada “cubierta Platino”. En la Isla, el sistema MC subsidia el programa Platino, que es
parte de la Reforma de Salud, pero destinado
a la población de los pacientes envejecientes.
Retos del Debate sobre el Presupuesto de
2014 en el Congreso de los Estados Unidos
y su impacto en PR
A nivel federal, los médicos de Estados Unidos y sus territorios, al igual que los pacientes,
se enfrentarán a los ajustes propuestos por el
“Affordable Care Act”. Además se enfrentan a
recortes presupuestarios.
Por otro lado, hay una disparidad en los fondos Medicare que afecta los proveedores de la
Isla y las facilidades médico-hospitalarias. Se
proyecta que hacia el 2017, el recorte para los
médicos de la Isla se acercará de un 25 a un
30%. El horizonte no es color de rosa.
El fenómeno del “secuestro” se lleva recursos
económicos de PR (desde 71 millones en el
2013 hasta 95 millones en el 2014). Esto afecta todos los programas de Medicare, incluyendo los MA.
Para el año fiscal de 2013, el presupuesto
federal de salud bajó un 22.2%. Interesantemente, el presupuesto federal para la defensa
bajó 1%. Es cierto que estamos en guerra. Lo
Qué hace MMAPA (Medicare y Medicare
Advantage Providers Association)
peor es que los Congresistas del Partido Republicano proponen recortar hasta el 26.5%
del presupuesto de salud en el futuro.
La Asociación (MMAPA) tiene varias funciones. Entre ellas, educar a los políticos a nivel
local y federal, el educa los médicos que laboran en la Isla en la urgente necesidad de comprender la implicación del sistema de estrellas
en la Isla. Además se esfuerza en educar a
CMS en los issues que afectan los pacientes y
los proveedores en PR. En este sentido, MMAPA ha cosechado algunas victorias.
Donde hay Problemas, hay oportunidades
En Puerto Rico los recortes son mayores que
en cualquier sitio de la nación de los Estados
Unidos. La disparidad entre Puerto Rico y el
promedio del reembolso por servicios prestados a nivel nacional ha aumentado. Los médicos en la Isla están 300 dólares por debajo
de la prima promedio de los Estados Unidos
Continental.
Si entendemos la incidencia de enfermedades
en la Isla, como la diabetes mellitus, la artritis
y enfermedades hereditarias, podemos entender los retos que enfrentan CMS y MMAPA.
Se sugiere la importancia de que las medidas
clínicas deben ser re-ajustadas a las realidades de la diferencias de la población isleña.
De hecho la Casa Blanca ha reconocido la disparidad. Además de los reembolsos, la disparidad es evidente en la falta de acceso de los
pacientes de escasos recursos a los subsidios
para los medicamentos.
Asociación Médica
de Puerto Rico
Objetivos
La Asociación Médica de Puerto Rico es fundada en el año de
1902, cuando por aquel entonces, el insigne doctor Manuel
Quevedo Báez ve la necesidad de aglutinar a la profesión médica puertorriqueña en un núcleo para la defensa de la colectividad y así fomentar el contínuo progreso de la ciencia y el arte de
la medicina y el mejoramiento de la salud del pueblo de Puerto
Rico. Tras vencer incontables dificultades e inconvenientes naturales de la época, se celebró la asamblea constituyente el día
21 de septiembre de 1902, en el salón de sesiones de la Cámara de Delegados en la ciudad de San Juan.
Inscripción abierta para médicos de
Puerto Rico, USA e Islas del Caribe
Alcanzando el Éxito, a partir de Cuatro
Lecciones Aprendidas
Se ha identificado que los pagos por los servicios de salud prestados en la Isla, están más
bajos comparados con los de Estados Unidos
continental y otros Territorios no-incorporados
de los Estados Unidos, debido a problemas en
la metodología de calcular los números. Este
issue ha sido presentado a los Directivos de
los Centros para Serrvicios Medicare y Medicaid.
El gobierno federal reconoce que hay disparidad entre los reembolsos por los servicios
prestados entre PR y los Estados Unidos. Se
sabe que hay fondos federales que los puertorriqueños de la Isla no reciben, como son
los fondos para las mejoras de infraestructura
hospitalaria, los llamados “Healthcare Innovations” grants.
Estos hechos una vez reconocidos y validados
deben ser vistos como oportunidades para
solicitar ayuda y hacer crecer nuestro presupuesto.
El problema de Medicare no es un issue de
reglamentos, es un issue político. Por tal razón
se debe preparar una estrategia política para
luchar con este reto. La estrategia de la “víctima” y “que nos cojan pena” ya no funciona.
Debemos impactar los líderes con issues
socio-culturales. Se debe mencionar el discrimen en términos del reembolso por servicios prestados a hospitales y proveedores de
salud. Tenemos que llegar a consenso, tener
una visión y una voz para alcanzar la victoria.
Nuevos Retos de Medicare
Varios factores conducen a la extinción de los
fondos del fideicomiso de Seguros Hospitalarios de Medicare (parte A). Se entiende que los
altos costos del sistema de salud, un cuidado
de salud fragmentado, la limitada información
que reciben los pacientes y proveedores y las
co-morbilidades de los pacientes que envejecen aceleradamente, conducen a este colapso.
El éxito debe incluir una gran dosis de educación a todos los niveles: tanto a los profesionales de la salud, a los pacientes y familiares,
la industria aseguradora y la médico-hospitalaria.
Retos de los médicos con los planes
“Medicare Advantage” (MA)
Se le pide al Centro de Servicios de Medicare
y Medicaid (CMS) que sea más sensible en
términos a la variabilidad cultural. Se deben
entender las diferencias culturales, de la educación, socio-económica, y la práctica de la
medicina en la Isla. La población de pacientes
en la Isla es definitivamente distinta.
Referencias
http://www.medicare.gov/navigation/medicare-basics/medicarebenefits/part-c.aspx
http://www.cms.gov/
http://www.upcap.org/programs_services/mmap.html
6
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Original Article/Artículos Originales
NEUTROPENIA AND
THROMBOCYTOPENIA IN
VERY LOW BIRTH WEIGHT
INFANTS OF WOMEN WITH
PREECLAMPSIA
Norma A. Claudio MDa, Inés García MDa*, Lourdes García MDa,
Marta Valcárcel MDa
9
Department of Pediatrics, Neonatology Section, UPR School
of Medicine and University Pediatric Hospital, San Juan, Puerto
Rico.
*Corresponding author: Inés García, MD - UPR School of Medicine, Department of Pediatrics, Neonatology Section, PO Box
365067, San Juan, PR 00936-5067. E-mail: ines.garcia@upr.
edu
a
ABSTRACT
Objective: Determine the incidence of neutropenia and thrombocytopenia during the first
week of life in very low birth weight (VLBW) infants born to mothers with preeclampsia.
Methods: Medical records of infants born to mothers with preeclampsia admitted to NICU
from 2005-2007 were reviewed. Results: A total of 93 infants were included with a mean
birth weight of 988 g and gestational age of 29 weeks. Neutropenia was present in 49% of
the infants and thrombocytopenia in 56%. Infants with neutropenia had lower birth weights
(p<0.01) and were born at lower gestational ages (p<0.01). Neutropenia was associated to a
higher prevalence of positive blood cultures during the first week of life especially coagulase negative organisms. Conclusions: In this group of VLBW infants born to mothers with
preeclampsia, neutropenia was common and it was associated to increase risk of bacterial
infections during the first week of life.
Index words: neutropenia, thrombocytopenia, low, birth, weight, infants, women, preeclampsia
INTRODUCTION
Preeclampsia is a potentially life-threatening
disease for both mother and fetus and it is
seen in 5% to 8% of all pregnancies (1, 2). It is
primarily a disease of nulliparous women, with
an incidence ranging from 3 to 7% of nulliparous women. In addition, preeclampsia is significantly increased in multifetal pregnancies,
in women with previous preeclampsia, and in
patients with some medical disorders, such as
renal disease, diabetes mellitus, and thrombophilias (3). HELLP syndrome is a variant of
severe preeclampsia, named for the associated constellation of abnormal laboratory values: Hemolysis, Elevated Liver enzymes, and
Low Platelets (2). Hemolysis, defined as the
presence of microangiopathic hemolytic anemia, is the hallmark of the HELLP syndrome.
The cause of preeclampsia is unknown. It is a
multisystemic disorder characterized by vasospasm and coagulation abnormalities and defined by the development of hypertension and
proteinuria appearing after 20 weeks of gestation (1, 2).
Preeclampsia can affect the fetus because of
utero-placental insufficiency and decreased
maternal-fetal oxygen transfer and exchange
of metabolites. The literature reports several
complications in infants of preeclamptic moth-
ers including premature birth, low birth weight
and intrauterine growth restriction, low Apgar
score, microcephaly, leukopenia, neutropenia,
and thrombocytopenia (4). Neonatal morbidity
related to preeclampsia results from associated prematurity, intrauterine growth restriction
(IUGR), or hypermagnesemia (2). These neonates may also have a spectrum of hematological changes that may add to their existing
morbidity (5).
Maternal hypertension and preeclampsia can
lead to unexplained neutropenia that lasts for
several days to weeks in affected infants, associated to the production of an inhibitor of
myeloid progenitor cell proliferation that transplacentally inhibits fetal bone marrow production of neutrophils (6). It has been shown that
neonatal neutropenia associated with maternal hypertension is due to transiently reduced
neutrophil production. However, it is unclear
whether the etiology of this diminution is due
to decreased production of neutrophilic growth
factors, reduced responsiveness of neutrophil
progenitors to these factors, or the presence
of inhibitors (7). Guner and coworkers (7),
showed that the development of neutropenia in
infants of preeclamptic mothers does not seem
to be the result of granulocyte colony stimulating factor (G-CSF) deficiency, since they
found high levels of serum G-CSF, which might
represent a decreased or altered response to
G-CSF in neutropenic infants of preeclamptic
mothers. Doron and coworkers (8), reported
that neutropenia is present at birth in 40% to
50% of infants born to mothers with preeclampsia being most common in very premature infants. Studies show that neutropenia seen in
infants born to mothers with preeclampsia is
mostly transient, tending to resolve naturally
after several days to weeks of life. In some
cases, it may be severe enough as to require
treatment with G-CSF. Some studies suggest
that there may be a propensity to nosocomial
infection, even after resolution of neutropenia. A recent study involving the use of G-CSF
as prophylaxis for the reduction of sepsis in
preterm, small for gestational age neonates
showed no reduction in systemic sepsis or
mortality (9). The objective of this study is to
determine the incidence of neutropenia and
thrombocytopenia during the first week of life
in very low birth weight (VLBW) infants born to
mothers with preeclampsia, to describe its timing of onset and resolution, and to describe the
presence of neutropenia related sepsis.
PATIENTS AND METHODS
Subjects
We reviewed the medical records, the Vermont
Oxford Network forms, and the study protocol
data sheets of very low birth weight (VLBW)
neonates admitted to the Neonatal Intensive
Care Unit of the University Pediatric Hospital
from January 2005 to December 2007. Analysis of the cohort of infants born to mothers
with preeclampsia was performed comparing VLBW newborns with neutropenia and/
or thrombocytopenia during the first week of
life with VLBW newborns without neutropenia
and/or thrombocytopenia. For this study preeclampsia was defined as an elevated blood
pressure of ≥ 140 mmHg systolic or ≥ 90
mmHg diastolic twice after 20 weeks of gestation, and ≥ 300 mg protein in a 24 hour urine
collection as established by the National High
Blood Pressure Education Working Group on
High Blood Pressure in Pregnancy (10). Neonates of eclamptic mothers and HELLP syndrome were also included. The diagnosis was
made by the obstetrician in charge following
the standard criteria described.
For additional analysis a cohort of 70 babies
matched by gestational age and birth weight
was also analyzed. One infant with neutropenia (case) was matched with one infant without
neutropenia (control) on the basis of gesta-
tional age (+1 week) and birth weight (+100
grams).
Data
Patient demographics included maternal age,
infants’ birthweight and gestational age. Hematologic data during the first week of life was
analyzed to record white blood cells (WBC)
count, neutrophil count, absolute neutrophil
count (ANC), immature/total neutrophil ratio,
and platelet count. All infants born to mothers
with preeclampsia had a complete blood count
(CBC) performed at birth, on the second day
of life, and then as clinically indicated. All the
CBC’s performed during the first week of life
were analyzed. Blood cultures performed at
birth and before a change in antibiotic therapy
were included as well as C-reactive protein obtained in the first day of life.
Neonatal neutropenia was defined as a neutrophil count less than 1,500/microL (11). Neutrophil count was calculated as follows: Neutrophil count = WBC/microL x % neutrophils
on the differential count. The immature to total
(I/T) neutrophil ratio was calculated as: I/T =
(Bands)/(neutrophils+bands). Neonatal thrombocytopenia was defined as a platelet count
less than 150,000/microL (12).
Sepsis was defined as the presence of a positive blood culture during the first week of life.
Negative C-reactive protein value was defined
as less than 1 mg/L. Other clinical data recorded included signs and symptoms of sepsis,
changes in antibiotic therapy, metabolic acidosis defined as pH <7.3 and HCO3 < 18 meq/L,
abdominal distention, disseminated vascular
coagulation (DIC), and use of immunoglobulin.
Statistical analysis
Statistical analysis of the collected data was
performed using frequency, mean and range.
Differences among groups were evaluated using Pearson’s chi-square and t-test as appropriate. A p-value of less than 0.05 was considered statistically significant. Statistical analysis
was performed using Statistix 8.0 software.
The University of Puerto Rico Medical Sciences Campus Institutional Review Board approved this study.
RESULTS
Five hundred and sixty seven VLBW infants
were admitted to NICU during the study period with 93 (16%) born to mothers with pre-
10
11
eclampsia. Fifteen percent of those mothers
had HELLP syndrome. Analysis of infants born
to mothers with preeclampsia showed a mean
maternal age of 26 years (range 14-36 years).
The mean birthweight of the infants was 988
grams (ranging from 430-1,460g) and the
mean gestational age was 29 weeks (range
29-36 weeks). Three percent of the babies
(n=3) were multiples.
Laboratory data was available for 80 infants.
Neutropenia was present in 15% (n=12) of the
infants at birth. The incidence of neutropenia
during the first week of life was 49%. Table 1
shows the laboratory data of patients with neutropenia during first week of life. Neutropenia
was first seen at a mean of two days of life
(range 0-7 days), with the lowest absolute neutrophil count (ANC) seen on the 3rd day of life
(range 0-8 days). It resolved at seven days of
life (range 1-13 days). Infants with neutropenia had lower birth weights (851g vs. 1,034g,
p<0.01) and were born at lower gestational
ages (28 weeks vs. 30 weeks, p<0.01). To adjust for these differences, which may be confounders when analyzing the complications associated to neutropenia, a cohort of 70 babies
born to mothers with preeclampsia matched by
gestational age and birthweight was analyzed.
The prevalence of positive blood cultures was
24% (Staphylococcus epidermidis 8%, Klebsiella pneumonia 3%, Enterococcus faecalis
1%, Other organisms 3%). After controlling for
birth weight and gestational age, neutropenia
was associated to a higher prevalence of positive blood cultures during the first week of life
(26% vs. 3%, p=0.0127) especially Staphylococcus epidermidis (18% vs. 0%, p=0.0174)
(See Table 2). C-reactive protein was obtained
in the first day of life in 53 patients (76 %); all
of them were reported negative. CRP was obtained between 2-7 days of life in 10 patients.
Six patients (60%) had positive CRP levels. All
patients with negative CRP had negative blood
cultures. Three patients (50%) with positive
CRP had positive blood cultures (2 cases of
Staphylococcus epidermidis).
Thrombocytopenia was present in 56% (n=52)
of all infants born to mothers with preeclampsia with lowest counts observed ranging from
10,000 to 147,000/microL; it was present in a
mean of two days after birth. The lowest platelet count was seen on the 4th day of life (range
1-10 days) with resolution at 8 days of life (see
Table 3). Thrombocytopenia was present in
18% of infants born to mothers with HELLP
syndrome. Thrombocytopenia was associ-
ated to lower gestational age (28 weeks vs.
30 weeks, p<0.01) and lower birth weight (909
grams vs. 1,087 grams, p<0.01). Thirty-seven
percent of the infants were both neutropenic
and thrombocytopenic.
Regarding clinical signs of sepsis during the
first week of life, 34% (n=26) of the patients
developed hypotension requiring inotropic
support, 41% (n=31) had metabolic acidosis
(pH <7.3 and HCO3 < 18 meq/L), 30% (n=23)
presented abdominal distention, and 5% (n=4)
developed disseminated intravascular coagulation (DIC). In terms of treatment regime,
all the patients were started in antibiotics on
admission and 53% (n=44) had a change in
antibiotics during the first week of life due to
suspected sepsis. Forty two percent (n=32)
received intravenous immune globulin, all of
them in the presence of neutropenia.
DISCUSSION
The neonatal intensive care unit of the University Pediatric Hospital provides services to
infants born to mothers with high-risk pregnancies in Puerto Rico. In our study, neutropenia
was present in 15% of VLBW infants at birth
and in 49% during the first week of life, within
the range reported by previous studies. The
prevalence of thrombocytopenia was 56%.
We do not have information on infants born to
mothers without preeclampsia for comparison.
Others authors have reported the incidence
of neutropenia to be 38% and thrombocytopenia 58% among extremely low birth weight
(ELBW) neonates during the first week (13).
In our study thrombocytopenia was present
in 18% of infants born to mothers with HELLP
syndrome. Nikischin and coworkers (14), reported its presence in 11% of premature infants of mothers with HELLP.
The fact that some infants developed neutropenia after birth may represent nosocomial infection rather than direct effects from preeclampsia. Infants with neutropenia had lower birth
weights and were born at lower a gestational
age that is similar to what has been reported
recently by Zook and colleagues (15). Gunner and colleagues (7), reported that although
80% of preeclampsia associated neutropenia
resolves by 60 hours of postnatal age, it may
persist for as long as 30 days. Koenig and
Christensen in 1989 (16) reported that 49% of
newborns of hypertensive mothers had neutropenia, which is transient (range 1 to 60 hours)
in 83% of the infants and prolonged (range 3
to 30 days) in 17%. In our study, resolution of
12
neutropenia occurred at a mean of 7 days after birth; resolution was observed in 1 to 13
days of postnatal age. Due to the retrospective nature of our study we may have missed
the exact timing of onset and recovery in some
infants since after the second day of life the
blood counts were done as clinically indicated.
The risk of sepsis associated with neutropenia
in infants born to mothers with preeclampsia
remains controversial (17). Fraser and colleagues (18) performed a retrospective review
of the hematology of newborns of hypertensive mothers born over a two-year period. Two
hundred forty nine infants had full blood examinations. They found 7.6% of these patients
to be neutropenic, 14.1% thrombocytopenic,
and 4.4% both neutropenic and thrombocytopenic. They reported that 10% of the neutropenic infants developed nosocomial infection,
concluding that although they found that hematological abnormalities in infants born to hypertensive mothers were uncommon, neonatal complications can occur, warranting early
hematological screening of these infants. The
study by Koenig and colleagues (16) showed
that nosocomial infections occurred during the
first 2 1/2 weeks of life in 23% of the newborns
with neutropenia but in only 3% of those without this disorder. In our study, 26% of neutropenic infants had bacterial sepsis during the
first week of life. The most common organism
reported was coagulase negative staphylococci (CoNS). It is known that a high proportion
of blood cultures obtained from preterm neonates show contaminants (9). Nevertheless,
we did not find any blood culture with CoNS in
the group of infants without neutropenia.
Due to the retrospective nature of this study,
we did not have complete CRP data available
and we did not analyze other markers of sepsis, such as procalcitonin. Nevertheless, all patients with negative CRP had negative blood
cultures. Ng and colleagues (19) reported that
C-reactive protein is the best single marker for
late onset neonatal sepsis in very low birthweight infants, with a sensitivity of 84% and a
specificity of 96%. While C-reactive protein is
a specific late infection marker, cytokines, cell
surface markers and procalcitonin are early infection markers (18). The use of multiple markers such as C-reactive protein, procalcitonin,
interleukin -6, among others have been shown
to be useful both to early (24-48 hrs.) diagnosis
of neonatal sepsis and to monitor the antibiotic
treatment while waiting for the results of culture examinations (20). Serum amyloid A has
also been studied as an accurate and reliable
marker for diagnosis and follow-up of neonatal
sepsis (21). It is especially useful at the onset
of inflammation for rapid diagnosis of neonatal
sepsis and can be safely and accurately used
in combination with other sepsis markers such
as C-reactive protein and procalcitonin in diagnosis and follow up of neonatal sepsis in preterm infants (21).
A limitation of this study is its retrospective nature. However, it confirms that VLBW infants
born to mothers with preeclampsia are at risk of
developing neutropenia and thrombocytopenia
during the first week of life. This neutropenia
increases the risk of bacterial sepsis. Further
prospective studies analyzing other markers
of sepsis will help understand better the relation between neutropenia and sepsis in infants
born to mothers with preeclampsia.
REFERENCES
(1) Mellembakken J, Aukrust P, Hestdal K,
Ueland T, Abyholm T, Videm V. Chemokines
and leukocyte activation in the fetal circulation during preeclampsia. Hypertension 2001;
38(3):394-398.
(2) Lyell DJ. Hypertensive disorders of pregnancy. Neoreviews 2004; 5(6) e240. Available:
http://neoreviews.aappublications.org/cgi/content/full/neoreviews;5/6/e240 via the INTERNET. Accessed Sep 2, 2005.
(3) Hnat MD, Sibai BM. Hypertensive Disorders
in Pregnancy. In: Spitzer A. Intensive Care of
the Fetus and Neonate. 2nd Ed. Philadelphia:
Elsevier; 2005. pp 292-310.
(4) Brazy JE, Grimm JK, Little VA. Neonatal
manifestations of severe maternal hypertension occurring before the thirty-sixth week of
pregnancy. J Pediatr 1982; 100(2):265-271.
(5) Sivakumar S, Vishnu B, Ashok B. Effect
of pregnancy induced hypertension on mothers and their babies. Indian J Pediatr 2007;
74(7):623-625.
(6) Koenig JM, Yoder MC. White blood Cell
Disorders in the Neonate. In: Spitzer A. Intensive Care of the Fetus and Neonate. 2nd Ed.
Philadelphia: Elsevier; 2005. pp 1313-1329.
(7) Guner P, Yioit P, Mualla C, et al. Evaluation
of serum granulocyte colony stimulating factor
levels in infants of preeclamptic mothers. Turk
J Pediatr 2007; 49(1):55-60.
(8) Doron MW, Makhlouf RA, Katz VL, Lawson
EE, Stiles AD. Increased incidence of sepsis
at birth in neutropenic infants of mothers with
preeclampsia. J Pediatr 1994;125:452-458.
(9) Carr R, Brocklehurst P, Doré C, Modi N.
Granulocyte-macrophage colony stimulating
factor administered as prophylaxis for reduc-
13
tion of sepsis in extremely preterm, small for
gestational age neonates (the PROGRAMS
trial): a single-blind, multicentre, randomized
controlled trial. Lancet 2009;373:226-233.
(10) National High Blood Pressure Education
Working Group on High Blood Pressure in
Pregnancy. Report of the National High Blood
Pressure Education Program Working Group
on High Blood Pressure in Pregnancy. Am J
Obstet Gynecol 2000; 183(1):S1-S22.
(11) Maheshwari A, Christensen RD. Neutropenia in the neonatal intensive care unit. Neoreviews 2004;5(10): 431.
(12) Sola MC, Christensen RD. Developmental
aspects of platelets and disorders of platelets
in the neonatal period. In: Christensen RD.
Hematologic problems of the neonate. 1st Ed.
Philadelphia (PN): W.B. Saunders Company;
2000. pp 273-309.
(13) Christensen RD, Henry E, Wiedmeier SE,
Stoddard RA, Sola MC, Lambert DK. Thrombocytopenia and neutropenia among extremely low birth weight neonates. Haematologica
Reports 2006; 2(10):126-132
(14) Nikischin W, Conradt A, Schroder H. Clinical course of premature and newborn infants
of mothers with HELLP syndrome. Z Geburtshilfe Perinatol 1991; 195(1):16-20
(15) Zook KJ, Mackley AB, Kern J, Paul DA.
Hematologic effects of placental pathology on
very low birth weight infants born to mothers
with preeclampsia. J Perinatol 2009;29:8-12.
(16) Koenig JM, Christensen RD: Incidence,
neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension. N Engl J Med 1989;321:557.
(17) Paul D, Leaf K, Sciscione A, Tuttle D, Stefano J. Preeclampsia does not increase the
risk for culture proven sepsis in very low birth
weight infants. Am J Perinatol 1999; 16(7):
365-372.
(18) Fraser SH, Tudehope DI. Neonatal neutropenia and thrombocytopenia following maternal hypertension. Journal of Pediatrics &
Child Health 1996;32(1):31-34.
(19) Ng PC, Cheng SH, Chui KM, et al. Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive
protein in preterm very low birthweight infants.
Arch Dis Child Fetal Neonatal Ed 1997; 77(3):
F221-7
(20) Zuppa AA, Calabrese V, D’Andrea V, et
al. Evaluation of C-reactive proteína and others immunologic markers in the diagnosis of
neonatal sepsis. Minerva Pediatr 2007 Jun; 59
(3): 267-74
(21) Cetinkaya M, Ozkan H, Koksal N, Celebi
S, Hacimustafaoglu M. Comparison of serum
amyloid A concentrations with those of C-re-
14
active protein and procalcitonin in diagnosis
and followup of neonatal sepsis in premature
infants. J Perinatol 2009 Mar; 29(3):225-31
DIFFERENCES IN
PREVALENCE OF
INFLAMMATORY BOWEL
DISEASE IN PUERTO RICO
BETWEEN COMMERCIAL
AND GOVERNMENTSPONSORED MANAGED
HEALTH CARE INSURED
INDIVIDUALS
Roberto Vendrell MDa*,
Heidi L. Venegas PhDb, Cynthia M.
Pérez PhDb, Carlos Morell MSc, Ruth V.
Román MPHc, Esther A. Torres MDa
ABSTRACT
RESUMEN
Objetivos: Determinar la incidencia
de neutropenia y trombocitopenia
durante la primera semana de vida
en infantes de bien bajo peso nacidos de madres con preeclampsia.
Métodos: Se revisaron los expedientes médicos de infantes nacidos
de madres con preeclampsia admitidos al NICU entre 2005-2007.
Resultados: Un total de 93 infantes
fueron incluidos con peso promedio al nacer de 988g (430-1,460g)
y edad gestacional de 29 semanas
(24-36 semanas). Ocurrió neutropenia en 49% de los infantes y trombocitopenia en 56%. Infantes con
neutropenia tuvieron pesos más
bajos al nacer (p<0.01) y fueron
de edades gestacionales menores
(p<0.01). Neutropenia estuvo asociada a una mayor prevalencia de
cultivos de sangre positivos durante la primera semana de vida
especialmente con organismos
coagulasa negativo. Conclusión:
En infantes de bien bajo peso nacidos de madres con preeclampsia,
la neutropenia fue común y estuvo
asociada a un riesgo aumentado de
infecciones bacterianas durante la
primera semana de vida.
Background: Evaluation of ethnic and racial
patterns of Inflammatory Bowel Disease
(IBD) has demonstrated a higher incidence
of IBD in Jews, and lower rates in blacks
and Hispanics when compared to whites.
There is limited data describing incidence
and prevalence among Hispanics, the fastest growing minority in the United States.
Methods: To estimate the prevalence of IBD
computerized records of all physicians billing and hospital discharges classified with
ICD-9-CM IBD related codes were searched.
Prevalence was estimated by age group,
sex, and type of insurance (commercial
versus government-sponsored managed
care). Results: Of 1,248,993 insured individuals in 2005, 186 had a diagnosis of
Crohn’s disease and 291 of ulcerative colitis. The estimated prevalence per 100,000
was 14.9 for Crohn’s disease, 23.3 for ulcerative colitis, and 38.2 cases for IBD. The
most significant difference was found when
comparing insurance type, with a total IBD
prevalence rate of 61.75 cases among commercial versus 14.36 cases among government-sponsored insured. Conclusions:
The prevalence of IBD in this insured population in Puerto Rico places it among the
highest described in a Hispanic population.
Given the continued rise in prevalence of
IBD and the limited studies describing the
epidemiology of IBD in Hispanics, further
studies which may provide important clues
to the etiology of the disease as well as
valuable information for appropriate health
care planning are important.
Index words: prevalence, inflammatory,
bowel, disease, commercial, government
15
Department of Medicine, School of Medicine, University of
Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
Department of Biostatistics and Epidemiology, School of Public Health, University of Puerto Rico Medical Sciences Campus,
San Juan, Puerto Rico
c
Statistical and Research Analysis Department, Triple S Inc, San
Juan, Puerto Rico
*Corresponding author: Roberto Vendrell MD – Department of
Medicine, UPR School of Medicine, PO Box 365067 San Juan,
PR 00936-5067. E-mail: robertovendrell@yahoo.com
a
b
INTRODUCTION
The inflammatory bowel diseases (IBD),
Crohn’s Disease (CD) and Ulcerative Colitis
(UC) are disorders of the gastrointestinal tract
that have both distinct and overlapping pathologic and clinical characteristics. Their pathogenesis remains incompletely understood.
Recent studies suggest genetic and environmental components in the development of
disease, as well as possible dysregulation of
the gastrointestinal immune system (1, 2). The
geographical incidence of IBD varies considerably with the highest incidence rates reported
in Northern and Western Europe and North
America. Recent data suggests that incidence
rates in these developed, more industrialized
areas, are beginning to stabilize while areas
with lower incidence rates, such as Asia, southern Europe, and the developing world continue
to rise considerably (3-5).
Evaluation of ethnic and racial patterns of IBD
has demonstrated a higher incidence of IBD in
Jews, and lower rates in Black and Hispanic
populations when compared to Whites. There
is limited data describing incidence and prevalence among Hispanics, the fastest growing minority in the United States. A population-based
survey conducted in Panama and Argentina
during 1987-1993 estimated an annual incidence of UC of 1.2/100,000 in Panama, and
2.2/100,000 in Argentina. Only a single case of
CD was identified. A study by Kurata reported
a prevalence of CD in Hispanics subscribed
to the Southern California Kaiser Permanente
Medical Care Program of 4.1/100,000 from
1982 to 1988 (6). A study of Medicare patients
in the 1980’s showed that hospitalization for
IBD among Hispanics was uncommon (7).
In Puerto Rico, few studies have been conducted describing the epidemiology of IBD. A
study estimating prevalence of inflammatory
bowel disease in an insured patient population in 1996 reported 106.1 cases per 100,000
(8). In this study, a case was defined as one
physician-billing claim classified with the ICD9-CM for CD or UC. Another study describing
the basic epidemiology of inflammatory bowel
disease in southwest Puerto Rico from private gastroenterology offices, estimated an
incidence rate of 7.74 cases per 100,000 and
prevalence of 24.81 cases per 100,000 (9).
cerative colitis by age group, sex, and type of
insurance (private vs. government-sponsored)
was calculated. All estimations were performed
using STATA version 9 (Stata Corporation, College Station, Texas).
The objective of this study was to estimate the
most current prevalence of IBD in Puerto Rico
and to compare the prevalence between individuals with commercial insurance and those
with a government-sponsored managed care
plan for the low-income population.
Of 1,247,792 insured individuals in 2005, 186
had a diagnosis of Crohn’s Disease and 291
had ulcerative colitis. The estimated prevalence per 100,000 was 14.9 for Crohn’s Disease, 23.3 for ulcerative colitis, and 38.2 cases
for IBD. From 2002-2005 there was a significant increase in prevalence of IBD in Puerto
Rico (see Table 1).
METHOD
The data was obtained from Triple S, the major health insurance company in Puerto Rico,
which offers commercial health insurance and
a government-sponsored managed care plan
for the low-income medically indigent population that previously received services directly
from the Puerto Rico, Department of Health.
In 2005, Triple S had an estimated 1,247,792
insured participants over the island, representing all geographic and socioeconomic groups,
including 619,441 from the governmentsponsored managed care plan and 628,351
from commercial insurance. This represents
approximately 33% of the total population of
Puerto Rico, estimated at over 3.8 million in
the 2000 census.
Computerized records of all physician billing claims and hospital discharges classified
with ICD-9-CM codes 555.0-555.9 (Crohn’s
Disease) and 556.0-556.0 (ulcerative colitis)
from January 1, 2002 through December 31,
2005 were identified. Cases were defined as
individuals having had at least two health system contacts with the ICD-9 codes specified
above, and at least one of which was from a
gastroenterology specialist. By utilizing this algorithm for case ascertainment we attempted
to include the majority of patients who have
met diagnostic criteria for IBD, but at the same
time being careful not to exclude those patients
with the actual diagnosis who did not meet our
criteria. Because of contractual privacy clauses, the medical records were not available for
review and confirmation of the diagnosis.
The annual prevalence was estimated as the
number of cases divided by the mid- year
number of insured participants with Triple S.
Prevalence was estimated with 95% confidence (95% CI) using Poisson exact methods.
Specific prevalence of Crohn’s disease and ul-
RESULTS
The most significant difference was found
when comparing insurance type, with a total IBD prevalence in 2005 of 61.75/100,000
cases among the commercially insured versus 14.36/100,000 cases among government
sponsored insured (see Table 2). For CD, the
prevalence in the commercially insured group
and government-sponsored group was estimated at 23.08/100,000 and 6.62/100,000 respectively. For UC, a similar pattern was observed with a much higher prevalence in the
commercially insured group (38.7/100,000 vs.
7.8/100,000). When comparing prevalence
throughout the study period 2002-2005, the
government-sponsored insured reveal an increasing trend in all groups, whereas in the
commercially insured group no specific trend
was identified.
Peak prevalence of IBD in the commercially
insured occurred in the group ages 40-49 and
in the government-insured in the group ages
30-39 (see Table 2). Peak prevalence of CD
in the commercially insured occurred among
the group ages 20-29 (see Table 3). Ulcerative
colitis was most prevalent among the group
ages 40-49 in the commercially- insured. In
the government-sponsored group, UC was
most prevalent in the age group 30-39 (see
Table 4). The prevalence of CD was higher
among males in both groups, while for UC the
disease was more prevalent among females.
DISCUSSION
The prevalence of IBD in insured people in
Puerto Rico places it at the highest described
in a Hispanic population. The present study
reveals an increase in prevalence when compared with a recent study in southwest Puerto
Rico that estimated a prevalence of 24.81 cases per 100,000 in 2000. This study was carried
16
17
out with representation of the general population of Puerto Rico across all geographic and
socioeconomic groups, unlike the previous
study that was carried out in a specific region
of Puerto Rico from private gastroenterology
offices. Also, contrary to the study carried out
in 1996, a more stringent case definition for
case ascertainment was now used.
The prevalence of Ulcerative colitis was higher
than that of Crohn’s disease. It has been suggested that as societies become more industrialized, ulcerative colitis emerges. Over time
Crohn’s disease becomes more prevalent, ultimately matching that of ulcerative colitis. This
pattern has been observed in previously low
incident areas. It is interesting to note that in
fact trends from 2002-2005 reveal an increasing prevalence of Crohn’s disease and stable
prevalence of ulcerative colitis.
The prevalence of CD was higher in males
than in females, contrary to what has been observed in Northern and Western Europe and
North America. Interestingly, the two previous
studies carried out in Puerto Rico found similar
results (8, 9).
There is a clear difference in prevalence between commercially insured individuals and
government-sponsored insurers. This difference could represent the impact of socioeconomic factors in the emergence of these diseases. A recent study by our group found both
Crohn’s Disease and ulcerative colitis to be
less common in the Puerto Rican population
who grew up in a less “hygienic” environment
with lack of running water in the house and a
system of public sewer (10). This correlates
with a lower prevalence rate found in the population enrolled in the government-sponsored
insurance; hence, belonging to a lower socioeconomic status.
18
This difference between insurance types could
also be explained by disparities in access to
medical care, more specifically, to subspecialty
care. The government-sponsored program is a
managed care capitated system requiring referrals from primary care providers for specialty care. Further investigation is warranted to
determine whether insurance type and limited
access to care is contributing to the reported
lower prevalence among lower income individuals. If this is the case, the real prevalence of
IBD in Puerto Rico may be much higher.
The methodology to estimate prevalence may
have led to misclassification of disease since
medical records were unavailable for review
and confirmation of diagnosis. However, requiring at least two health system contacts
with the ICD-9 codes, of which at least one of
them was from a gastroenterology specialist,
is expected to yield a more accurate estimate.
A similar method of case definition has been
used by others to identify true IBD cases (11).
Given the continued rise in prevalence of IBD
and the limited studies describing the epidemiology of IBD in Hispanics, it is important to
conduct current studies which may provide important clues to the etiology of the disease, as
well as provide valuable information for appropriate health care planning. Whether this increasing prevalence of disease in developing
countries is due to greater awareness, better
access to health care and diagnostic practices
or environmental factors needs to be further
evaluated.
REFERENCES
1. Podolsky DK. Inflammatory bowel disease. N Engl J Med
2002; 347:417-429.
2. Bamias G, Nyce M, De La Rue S, Cominelli F. New concepts
in the pathophysiology of inflammatory bowel disease. Ann Intern Med 2005; 145:895-904.
3. Loftus E. Clinical epidemiology of inflammatory bowel dis-
ease: Incidence, prevalence, and environmental influences.
Gastroenterology 2004; 126:1504-1517.
4. Lakatos PL. Recent trends in the epidemiology of inflammatory bowel disease: Up or down? World J Gasgtroenterol 2006;
12(38):6102-6108.
5. Thia K, Loftus E, Sandborn W, et al. An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenteol 2008; 103: 3167-3182..
6. Kurata JH, Kantor-Fish S, Frankl H, et al. Crohn’s disease
among ethnic groups in a large health maintenance organization. Gastroenterology 1992; 102:1940.
7. Sonnenberg A, Wasserman IH. Geographic variation of inflammatory bowel disease within the United States. Gastroenterology 1991; 100:143-149.
8. Torres EA, De Jesús R, Pérez C, et al. Prevalence of inflammatory bowel disease in an insured population in Puerto Rico
1996. PRHSJ 2003; 22(3): 253-258.
9. Appleyard CB, Hernández G, Ríos-Bedoya C. Basic epidemiology of inflammatory bowel disease in Puerto Rico. Inflamm
Bowel Dis 2004; 10:106-111).
10. Vendrell R, Cruz A, Ortiz Z, et al. Childhood environmental
factors in Hispanics with inflammatory bowel disease: A casecontrol study [abstract]. Gastroenterology 2007; T1308-A517.
11. Bernstein C, Wadja A, Svenson L, et al. The epidemiology
of inflammatory bowel disease in Canada: A population-based
study. Am J Gastroenteol 2006; 101: 1559-1568.
RESUMEN
Evaluación de patrones étnicos y raciales en
la enfermedad inflamatoria del intestino (EII)
ha demostrado una mayor incidencia en judíos
y tasas más bajas en los negros e hispanos
en comparación con los blancos. Los datos
epidemiológicos en poblaciones hispanas
son limitados, la minoría de más rápido
crecimiento en los Estados Unidos Métodos:
Para estimar prevalencia de EII, se analizaron todas las reclamaciones medicas y las
altas hospitalarias con el diagnostico principal
(ICD-9 CM) de enfermedad de Crohn y colitis
ulcerosa durante los anos 2002-2005. Prevalencia se estimo por grupo de edad, sexo, y
el tipo de seguro medico (comercial versus
Reforma de Salud). Resultados: De 1,248,993
participantes en 2005, 186 tenían un diagnostico de enfermedad de Crohn y 291 de
colitis ulcerosa. La prevalencia estimada por
cada 100,000 fue de 14.9 para enfermedad de
Crohn, 23.3 para colitis ulcerosa y 38.2 total
de EII. La diferencia mas significativa ocurrió
cuando se comparo el tipo de seguro medico,
con una prevalencia total de EII de 61.75 en
asegurados comerciales versus 14.36 en asegurados con Reforma de Salud del gobierno
de Puerto Rico. Conclusiones: La prevalencia
de EII en este grupo de asegurados en Puerto
Rico la coloca en la más alta descrita en una
población hispana. Debido al continuo incremento en la prevalencia de EII y los pocos
estudios descriptivos en hispanos, más estudios son necesarios que puedan proveer información sobre la etiología de la enfermedad e
información esencial para la planificación del
cuidado de salud.
20
EMBOLIZACION DE TUMORES HIPERVASCULRES
DE LA BASE DEL CRANEO:
Descripción de una serie de casos y propuesta de
un algoritmo terapéutico
Rafael Almeida Pérezab, Héctor Espinosa-Garcíab, Gabriel Alcalá-Cerraac*, Ginna de
la Rosa Manjarrézb, Fernando Orozco Gómezb, Adalberto Rafael Mejía Barriosd
Sección de Neurocirugía, Universidad de Cartagena, Cartagena de Indias, Colombia.
Servicio de Neurocirugía Endovascular y Neuroradiología Intervencionista. Neurodinamia S.A. Cartagena de Indias, Colombia.
c
Grupo de Investigación en Ciencias de la Salud y Neurociencias (CISNEURO). Cartagena de indias, Colombia.
d
Sección de Radiología. Universidad del Norte. Barranquilla,
Colombia.
*Autor correspondiente: Gabriel Alcala-Cerra - Neurodinamia
S.A. Barrio Manga, Callejón Santa Clara. Carrera 19 # 24-183,
piso 2. Tel +57-6606225. Cartagena de Indias, Colombia. Email: alcalagabriel@gmail.com
a
b
Agradecimientos
A todo el grupo de Neurodinamia S.A. por
el esfuerzo y dedicación durante el tratamiento de los pacientes incluidos en este
estudio.
profundidad del tumor o guardan relación con
estructuras neurovasculares que deben ser
preservadas. Para el control vascular de estos
tumores, la embolización prequirúrgica (EPQ)
ha ganado aceptación como terapia adyuvante
en la disminución del sangrado intra-operatorio
y sus riesgos asociados. Sin embargo, en algunos casos, la embolización puede de tener
poca utilidad o conllevar riesgos inaceptables,
por lo que su indicación debe con base en el
análisis de los estudios preoperatorios.
En el presente estudio se describen las experiencias con el uso de la embolización endovascular de los tumores hipervasculares de la
base del cráneo y se presenta una revisión de
la literatura enfocada a la selección racional
de los casos que más pueden beneficiarse de
este tratamiento.
En casos seleccionados a criterio del intervencionista, se realizaron evaluaciones neurológicas clínicas posteriores a la inyección
de lidocaína diluida y/o propofol, con el fin de
evaluar potenciales déficits neurológicos que
pudiesen ser ocasionados por la oclusión definitiva de la arteria.
Para la embolización se utilizaron partículas
de polivinilo-alcohol (PVA) entre 150 y 450
micras suspendidas en medio de contraste,
esponja quirúrgica absorbible (GELFOAM®,
Baxter Healthcare Corporation. CA, USA)
embebida en medio de contraste y/o líquidos
embolizantes (Onyx®; ev3 Inc. Irvine, CA). En
los casos en que la cirugía se planea realizar
dentro de las siguientes 72 horas de la embolización, se prefirieron las partículas de PVA,
mientras que en aquellos en los que la cirugía
se diferiría más allá de este periodo, se consideró la utilización de líquidos embolizantes.
RESUMEN
MATERIALES Y METODOS
La embolización prequirúrgica permite la reducción del sangrado intraoperatorio de los tumores intracraneales hipervasculares y sus consecuencias indeseables. Objetivo: Describir la experiencia con la embolización endovascular de los tumores basicraneales hipervasculares y
construir un algoritmo terapéutico. Materiales y Métodos: Se realizó una
revisión retrospectiva de los estudios imagenológicos preoperatorios
y los resultados de la embolización prequirúrgica. Resultados: Fueron
identificados un total de 15 casos, con una mediana de edad de 36 años,
en su mayoría, portadores de meningiomas, angiofibromas nasofaríngeos o paragangliomas. La arteria carótida externa estuvo involucrada
en 93% de los casos y era la única aferente en 60%. En 27%, existían simultáneamente ramas procedentes de la carótida interna y externa. En
95% de los ramos de la arteria carótida externa se lograron oclusiones
extensas o completas. Ningún ramo de la carótida interna fuer tratado,
debido a que aportaban muy poca irrigación al tumor o no fue posible
cateterizar el pedículo. No se registraron complicaciones relacionadas
con el procedimiento. Conclusiones: Con base en la unificación de las
experiencias descritas en este estudio, con los datos extraídos de las
series publicadas en la literatura, se presenta un algoritmo didáctico
para la selección racional de los tumores de la base del cráneo que pueden beneficiarse de la embolización prequirúrgica.
Se realizó un estudio observacional, descriptivo y retrospectivo, revisando los resultados de
exclusión vascular de tumores hipervasculares de la base de cráneo que fueron remitidos
para embolización preoperatoria en el servicio
de neurocirugía endovascular de Neurodinamia S.A. (Cartagena de Indias, Colombia)
durante el periodo comprendido entre Enero 1
de 2010 hasta Diciembre 31 de 2011.
Análisis de los resultados postoperatorios
Técnica quirúrgica
Fueron sistemáticamente registradas las
siguientes variables: edad, género, histología
del tumor, número de afluentes arteriales y
porcentaje de oclusión de cada arteria tratada.
Palabras índices: embolización, tumor, hipervascular, base, cráneo, algoritmo
INTRODUCCION
Las pérdidas sanguíneas que generan los
tumores hipervasculares de base de cráneo
durante el acto quirúrgico pueden poner en
riesgo la vida del paciente y/o ocasionar morbilidades relacionadas con la transfusión de hemoderivados. Asimismo, la disminución de la
visibilidad dificulta la manipulación de las estructuras intracraneales, aumentando el riesgo
de lesiones neurales y vasculares, y disminuyendo la eficacia de la resección quirúrgica .
Durante la década de los 80´s, Yasargil popularizó el control vascular precoz como principio
general para optimizar el tratamiento de los tumores intracraneales. Este precepto, sin embargo, no siempre puede ser cumplido cuando
se abordan tumores de la base del cráneo, debido a que los vasos nutricios se originan en la
Todos los pacientes fueron intervenidos vía
trans-femoral por el mismo equipo de neurocirugía endovascular utilizando neuro-leptoanestesia o anestesia general inhalatoria,
dependiendo el caso y la necesidad prevista
de realizar evaluaciones funcionales intra-operatorias.
A todos los pacientes se les realizó angiografía convencional con sustracción digital,
utilizando un angiógrafo con mapa de trabajo (Innova® 3100; General Electric, Fairfield,
Connecticut). Se realizaron sistemáticamente
las inyecciones selectivas del medio de contraste no iónico en las arterias carótidas externas, carótidas internas y vertebrales. Posteriormente, se procedió con la cateterización
y angiografía supra-selectiva de las ramas arteriales que mayor suplencia aportaban al tumor. El estudio angiográfico permite además,
identificar anastomosis arteriales intra-extracraneales, que contraindiquen la embolización
debido al alto riesgo de migración del material
embolizante .
Para la evaluación de los resultados de la
oclusión de la vasculatura tumoral, fueron
revisadas las angiografías preoperatorias y
postoperatorias por un grupo de cuatro neurocirujanos o neuroradiólogos con sub-especialidad en terapia endovascular neurológica (por
lo menos dos).
El porcentaje de oclusión se estableció mediante la escala propuesta por Trivelatto y colaboradores en 2011 . De acuerdo a esta clasificación, la oclusión se considera: Escasa, si
la desaparición de la impregnación de todo el
lecho tumoral es menor al 30%, moderada entre 30 y 60%, extensa entre 60 y 90% o completa si es mayor del 90%.
El registro y análisis de datos se realizó en
una base de datos de ‘Microsoft Excel Spreadsheet’ (Londres, UK).
RESULTADOS
Durante el periodo de estudio fueron tratados
15 pacientes portadores de tumores hipervasculares en la base del cráneo, de los cuales ocho (53,3%) eran varones. Todos los
pacientes tenían edad entre los 12 y 70 años
de edad, con una mediana de edad de 36,3
(rango inter-cuartílico: 18 a 53). La histología
21
de los tumores intervenidos es detallada en la
Tabla 1.
La cateterización selectiva de los vasos intracraneales demostró que en 93,3% de los casos, la arteria carótida externa participó en la
irrigación de estos tumores, y en 60% era la
única arteria que los nutría. Asimismo, esta arteria participaba de la suplencia en conjunto
con la arteria carótida interna en 26,7%. En un
caso (6,7%), el tumor recibía irrigación simultáneamente por ramas de la arteria vertebral
y la carótida externa, y en otro, solamente a
través de la arteria vertebral, por medio de las
dos arterias cerebelosas postero-inferiores.
No fueron encontrados casos cuya irrigación
fuese exclusivamente derivada de la arteria
carótida interna.
En el 95,2% de los ramos de la arteria carótida
externa embolizados, se lograron porcentajes
de oclusión extensos o completos, de acuerdo
a la clasificación de Trivelatto y colaboradores
. Sin embargo, en un caso (glomus timpánico),
los ramos tumorales procedentes de la arteria
occipital no fueron tratados debido a la presencia de anastomosis con la arteria meníngea
posterior y se percibió alto riesgo de migración
del material embolizante hacia la arteria vertebral.
Uno de los casos que no fue devascularizado
en su totalidad, corresponde a un hemangioblastoma que se nutría a través de ambas ar-
terias cerebelosas postero-inferiores, aunque
la gran mayoría del aporte provenía de la
derecha. Esta última fue embolizada, mientras
que la contralateral no fue tratada debido a su
tortuosidad y fino calibre (Caso ejemplo No. 2).
Ninguno de los ramos tumorales de la arteria
carótida interna fue tratado, debido a que aportaban muy poca irrigación al tumor (tres casos)
o no era posible acceder al pedículo (un caso).
Asimismo, un ramo originado en la arteria vertebral (meningioma petro-clival) no se intentó
cateterizar con los microsistemas debido a su
diámetro extremadamente pequeño.
de perfusión por tomografía, el cual confirmó
la abundante vascularización del tumor.
En ningún caso se presentaron complicaciones neurológicas, médicas, técnicas ni relacionadas con el acceso femoral ni con el procedimiento.
El estudio angiográfico demostró una tinción
capilar neoformada tumoral que se impregnaba por ramas de la arteria maxilar interna y
meníngea media, las cuales fueron completamente ocluidos con partículas de PVA. Durante la resección quirúrgica, se apreció reblandecimiento del tumor y se logró una resección
extensa (Simpson II) con poco sangrado intraoperatorio (ver Figura 2).
Caso ejemplo No. 1.
Caso ejemplo No. 2.
Paciente masculino, de 59 años de edad con
cuadro clínico de cefalea, náuseas, vómitos y
hemiparesia izquierda. Se realizó inicialmente
una tomografía cerebral contrastada y se estableció la impresión diagnóstica de un meningioma gigante del ala del esfenoides derecha
Bonnal D. Para definir la indicación de la embolización pre-quirúrgica, se realizó el estudio
Paciente femenino, de 24 años de edad con
cuadro clínico de cefalea matutina, náuseas,
vómitos y amaurosis rápidamente progresiva.
Una resonancia magnética cerebral contrastada demostró una lesión tumoral cerebelosa
derecha, de intensidad heterogénea, con imágenes serpiginosas y vacíos de señal, alta-
En la Figura 1 se especifican los porcentajes
de oclusión de cada uno de los casos analizados.
22
mente sugestivas de un hemangioblastoma.
Durante la angiografía cerebral se evidenció
gran impregnación en fase capilar neoformada
en hemisferio cerebeloso derecho y vermis,
suplida por medio de ambas arterias cerebelosas postero-inferiores. Se procedió a la embolización de los vasos tumorales provenientes de la arteria cerebelosa postero-inferior
derecha, lográndose gran disminución en la
impregnación del tumor (ver Figura 3).
Caso ejemplo No. 3.
Paciente femenino, de 64 años de edad con
cefalea intensa de ocho meses de evolución,
asociado a crisis epilépticas tónico-clónicas
focales que comprometían el miembro inferior derecho. Se realizó tomografía cerebral
sin contraste que demostró una lesión tumoral
que se extendía por la parte medial del piso
de la fosa anterior, compatible con un meningioma gigante del surco olfatorio.
23
La evaluación angiográfica demostró impregnación capilar tumoral anómala en la región
mesial del lóbulo frontal, a través de las ramas
etmoidales anteriores de las arterias oftálmicas. Debido al alto riesgo de complicaciones
visuales que podría conllevar la embolización,
no se procedió con el procedimiento (ver Figura 4).
DISCUSION
La embolización de los tumores intracraneales
hipervasculares permite acceder al control de
la irrigación antes del procedimiento quirúrgico. Varios estudios han demostrado sus beneficios en términos de reducción del sangrado,
tiempo operatorio, estancia hospitalaria postoperatoria, requerimientos de hemoderivados,
morbilidad y mortalidad . Adicionalmente, se
ha evidenciado que los tumores resecados
parcialmente previamente embolizados tienen
menor riesgo de progresión . Estos conceptos
han resultado del análisis de varias series que
estudiaron tumores intracraneales hipervasculares; sin embargo, las experiencias publicadas con el manejo de las lesiones que comprometen la base del cráneo es notablemente
escasa .
Las más recientes guías de la Sociedad de
Cirugía Neurointervencionista recomiendan
24
25
considerar la embolización preoperatoria en
los casos en que se sospechen angiofibromas
nasofaríngeos juveniles, hemangiopericitomas, hemangioblastomas, meningiomas, metástasis, paragangliomas y paragangliomas .
Estos lineamientos, sin embargo, no realizan
propuestas específicas de acuerdo a la ubicación de la lesión, ni tampoco hacen referencia a la utilidad de los estudios de perfusión
por neuro-imágenes para la indicación racional del procedimiento.
Las observaciones de este estudio y la revisión de la literatura resaltan la importancia
de la evaluación imagenológica no invasiva
como herramienta fundamental para la indicación racional de la embolización, ya que
existen lesiones cuya utilidad puede ser limitada o nula, bien sea por su naturaleza relativamente avascular o por los riesgos previstos
que acarrearía su tratamiento.
Se ha encontrado que aproximadamente
el 10% de los pacientes referidos para una
eventual embolización poseen tumores angiográficamente avasculares, aun cuando las
neuro-imágenes convencionales sugieren la
presencia de un tumor hipervascular . Actualmente se cuenta con estudios de perfusión por
resonancia magnética o tomografía que permiten estimar de forma segura y objetiva si la
lesión es altamente vascularizada (Caso ejemplo No. 1) . La realización de estos estudios
debe considerarse de forma rutinaria con el fin
de evitar los costos y potenciales morbilidades
de una angiografía cerebral innecesaria.
La ubicación de la lesión es otro factor importante para la toma de decisiones. Debido a
que la mayoría de los tumores hipervasculares
de la base del cráneo reciben su irrigación a
través de su sitio de implantación en la duramadre; éste debe identificarse en los estudios
de imagen para así determinar las posibles arterias que irrigan la lesión y por tanto, la probabilidad de éxito del procedimiento. En la gran
mayoría de los casos analizados en el presente estudio, se encontraron ramas de la arteria
carótida externa involucradas en la suplencia
del tumor. Asimismo, en aproximadamente un
tercio de los casos, también se encontraron
aportes arteriales a través de la arteria carótida interna. Estos hallazgos son consistentes
con la serie de meningiomas de la base del
cráneo estudiados por Waldron et al; en la cual
se encontró que las arterias tumorales se originaban exclusivamente de la arteria carótida
externa en 22% de los casos y en 25% exclusivamente de la arteria carótida interna. El
mismo estudio, también describió que el 45%
de los tumores recibían irrigación por ramos
de las arterias carótida interna, carótida externa y vertebral; mientas que el 8% solo tenían
irrigación pial .
La mayoría de los tumores hipervasculares ubicados en la fosa posterior, tentorio y
la parte lateral de la fosa media, pueden ser
embolizados de forma segura . Sin embargo,
las lesiones ubicadas en la fosa craneal anterior, como es el caso de los meningiomas del
tubérculo sellar, plano esfenoidal y surco olfatorio, son irrigados por ramos etmoidales de
la arteria oftálmica y por tanto, rara vez son
embolizados debido al riesgo de oclusión de
la arteria central de la retina en caso de presentarse reflujo del material embolizante o cateterismo sub-oclusivo (Caso ejemplo No. 3).
Aunque se han informado recientemente algunas embolizaciones exitosas a través de la
arteria oftálmica sin complicaciones visuales;
la evidencia disponible no permite recomendar
esta práctica debido al alto riesgo de amaurosis . La excepción más notable son los nasoangiofibromas juveniles, ya que usualmente
reciben la mayoría de su irrigación a través de
ramas de la arteria maxilar interna. Todos los
nasoangiofibromas juveniles estudiados en la
presente serie fueron devascularizados satisfactoriamente y sin complicaciones visuales,
tal como ha sido previamente descrito en la
literatura .
La identificación del pedículo dural es muy
importante en el abordaje de los tumores de
la fosa media que se relacionan con el ala
esfenoidal. Las lesiones de esta región usualmente se irrigan tanto por ramas de la arteria carótida interna, como de la carótida
externa. Se ha demostrado que los tumores
paraselares y de las apófisis clinoides reciben
aporte vascular a través de las ramas durales
del tronco meningo-hipofisiario y del tronco
inferolateral de la arteria carótida interna. Es
por ello que la probabilidad de lograr una adecuada embolización de los meningiomas del
tercio medio e interno del ala esfenoidal son
muy bajas ; mientras que los tumores del tercio externo la tasa de éxito es mayor, debido a
que generalmente se irrigan por la arteria recurrente del agujero rasgado anterior, meníngea accesoria y/o ramos anterior y petroso de
la arteria meníngea media .
Seguridad
Los resultados de los estudios realizados en
pacientes portadores de tumores de la base
del cráneo han demostrado que la mayoría de
las complicaciones están relacionadas con los
intentos exhaustivos de realizar una devascularización completa. Rosen et al reportaron una
tasa de complicaciones de 21%, de las cuales
9% presentaron secuelas neurológicas permanentes, relacionadas con la embolización
de ramas de la arteria carótida interna, lo cual
es inaceptablemente alto en comparación con
los beneficios obtenidos con la embolización.
En su estudio, más del 90% de los tumores
fueron devascularizados de forma extensa .
En otro informe, Waldron et al solo devascularizaron completamente al 9,3% de los casos
y la incidencia de complicaciones fue tan solo
del 2,5%; argumentando que su baja tasa de
complicaciones se obtuvieron mediante un
abordaje conservador, priorizando la seguridad del paciente sobre la devascularización
completa. De forma similar, los casos presentados en este estudio se trataron bajo los mismos lineamientos y en ningún procedimiento
se registraron complicaciones (Caso ejemplo
No. 2). En el presente estudio, ninguna de las
ramas de la arteria carótida interna fue tratada,
debido a que aportaban muy poca irrigación al
tumor (tres casos) o no fue posible acceder al
pedículo (un caso). Varios autores coinciden
con estos hallazgos, evitando al máximo la
embolización de estas ramas; las cuales solo
son tratadas cuando son la principal afluente
del tumor y su oclusión aparente ser segura .
26
CONCLUSION
El control vascular preoperatorio de los tumores de la base del cráneo es una alternativa
útil para disminuir el sangrado intra-operatorio
y la morbi-mortalidad asociada a la resección
quirúrgica; sin embargo, cada caso debe ser
analizado cuidadosamente antes indicarse el
procedimiento, ya que a través del análisis
cuidadoso de las relaciones anatómicas de la
lesión y los estudios de perfusión por tomografía y resonancia magnética, puede estimarse la relación riesgo/beneficio de la embolización.
La unificación de las experiencias descritas
en este estudio, con los datos extraídos de las
series publicadas previamente en la literatura,
permiten presentar una propuesta de algoritmo de manejo para la selección racional de
los tumores de la base del cráneo que pueden
beneficiarse de la oclusión endovascular de
sus vasos tumorales. Aunque este algoritmo
requiere su validación prospectiva, constituye
una orientación práctica basada en la literatura disponible para optimizar los resultados de
la embolización prequirúrgica de los tumores
de la base del cráneo.
.
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ABSTRACT
Preoperative embolization allows reducing intraoperative blood loss caused by hypervascular intracranial tumors and its undesirable consequences. Aim: To describe the experience
with preoperative endovascular embolization
of hypervascular skull base tumors, and to develop a therapeutic algorithm. Materials and
Methods: A retrospective examination of preoperative neuroimaging and results of preoperative embolization was carried out. Results:
Fifteen cases were identified, with a median
age of 36 years old, most of them harboring
meningiomas, nasopharyngeal angiofibromas
or paragangliomas. The external carotid artery was involved in 93% of cases and was
the only afferent to 60%. In 27%, there were
branches from the internal and external carotid
arteries simultaneously. An extensive or complete occlusion grade was achieved in 95%
of the branches of the external carotid artery.
No branch of the internal carotid artery was
treated, because poor contribution to tumor irrigation or was not possible to catheterize the
pedicle. There were not recorded procedurerelated complications.
Conclusion: Based on the unification of the
experiences described in this study and using data from published series, we present an
algorithm for rational selection of skull base
tumors that can benefit from preoperative embolization.
27
28
ESTUDIO DE EXPLORACION
DE CONOCIMIENTOS Y
ACTITUDES EN RELACION A
LA PREVENCION Y
TRANSMISION DEL DENGUE
EN PUERTO RICO EN EL 2012
Ian J. Rivera Rodrígueza, Augusto A.
Puig Rivera a, Raúl H. Morales-Borges b*
Escuela Secundaria Especializada en Ciencias Matemáticas y
Tecnología de Caguas, Puerto Rico.
b
Cruz Roja Americana, Servicios de Sangre, San Juan, Puerto
Rico.
*Autor Correspondiente: Raúl H. Morales-Borges, MD - Director
Médico, Cruz Roja Americana, Servicios de Sangre, PO BOX
366046, San juan, Puerto Rico, 00936-6046. E-mail: Raul.MoralesBorges@redcross.org
a
INTRODUCCION
RESUMEN
En Puerto Rico estamos pasando en el 2012
por la epidemia de Dengue más significativa
en nuestra historia a pesar de múltiples esfuerzos educacionales. El objetivo de este
trabajo consiste en determinar cuanto conocimiento tienen las personas en cuanto a
la transmisión y prevención del Dengue. Se
administró un cuestionario de quince preguntas a 140 personas de diferentes comunidades en el área metropolitana y este de
Puerto Rico durante los meses de septiembre a noviembre de 2012 de forma aleatoria. El 88% fueron adultos, 100 fueron mujeres y 40 hombres. La mayoría fueron de
los pueblos de Caguas, Carolina, San Juan
y Bayamón. El 60% eran profesionales. El
100% saben qué es el Dengue y el 90% conocen el mosquito. El 77% conocen de la epidemia actual, pero los hombres acertaron
más con una diferencia de un 10% que las
mujeres. Solo el 47% no están preparados
para la lucha contra el Dengue, pero tiene
un gran conocimiento de las medidas de
prevención y manejo del cuadro clínico
del Dengue. El 66% no sabían que existe
un Centro del Dengue del CDC. El 17.5%
de los encuestados tiene el conocimiento
de que el Dengue puede ser transmitido a
través de transfusión de componentes de
la sangre. Nuestro estudio cumplió con los
objetivos demostrando que existe un buen
conocimiento del Dengue, pero se desconoce la transmisión por transfusión de sangre. Hay una gran necesidad de desarrollar estrategias comunitarias para erradicar
esta enfermedad. Recomendamos repetirlo
con una muestra de mayor participación a
nivel Isla ampliando las preguntas.
Palabras índices: conocimiento, actitudes,
prevención, transmisión, Dengue, Puerto
Rico, 2012
El Dengue es una infección causada por un virus propagada por un mosquito, en particular,
por cuatro viruses del género Flavivirus. Estos son el virus del Dengue (DENV) tipos -1,2,-3, y -4. El mosquito, como vector principal,
es el Aedes Aegypti y el DENV es transmitido
de persona a persona siendo los humanos
el huésped principal amplificador. La enfermedad va desde un cuadro febril leve agudo
hasta fiebre hemorrágica y colapso severo (1).
De acuerdo a Pérez-Guerra y su grupo (2),
el Dengue clásico, junto con sus formas mas
graves, el Dengue hemorrágico y el síndrome
de choque o colapso del Dengue, es un grave
problema de salud en Puerto Rico y muchas
partes de las Américas y puede afectar negativamente las economías nacionales de dichas
áreas.
Petersen y su grupo (3) mencionan en su
artículo que en Puerto Rico, el Dengue fue
reconocido por primera ves en el año 1915 y la
epidemia más fuerte reciente de la Isla ocurrió
en el año 2010. El Dengue ha sido endémico
en Puerto Rico por tres décadas. Múltiples esfuerzos educacionales y de comunidad se han
desarrollado para informar la población sobre
la prevención del Dengue. Un estudio realizado por Pérez-Guerra y su colaboradores de la
división de enfermedades infecciosas transmitidas por vectores del Centro de Control y Prevención de Enfermedades (2) con 34 participantes demostró en general que ellos tienen
un conocimiento correcto sobre la prevención
del Dengue, pero existen tres patrones de
conocimiento y opinión desde niveles bajos
hasta niveles altos de conocimiento del tema.
Otro estudio, pero en Argentina y con niños,
se encontró que hay un alto porcentaje de
desconocimiento por parte de los alumnos (4).
de varias comunidades de Puerto Rico, acerca del control de los mosquitos y del Dengue.
También queremos investigar los conocimientos y actitudes que tienen en relación a los
modos de transmisión del Dengue inclusive a
través de transfusión de componentes sanguíneos, según demostrado en estudios realizados por la Cruz Roja Americana, y determinar
la prevalencia del conocimiento del Dengue en
Puerto Rico.
MATERIALES Y METODO
Se seleccionó una muestra aleatoria para
que represente la población puertorriqueña,
comprendiendo desde niño hasta anciano.
La población estudiada fueron jóvenes preadolescentes, adultos y envejecientes. A cada
sujeto se le explicó los riesgos y los beneficios
de la investigación para ver si deseaba participar de la misma. La población fue tomada de
forma aleatoria de comunidades urbanas de
diferentes municipios en Puerto Rico. Luego,
se aplicó un cuestionario a 140 personas que
aceptaron participar en el estudio (ver Apéndice #1). El estudio se realizó durante los meses de septiembre a noviembre de 2012.
Los datos de los cuestionarios fueron tabulados y se aplicaron gráficas de barras utilizando principios de estadísticas básicas con
el propósito de facilitar la comprensión del
proyecto. Se hizo un análisis y comparación
necesaria y con un estudio de nuestros datos
con los resultados de estudios previos publicados. Se realizaron tablas y gráficas de barras
y lineares con los datos demográficos de los
encuestados al igual que gráficas de barras y
circulares con la data de las 15 preguntas de
las encuestas utilizando el programa Microsoft
Excel.
RESULTADOS
En el estudio se encuestaron 140 personas
de las cuales, según la Tabla #1, el 88% fueron
adultos de 18 a 60 años de edad siendo las
mujeres la mayoría con un 64%. Solo participaron 3 personas de 13 a 17 años de edad.
Los encuestados fueron de 25 pueblos de un
total de 78 que tiene Puerto Rico para una
muestra representativa de 32%. La mayoría
de los participantes fueron de los pueblos de
Caguas, Carolina, San Juan y Bayamón según
podemos ver en la Tabla #2. En cuanto al área
representativa de Puerto Rico, vemos que los
encuestados en su mayoría eran del área metropolitana, central y este de la Isla. La mayoría
de los participantes eran ingenieros(as), secretarias/oficinistas y gerentes/administradores
para un 39% de los encuestados seguido por
amas de casa, estudiantes, cajeros, ajustadores de cuentas y enfermeros(as) según la
Tabla #3 demostrando una variedad de ocupaciones y profesiones dentro de la población
estudiada.
Se realizaron 15 preguntas del tema del
Dengue para ver cuanto conocimiento tiene
la población encuestada (ver Tabla #4). El
100% contestó correctamente las primeras
dos preguntas: ¿Sabes que es el Dengue?
y ¿Escuchó hablar del Dengue?. En relación
al mosquito como vector del Dengue, el 90%
saben que no todo mosquito puede transmitir
el Dengue y el 91% saben que el mosquito
Aedes Aegypti es el mosquito que lo transmite. Aun así, existe un 10% que contestaron
incorrectamente o desconocen la respuesta.
No hubo una diferencia significativa en como
contestaron los varones y las mujeres en las
preguntas #3 y #4 ya que los porcientos eran
85% vs 90% y 85% vs. 93% respectivamente.
Un 77% acertó en la pregunta 5 de la epidemia
actual del Dengue en la Isla., pero los varones
acertaron más con un 85% que las mujeres
con un 74%.
Las preguntas 6 y 7 se refieren si la persona o
alguien de su familia ha tenido la enfermedad
Por lo tanto, el objetivo general del presente
trabajo es investigar los conocimientos, actitudes y practicas que poseen una muestra
representativa aleatoria de jóvenes y adultos
29
del Dengue. Un 20% lo han tenido mientras
que el 44% refiere que alguien de su familia
lo ha tenido. En general, un 60% - 80% de
los participantes y sus familiares no han tenido
Dengue y un 5% no saben si les ha dado Dengue o no. En cuanto a diferencia por sexo, el
85% y el 47.5% de los hombres contestaron
las preguntas #5 y #6 respectivamente que ellos como alguien de sus familiares han tenido
el Dengue, por lo contrario, las mujeres fueron
el 74% y el 42% respectivamente.
La preguntas 8 a la 14 son de conocimiento
general del cuadro clínico, su manejo, prevención del mismo y si conoce las agencias
pertinentes del gobierno estatal como federal
que participan en la educación y prevención
del Dengue en la Isla. La gran mayoría (95%)
conoce qué es el Dengue hemorrágico y el
91% acertó correctamente la pregunta 14 en
cuanto al manejo clínico del paciente con Dengue.
Según la pregunta 9, solo el 19% de los encuestados (de los cuales el 25% de los hombres) están preparados para luchar contra el
Dengue y la mayoría (47%) no están preparados. El 66% no sabían que el CDC tiene un
Centro de Dengue en Puerto Rico. El 81%
conoce las medidas de prevención que presenta el Departamento de Salud de Puerto
Rico y no hubo diferencia significativa entre
los hombres y las mujeres. En las preguntas
12 y 13, el 92.5% contestó correctamente en
cuanto como prevenir el Dengue deteniendo la
producción de larvas y corrigiendo estanques
de aguas después que llueve, pero en las mujeres se observó que un 10% tenían más conocimiento en cuanto al manejo de las larvas
del mosquito que los hombres.
La última pregunta del estudio es en cuanto a
otro medio de transmisión del Dengue a través
de transfusión de componentes de sangre. Se
conoce debido a reportes de casos publicados
en la literatura médica y evidencia que se está
levantando por estudios del Centro del Dengue del CDC de Puerto Rico y los Servicios de
Sangre de la Cruz Roja Americana de Puerto
Rico y los Estados Unidos de América. En este
estudio, nosotros queremos saber qué nos
dice las personas en general. El 83% contestaron incorrectamente o desconocían de este
modo de transmisión del virus del Dengue,
mientras que el 17% si tiene el conocimiento
sin diferencia alguna en cuanto al sexo.
30
DISCUSION
Nuestro estudio sigue una estructura similar
a los estudios publicados en los años 2005 y
2009 por la Dra. Carmen Pérez-Guerra y su
grupo de la División del Dengue del CDC en
San Juan, PR (2, 5). En el primer estudio realizado entre los meses de febrero a mayo del
2001, participaron 34 personas, del sistema
de vigilancia del Dengue en Puerto Rico, los
cuales conocen bien la prevención del Dengue, pero reconocen que hay poco control de
las larvas ente sus vecinos y le pidieron al Gobierno que fumigue (2). En el segundo estudio
de septiembre a octubre de 2003 participaron
59 personas de las cuales 35 fueron mujeres
siendo estas las que consideraron el Dengue
importante por su impacto económico, emocional y de salud (5). En ese estudio fueron
más específicos y encontraron más diferencias en el sexo y en aquellos que ya habían
tenido Dengue. En nuestro estudio participaron 140 personas (100 mujeres y 40 hombres) de forma aleatoria en diferentes escenarios y comunidades de Puerto Rico entre los
31
conocimiento tuvo una asociación significativa
con el grado de educación y la clase socioeconómica. Nosotros obtuvimos un porciento
mayor de conocimiento (90-100%) con aproximadamente un 60% de los encuestados siendo personas profesionales con educación universitaria y clase socioeconómica adecuada.
meses de septiembre a octubre de 2012. Cuando buscamos los pueblos de los encuestados de nuestro estudio, el mapa es similar al
mapa de los municipios con presuntos casos
de la semana 45 según el Informe Semanal
de Vigilancia del Dengue de la Subdivisión de
Dengue de los CDC y Departamento de Salud
de Puerto Rico (6).
Encontramos que se tiene un buen conocimiento del Dengue y se conocen sus medidas preventivas como se observó en los estudios previos, pero no están organizados en sus
comunidades para luchar contra el Dengue ni
conocen que existe una división del Dengue
del CDC en Puerto Rico. Si concordamos con
los estudios de la Dra. Pérez-Guerra que tenemos que educar mas las comunidades y trabajar con ellas.
La Dra. Combina (4) realizó un estudio del nivel
de conocimiento del Dengue con 234 alumnos
de 4 escuelas de Argentina donde el 85.47%
y el 100% contestaron que escucharon hablar
del Dengue en la primera y la segunda encuesta respectivamente. Estos resultados son
similares a los nuestros aunque en nuestro
estudio solo participaron 3 jóvenes de 13 a
17 años de edad. En el estudio de Argentina,
los jóvenes no conocían exactamente donde
podían alojarse los criadores de mosquitos ni
como prevenirlos. Ya en el nuestro, se conocen dichas medidas, pero los participantes
eran adultos en un 88% de los encuestados.
El estudio de Benítez-Leite y su grupo de Paraguay (7) en el 2000 tuvo una muestra mayor
de participantes con 187 personas donde el
84.5% correspondió al sexo femenino con un
rango de edad entre 13 y 85 años y una media
de 40.3 años. El 100% de la población conoce
el mosquito que transmite la enfermedad, que
se está ante la presencia de una epidemia y
que el Dengue hemorrágico puede ser mortal. Sin embargo, el 89% no están organizados en su comunidad para luchar contra el
Dengue. La prevalencia de la enfermedad fue
del 41.2%. Comparándolos con nuestro estudio, el grupo de participantes fue similar en
sus características y resultados, excepto una
prevalencia de 20%. Esto demuestra una vez
más la falta de organización a nivel de comunidades.
M. Syed et al de Pakistán (8) realizaron un
estudio con 400 participantes, 244 eran masculinos, donde un 35% de la muestra tenia un
conocimiento adecuado del Dengue, pero el
32
Otros estudios de conocimiento y actitudes
relacionadas al Dengue en México (9, 10),
Colombia (11) y Jamaica (12) han confirmado que existe un buen conocimiento y que la
educación a la comunidad es clave en la prevención del mismo. En uno de los estudios de
México, realizado por Teresa M. Torres López
de Guadalajara, México, han identificado tres
dimensiones culturales que obstaculizan la
prevención del Dengue: información confusa
e insuficiente, la atribución de la responsabilidad de prevenir a otras personas u organismos públicos y la excesiva confianza en la
fumigación como medida preventiva (9). Seria recomendable incluir dichas dimensiones
como variables en un estudio en Puerto rico
para ver si tenemos las mismas a pesar ser
latinoamericanos. En los tres estudios se propone promover la participación comunitaria
en función del ecosistema como herramienta
para controlar al mosquito y la transmisión del
Dengue.
Algo importante que observamos fue que el
77% tiene conocimiento de una epidemia en
Puerto Rico a pesar de las publicaciones realizadas en la prensa escrita. Para el 7 de
octubre de 2012, fecha durante la cual estábamos realizando la encuestas, se publicó
el titular “Epidemia de Dengue en la Isla” en
el periódico El Nuevo Día (13) en donde se
informa que durante más de un mes, los casos
de Dengue reportados al Departamento de
Salud sobrepasan la cifra de 200 por semana,
rebasándose el límite histórico que, según el
CDC da paso a una epidemia, aunque el Departamento de Salud no ha emitido al país una
notificación a esos efectos.
En relación a la transmisión del Dengue a
través de transfusión de componentes sanguíneos, esto se ha demostrado en estudios
realizados por el CDC y la Cruz Roja Americana según KM Tomashek (14), SL Stramer
(15), H Mohammed (16) y LR Petersen (3)
desde el año 2005. Esto aun se encuentra
en investigación, pero aparentemente según
nuestro estudio, el 24% tiene el conocimiento
de que puede ser transmitido por componentes de sangre. Según la revisión de la literatura médica, este es el único estudio de cono-
cimientos y actitudes del Dengue publicado en
donde se cuestiona este asunto. Esto implica
que una vez las autoridades debidas y el gobierno decida públicamente darlo a conocer, se
debe educar más las personas para prevenir
la transmisión del Dengue.
En general, el Dengue es un problema de
salud pública que va escalando en Latinoamérica (17) y esto requiere revisar las políticas
de salud pública centradas en ataque hacia el
vector y el desarrollo de un programa de vacunación del Dengue efectivo una vez la vacuna
sea aprobada. De acuerdo a un artículo publicado en El Nuevo Día el 14 de mayo de 2012,
en Puerto Rico, el costo de enfermarse con
Dengue, supera los $46 millones al año, y el
48% de ese gasto lo pagan las familias puertorriqueñas (18). Por esto entendemos que no
solo es un problema grave de salud física sino
también de salud fiscal-económica.
CONCLUSION
Según las respuestas de nuestros participantes, la gran mayoría tiene conocimiento
del Dengue y de medidas generales de prevención del mismo divulgadas por el Departamento de Salud, pero menos de la mitad están
organizados en su comunidad y no conocen
que existe un Centro de Dengue del CDC en
Puerto Rico. Menos aun, una quinta parte de
los participantes solo conocen que el virus se
puede transmitir a través de transfusión de
componentes sanguíneos. Por lo tanto, se
ha confirmado nuestra hipótesis. Un aspecto
negativo es que el número de encuestados
fue pequeño y nosotros recomendamos realizar un estudio más grande con una muestra
más representativa ampliando el cuestionario
cubriendo aquellas áreas ya discutidas.
Del estudio se desprende que hay una gran
necesidad de crear grupos de lideres y expertos en el Dengue para que organicen grupos
focales para discusión de estrategias de prevención y manejo del Dengue en sus comunidades a través de toda la Isla. Debemos tomar
las recomendaciones del grupo de Roberto
Tapia-Conyer de México, en donde lideres
políticos efectivos, mecanismos financieros
innovadores y cooperación a través de varias
disciplinas son esenciales para la erradicación
de dicha enfermedad. Otra estrategia recomendada es motivar a las personas a que participen en el estudio del desarrollo de la vacuna del Dengue para así obtenerla mas rápido
y poder tenerla accesible con un programa de
vacunación vital y efectivo a nivel no solo de
33
Puerto Rico sino de toda América y el Caribe.
En relación a la confirmación de la transmisión por productos de sangre, recomendamos
cooperación con los estudios en progreso del
CDC y la Cruz Roja Americana para que se
adelanten los trabajos y se obtenga la aprobación de la prueba más rápida pero a su vez
sensitiva y especifica por la Agencia Reguladora de Drogas y Alimentos (FDA). Una vez
obtenida la aprobación, tendremos mayor seguridad y control.
Dengue: an escalating public health problema in Latin America.
Paediatrics and International Child Health 2012; 32(S1): 14-17.
18. Parés Arroyo M. El Dengue nos chupa el vivir. Estudio señala el alto costo de manejar esta enfermedad. El Nuevo Día;
14 de mayo de 2012, San Juan, PR. Año XLI, Vol. 15221: 1, 4,5.
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ABSTRACT
We got one of the most significant epidemics of the history of
Dengue in Puerto Rico despite all
major educational efforts made.
The objective is to determine
how much knowledge the people
have about the prevention and
transmission of Dengue virus.
We administered a questionnaire
of fifteen questions to 140 people of different communities at
the metropolitan area as well as
in the East area of Puerto Rico
during the months of September
to November of 2012. 88% were
adults, 100 were women and
40 men. The majority was from
Caguas, Carolina, San Juan, and
Bayamon. 60% were professionals. One hundred percent knew
what Dengue is and 90% knows
the mosquito. 77% of the participants know the actual epidemics, but the men got a 10% higher knowledge than women on the
subject. Around 47% are not prepared to fight the Dengue virus,
but they have great knowledge
about the preventive measures
and the clinical Management of
Dengue Syndrome. 66% did not
know that Puerto Rico has a Dengue Center from the CDC located at the Island. Only 17.5% of
the participants knows that the
Dengue Virus can be transmitted through transfusion of blood
components. Our study met our
objectives showing that we have
good knowledge about Dengue,
but there is poor knowledge
about the transmission of Dengue Virus through transfusion
of blood components. There is
a big necessity to develop community strategies to eliminate
this disease. We recommend repeating this study with more collaboration from other entities,
more questions, and more participants.
Apéndice # 1
Cuestionario: Estudio de Prevalencia de Conocimiento y Actitudes en Relación a la Prevención y
Transmisión del Dengue
Instrucciones: Favor de completar el siguiente cuestionario al momento de ser entregado. Contestar con consciencia y honestidad. Hacer una marca (X) en el encasillado que usted considere
apropiado para su contestación. Escribir lo mas legible posible donde aplique. Favor de entregarlo al encuestador o investigador tan pronto haya sido terminado. Gracias.
Datos Demográficos:
Iniciales:_____________
Pueblo de Residencia:_______________________________
Edad: _____________________
Sexo: ______________________
Ocupación: ___________________________
Preguntas:
35
36
CERVICAL DYSPLASIA AND
PRE-TERM BIRTH IN SAN
JUAN CITY HOSPITAL:
A Cohort Retrospective Study
Axel Torres MDa, Edgardo Rivera Rosa
MDa, Keimari Méndez MDc, Ana Menéndez MDd, Josefina Romaguera MDabc*
ABSTRACT
Cervical dysplasia alters the release of
cytokines and inflammatory mediators
in pregnant woman with cervical dysplasia. This study evaluates a cohort of
pregnant patients screened for cervical
dysplasia to determine the relationship
between cervical dysplasia and preterm labor (PTL). Methods: Retrospective chart review of pregnant patients
screened for cervical dysplasia at the
San Juan City Hospital between October
2006 and December 2010. Patients with
low or high-grade squamous intraepithelial lesions (LGSIL or HGSIL, respectively) were evaluated with colposcopy.
Primary outcome was the event of PTL
and the risk factor evaluated was presence of cervical dysplasia. Results: A
total of 2,059 patients were screened for
cervical dysplasia and 59 were evaluated with colposcopy due to LGSIL or HGSIL. From those, 29% were negative for
intraepithelial lesions and malignancy
(NILM), 54% had cervical intraepithelial
neoplasia (CIN)-1, 17% where diagnosed
as CIN-2/3 where no invasive cervical
cancer was identified. In the group of
NILM, 24% had PTL compared to 18% in
patients who screened negative on initial
cytological evaluation. In cases where
CIN-1 was confirmed by colposcopy 28%
had PTL compared with 40% in patients
with CIN-2/3. Other risk factors associated with PTL were not significantly different among the groups. Conclusions:
Cervical dysplasia in pregnancy may
represent an increase risk for premature
labor.
Key Words: cervical, dysplasia, preterm, birth, cohort, study
Obstetrics and Gynecology Residency Program, San Juan City
Hospital, Puerto Rico Medical Center, San Juan Puerto Rico.
Cancer Control and Population Sciences Program, University of
Puerto Rico Comprehensive Cancer Center, San Juan, Puerto
Rico.
c
University of Puerto Rico, Medical Sciences Campus, Obstetrics and Gynecology Department, San Juan, Puerto Rico.
d
University of Puerto Rico, Rio Piedras Campus, San Juan,
Puerto Rico.
*Corresponding author: Josefina Romaguera: Department of
Obstetrics and Gynecology, Medical Sciences Campus, GPO
Box 36-5067, San Juan, Puerto Rico, 00936-5067, e-mail: josefina.romaguera@upr.edu
a
b
INTRODUCTION
Obstetrics and Gynecology specialty has a
high level of expertise with screening, evaluation and management of patients with cervical dysplasia and patients with premature
labor. However, very little is known about the
relation, if any, between premature birth and
cervical dysplasia. Pregnant women should
undergo cervical cytology screening for cervical dysplasia. Prenatal care includes a cervical
cytology screen, and it is relevant to determine
if there is a relationship between cervical dysplasia and premature labor. Cervical dysplasia
is an abnormal process of cellular maturation
and replication of the squamous epithelium of
the cervix that almost always has its origin in
the transformation zone (1). There is evidence
that high-risk serotypes of human papillomavirus (HPV) and cervical dysplasia alters the release of cytokines and inflammatory mediators
in woman with cervical dysplasia (2,3). Those
inflammatory mediators play a role in the event
of labor onset (4,5).
The importance of this investigation is that Obstetrics have being challenge by the increase
in the premature birth rate in the last decades
(6). To the moment many risk factors has being identified. Management with 17- hydroxyprogesterone has produce evidence to prolong
labor when properly used (7). On the other
hand, HPV vaccination has shown evidence
to decrease the incidence of cervical dysplasia
(8). Our mission is to continue to identify all risk
factors for premature labor and expand the criteria for effective interventions in preterm birth
prevention.
MATERIALS AND METHODS
We performed a retrospective observational
study of a cohort of pregnant patients who
were screened during pregnancy for cervical
dysplasia and had no identifiable risk factors
for premature birth (PTB) before delivery (see
Table 1 & 2). A cohort of pregnant patients was
identified and referred to the colposcopy clinic
at San Juan City Hospital (SJCH) between October 2006 and December 2010. All patients
with low or high-grade squamous intraepithelial lesions (LGSIL or HGSIL respectively) were
evaluated. Patients with ASCUS (Atypical
Squamous Cells of undetermined significance)
were excluded from the study, since most of
them were referred for evaluation after delivery. Descriptive statistics were used to tabulate
numbers and percentages for all variables.
Chi-square was utilized to determine the association of cervical dysplasia to premature
labor. Patients with identifiable risk factors for
premature labor in the obstetric history (history
of PTB, morbid obese, underweight, diabetes
mellitus etc.) where excluded a priori from the
study.
The study was conducted at the San Juan
City Hospital Prenatal Clinics. Patients were
managed since their first trimester and had a
complete prenatal work up and delivery at the
SJCH. The institutional review board of SJCH
approved the study.
RESULTS
From the 6,804 pregnant patients delivered
at SJCH only 5,001 had a complete prenatal
care and screened for cervical dysplasia. From
those 2,942 patients were excluded due to an
identifiable risk factor for PTB. From the 2,059
patients without identifiable risk factors for
PTB, 59 patients were evaluated with colposcopy due to LGSIL or HGSIL cytology screening. From the 2,000 patients who presented a
normal cytology screen, 235 (11.75%) had a
PTB (see Table 3), compared with those with
LGSIL or HGSIL cervical cytology, on which 18
(30.5%) had a PTB (OR=3.14(CI95%: 1.427.5) p=0.002). In the cases where cervical dysplasia was confirmed by colposcopy with cervical intraepithelial neoplasia (CIN)-1, 10 (31%)
had premature labor compared with 4 (40%)
premature labor in patients with CIN-2/3 (see
Table 3) (OR=1.55(CI95%: 0.54-4.4), p=0.36).
CONCLUSIONS
Cervical dysplasia in pregnancy may represent an increase risk for premature labor (9).
Our results showed that patients with abnormal cervical cytology have 3.14 times the risk
for preterm delivery, compared to those with
normal cervical cytology. The degree of cervical dysplasia is also related to the incidence of
premature labor among this cohort of patients,
but it was not statistically significant. Limitations of this study include the limited number
of patients and missing information of some
of the participants, which increased the number of excluded patients from the analysis. In
our population, cervix dysplasia seems to be
another factor for PTL. Our recommendation
is to continue routine prenatal care with cervix
cytology and colposcopy as per the American
Society of Colposcopy and Cervical Pathology
until more data becomes available.
37
Case Reports / Reporte de Casos
CARDIAC AMYLOIDOSIS
SECONDARY TO MULTIPLE
MYELOMA
Francisco Parrilla MDa*, Rafael E. Calderon MDa, Rafael Figueroa MDa, Carmen
Gurrea MDb
ABSTRACT
REFERENCES
1. Berek JS, Rinehart R, Hengst TC. Berek and Novak’s Gynecology, Ch. 17, 4th
Ed; Philadelphia, PA, USA; Williams and
Wilkins; 2007. p. 564-564.
2. Passmore JA, Milner M, Denny L, et al.
Comparison of cervical and blood T-cell
responses to human papillomavirus-16
in women with human papillomavirus-associated cervical intraepithelial neoplasia. Immunology 2006; 119(4): 507–514.
3. Bais AG, Beckmann I, Ewing PC, et al.
Cytokine Release in HR-HPV(+) Women
without and with Cervical Dysplasia (CIN
II and III) or Carcinoma, Compared with
HR-HPV(-) Controls Mediators Inflamm.
2007: 241-47.
4.Bowen JM, Chamley L, Keelan JA and
Mitchell MD. Cytokines of the Placenta
and Extra-placental Membranes: Roles
and Regulation During Human Pregnancy and Parturition. Placenta(2002);23:
257-273.
5. Gabbe SG, Niebyl JR, Simpson JL;
Obstetrics, Normal and Problem Pregnancies; Ch. 12; 5th Ed; Philadelphia,
PA, USA; Elsevier. 2007: p. 304-305.
6. Gabbe SG, Niebyl JR, Simpson JL;
Obstetrics, Normal and Problem Pregnancies; 5th Ed; Philadelphia, PA, USA;
Elsevier; 2007: p. 669-670.
7. Gabbe SG, Niebyl JR, Simpson JL;
Obstetrics, Normal and Problem Pregnancies; Ch. 26; 5th Ed; Philadelphia,
PA, USA; Elsevier; 2007: p. 696-697.
8. Human Papillomavirus Vaccination.
ACOG Committee Opinion No. 467.
American College of Obstetricians and
Gynecologists. Obstet Gynecol 2010;
116:800-3.
9.Bruinsma F, Lumley J, Tan J and Quinn
M. Precancerous changes in the cervix
and risk of subsequent preterm birth.
BJOG (2007);114: 70-80.
RESUMEN
La displasia cervical altera la liberación de citoquinas y
de mediadores inflamatorios en mujeres embarazadas
con displasia cervical. Esos mediadores inflamatorios
tienen un rol en el inicio de un parto prematuro (PP).
Este estudio evalúa una serie de pacientes embarazadas con displasia cervical para determinar la relación
entre displasia cervical y PP. Metodología: Revisión retrospectiva de un grupo de pacientes embarazadas en
el San Juan City Hospital entre octubre 2006 y diciembre 2010. Pacientes con lesión intra-epitelial escamosa
de bajo o alto grado (LGSIL o HGSIL, respectivamente)
fueron evaluadas con colposcopía. El resultado fue el
nacimiento prematuro y la presencia o ausencia de displasia. Resultados: De 2,059 pacientes examinadas por
displasia cervical sin que se identificara algún factor de
riesgo para PP, 59 pacientes fueron examinadas con colposcopía debido a LGSIL o HGSIL. De estos, 28% fueron negativos para lesiones intraepiteliales y malignidad
(NILM), 54% presentaron CIN-1 (displasia cervical), 17%
fueron diagnosticadas como CIN-2/3 y no hubo cáncer
cervical invasivo. En el grupo de NILM, 24% tuvieron un
PP en comparación a 18% PP en pacientes con citología
negativa. En los casos con CIN-1 confirmados por colposcopia, 28% tuvieron PP en comparación con 40% PP
en pacientes con CIN-2/3. Otros factores de riesgo asociados con PP no fueron significativamente diferentes
entre estos grupos. Conclusiones: La displasia cervical
durante el embarazo puede representar un riesgo alto
de parto prematuro.
38
Amyloidosis is a multisystemic
disease caused by extracellular
deposition of pathologic beta fibrillar proteins in multiple organs.
Deposited fibrils can be either immunoglobulin light chains or amyloid-A protein. The incidence of
amyloidosis derived from amyloidA protein, usually associated to an
underlying disease, has been diminishing over the decades in the
United States producing clinical
evidence of cardiac involvement
in less than 5% of all cases. The
extent of cardiac involvement is
the determining prognostic factor.
Early diagnosis and therapy aimed
at the underlying disease may halt
progression of cardiac dysfunction and improve prognosis. We report a case of a 63-year-old man
who was diagnosed with cardiac
amyloidosis secondary to multiple
myeloma.
Index words: amyloidosis, cardiac, secondary, multiple, myeloma
INTRODUCTION
Amyloidosis is a multisystemic disease caused
by extracellular deposition of pathologic beta
fibrillar proteins in multiple organs (1). This
condition is particularly difficult to diagnose because the presenting symptoms can be very
broad and are often mimicked by more common disorders (2, 3). Diagnosis and classification of amyloidosis is based on the analysis of
the deposited insoluble abnormal fibrils (1,4).
Deposited fibrils can be either immunoglobulin
light chains or amyloid-A protein. Immunoglobulin light chain amyloidosis is a clonal plasma
cell disorder in which fragments of an IG light
chain are deposited in tissues. Immunoglobulin light chain amyloidosis, so called primary
39
Section of Cardiology, Department of Medicine, School of Medicine, University of Puerto Rico Medical Science Campus.
b
Section of Pathology, Cardiovascular Center Of Puerto Rico
and the Caribbean.
*Corresponding author: Francisco Parrilla MD – University of
Puerto Rico, School of Medicine, Internal Medicine Department Cardiology Section, PO Box 365067 San Juan, PR 00936-5067.
E-mail: frankie_parrilla@yahoo.com
a
amyloidosis, occurs in 8 per million persons
per year, which are approximately 3000 new
cases annually in the United States (2). In
contrast, amyloidosis derived from amyloid-A
protein fibrils are usually associated with other
conditions, so called secondary amyloidosis.
The incidence of amyloidosis derived from amyloid-A protein has been decreasing over the
decades in the United States, and accounts for
only 3% of systemic amyloidosis (2).
Amyloid deposits can occur in several organs,
including the heart. Significant deposits can be
found in the intramyocardial and epicardial coronary arteries, myocardium, heart valves and
pericardium (5). Clinical evidence of cardiac involvement occurs in up to 50 percent of patients
with immunoglobulin light chains, compared to
less than 5 percent of amyloidosis derived from
amyloid-A protein (3). Progressive deposition
of amyloid is disruptive to tissue causing organ
dysfunction and significant morbidity and mortality. We report a case of a 63-year-old man
who was diagnosed with cardiac amyloidosis
secondary to multiple myeloma.
Case History
A 63-year-old man with coronary artery disease status-post stenting to the left anterior
descending artery, arterial hypertension and
prostate cancer status-post brachytherapy,
presented for evaluation at our institution because of leg swelling and fatigue of approximately six-months of evolution. He denied
chest pain, palpitations, paroxysmal nocturnal
dyspnea, dizziness, chills, decreased urine
output, joint pain, skin rash, easy bruising or
any other complaint.
Physical examination with adequate vital
signs and except for pitting edema plus one,
the rest of the evaluation including oral cavity
inspection, skin examination and cardiovascular auscultation were within normal limits.
Laboratories remarkable for increased White
Blood Cells (11,400), with elevated eosinophils
(5.0%) and monocytes (9.0%) levels; normochromic normocytic anemia (Hgb 12.6g/dL, Hct
38%, MCV 89 f/L, MCH 29 p/g ); renal dysfunction with estimated 50 ml/min/m2 of GFR by
MDRD and proteinuria (>300mg/dL). Twelveleads electrocardiogram recording showed
normal sinus rhythm, normal atrio-ventricular
conduction, uniform frequent ventricular premature complexes consistent with ventricular
bygeminy, voltage criteria and ST changes
consistent with left ventricular hypertrophy and
Q wave from V1 to V2 suggesting an anterior
scar. Two-dimensional transthoracic echocardiography showed normal LV systolic and
diastolic function with marked hypertrophy of
myocardium and sparkling granular appearance (see Figure 1), which led to suspect the
possibility of cardiac amyloidosis. A right ventricle endomyocardium biopsy was performed
and four fragments of dark-tan soft tissue were
fixed in formalin and sent to pathology laboratory for examination. Hematoxylin & eosin
stain disclosed myocardial tissue with interstitial deposits of amorphous hyaline material
(see Figure 2). Congo red staining later shown
green birefringence when viewed under polarized light (see Figure 3). Samples were also
submitted to immunohistochemistry analysis.
Phenotype study detects amyloid deposits
and antibodies were positive to amyloid-A protein, and negative for kappa and lambda light
chains. Right cardiac catheterization showed
normal cardiac chambers pressures (RV= 22/5
mmHg, RA mean 5), normal pulmonary artery
pressures (PA=19/6mmHg; mean = 12mmHg),
and normal cardiac output (5.10 L/min).
In view of two-dimensional echocardiographic
findings, microscopic examination of cardiac
biopsy and immunohistochemistry analysis
secondary cardiac amyloidosis was diagnosed.
Confirmation of the presence of secondary
cardiac amyloidosis with unexplained anemia,
proteinuria and renal dysfunction led to further
testing and a diagnosis of multiple myeloma by
urine electrophoresis .The patient was started
on melphalan and prednisone therapy with significant improvement of symptoms.
DISCUSSION
Secondary systemic amyloidosis is caused by
deposition of serum amyloid-A protein, an acute
phase reactant, which is associated with a variety of chronic inflammatory disorders. This
type of amyloidosis produces clinically apparent heart disease in less than 5% of the cases
(1). The major determinant of outcome in amyloidosis is the extent of cardiac involvement.
The accurate definition of cardiac involvement
has evolved over the past three decades. Initially, cardiac involvement meant cardiac failure with cardiomegaly, pleural effusions, and
Kerley-B lines on the chest radiograph (5-8).
However, clinical cardiac assessment has
40
41
been largely supplanted by echocardiography. Amyloid infiltration of the heart results in
increased echogenicity and sparkling granular
appearance. However, this is not sensitive for
amyloidosis, as only a minority of patients has
this pattern. Left ventricular thickening due to
amyloid infiltration may be misdiagnosed on
echocardiography as left ventricular hypertrophy. Other echocardiographic found in cardiac amyloidosis includes diastolic relaxation
abnormalities, right ventricular dysfunction,
valvular thickening, and decreased fractional
shortening, all been shown to be associated
with poor prognosis (8).
Some patients have a predisposing underlying disorder before the presentation with amyloid, while others present with no such history
but with an amyloid manifestation. In such
patients, the diagnosis of amyloidosis comes
first, followed by an evaluation for an underlying cause. The diagnosis of cardiac amyloidosis can be confirmed only either by demonstrating amyloid deposits on endomyocardial
biopsy or, in patients with appropriate cardiac
findings, by demonstrating amyloid deposits
on histologic examination of a biopsy from
other tissues. Although the presence of amyloidosis may be suggested by the history and
clinical manifestations, tissue biopsy is important because assumptions regarding the type
of amyloid may be incorrect (9-11).
Treatment for amyloidosis is aimed at reducing or eliminating the plasma cells that are responsible for the production of the abnormal
proteins. Such treatment reduces the accumulation of light chains throughout the body,
which can alleviate some of the symptoms.
Treatment for amyloidosis is similar to treatment for multiple myeloma, including stem cell
transplantation. Patients who are not candidate for transplant may receive oral melphalan
and prednisone. They may also be treated with
intravenous chemotherapy in the form of medium- or high-dose melphalan or vincristinedoxorubicin-cyclophosphamide (12, 13).
In conclusion, we presented a case of a
63-year-old man who developed cardiac amyloidosis, an uncommon complication of secondary systemic amyloidosis leading to a diagnosis and treatment for multiple myeloma.
Since cardiac involvement is the determining
prognostic factor. Early diagnosis and therapy
aimed at the underlying disease may halt progression of cardiac dysfunction and improve
prognosis.
42
REFERENCES
HYPERSENSITIVE PNEUMONITIS: A Case Report
1. Merlini G, Bellotti V. Molecular Mechanisms of Amyloidosis; N
Engl J Med 2003; 349: (583-596))
2. Hazenberg BP, Van Rijswijk MH. Where has secondary amyloid gone? Ann Rheum Dis. 2000; 59: 577-579
3. Dubrey SW, Cha K, Anderson J, et al. The clinical features of
immunoglobulin light-chain amyloidosis with heart involvement.
QJM 1998; 91:141
4. Gertz M. Immunoglobulin light chain amyloidosis: 2011 update on diagnosis,risk-stratification, and management; American Journal of Hematology. 2011; 86;180-186.
5. Gertz MA, Greipp PR, Kyle RA. Classification of amyloidosis
by the detection of clonal excess of plasma cells in the bone
marrow. J Lab Clin Med 1991;118:33–9.
6. Smith TJ, Kyle RA, Lie JT. Clinical significance of histopathologic patterns of cardiac amyloidosis. Mayo Clin Proc 1984;
59:547.
7. Dubrey SW, Cha K, Simms RW, et al. Electrocardiography
and Doppler echocardiography in secondary (AA) amyloidosis.
Am J Cardiol 1996; 77:313.
8. Mizuguchi Y, Oishi Y, Miyoshi H, Luchi A, Nagase N, Oki T.
The functional role of longitudinal, circumferential, and radial
myocardial deformation for regulating the early impairment of left
ventricular contraction and relaxation in patients with cardiovascular risk factors: a study with two-dimensional strain imaging. J
Am Soc Echocardiogr 2008; 21:1138–44.
9. Marcu CB, Niessen HW, Brouer WP, et al. Cardiac involvement with
amyloidosis: mechanism of disease, diagnosis and management.
Conn Med. 2011 Nov; 75(10):581-90.
10. Leone O. New pathological insights into cardiac amyloidosis:
implications for non invasive diagnosis. Amyloid. 2012 Jun;
19 (2): 99105.
11. Kholova I, Niessen HW. Amyloid in the cardiovascular system: a
review. J Clin Pathol. 2005 February; 58 (2) 125-133.
12. Kappor P, Thenappan T. Cardiac Amyloidosis: A Practical
Approach to
Diagnosis and Management. The American Journal of Medicine. 2011
November; 124 (11): 1008-1015.
13. Oh JK, Seward JB, Tajik AJ. The Echo Manual, 3rd Ed;
Philadelphia.
Williams & Willliams, 2006: 274-279.
Libertad I. Ruscalleda Reyes MDa*,
Jesús M. Román Vélez MDa
RESUMEN
La amiloidosis es una condición multisistémica
causada por la deposición extracelular de proteínas patológicas de fibrillas beta en múltiples
órganos. Los depósitos de fibrillas pueden ser
de cadenas livianas de inmunoglobulinas o de
proteínas amiloides-A. En los Estados Unidos
la incidencia de la amiloidosis causada por la
deposición de proteínas amiloides-A, usualmente asociada a otras condiciones, ha disminuido a lo largo de las pasadas décadas.
Esta produce evidencia clínica de envolvimiento cardiaco en menos de 5% de los casos.
El grado de envolvimiento cardiaco es el factor prognóstico determinante. El diagnóstico
y tratamiento temprano de la condición asociada puede detener la progresión de la disfunción cardiaca resultando así en un mejor
prognóstico. Reportamos el caso de un hombre de 63 años con diagnostico de amiloidosis
cardiaca secundaria a myeloma multiple.
43
Internal Medicine Residency Program, Mayagüez Medical Center & Hospital Ramón Emeterio Betances, Mayagüez, Puerto
Rico.
*Corresponding author: Libertad I. Ruscalleda Reyes MD - PO
Box 25028, Aguadilla PR 00604-0283. E-mail: libertad_i@yahoo.com
Poster Presentation in the Clinical Medicine, Category of the
2012 AMA-RFS Research Symposium in Honolulu, Hawaii.
a
ABSTRACT
Hypersensitivity pneumonitis, also
known as extrinsic allergic alveolitis, constitutes a spectrum of granulomatous, interstitial, bronchiolar,
and alveolar-filling lung diseases
resulting from repeated inhalation
and sensitization to a wide variety
of organic aerosols and low-molecular-weight chemical antigens. We
report a case of a 57 year-old-female with hypersensitive pneumonitis due to pigeon droppings. Early
diagnosis during the acute phase
of hypersensitive pneumonitis is
important due to the irreversible
damages caused by this chronic
disease.
Index words: hypersensitive, pneumonitis
INTRODUCTION
Hypersensitivity pneumonitis (HP), also known
as extrinsic allergic alveolitis, constitutes a
spectrum of granulomatous, interstitial, bronchiolar, and alveolar-filling lung diseases resulting from repeated inhalation and sensitization to a wide variety of organic aerosols
and low-molecular-weight chemicals antigens
(1-3). The agents responsible for inducing
this entity are numerous, and are categorized
as follows: microbial agents, animal proteins
and low-molecular-weight chemicals. Most of
the exposures go unrecognized therefore it is
important to have a high index of clinical suspicion upon evaluating the patient. In Puerto
Rico it is imperative to contemplate this possibility since the weather is mostly warm and
moist leading to proliferation of these microbial
agents.
Animal antigenic proteins that cause HP are
mostly found on feathers, droppings and se-
rum of birds, especially pigeons and parakeets.
Immunoglobulins, particularly IgA and IgG are
secreted from coat bird’s feathers creating a
fine dust called “bloom”. Flying birds such as
pigeons and parakeets produce the largest
amount of bloom and are the birds most often
associated with HP (3, 4).
The epidemiology of HP is mostly unknown
since most of the populations studied are agricultural workers and bird fanciers. Risk factors
can be divided between environmental, occupational and host factors. Given the latency
period between exposure and the development of symptoms it is difficult to estimate if
an intense antigen exposure vs. low level more
prolongs exposure will be more predictive of
developing HP. The genetic differences found
in polymorphisms in the major histocompatibility complex and in tumor necrosis factor apha
between individuals could be more important
than the level of exposure (5-7).
A high level of suspicion is the most important
aspect to make the diagnosis of HP since most
of the radiological and laboratory tests are
nonspecific. In most cases there is not enough
clinical findings to sustain the diagnosis and
lung biopsy becomes an essential tool for the
physician. HP can be classified as acute, subacute and chronic based on clinical findings,
but they can overlap one another. This classification is important to guide medical therapy
and is associated with the final prognosis.
We report a case of a 57 year-old-female with
hypersensitive pneumonitis due to pigeon
droppings.
Case History
A 57 year-old-female with past medical history
of high blood pressure and bronchial asthma
was admitted to the hospital because of shortness of breath. She referred a two-weeks history of progressive shortness of breath with
mild exertion, nonproductive cough, chest
tightness and non-quantified fever. She had no
pets or birds. Primary care physician managed
her with anti-cough medicine without improvement. She denied toxic habits. Upon arrival to
the hospital vital signs were stable, physical
exam unremarkable, no leukocytosis, but hypoxemia was noted. Chest films demonstrated
bilateral pulmonary nodules confirmed by high
resolution Chest CT-Scan as specified reticulonodular infiltrates and ground glass pattern
in both upper lobes (see Figure 1). Patient was
started on IV antibiotics and further work up
was continued. During initial evaluation differential diagnosis included atypical pneumonia,
lung malignancy, miliary tuberculosis and bronchial asthma exacerbation with pneumonia.
Diagnosis workup for tuberculosis, HIV, collagen vascular diseases and neoplastic growth
where negative (see Table 1 & 2). No clinical
improvement was noted during initial treatment. Bronchioalveolar lavage (BAL) was
performed. Results of the BAL cultures where
negative for bacteria, fungi and mycobacteria.
Histological findings of video-assisted thoracoscopic (VATS) lung biopsy showed bronchocentric inflammatory process, inflammatory
cells consisting of lymphocytes, plasma cells
and histiocytes. Also it was noted the presence
of intraalveolar macrophages (see Figures 3 to
6). While the case was reviewed and patient
re-evaluated, she confirmed recent change in
work place to a new school with zinc aluminum
roofing sheets that served as pigeon nesting
area. Patient was started with IV steroids with
clinical improvement. On the basis of this information, a diagnosis of hypersensitivity pneumonitis due to pigeon droppings was done.
Patient was oriented continuing treatment with
oral steroids, exposure avoidance and work
44
place change. Follow up at outpatient clinic
with another chest CT-Scan showed resolution
of previous findings (see Figure 2).
DISCUSSION
The patient medical history, physical exam, and
lung biopsy by VATS supported the diagnosis
of hypersensitivity pneumonitis. She referred
unspecific clinical symptoms such as progressive shortness of breath, nonproductive cough,
and non-quantified fever. It was determinant to
have a social history because she stated that
the symptoms began after changing jobs. She
described the area as having pigeon nest,
which were thought to be the antigen causing
HP. Once the patient was removed from exposure complete resolution was noted.
At first the presence of numerous poorly defined small opacities with apical predominance
throughout pulmonary fields broaden the differential diagnosis. Later it was narrowed with
HRCT because of the ground-glass opacities,
apical predominance of reticulonodular infiltrates and lack of pulmonary fibrosis that was
highly suggestive of HP on appropriate clinical
setting. VATS biopsy confirmed our diagnosis
because few areas of fibrosis were found and
most of the inflammatory process was bronchocentric.
In conclusion, high clinical suspicion of HP
is needed when respiratory symptoms follow
change of daily environment. A detailed history of present illness would provide the tools
to detect a relationship between the patient’s
surroundings and clinical symptoms. If there
still are doubts of the correct diagnosis a lung
45
THE CARDIOLOGY AND ENDOCRINOLOGY
CONNECTION BETWEEN
AMIODARONE AND
THYROTOXICOSIS:
Case Report and Review of
the Literature
Coromoto Palermo-Garófalo MDa*, José
Hernán Martínez MDa, Frieda Silva MDb,
Eva González MDa, Oberto Torres MDa,
Jannette Figueroa MDb, José González
MDb, María de Lourdes Miranda MDa
Internal Medicine and Endocrinology Department, San Juan
City Hospital, San Juan Puerto Rico.
Department of Nuclear Medicine, UPR School of Medicine,
San Juan, Puerto Rico.
*Corresponding author: Coromoto Palermo-Garofalo MD - PO
BOX 191177, San Juan, Puerto Rico 00919-1177. E-mail: coropalermo@caribe.net
a
b
INTRODUCTION
REFERENCES
1. Rose CS, Lara AR. (2010). Hypersensitivity Pneumonitis. In:
Mason RJ, Broaddus VC, Martin TR, King TE, Schraufnagel DE,
Murray JE, Nadel JA Murray & Nadel's Textbook of Respiratory
Medicine. 5th ed. United States of America: Saunders Elsevier.
1587-1598.
2. Weinber SE, Cockrill BA, Manderl J. (2008). Diffuse Parenchymal Lung Diseases Associated with Known Etiologic Agents
. In: Principles of Pulmonary Medicine . 5th ed. Philadelphia PA:
Saunders Elsevier. 141-153.
3. Hansell DM, Lynch DA, McAdams HP, Bankier AA. (2010).
Hypersensitivity Pneumonitis. In: Imaging Diseases of the
Chest. 5th ed. USA: Mosby Elsevier. 1485-1501.
4. Hischmann JV, Pipavath SN, Goldwin FD. (2009). Hypersensitivity Pneumonitis: A Historical, Clinical, Radiologic Review.
RadioGraphics. 29 (1), 1921-1938.
5. Takemura T, Akashi T, Ohtani Y, Inase N, Yoshizawa Y. (2008).
Pathology of Hypersensitivity Pneumonitis. Current Opinion in
Pulmonary medicine. 14 (1), 440-454.
6. Herbst JB, Myers JL. (2012). Hypersensitivity Pneumonia:
Role of Surgical Lung Biopsy. Arch Pathol Lab Med. 136 (1),
889-895.
7. Matar LD, McAdams HP, Sporn TA. (2000). Hypersensitivity
Pneumonitis. AJR. 174 (1), 1061-1066.
46
RESUMEN
Neumonitis por hipersensibilidad,
también conocida como alveolitis
alérgica extrínseca constituye un
espectro de enfermedades pulmonares granulomatosas, intersticiales bronquio-alveolares que resultan de la inhalación repetitiva
y sensibilización a una gran variedad de aerosoles orgánicos y antígenos químicos de bajo peso molecular. Se reporta el caso de una
fémina de 57 años que desarrollo
neumonitis de hipersensibilidad
por desechos de palomas. El diagnóstico y tratamiento temprano
evitan los cambios irreversibles
causados por la fase crónica de la
enfermedad.
Amiodarone is an effective; well establish type
III anti-arrhythmic drug commonly used worldwide (1-9). Despite its impressive profile in the
treatment of recurrent severe ventricular arrhythmias, atrial fibrillation, and paroxysmal
atrial tachycardia, its use is hampered by a
number of potential adverse effects, including
thyroid dysfunction (4-8). Each molecule of
amiodarone has a structural resemblance to
the thyroid hormone (see Figure 1), and contains two iodine atoms, which constitute 39%
of its mass (4-6,15).
Chronic treatment is
associated with a 40fold increase in plasma and urinary iodine levels, which are
mostly responsible for
the thyroid dysfunction (6). Therefore, a
patient who is taking a
standard 200 mg daily
dose of amiodarone
ingests 75 mg of organic iodine each day.
Subsequent deiodination through drug
metabolism yields 6
mg of free iodine into
the circulation that is
20-40 times higher
than the daily iodine
47
ABSTRACT
Amiodarone is used in a large
number of cardiac conditions.
Amiodarone-induced thyroid dysfunction has been reported to
affect up to 20% of users. Amiodarone can lead to both amiodarone-induced
hypothyroidism
(AIH) and less commonly amiodarone-induced
thyrotoxicosis
(AIT). There are two main forms
of AIT. Type 1 AIT, a form of iodine-induced
hyperthyroidism,
and type 2, a drug-induced destructive thyroiditis. Type 1 AIT
develops on individuals with underlying thyroid disease. Treatment of Type 1 AIT includes the
use of antithyroid drugs and discontinuation of amiodarone. Type
2 AIT is commonly self-limiting in
nature. In this article we describe
a patient with Amiodarone-induced thyrotoxicosis discussing
its clinical features and medical
therapeutic approach.
Index words: cardiology, endocrinology, amiodarone, thyrotoxicosis, case, report
Figure 2. Thyroid sonogram findings in our
patient with evidence of multinodular goiter
and hypervascularity
intake in the general population that approximate 0.15-0.30 mg (1,4,5). This excessive load
of iodine generates important adjustments in
hormone metabolism and physiological alterations in serum thyroid function tests (see Table
1).
Amiodarone can cause a spectrum of effects
on the thyroid, which can begin as early as a
few weeks after starting treatment and up to
4 years after its continuous use (8). Because
amiodarone accumulates in liver and adipose
tissue, it can continue to affect the thyroid
many months after it is discontinued (5,7).
Body iodine stores remain elevated for up to
nine months after stopping its intake. (7,14)
Amiodarone affects the thyroid gland by different mechanisms. These can be divided into
iodine-induced effects (related to the large iodine load of amiodarone) and those due to the
intrinsic properties of amiodarone (4). Amiodarone inhibits the 5’-deiodinase activity, leading
to a decrease in the generation of T3 from T4,
a decrease in the clearance of reverse T3 and
increased rT3 accumulation. Amiodarone also
inhibits T4 and T3 entry into the peripheral tissues. Amiodarone has a direct cytotoxic effect
leading to a destructive thyroiditis (4). On the
other hand, the Wolff-Chaikoff effect is lost because of the relatively high iodine content of
amiodarone. This tends to occur in patients
with underlying Hashimoto’s disease. In addition there may be iodine-related potentiation of
thyroid autoimmunity and unregulated thyroid
hormone synthesis in patients with underlying
Grave’s disease (4,5,8,9-14).
The majority of patients (>70%) on amiodarone
will remain euthyroid (4). Amiodarone-induced
thyroid dysfunction occurs in 15-20% of amio-
48
darone-treated patients (1,5,6,15). The prevalence of Amiodarone-induced hypothyroidism
(AIH) ranges from 5% to 22%. (4,5,8,17-19).
(AIH) is more frequent in iodine-sufficient populations, most preponderant in female (probably because underlying Hashimoto’disease is
more common in females). AIH occur typically
between six and 12 months of treatment (WolffChaikoff effect or a consequence of chronic
autoimmune thyroiditis induced by iodine excess). AIH does not pose relevant problems, is
easily controlled by L-thyroxine replacement,
and does not require amiodarone withdrawal
(1-5).
Figure 1. Amiodarone molecular structural resemblance
to the thyroid hormones
Amiodarone-induced thyrotoxicosis (AIT) occurs in iodine deficient populations and is more
common in males. AIT affects 2% to 9.6% of
amiodarone-treated patients (4). It may occur
4 months to 3 years after initiating therapy or
after drug withdrawal although it can develop
in the first few weeks of treatment (4). A diagnosis of AIT can also be considered at any
time in a patient who develops clinical signs
of thyrotoxicosis (see Table 2). Two types of
AIT have been described (see Table 3). Excess iodine-induced thyroid hormone synthesis is known as type I AIT, whereas destruction
of thyroid follicles resulting in a thyroiditis with
excess release of T3 and T4 is known as type
II AIT (1-8). Type II AIT occurs in normal thyroid
gland and is the result of a direct toxic effect
of amiodarone itself leading to a subacute and
destructive thyroiditis. Type II AIT is more frequent in iodine sufficient area (4,5).
Type I AIT develops on individuals with underlying thyroid disease (latent Graves’ disease
or nodular goiter) or positive circulating thyroid
peroxidase antibodies (TPOAb) and is due
to increased synthesis and release of thyroid
Figure 3. Thyroid uptake (24 hours) 26%
(N=10-40%) Thyroid scan: multinodular
goiter with adequate trapping and several
functional and non functional nodules.
Figure 4. Pre-evaluation and follow-up for patients for amiodarona
treatment
49
pg/ml (NV: 2.0-4.4 pg/ml), 24 hours urine iodine: 6428.1 ug/L (NV: 28-544 ug/L), TSI: 91%
(NV:0-139 %). Thyroid sonogram: multinodular
goiter (hypervascularity) (see Figure 2). Thyroid uptake (24 hours) 26% (N=10-40%) and
thyroid scan: multinodular goiter with adequate
trapping and several functional and non-functional nodules (see Figure 3). Type 1 AIT was
suspected. Patient improved and subsequently discharged on methimazole 30 mg po daily,
carvedilol, digoxin and warfarin. At OPD, methimazole was switch to PTU due to body rash.
Fine needle aspiration biopsy was compatible
with benign adenomatous goiter. Three months
after discharge patient remained clinically and
biochemically hyperthyroid (TSH: 0.001; Free
T4: 1.88; FreeT3: 3.78).
In view that patient remained clinically and biochemically hyperthyroid, radioiodine therapy
has been schedule for definitive treatment.
DISCUSSION
hormone (Jod-Basedow effect) (4,5). It can
frequently be difficult to differentiate between
these two types of AIT producing a significant diagnostic and treatment challenge (4,5).
Treatment of type 1 AIT includes the use of antithyroid drugs and discontinuation of amiodarone is necessary, if clinically possible. Type
2 AIT is self-limiting in nature; however, treatment requires glucocorticoids administration
and amiodarone should be discontinued (1-3).
Continuation of amiodarone has recently been
associated with a delayed restoration of euthyroidism and a higher chance of recurrence
after glucocorticoids withdrawal (1). Cases of
mixed AIT may respond to both agents given
together. If there is a very rapid response (within 1-2 weeks), then the patient is very likely to
have type 2 AIT.
In this article we describe a patient with amiodarone-induced thyrotoxicosis and discuss its
clinical features and medical therapeutic approach.
Case History
A 67-years-old-female, native of the Dominican
Republic, with a long history of hyperthyroidism (21 years) and an unclear medical therapy
is the subject of our report. Two months prior to
admission, she received amiodarone 200 mg
po daily due to cardiac arrhythmia. One week
prior to admission, she developed palpitations,
shortness of breath, dyspnea on exertion, orthopnea, lower extremities edema, weakness,
weight loss and dry cough. The patient had
past history of hypertension. Allergies: enalapril, atenolol due to rash. Family history: hyperthyroidism in two sisters. Physical examination:
acutely ill, thin female, in moderate respiratory
distress, alert, oriented. BP: 155/119 mmHg,
HR: 150, RR: 20, T: 37.1 Wt: 115 lbs. H: 59’’
BMI: 23.28. Prominent findings: multinodular goiter. Lungs: bilateral crackles up to 2/3
lung fields. Heart: irregular rhythm, no audible
murmurs. Extremities: bilateral pitting edema.
Neurologic: no abnormal findings. Electrocardiogram: Atrial Fibrillation with fast ventricular
response. Echocardiogram findings: Left and
right atrial enlargement with moderate to severe mitral regurgitation, and mild aortic regurgitation. Because of suspected intraauricular
thrombus, Transesophageal echocardiogram
was performed reported as negative. Diuretics,
nitrates, morphine, valsartan, anticoagulants
were administrated and an Amiodarone drip
started. Subsequent laboratory tests showed:
TSH: 0.02 mIU/mL (NV: 0.350-5.500 mIU/mL)
Free T4: 3.43 ng//dL (NV: 0.71-1.85 ng//dL),
T4: 16.57 ug/dL (NV: 4.5-12 ug/dL), After Endocrinology evaluation, Amiodarone drip was
discontinued and methimazole was started.
Subsequent laboratory tests showed: Anti –
TPO: 56 UI/mL (NV:0-34 UI/mL), Free T3: 8.8
50
We describe a case of thyrotoxicosis in a patient taking amiodarone, associated with cardiovascular disease. Her main clinical picture
was sudden onset and progressive worsening
of cardiac arrhythmia (Atrial fibrillation with fast
ventricular response and Congestive Heart
Failure) after short term of amiodarone ingestion. Patient had findings suggestive of type 1
AIT such as previous thyroid pathology, short
duration of amiodarone therapy, normal RAIU,
thyroid ultrasound with increased parenchymal
blood flow and evidence of very high iodine
load, attributable to chronic administration.
Even knowing the effects of amiodarone in the
thyroid gland, many physicians do not proceed
with an adequate evaluation (5). Only 49.2% of
the cardiologists use to follow thyroid function
frequently (5). It is essential to carefully evaluate patients, focusing on thyroid gland examination, before and during amiodarone therapy.
Baseline thyroid labs, such as TSH, FT4 and
TPOAb, repeated after 3 months of therapy,
then semiannually, are suggested guidelines
for follow-up (5). There are concerns about how
frequently a patient taking amiodarone should
be screened for thyroid dysfunction. However,
these is no consensus; intervals varying from
three months to more than 1 year (see Figure
4). A deterioration of cardiac function implies
the suspicious of associated thyroid dysfunction, even in the absence of classic symptoms
(5).
AIT is a dangerous and critical situation for the
patient with underlying cardiac abnormalities.
AIT is related to an increased cardiovascular
morbidity and mortality, especially in older patients with impaired left ventricular function, as
our patient (31.6% and 12.6% respectively)
(6).
In this patient with no treatable underlying
thyroid disease and previous cardiac ailment,
amiodarone was started with sudden and
abrupt deterioration of cardiac function.
While mild amiodarone-induced thyrotoxicosis subsides spontaneously in up to 20% of
cases, treatment is usually a challenge, especially if the type is uncertain (5,21). Type 1 AIT
must be treated with a thionamide 30 mg/day
or propylthiouracil 200 to 300 mg/day (5,22).
Although, antithyroid drugs are the best treatment for type 1 AIT, an iodine-repleted thyroid
gland is less responsive to the inhibitory action of thionamides. In our case, after changing
methimazole to propylthiouracil, euthyroidism,
however, was not achieved. Higher doses (4060 mg/d methimazole or equivalent doses of
propylthiouracil) and longer periods of therapy
are required before euthyroidism is restored
(4). This is obviously not ideal in patients with
cardiac problems, as in our case. In North
America, most thyroidologists employ thionamides alone as first line treatment for type 1
AIT (6). The use of the combined thionamidepotassium perchlorate treatment seems to be
more popular in Europe being the first-line
treatment for type 1 AIT (4). Potassium perchlorate decreases thyroid iodine uptake and
increases the sensitivity of the thyroid gland
to thionamides, resulting in good clinical response. (4).
Type 2 AIT may be self-limiting, and some authors have suggested continuation of amiodarone without minimizing the effectiveness
of steroids (6). The initial prednisone dose is
0.5-0.7 mg/kg body weight/day, and treatment
should be continued for three months (6). The
response to treatment often is dramatic, and
50% of patients are cured within 4 weeks (6).
Mixed or indefinite forms of AIT can occur. Both
pathogenetic mechanisms may be involved.
The best treatment is achieved by a combination of thionamides with or without potassium
perchlorate and oral glucocorticoids (4). Clinical features of hyperthyroidism and destructive
thyroiditis may be present concomitantly. If a
patient with diagnosis of type 1 AIT does not
respond to thionamides in four weeks, most
thyroidologists usually add perchlorate and/or
51
steroids. In North America, most of these patients are managed with a combination of antithyroid drugs and steroids initially.
Other therapies have been proposed to treat
AIT, such as lithium, iopanoic acid but the
evidence is too limited to support its effectiveness, which is certainly less than glucocorticoids (4). Total thyroidectomy is not the first
line treatment for AIT; however, this therapeutic maneuver may be necessary in patients
who are resistant to treatment and in very sick
patients who must continue amiodarone intake
(5). Total thyroidectomy controls thyrotoxicosis
and permits amiodarone to be safely continued. Our patient is a high-risk patient due to
her cardiac conditions for which surgery was
not an alternative therapeutic option.
The decision of whether amiodarone therapy
can be discontinued requires a strict interaction between cardiologists and endocrinologists. In a recent survey among European and
North American thyroidologists, amiodarone
withdrawal was considered necessary by 90%
of European and 79% of North Americans in
cases of type 1 AIT and 80% and 66% in type
2 AIT (4). Most endocrinologists are favoring
amiodarone withdrawal if it is not too risky for
patient’s condition.
Once euthyroidism has been restored, amiodarone withdrawn, and urinary iodine excretion
normalized, the European, North American
and Latin Survey (23-25) recommended, thyroid ablation (either by RAI therapy or thyroidectomy) by three quarters of responders for
the underlying thyroid disorder in type 1 AIT,
particularly if thyrotoxicosis recurred. Instead,
for type 2 AIT a wait-and-see strategy was suggested, unless relapse occurred (23-25).
CONCLUSION
The described case represented a diagnostic
and therapeutic challenge of type 1 AIT, due
to patient old age, underlying cardiac disease
with poor left ventricular dysfunction, and poor
response to medication. Identification of different types may be difficult and often imprecise.
The initial assessment is important for a correct
therapeutic approach. First line treatment of
AIT is medical. If type 1 AIT diagnosis is made,
thionamides are the best treatment; if type 2
AIT is diagnosed, steroids are the treatment of
choice. A rapid restoration of euthyroidism is
imperative because the general conditions of
the patients might deteriorate due to thyrotoxicosis. Additional short course therapy such as
52
iopanoic acid, lithium or steroids followed by
total thyroidectomy is alternative therapeutic
options. However, therapy should be individualized and RAI might be also considered in selected patients.
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3. Maseeh-uz-Zaman. Amiodarone therapy: don’t forget thyroid.
J PA Meda Assoc 2012 Mar 62 (3)268-72.
4. Shashithej K. Management of Amiodarone-related thyroid
problems. Ther Adv in Endo and Met. 2001. 2(3):115-126.
5. Winter A. Amiodarone and Thyrotoxicosis: Case Reports. Arq
Bras Cardiol 2010:95(5):e122-124
6. Fausto Bogazzi. Approach to the patient with Amiodaroneinduced Thyrotoxicosis. JCEM June 2010, 95(6):2529-2535
7. Cardenas G. Amiodarone-induced thyrotoxicosis: Diagnostic
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Vol 70 N 7. July 2003.
8. Tsang W. Amiodarone-induced thyrotoxicosis: A review. Can
J. Card Vol 25 N7 July 2009
9. Kai-Hang Y. Amiodarone-induced Thyrotoxicosis is a predictor of adverse cardiovascular outcome. JCEM, January
2009,94(1):109-114
10. Chinnadorai Rajeswaram Management of amiodarone-induced thyrotoxicosis. Swiss Med Wkly 2003;133:579-585
11. Gursoy A. Radioactive iodine in the treatment of thype 2
amiodarone-induced thyrotoxicosis Jnatl Med Assoc 2008
Jun;100(6):716-9
12. Pedro T. Difficult treatment of amiodarone-induced thyrotoxicosis: a case report. An Med Interna, 2007 Nov;24(11):543-6
13. Pacheco Capote Usefulness of thyroid scintigraphy in the
therapeutic management of amiodarone induced hyperthyroidism Rev Esp Nucl, 2007 Sep-Oct;26(5):270-6
14. Fausto Bogazzi Proportion of type 1 and type 2 amiodaroneinduced thyrotoxicosis has change over a 27 year period in Italy.
Clin Endocrinol (Oxf) Oct;67(4);533-7. Epub 2007 Jun 11.
15. Kurt IH Atrial fibrillation due to late amiodarone-induced thyrotoxicosis Clin Drug Investig, 2008:28(8);527-31
16. Fausto Bogazzi. Glucocorticoids are preferable to thionamides as first line treatment for Amiodarone –induced thyrotoxicosis due to destructive thyroiditis: A matched retrospective
Cohort Study. JCEM October 2009,94(10):3757-3762
17. Faizel Osman Successful Treatment of amiodarone-induced
thyrotoxicosis Circulation, 2002:105;1275-1277
18. Ian R Gough Surgical management of amiodarone-associated thyrotoxicosis MJA, 2002:176;128-129
19. O’Sullivan A Amiodarone-induced thyrotoxicosis: left ventricular dysfunction is associated with increased mortality European
Journal Endocrinology 2006:154;533-536
20. Pazin-Filho A How frequently should a patient taking amiodarone be screened for thyroid dysfunction? Brazilian Journal of
Medical and Biological Research, 2009:42;744-49
21. Conen D Amiodarone-induced thyrptoxicosis: clinical
course and predictors of outcome J Am Coll Cardiol, 2007:Jun
19:49(24);2350-5
22. Ursella S Amiodarone-induced thyroid dysfunction in
clinical practice Eur Rev Med Pharmacol Sci, 2006 SepOct:10(5);269-78
23. Diehl LA, Management of amiodarone-induced thyrotoxicosis in Latin America: an electronic survey Clin Endocrinol ( Oxf
) 65:433-438
24. Bartalena L, Diagnosis and management of amiodaroneinduced thyrotoxicosis in Europe:results of an international survey among members of the European Thyroid Association. Clin
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25. Tanda ML, Diagnosis and management of amiodarone-induced thyrotoxicosis: similarities and differences between North
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69:812-818.
RESUMEN
Amiodarona, es un agente antiarrítmico usado en varios tipos
de taquiarritmias, tanto ventriculares como supraventriculares.
La disfunción tiroidea inducida
por Amiodarona
ocurre entre
hasta en un 20% de usuarios. La
disfunción tiroidea varía entre
hipotiroidismo por Amiodarona
y menos comúnmente el hipertiroidismo por Amiodarona. Se
han descrito dos tipos de hipertiroidismo por Amiodarona. El
hipertiroidismo por Amiodarona
tipo 1, que es una forma de hipertiroidismo inducido por iodo; y
el hipertiroidismo por Amiodarona tipo 2 , que se describe como
una tiroiditis destructiva inducida por el medicamento. El hipertiroidismo por Amiodarona tipo 1
se desarrolla en individuos con
enfermedad tiroidea subyacente. El tratamiento usualmente
incluye el uso de medicamentos
antitiroideos y descontinuar la
Amiodarona. El hipertiroidismo
por Amiodarona tipo 2, se caracteriza generalmente por un
cuadro auto limitado. En este
articulo describimos un paciente con tirotoxicosis inducida
por Amiodarone discutiendo su
cuadro clínico y abordaje terapéutico.
http://www.youtube.com/AMPRTube
y
http://asocmedpr.org/TV.aspx
los canales de video de la
Asociación Médica de
Puerto Rico orientados a los
profesionales de salud
con material educativo y de
investigación.
Suscríbase gratis
Publique sus trabajos
Estudie en su oficina u hogar
53
54
around the world, misdiagnosis and incorrect
treatment still frequently take place given lack
of knowledge about SPT (6,7). We describe
the first reported case of SPT associated with
portal hypertension in Puerto Rico to stimulate
consideration of this tumor and its manifestations. A review of the relevant current literature
is also presented.
SOLID
PSEUDOPAPILLARY
PANCREATIC TUMOR AS A
PORTAL
HYPERTENSION
CAUSAL: The first reported
case in Puerto Rico
Daisy Torres-Miranda MSa*, Carlos Garcia-Gubern MDab, Maruja Santiago MDac,
Felipe Sanchez-Gaetan MDad
Ponce School of Medicine and Health Sciences, Ponce, Puerto
Rico.
b
Department of Emergency Medicine, Hospital San Lucas,
Ponce, Puerto Rico.
c
Department of Radiology, Hospital Metropolitano Dr. Pila,
Ponce, Puerto Rico.
d
Department of Surgery, Hospital San Lucas, Ponce, Puerto
Rico.
*Corresponding author: Daisy Torres-Miranda MS - Parc. Sabanetas #172 Munoz Rivera, Ponce, PR 00716-4511. E-mail:
darcy237@hotmail.com
Case History
Figure 1. Pancreatic mass coarse calcifications
a
Figure 2. The mass had heterogeneous zones containing cystic (necrotic) and solid portions
A 64-year-old male with relevant past medical history of pancreatic cancer diagnosed
five years ago and treated with chemotherapy
without significant clinical response is the propositus. The patient presented to the emergency department (ED) with a chief complaint of
intractable epigastric pressure type pain that
was worsening in the last days, with non relieving factors, also related with nausea and
Figure 3. mas effect to left kidney caused by
huge pancreatic mass.
Figure 4. Collateral vessels along the wall of
the stomach
ABSTRACT
We describe the first reported case
in Puerto Rico of Solid Pseudopapillary Tumor (SPT) of the pancreas
causing portal hypertension. Clinical presentation and characteristic imaging findings are helpful to
differentiate SPT from pancreatic
carcinoma. Diagnosis can be confirmed by histopathological and
immunohistochemical approach
through biopsy. Timely surgical intervention can prevent portal hypertension as manifestation and
be lifesaving in case of malignant
degeneration, giving the patient
an excellent prognosis after tumor
surgical resection.
Index words: solid, pseudopapillary,
pancreas, tumor, portal, hypertension
INTRODUCTION
The vast majority of pancreatic tumors are
malignant, having a dismal prognosis (1-3).
However, Solid Pseudopapillary Tumor (SPT)
of the pancreas is a low-grade malignant epithelial neoplasm comprising 1-2% of all pancreatic tumors, occurring mainly in young females in the second to fourth decades of life
(1-8). Surgical resection of the lesion is usually curative and the prognosis is excellent
(1-3). Histopathologic and radiologic findings
describe a well-defined, encapsulated pancreatic mass with cystic and solid components
with evidence of hemorrhage (1,2,4). Isolated
splenic vein thrombosis due to adjacent pancreatic mass may result in portal hypertension,
one of the common manifestations of this type
of tumor (1,5). Although increasing number
of cases has been reported in recent years
Figure 5. Delayed contrast enhanced CT scan
reveels filling defect in the splenic vein with
dilatation related to thrombus.
Figure 6. Another view of filling defect in the
splenic vein related to thrombus.
Figure 7. MRI confirmed the heterogeneous
lobulated mass in pancreas.
55
ish-tan, rubbery tissue with dark-reddish areas
of necrosis. Neither lymph node involvement
nor capsular invasion was seen. Lymph node
was negative for malignancy.
Immunostaining studies for tumor cells were
reactive for progesterone, beta catenin, CD10,
Ki67 in scattered cells, CD56, neuron-specific
enolase (NSE), and synaptophysin but not reactive for chromogranin, CD38, CK7, CK20,
and pankeratin. Diagnosis was most consistent with solid pseudopapillar neoplasm. The
patient had no evidence of recurrence 18
months after the surgery.
DISCUSSION
vomiting. He stated intermittent vague upper
abdominal discomfort per years. Patient had
history of hypertension and chronic renal failure. The social and family histories were noncontributory. At presentation to ED, the patient
had normal vitals signs and was afebrile. On
physical examination there was a palpable
large epigastric mass of about 8 cm extending from epigastrium to left and right upper
abdominal quadrants, tender to palpation,
but was otherwise unremarkable. Laboratory
parameters such as serum amylase and liver
function tests were normal. Carcinoembryogenic antigen (CEA), alpha-fetoprotein (AFP),
and carbohydrate antigen (CA) 19-9 were all in
the normal range.
Contrast enhanced CT-Scan of the abdomen
showed a well-defined large intra-abdominal
lobulated mass occupying most of the body
and tail of pancreas that measured approximately 13.1 cm in transverse diameter x 9.64
cm in AP diameter and 12.87 in cranio-caudal
extension. The mass had associated coarse
calcifications and heterogeneous zones containing solid and cystic (necrotic) portions (see
Figures 1 & 2). The tumor was displacing surrounding structures causing mass effect of the
pancreas especially to left kidney (see Figure
3) and was entering to the zone of the lesser
sac. There were no liver metastasis or enlarged
lymph nodes. Multiple collateral vessels were
seen extending from the splenic hilum and
extending along the wall of the stomach (see
Figure 4). Delayed contrast CT-Scan revealed
filling defect in the splenic vein with dilatation
related to thrombus (see Figures 5 & 6).
MRI post contrast confirms the presence of a
heterogeneous lobulated mass in the pancreas
(see Figure 7). Two percutaneous biopsies of
the mass were performed under CT guidance
without complications for histopathologic diagnosis. Microscopic examination revealed solid
areas alternating with pseudopapillary growth
pattern and small uniform cells surrounding fibrovascular cores in a myxoid mucinous stroma suggestive of SPT (see Figure 8).
The patient was taken to the operating room
where an exploratory laparotomy was performed. There, a large pancreatic mass was
found over the body and tail of pancreas, adhered to the posterior gastric wall and extending to the splenic hilum. Surgeon described
marked dilatation of splenic vein, gastroepiploic veins and short gastric veins in omentum
diagnostic of portal hypertension. The mass
was resected through distal pancreatectomy
and splenectomy. Patient tolerated procedure
well. Gross examination showed a huge encapsulated mass of 955 gm measuring 15 x
13 x 8 cm (see Figure 9), which on cut section
revealed solid areas along with intraparenchymal hemorrhages and necrotic zones. Externally, it was purplish tan in color, covered by
fibro-membranous soft tissue accompanied of
5 x 3.5 x 1.2 cm area of yellow pancreatic tissue. Surgical margins were free of tumor. After
serially sectioned, it was composed of a whit-
56
Solid pseudopapillary tumor of the pancreas was first described by Frantz in 1959 and
renamed by the World Health Organization
(WHO) in 1996 as it is today for the international histologic classification of tumors of the exocrine pancreas (1,2,8). It comprises 1-2% of
all tumors of the pancreas, and seems to have
a predilection for Asian and African-American
women, although rare cases have been seen
in men (1-3,7), as in our case. Patients with
SPT of the pancreas are often clinically asymptomatic or present with unclear clinical features including mild abdominal pain, increased
abdominal girth, poor appetite and nausea
which are related to tumor compression on
adjacent organs (1,2,6,8). Although most SPT
exhibit benign behavior, malignant degeneration does occur in about 15% of cases (1,2).
SPT have not been associated with any specific clinical laboratory test findings nor serum
tumor markers. Metastases have an incidence
of 15%; most of which are hepatic, and local
recurrence have rarely been reported in the
long-term follow-up of patients (8).
Imaging features can be highly suggestive for
diagnosis of SPT. This tumor should be considered when well marginated, large, encapsulated, solid and cystic masses with areas of
hemorrhagic degeneration are found. Biopsy
will help to confirm the diagnosis given that
microscopy and immunohistochemical patterns are peculiar in the case of SPT (1,2,4,7).
The microscopic characteristics of SPT are
solid areas that alternate with a pseudopapillary pattern composed of a fibrovascular stalk
surrounded by several layers of epithelial cells.
Immunohistochemical studies of SPT are typically reactive for NSE but not for chromogranin
and pankeratin (1,2). Even though this tumor
is rare in men of this age, positivity for betacatenin (cytoplasmic and nuclear) and pro-
gesterone receptors seen in our case are also
consistent with diagnosis.
Once the diagnosis of SPT is made, surgery
is the first choice of treatment, since other adjuvant therapies, including chemotherapy and
radiotherapy, had shown no demonstrable response in patients with or without the presence
of metastatic disease (1,2,6-8). Indeed, some
experimental regimes of chemotherapy have
been used without any significant clinical response (8). Overall five-year survival is as high
as 97% in patients undergoing surgical resection (8).
In cases of SPT, the splenic vein has been
seen to be susceptible to compression or infiltration by adjacent pancreatic mass. This has
resulted in isolated splenic vein thrombosis
and an unusual form of extrahepatic portal hypertension confined to the gastrosplenic side
of the portal venous circulation. Splenic vein
thrombosis and/or nonvisualization of it can
help to make the diagnosis of portal hypertension on CT-Scan in the presence of patent
portal vein and normal liver function (1,2,5).
Even though our patient had documented portal hypertension, he did not report any incident
of hematemesis or melena. Management of
this type of cases involves surgical removal of
tumor if possible, combined with splenectomy.
Splenectomy decreases the arterial inflow into
the left portal system by ligation of the splenic
artery, resulting in decompression of the varices, if present (1,5).
In conclusion, clinical presentation and characteristic imaging findings are helpful to differentiate SPT from pancreatic carcinoma, the initial
incorrect diagnosis of our patient. We would
like to emphasize the importance of pancreatic
neoplasm workup before a definitive diagnosis
of malignancy because it could be cured with
57
aggressive surgical resection before having
to expose the patient to any kind of chemotherapy. Timely surgical intervention also can
prevent the portal hypertension as manifestation and be lifesaving in case of malignant
degeneration. Diagnosis can be confirmed by
histopathological and immunohistochemical
approach through biopsy. Because of the lowgrade malignant potential and good prognosis
after complete resection of this type of tumor, it
is important to make a correct diagnosis before
treatment administration.
RESUMEN
Se presenta el primer caso reportado en Puerto Rico de un tumor sólido seudopapilar de páncreas causando hipertensión
portal. La presentación clínica y
los hallazgos característicos de
radiología son útiles para diferenciar este tipo de tumor de un
carcinoma de páncreas. El diagnóstico puede ser confirmado
con estudios histopatológicos e
inmunohistoquímicos mediante
biopsia. Una intervención quirúrgica a tiempo puede prevenir la
hipertensión portal como manifestación secundaria y hasta salvar la vida en caso de degeneración maligna, dando al paciente
una excelente prognosis después
de la resección quirúrgica del tumor.
REFERENCES
1. Wani NA, Lone TK, Shah AI, Khan AQ, Malik RA: Malignant
solid pseudopapillary tumor of pancreas causing sinistral portal
hypertension, Indian J Pathol Microbiol 2011; 54:152-5.
2. Coleman K, Doherty M, Bigler S: Solid-Pseudopapillary Tumor of the Pancreas, RadioGraphics 2003; 23:1644-1648.
3. Huang HL, Shih SC, Chang WH, Wang TE, Chen MJ, ChaYJ.
Solid-pseudopapillary tumor of the pancreas: Clinical experience and literature review, World J Gastroenterol 2005; 11(9):
1403-1409.
4. Dong PR, Lu DS, Degregario F, Fell SC, Au A, Kadell BM:
Solid and papillary neoplasm of the pancreas: radiologicalpathological study of five cases and review of the literature, Clin
Radiol 1996; 51:702-705.
5. Thompson RJ, Mark T, McKie LD, Diamond T: Sinistral portal
hypertension, Ulster Med J 2006; 75: 175–177.
6. Chen SQ, Zou SQ, Dai QB, Li H: Clinical analysis of solid-pseudopapillary tumor of the pancreas: report of 15 cases,
Hepatobiliary Pancreat Dis Int 2008; 7:196-200.
7. Chang H, Gong Y, Xu J, Su Z, Qin C, Zhang Z: Clinical Strategy for the Management of Solid Pseudopapillary Tumor of the
Pancreas: Aggressive or Less?, Int J Med Sci 2010; 309-313.
8. Bostanoglu S, Otan E, Akturan S, Hamamci EO, Bostanoglu
A, Gokce A, Albayrak L: Frantz's Tumor (Solid Pseudopapillary
Tumor) of the Pancreas. A Case Report, J Pancreas (Online)
2009; 10(2): 209-211.
Acknowledgments
Dr. Edgar Belmonte of the Pathology Department, Hospital San Lucas,
Ponce, Puerto Rico for his contribution providing us with the images presented in this case report.
PENETRATING EYE GLOBE
INJURY FROM TRAUMA WITH
A METALLIC NAIL:
A Case Report
Juan C Almodóvar-Mercado MDa*,
Vanessa López-Beauchamp MDa
Department of Ophthalmology, UPR School of Medicine, Medical Sciences Campus, Puerto Rico.
*Corresponding author: Juan C Almodóvar-Mercado MD - University of Puerto Rico School of Medicine, Department of Ophthalmology, PO Box 365067, San Juan, PR 00936-5067. E-mail:
juan.almodovar@upr.edu
a
ABSTRACT
We report a case of penetrating
eye globe injury due to a metallic
nail. This is the first case evaluated by our service that presented
with an intact 2.5-centimeter nail
penetrating the right eye with a
significant intraocular component that the patient did not remove. We describe the initial
presentation and the multi-step
surgery that this complicated
injury required. The early postoperative visual acuity remained
unchanged when compared to
the presenting. In addition, the
patient had no retinal pathology
or optic nerve damage after the
procedure.
INTRODUCTION
Ocular trauma is one of the leading preventable causes of monocular blindness and visual impairment (1-4). Intraocular foreign
bodies are major contributors to such cases
(1,2). Penetrating injury usually occurs when
an object is propelled at high velocity towards
the eye globe. Surgery is indicated in these
cases in order to remove the offending agent
and repair affected ocular structures. Final
visual outcomes have been reported to be
promising, with some reports showing 71%
of patients with final visual acuity at 20/40 or
better. However, these results vary depending on several factors, such as affected ocular
structures, presenting visual acuity after the
58
59
trauma and damage to the optic nerve (2). The
location of the injury also affects significantly
the visual acuity. Our report is that of a case of
a young man who presented to the Emergency
Room after having a penetrating eye globe injury due to a metallic nail and underwent foreign body removal, corneal laceration repair
with cataract extraction and intraocular lens
implantation in a single stage procedure.
Case History
A 20-year-old male patient presented to the
Emergency Room due to trauma to his right
eye after being stabbed accidentally by a nail
that he was hammering on the same day of
presentation. The patient reported no manipulation of the foreign body after the accident. He
was not using protective eyewear at the time
of the accident. Initial physical appearance of
the right eye showed part of the metallic nail
penetrating the cornea and extending to the
intraocular components, while the other part
was in the external ocular area (see Figure 1).
The presenting visual acuity was at 20/200.
The rest of the ocular exam showed corneal
laceration with corneal edema, formed anterior
chamber, traumatic cataract preventing direct
made using 15-degree blade and 3.0-millimeter keratome, respectively. Capsulorrhexis
was made using cystotome with subsequent
extracapsular lens aspiration using a Simcoe
cannula. Posterior capsular tear was seen in
the area where the nail was removed. Vitreous prolapsed to the anterior chamber was
removed with anterior vitrectomy. An intraocular lens implant was placed in the sulcus.
Acetylcholine chloride intraocular solution was
placed and the pupil was seen to constrict in a
circular fashion, except for the area affected by
the trauma. Wounds were found free of vitreous and closed with 10-0 nylon sutures.
On the first post-operative day (see Figure 4),
ocular exam showed 20/200 visual acuity in
the right eye with intraocular pressure at 9 millimeters of mercury, a sealed corneal laceration with sutures in place and corneal edema,
formed anterior chamber and the intraocular
lens implant in place. The posterior chamber
view was hazy and ultrasonography showed
no vitreous cavity intensities and retina attached grossly. Patient was started on a treatment regime, which consisted of one eye drop
of prednisolone acetate every two hours, one
drop of ofloxacin every two hours and one drop
of ketorolac every six hours.
visualization of the posterior chamber. Computed tomography scan showed penetrating
injury of the anterior aspect of the right eye
globe without perforation of the posterior aspect (see Figure 2a & 2b). The left eye examination was unremarkable and biometry was
done for this eye.
Under general anesthesia, the first approach
made was to remove the metallic nail in a reverse fashion following the trail that was made
when it penetrated the eye. The intraocular
foreign body measured 2.5 centimeters and
was sent for pathology and microbiology (see
Figure 3). The resulting corneal laceration had
clean borders that were well appositioned and
closed using interrupted 10-0 nylon sutures.
Corneal paracentesis and main wounds were
Patient returned to the clinics for seventh postoperative day evaluation and was found with
unchanged ocular exam from previous, except
for a better visualization of the retina, which
had no retinal tears or holes. He was scheduled for evaluation in three weeks but was lost
to follow-up after several attempts to contact
him. No microorganisms were reported in the
eye cultures. Final pathology report was consistent with a nail as the intraocular foreign
body.
DISCUSSION
Ocular trauma injuries related to intraocular foreign bodies can have disastrous effect
on vision (1-4). This is the first case evaluated by our service with a penetrating ocular
injury where a large intraocular foreign body
was found intact and without signs of external manipulation by the patient upon presentation. There was a multi-step surgical approach to this case, which included foreign
body removal, corneal laceration repair and
traumatic cataract extraction with intraocular
lens implant placement. Even though the patient was lost to follow up, his post-operative
evaluations the next day and week showed expected findings for the type of complex injury.
60
His retina remained attached without apparent
tears or holes and there was no sign of optic
nerve damage, which are signs of good visual
prognosis. It is important to recall that visual
rehabilitation is an important process following
ocular trauma. In this case, the patient would
benefit from repeated dilate fundus exam and
suture removal in order to reduce the corneal
astigmatism. He might then be refracted and
evaluated for a possible rigid gas permeable
lens to improve his visual acuity.
REFERENCES
1. Chen, K.-J. (2010). Retained Intraocular Nail With Perforating
Injury of the Eye. Journal of Trauma, 68(2), 503.
2. Greven, C., Engelbrecht, N., Slusher, M., & Nagy, S. (2000).
Intraocular foreign bodies: management, prognostic factors, and
visual outcomes. Ophthalmology, 107(3), 608-612.
3. Parver, L. M., Dannenberg, A. L., Blacklow, B., Fowler, C.
J., Brechner, R. J., & Tielsch, J. M. (1993). Characteristics and
Causes of Penetrating Eye Injuries Reported to the National
Eye Trauma System Registry, 1985-91. Public Health Reports,
108(5), 625-632.
4. Thylefors, B. (1992). Epidemiological patterns of ocular trauma. Australian and New Zealand Journal of Ophthalmology,
20(2), 95-98.
Since most of these ocular traumas are preventable, the emphasis on the use of safety
equipment is imperative during certain work
and daily activities. In addition, it is to our belief
that avoiding external manipulation of a penetrating foreign body by the patient and prompt
ocular examination by an ophthalmologist may
contribute to a better visual prognosis.
RESUMEN
En este artículo reportamos el caso
de un hombre de 20 años de edad
que sufrió una herida penetrante
de su ojo por un objeto extraño.
Éste es el primer caso evaluado
en nuestro servicio que presentó
con parte de un clavo metálico
intacto de 2.5 centímetros penetrando el globo ocular derecho
extendiéndose al compartimiento
intraocular, mientras que el resto
del objeto se encontraba en la parte externa ocular. Se realizó una
evaluación inicial y se determinó
que el paciente necesitaba cirugía
para remoción del objeto extraño,
reparación de la herida y extracción de la catarata. La agudeza
visual del paciente se mantuvo estable en el periodo post-operatorio
temprano en comparación con la
inicial. En adición, no se halló patología retiniana ni daño al nervio
óptico, lo cual confiere un posible
buen pronóstico visual. Debido a
que los traumas oculares son mayormente prevenibles, es importante enfatizar el uso de equipo de
seguridad en situaciones riesgosas. Además, creemos que evitar
la manipulación externa del objetivo extraño penetrante junto a una
evaluación oftalmológica rápida
puede contribuir a un pronóstico
visual positivo.
61
62
OCULAR FINDINGS IN PATIENTS WITH OCULOCUTANEOUS ALBINISM TYPE IA WITH G47D TYROSINASE GENE MUTATION IN PUERTO RICO:
A Case Report
Ferdinand Rodríguez-Agramontea,
Natalio J. Izquierdo MDb*, Carmen
Cadilla PhDc
UPR School of Medicine; Medical Sciences Campus, San
Juan, Puerto Rico.
Department of Surgery, UPR School of Medicine, Medical Sciences Campus, San Juan, Puerto Rico.
c
Department of Biochemistry, Medical Sciences Campus, San
Juan, Puerto Rico.
*Corresponding author: Natalio Izquierdo MD - 369 De Diego
St., Torre San Francisco, Suite 310, San Juan, Puerto Rico,
00923. E-mail: njuan@msn.com
a
b
INTRODUCTION
Previous studies have reported that the G47D
mutation leads patients to oculocutaneous
albinism (OCA) in Puerto Rico (1,2). Oetting
and co-workers suggested that the G47D missense substitution is a mutation leading to type
IA OCA in the northwestern quarter of the Caribbean Island (1).
Interestingly, this mutation has been described
in the Canary Islands (3). Immigrants from the
Canary Islands populated the western region
of Puerto Rico, due to tax incentives offered by
the Spanish monarchy to populate their colony
(4).
We report on the ocular findings of two patients
with OCA IA with the G47D Tyrosinase gene
mutation in Puerto Rico.
Case History
Patients underwent a comprehensive eye examination, and referred to a supratertiary center for genetic analysis of their mutation leading to OCA. A consent was obtained prior to
genetic sequencing.
Genomic DNA was isolated from blood using
QIAamp Blood Kits (Qiagen, Valencia, CA).
Mutations were screened for the TYR (OCA1)
genes by amplifying and directly sequenc-
ABSTRACT
Previous studies have suggested that the
G47D mutation leads patients to develop
Oculocutaneous albinism (OCA) type IA.
This mutation has been described in the
Canary Islands. Historically, there has
been a migration from the Canary Islands
to some regions of Puerto Rico. Objective: To report on the ocular findings of
two Puerto Rican patients with OCA IA
due to the G47D Tyrosinase gene mutation. Patient and findings: Two unrelated
patients with OCA underwent a comprehensive eye examination and were referred for genetic analysis. Patients had
almost total iris transillumination, clear
lenses, foveal hypoplasia with transparent maculae, and albinotic mid peripheries. Both patients had nystagmus, and
only one patient had strabismus. Conclusions: Patients with the G47D mutation leading to OCA IA have poor visual
acuities and poorly pigmented phenotypic ophthalmic findings. Further studies comparing ocular findings in patients
with several mutations leading to OCA
IA are warranted. To our knowledge this
is the first report on ocular findings in
Puerto Rican patients with OCA type IA
with the rare G47D mutation.
Index words: ocular, Oculocutaneous,
albinism, G47D, Tyrosinase, gene, mutation, Puerto Rico
ing exonic PCR products in both strands as
described by Giebel and co-workers, using
automated Sanger DNA sequencing and the
ThermoSequenase II Dye Terminator Cycle
Sequencing Kit from GE Healthcare, Life Sciences (5).
Patient #1 was a 12-year-old-male patient with
Type IA OCA who had a homozygous G47D
mutation on the TYR gene as described by
Sanbria and co-workers on chromosome
11q14.3 (6). Upon comprehensive ophthalmic
examination, Patient 1’s best-corrected visual
acuity (BCVA) was 20/400 in both eyes (using a contralateral +5.00 spherical lens as oc-
cluder). Patient’s cycloplegic retinoscopy was
-1.50 +4.00 X 90, and -0.50 +4.50 X 90 in the
right and left eye respectively. Patient had full
and orthophoric extraocular movements and a
periodic alternating nystagmus of low frequency, and small amplitude.
Upon slit lamp examination patient had almost
total iris transillumination, and clear lenses.
Upon Indirect Ophthalmoscopy patient had
healthy optic nerves, foveal hypoplasia with
transparent maculae, and albinotic mid-peripheries in both eyes. Upon Stratus Optical Coherence Tomography (OCT) patient showed
loss of foveal pit and a foveal minimum thickness of 169 microns and 213 microns, foveal
volume of 0.141 mm3 and 0.133 mm3; and total macular volume of 5.360 mm3 and 4.945
mm3, in the right and left eye respectively.
Patient #2 was a 5-year-old-male patient with
Type IA OCA with a homozygous G47D mutation of the TYR gene on chromosome 11q14.3.
Patient had history of bilateral medial rectus
recession strabismus surgery. His BCVA was
20/200 and 20/300 in the right and left eye respectively. His Cycloplegic Retinoscopy was
-1.75 +4.00 X 90 and -2.00 +4.00 X90 in the
right and left respectively. Patient had full and
orthophoric extraocular movements with periodic alternating nystagmus of low frequency
and small amplitude.
Upon slit lamp examination patient had almost
total iris transillumination and pigment only at
the colarette; and clear lenses. Upon Indirect
Ophthalmoscopy patient had healthy optic
nerves, intact vessels, and, foveal hypoplasia
with loss of foveal pit, transparent macula and
albinotic mid-peripheries in both eyes.
DISCUSSION
Santiago and co-workers have reported that at
least 3% of Puerto Rican patients with oculocutaneous albinism have OCA type 1 due to a
G47D substitution (2).
King and Summers (1), led correlation of clinical diagnosis of patients with OCA with systemic findings such as skin and hair hypopigmentation and characteristic ocular findings
including: nystagmus; reduced iris pigment
and transillumination; reduced retinal pigment
leading to visualization of choroidal blood vessels upon ophthalmoscopic examination (7).
Far along, King and co-workers reported that
patients with OCA have misrouting of the optic
nerves, including abnormal decussation of the
optic nerves (8). Both of our patients had periodic alternating nystagmus. This may be due
to King and Summers findings.
Summers previously reported that patients
with OCA have strabismus (9). However, strabismus does not occur in all patients with OCA
type IA (10,11). Patient #2 had undergone strabismus surgery, as opposed to Patient 1 who
did not have strabismus. Both our patients had
the exact mutation indicating that strabismus is
not a consistent sign and may not be suitable
as an inclusion or exclusion criteria for diagnosis of OCA type IA.
Earlier studies have reported that patients with
OCA type IA have the worst visual acuities of
all OCA subtypes (12-14). Yahalom and coworkers, found that hypermetropia was the
most common refractive error in patients with
OCA IA using an average of 5 or more diopters,
thus having the highest index of hypermetropia
among other OCA subtypes (12). Patient #1’s
BCVA was 20/400 in both eyes. Patient #2’s
BCVA was 20/200 and 20/300 in the right and
left eye respectively. Our findings are compatible with Scriver’s suggestion that OCA IA positions among the most severe visual acuities in
patients with albinism (14). Patient #1’s corrective glasses had 5 diopters compatible with
the average diopters required by patients of
the Yahalom study.
Karaman and co-workers reported that patients with OCA type IA have a wide variety of
iris transillumination (15). Both of our patients
had almost total iris transillumination with pigment on the colarette area. This finding may be
affected by the parents’ phenotype.
Foveal hypoplasia has been reported in patients with OCA (16,17). Upon ophthalmoscopic examination both patients had foveal
hypoplasia with transparent maculae in both
eyes. Stratus Optical Coherence Tomography
(OCT) patient’s findings showed increased foveal thickness associated to lack of foveal pit
and decreased macular volume in both eyes.
According to Thomas and co-workers arrested
development of the fovea leads to foveal hypoplasia, which causes a reduction in visual
acuity (18). Both our patients had foveal hypoplasia and transparent macular appearance,
as part of their OCA diagnosis.
Previous studies have reported ocular findings
in patients with OCA1 (15). Except for strabismus, ocular findings in both patients were
63
similar. We hypothesize that patients with the
Tyrosinase gene G47D mutation resulting in
OCA type IA have consistent ocular findings.
Limitations of this study include the low number of patients used to describe ocular findings, biased selection of subjects make conclusions difficult to generalize, data collected
is qualitative in nature and cannot be assessed
for statistical significance.
Additional studies comparing ocular findings
in patients with the various mutations leading
to OCA type I are warranted. Analysis of the
gene mutations in patients from the Canary Islands and other Spanish colonies in America
are needed.
RESUMEN
Estudios previos han sugerido que la mutación G47D del gen de tirosinasa causa
que pacientes a desarrollen Albinismo Oculocutáneo (OCA) tipo IA. Esta mutación
ha sido descrita en las Islas Canarias. La
migración de habitantes de las Islas Canarias hacia Puerto Rico es reconocida
históricamente. Objetivos: Reportar los
hallazgos oculares en dos pacientes puertorriqueños con OCA IA con la mutación
G74D del gen de tirosinasa. Pacientes y
hallazgos: Los pacientes tuvieron un examen oftalmológico comprensivo y fueron
referidos para análisis genético de su mutación. Presentaron hallazgos tales como:
transiluminación del iris casi total, lentes
claros, hipoplasia de la fóvea con macula
transparente, periferia albinótica y pérdida
de la región parafoveal. Ambos pacientes
tenían nistagmo. Solo un paciente tenía
estrabismo. Conclusiones: Nuestros hallazgos correlacionan con varios estudios
previos sobre Albinismo Oculocutáneo
tales como la severidad de la agudeza visual entre los pacientes de OCA IA. Se
necesitan estudios que comparen los hallazgos oculares en pacientes con mutaciones que llevan a OCA IA. A nuestro entender, este es el primer reporte sobre los
hallazgos oculares en pacientes puertorriqueños con la rara mutación G47D conducente al OCA IA.
In conclusion, to our knowledge this is the first
report on ocular findings in patients with OCA
type IA caused by the rare G47D Tyrosinase
gene mutation in Puerto Rico. These findings
include poor visual acuity, periodic alternating
nystagmus, almost-total iris transillumination,
and transparent foveal hypoplasia, macula
and albinotic mid-peripheries in both eyes.
MUCORMYCOSIS OF THE VULVA IN AN
IMMUNOCOMPROMISED PEDIATRIC PATIENT
Malieri Colón MDa, Josefina Romaguera MDa* , Keimary Mendez MDa,
Denise Vilchez MDb, Edward J Navas
MDa, José Perez MSa
65
Department of Obstetrics and Gynecology, UPR School of Medicine, Medical Sciences Campus, San Juan, Puerto Rico.
Universidad Ciencias Medicas, San José, Costa Rica.
*Corresponding author: Josefina Romaguera MD – Department of Obstetric and Gynecology, UPR School of Medicine,
PO Box 365067 San Juan, PR 00936-5067. E-mail: josefina.
romaguera@upr.edu
a
REFERENCES
1) Oetting WS, Witkop CJ Jr, Brown SA, Colomer R, Fryer JP,
Bloom KE, King RA. A frequent tyrosinase gene mutation associated with type I-A (tyrosinase-negative) albinism in Puerto
Rico. American Journal of Human Genetics. 1993; 52: 17-23.
2) Santiago PJ, Rodriguez Y, Renta J, Izquierdo N, del Fiero
L, Munoz D, Lopez N, Ramirez S, Pagan-Mercado G, Ortiz I,
Rivera-Caragol E, Spritz R, Cadilla C. Genetic Testing for Oculocutaneous Albinism Type 1 and 2 and Hermansky-Pudlak Syndrome Type 1 and 3 Mutations in Puerto Rico. The Society for
Investigative Dermatology. 2006; 126: 85-90.
3) Oetting WS, Hadoko HY, Mentink MM, Paller ASA, White JG,
King RA. Molecular analysis of an extended family with type IA
(tyrosinase-negative) oculocutaneous albinism. Journal of Investigative Dermatology. 1991a; 97: 15-19.
4) Valdés, A. "Real Cédula de 1789 "para el comercio de Negros"" (in (Spanish)). Proyecto Ensayo Hispánico. Ensayistas.
org. 1985. Retrieved 2013-03-30
5) Giebel LB, Strunk KM and Spritz RA. Organization and nucleotide sequences of the human tyrosinase gene and a truncated
tyrosinase-related segment. Genomics 1991; 9(3): 435-45.
6) Sanabria D, Groot H, Guzman J, Lattig MC. [An overview of
Oculocutaneous albinism: TYR gene mutations in five Colombian individuals]. Biomedica 2012; 32(2): 269-76
7) King RA, Summers CG. Albinism. Dermatol Clin 1998; 6:
217-228.
8) King RA. Oculocutaneous Albinism Type 1. 2000 Jan 19 [Updated 2004 Oct 1]. In: Pagon RA, Bird TD, Dolan CR, et al.,
editors. GeneReviews™ [Internet]. Seattle (WA): University of
Washington, Seattle; 1993-.
9) Summer CG. Albinism: classification, clinical characteristics, and recent findings. Optometry and Vision Science 2009;
86(6):659-62.
10) Jeffery G, Schutz G, Montoliu L. Correction of abnormal retinal pathways found with albinism by introduction of a
functional tyrosinase gene in transgenic mice. Dev Biol. Dec
1994;166(2):460-4.
11) Oetting WS, Summers CG, King RA. Albinism and the associated ocular defects. Metabolic, Pediatric, and Systemic Ophthalmology. 1994; 17 (1-4): 5-9
12) Yahalom C, Tzur V, Blumenfeld A, Greifner G, Eli D, Rosenmann A, Glanzer S, Anteby I. Refractive profile in Oculocutaneous albinism and its correlation with final visual outcome. The
British Journal of Ophthalmology. 2012; 96(4):537-9.
13) Dijkstal JM, Cooley SS, Holleschau AM, King RA, Summers
CG. Change in Visual Acuity in Albinism in the Early School
Years. Journal of Pediatric Ophthalmology Strabismus. 2011;
1-6.
14) Scriver CR, Beaudet AL, Sly WS, Valle D, King RA, Hearing VJ, Creel DJ, Oetting WS. Albinism. in The metabolic and
molecular bases of inherited disease (McGraw Hill, New York),
7th ed.II:4353-4392.
15) Karaman A. Oculocutaneous albinism type 1A: a case report. Dermatology Online Journal. 2008; 14(11):13.
16) Chong GT, Farsiu S, Freedman SF, Sarin N, Koreishi AF,
Izatt JA, Toth CA. Abnormal foveal morphology in ocular albinism imaged with spectral-domain optical coherence tomography. Archives of Ophthalmology. 2009; 127(1):37-44.
17) Seo JH, Yu YS, Kim JH. Correlation of visual acuity with
foveal hypoplasia grading by optical coherence tomography in
albinism. Ophthalmology. 2007;114(8):1547-51
18) Thomas M, Gottlob I. Optical Coherence Tomography Studies Provides New Insights into Diagnosis and Prognosis of Infantile Nystagmus: A Review. Strabismus. 2012; 20 (4): 175-180
64
b
ABSTRACT
Primary cutaneous mucormycosis
is very unusual and rarely reported in the literature. The diagnosis
is difficult and may mimic several
infectious and immunologic diseases. We report a case of vulvar
mucormycosis in a pediatric patient with end stage renal disease.
A female on her first decade of life
presented with a small scar on the
right labia majora that in matters
of weeks progressed aggressively,
ulcerated, extended to the contralateral labia and invaded the entire
vulvar region. Subsequent surgical debridement was undertaken.
Pathology revealed Mucor species
with progressive tissue necrosis.
The patient was successfully treated with systemic antifungal, wide
debridement of the affected area,
hyperbaric oxygen therapy and surgical reconstruction of the area.
Index words: mucormycosis, vulva, inmunocompromised, pediatric
INTRODUCTION
Primary cutaneous mucormycosis is very unusual and rarely reported in the literature. The
diagnosis is difficult and may mimic several infectious and immunologic diseases. We report
a case of vulvar mucormycosis in a pediatric
patient with end stage renal disease under immunosuppressive therapy. This is a rare progressive tissue necrosis on the vulva, especially rare in the pediatric population bridging
together multiple specialties such as obstetrics
and gynecology, oncology, pediatric surgery,
Figure 1: Vulvar mucormicosis necrotizing
infection upon physical examination
general pediatrics, nephrology, hematology,
infectious disease and rheumatology. Necrotizing soft tissue infections are characterized
clinically by fulminant tissue destruction, systemic signs of toxicity and high mortality. Accurate diagnosis and appropriate treatment
must include surgical intervention and antibiotic therapy (1-5).
Case History
A female on the first decade of life with previous medical history of chronic renal failure as
a result of renal vasculitis, peritoneal dialysis
and pulmonary fibrosis came to the pediatric
emergency room in status epilepticus and hypertensive crisis. The patient was admitted to
the pediatric intensive care unit where she was
stabilized and transferred to the nephrology
service for further care. During her initial stay,
a small black scar on the left labia majora was
noted, which in a matter of weeks progressed
aggressively, ulcerated, extended to the con-
tralateral labia and invaded the entire vulvar
region. Due to these findings, the case was
consulted to the Obstetrics and Gynecology
Department who decided to perform a joined
surgical intervention along with Pediatric Surgery. The primary surgeons were a Gynecology
Oncologist and a Pediatric surgeon who performed a wide excision and debridement of the
necrotic tissue of the bilateral labia majora and
vulva (see Figures 1, 2 & 3). The patient was
transferred to the ward with a urinary catheter,
intravenous antibiotics and wet-to-dry dressings in the excised area. The surgical pathology report described wide hyphae, irregular and
not-septated with 90-degree branching, highly
suggestive of Mucor species. As a result, the
patient was consulted with the Infectious Disease service, which directed she be managed
with the antifungal Posaconazole 200 mg PO
TID. Concomitantly the patient received twenty-one sessions of hyperbaric therapy demonstrating significant improvement. The patient
was later taken to the operation room for vulvar reconstruction with an adequate evolution.
DISCUSSION
borne. All humans have ample exposure to
these fungi during day-to-day activities. The
fact that mucormycosis is a rare human infection reflects the effectiveness of the intact human immune system. This is further supported
by the finding that almost all human infections
due to the agents of mucormycosis occur in
the presence of some underlying compromising condition (8-12).
Figure 2. Vulvar mucormicosis necrotizing
infection prior to surgical debridement.
Necrotizing soft tissue infections are characterized clinically by fulminant tissue destruction,
systemic signs of toxicity and high mortality.
Accurate diagnosis and appropriate treatment
must include surgical intervention and antibiotic therapy. The classification of these soft
tissue infections is based on clinical features
rather than surgical or pathological findings.
Fournier’s gangrene is caused by facultative
organism (Escherichia Coli, Klebsiella, Enterococci) along with anaerobes (Bacteroides,
Fusobacterium, Clostridium) and aerobic or
microphilic Streptococci. This infection is associated with diabetes, drug use, obesity, immunosuppression, recent surgery or traumatic
wounds.
Mucormycosis is a severe emerging invasive
fungal infection that occurs as a consequence
of environmental exposure (3-6). It is manifested by a variety of different syndromes in
humans, particularly in immunocompromised
patients. Devastating rhino-orbital-cerebral
and pulmonary infections are the most common syndromes caused by these fungi. Mucor
peritonitis has been described in peritoneal dialysis patients (7-9). The genera in the order
Mucorales cause most human infection. These
organisms are ubiquitous in nature, and can
be found on decaying vegetation and in the soil
(10,11). These fungi grow rapidly and release
large numbers of spores that can become air-
66
9. Petrikkos G, Skiada A, Lortholary O, Roilides E, et al. Epidemiology and Clinical Manifestations of Mucormycosis. Clin Infect
Dis. 2012; 54: 23-34
10. Spellberg B, Walsh T, Kontoyiannis D, et al. Recent Advances in the Management of Mucormycosis: From Bench to
Bedside. Clin Infect Dis. 2009; 48: 1743–1751.
11. Kwon-Chung K. Taxonomy of Fungi Causing Mucormycosis
and Entomophthoramycosis (Zygomycosis) and Nomenclature
of the Disease: Molecular Mycologic Perspectives. Clin Infect
Dis. 2012; 54: 8-15
12. Helenglass G, Elliot J, Lucie N. An Unusual Presentation of
Opportunistic Mucormycosis. British Medical Journal 1980; 282:
108-109.
The incidence of mucormycosis has increased
in the past twenty years, in part due to the increase use of immunosuppressive drugs or to
prolonged antifungal treatments lacking activity
against Mucorales (3). Despite its increasing
frequency, mucormycosis remains difficult to
diagnose. Radiographically and clinically, mucormycosis is often indistinguishable from other common invasive mold infections, such as
Aspergillosis. Histopathology is the “gold standard” for diagnosis. However, histopathologic
identification of Mucorales in tissue specimens
requires significant pathological expertise and
does not allow species identification. (4) As a
consequence of delayed diagnosis and lack of
optimal treatment, the mortality remains very
high and risk factors for death, such as therapeutic delay, have recently been individualized
(3, 6, 7, 10, 11). The occurrence of mucormycosis during healthcare procedures is not well
documented and is probably underestimated.
Cutaneous mucormycosis should be considered when skin necrosis continues despite
appropriate antibiotics and a history of risk
for immunosuppression. Definitive diagnosis
requires histological identification of the characteristic hyphae in tissue and blood vessels
and/or fungal cultures. Surgical debridement
is required for cure and adjunctive medical
therapy with amphotericin B is generally recommended (5).
REFERENCES
Figure 3. Vulvar mucormicosis necrotizing
infection post surgical debridement.
1. Rammaert B, Lanternier F, Zahar J, et al. Healthcare-Associated Mucormycosis. Clin Infect Dis. 2012; 54: 44-54
2. Nayak S, et al. Peritoneal mucormicosis in a patient on
CAPD. Perit Dial Int 2007
3. Cox G, Kauffman C, Thorner A. Mucormycosis (zygomycosis). Up to Date 2012.
4. Spellberg B, Walsh T, Kontoyiannis D, et al. Recent Advances
in the Management of Mucormycosis: From Bench to Bedside.
Clin Infect Dis. 2009; 48: 1743–1751.
5. Nomura J, Ruskin J, Sahebi F, et al. Case report: Mucormycosis of the vulva following bone marrow transplantation. Bone
Marrow Transplantation 1997; 19: 859–860.
6. Pak J, Tucci V, Vincent A, et al. Mucormycosis in Immunochallenged Patients. J Emerg Trauma Shock. 2008; 1: 106-113.
7. Karanth M, Taniere P, Barraclough J, Murray J. A rare presentation of zygomycosis (mucormycosis) and review of the literature. J ClinPathol 2005; 58: 879–881.
8. Täger M, Zaror L, Martínez P . Mucormicosis cutánea en un
paciente inmunocomprometido. Rev Chil Infect 2012; 29: 101107.
67
RESUMEN
Mucormicosis primaria cutánea
en el área de la vulva es inusual
y rara vez reportada en la literatura. Diagnosticarla es difícil debido a una gama de infecciones y
enfermedades inmunológicas que
expresan una apariencia similar
en las manifestaciones clínicas
del paciente. Reportamos un caso
de Mucormicosis de vulva en una
paciente pediátrica con fallo renal terminal que estaba recibiendo terapia inmunosupresora. Una
fémina en su primera década de
vida se presenta con una pequeña lesión ulcerativa en su labia
mayora derecha, que progresa
agresivamente en semanas hasta
extenderse a la labia mayora contralateral e invadir el área de la
vulva por completo. Se realizó un
desbridamiento quirúrgico La patología reporto la especie Mucor
con necrosis extensa del tejido.
La paciente fue manejada efectivamente con anti-fungal sistémico, desbridamiento extenso del
área afectada y terapia de oxigeno en una cámara hiperbárica.
Eventualmente se reconstruyó el
área quirúrgicamente de forma
satisfactoria.
68
Review Article/Artículo de Reseña
OVERVIEW OF THYROID
PHYSIOLOGY: An essential
for understanding Familial
Euthyroid Multinodular
Goiter
José Hernán Martínez MDa, Coromoto
Palermo MDa,
Francisco Fernández González MDb*,
Iván Laboy MDb
aDepartment of Endocrinology, San Juan City Hospital, San
Juan, Puerto Rico.
bDepartment of Internal Medicine, San Juan City Hospital, San
Juan, Puerto Rico.
*Corresponding author: Francisco Fernández-González MD 311 Teresa Jornet St, Condominium Tropical Courts, apartment
202, San Juan PR 00926. E-mail: frank1298@hotmail.com
the prevalence of endemic goiter accounts for more than 10%
within a population (4,5). The
prevalence for sporadic euthyroid goiter is 5% or less in nonendemic regions (6).
INTRODUCTION
The thyroid hormone is crucial for metabolism
of the body. Some of the fundamental functions includes activation of nuclear receptors,
increases in the activity of mitochondria, and
active transport of ions, promotes the development of brain during fetal life, stimulates carbohydrate and fat metabolism, and exerts effects
on sexual function. The human body could not
sustain life without this important hormone. We
present an overview on the thyroid physiology,
which is important for a better understanding
of familial euthyroid multinodular goiter. Every
step in thyroid hormone synthesis is emphasized in view that if any genetic defect occurs in
the pathway, this may provoke a multinodular
goiter state. Although scantly described in the
literature, this condition should be searched in
patients with goiter even in iodide sufficient areas for early diagnosis and management.
In a study by Tunbridge et al
from a iodide sufficient area
in northern England, using a
survey for 2,749 patients, nontoxic goiter was found in 5.9%
of patients, with a female to
male ratio of 13:1 (7). In Framingham, where iodine intake is
ample, 1.1% of 5,234 persons
examined were found to have
palpable multinodular thyroid
goiter (8). In other study by Rallison et al in United States, of
2,829 patients at Utah and Nevada, 23% had non-toxic goiter
(9).
Familial Euthyroid Multinodular Goiter
ABSTRACT
Nontoxic goiter is a diffuse or
nodular enlargement of the thyroid gland that does not result
from an inflammatory or neoplastic process and is not associated
with abnormal thyroid function.
Familial forms of goiter in areas
not known to feature iodine deficiency are much less common.
However, not all individuals in
the same iodine deficiency region develop goiter and iodine
supplementation does not prevent goiter development in all
treated individuals. The etiology
of euthyroid goiter is still incompletely understood. It is assumed
that the development of goiter
depends on various interactions
between genetic and environmental factors. We present an
overview on the thyroid physiology, which is important for a better understanding of Familial Euthyroid Multinodular Goiter.
Index words: overview, thyroid, physiology, familial, euthyroid, multinodular, goiter
In a recent publication by Palermo, Martinez
J.H, et al they determined the prevalence of
thyroid disease in an asymptomatic Puerto
Rican adult population within an iodine sufficient area. They correlated the clinical thyroid
features during palpation with sonographic
findings. The prevalence of thyroid pathology
detected by palpation was 53% and 38% by
ultrasound. The most frequent thyroid pathology found on palpation was goiter (41%) and
multinodular goiter (65%). Twenty four percent
of the participants with normal finding on palpation had abnormal finding by ultrasound.
Even in patients with negative family history of
thyroid pathology, abnormal thyroid ultrasound
findings were detected in 36%. The great majority of the study participants had normal thyroid stimulating hormone (TSH) values (1).
The above-mentioned results suggest that thyroid disease, especially multinodular goiter, is
frequently encountered in our adult Puerto Rican population. These prompted us to review
the incidence, causes, mutations, and factors
that contribute to the formation of multinodular
goiter as well as their management and treatment.
Familial euthyroid multinodular goiter, also
known as familial non-toxic multinodular goiter,
is a rare endocrinological condition, with scant
literature describing this entity. It consists of
hereditable multinodular goiter, non-toxic,
due to mutations or deletions in the synthetic
pathways of thyroid hormone (see Figure 1).
The most common cause of goiter is iodine
deficiency. Iodide is a required atom for the
synthesis of thyroid hormones. About 50 mg
of ingested iodine in the form of iodides are
required per week. It is absorbed from the gastrointestinal tract, with one fifth returning to the
circulation for synthesis of thyroid hormones.
Once the iodide is recycled and returned to
blood it enters the thyroid gland through a protein, an iodide pump, which uses sodium atoms as co-transport with iodide for entrance.
This process of entrance through basal membrane is called iodide trapping. A basic notion
of thyroid gland physiology is indispensable
in order to understand multiple thyroid conditions involved when a disorder is encountered
in each metabolic step (2,3). Figure 1 summarizes the thyroid gland physiology.
Familial euthyroid multinodular goiter is uncommon on developed countries such as
United States because iodine is richly supplied
on table salt and foods. Rather, it is commonly
seen in underdeveloped countries including for
example South America and Africa. However,
some cases of goiter (non-toxic, nor-malignant) are seen on geographic areas rich in iodide, and with negative family history of thyroid
pathology. This may be explained by mutations
of genes coding for proteins and enzymes vital in the synthesis of thyroid hormones (see
Table 1). The incidence varies by geographic
areas. In regions with mild iodine deficiency,
Davis Marine and Selwin Taylor
described the formation of nodular goiter. They described that it was the result of any chronic low grade, intermittent stimulus to thyroid hyperplasia (10,11). In a study
of a large Canadian family with 18 affected
patients, genetic studies identified a related affected chromosome 14q31, the MNG1 (12). A
similar study was performed in a German family with non-toxic multinodular goiter and the
same locus was observed affected in these individuals. A second locus, the MNG2, at Xp22
(X linked autosomal dominant) was identified
in an Italian family with the same condition
(13). Clinical examination may underestimate
the prevalence of mild thyroid enlargement,
since as many as a third of all thyroid glands in
one autopsy study contained multiple nodules
(14). A role for genetic factors in common multinodular goiter has been supported by a study
of Scottish twins, in which the contribution of
hereditary factors to nontoxic, simple goiter in
females was reported to approach 40%, and
by the existence of multinodular goiter families
with vertical male-to-male transmission suggesting an autosomal dominant susceptibility
(15). Although the biochemical and genetic
basis of many varieties of thyroid goiter have
been elucidated in most sporadic and familial cases of multinodular-goiter, investigations
failed to reveal any specific or consistent biochemical abnormality (16-19).
Factors that contribute to the formation of a
multinodular goiter state include genetic aber-
69
rations, female gender, medications or goitrogens, stress, advanced age, smoking, certain
hormones (such as insulin-like growth factor)
and iodide deficiency. Any of these problems
may induce overstimulation of TSH for compensation due to abnormality in thyroid hormone synthesis (20). Overstimulation with
TSH will cause excessive growth of the thyroid
gland. This will create areas of nodes, progressing to hemorrhage and fibrosis, hence
changing the thyroid gland morphology. The
above mentioned risk factors that are present
on patients with mutations in proteins involved
on thyroid syntesis may aid the triggering of
multinodular goiter formation (21,22).
Most cases of familial euthyroid multinodular goiter are present as autosomal dominant
pattern of inheritance. It is more common in
females than males (5). The most common
genes involved are the ones that codify for
proteins, including: thyroglobulin gene, thyroid
peroxidase gene, sodium iodide symporter
gene, the Pendred Syndrome gene, the TSH
receptor gene, the iodotyrosine deiodinase,
and the thyroid oxidase 2 gene 3 (23). Any
mutation associated in the synthesis of thyroid
hormones is involved in the formation of goiter. A defective iodination enzymatic process
may result due to mutations in enzymes peroxidase involved in oxidation of iodide prior to
bind to tyrosine. Thyroglobulin gene abnormalities may result from defects in the organification process. Defects in iodide recycling result
from excessive renal secretion of iodine in the
form of monoiodotyrosine and diiodotyrosine.
Reduced responsiveness of tissues to thyroid
hormones may result from point mutations,
deletions, and is usually inherited autosomal
dominant (24,25).
Pendred syndrome was first described by the
English doctor Vaughan Pendred (1869-1946),
in a study of an Irish family living in Durham in
1896. This condition is a genetic disorder leading to congenital bilateral sensorineural hearing loss and goiter with occasional hypothyroidism (26,27). It has been linked to mutations
in the PDS gene (SLC26A4), which codes for
pendrin, which is a protein involved in anions
transportation of Iodide and Chloride for thyroid hormone synthesis. The gene is located
on the long arm of chromosome 7, (7q31). The
syndrome is acquired as an autosomal recessive pattern. Goiter is present in 75 % of affected patients. It is diagnosed by obtaining an
abnormal perchlorate discharge test (28). Magnetic resonance imaging of the inner ear might
reveal widened or large vestibular aqueducts
with enlarged endolymphatic sacs. It may also
show abnormalities in the cochlea known as
Mondini dysplasia. There is no specific treatment for this condition. Cochlear implants is
recommended for audition problems. Speech
and language therapy is also recommended. If
thyroid hormones are decreased, it should be
replaced exogenously (29).
Once the patient is diagnosed with any type
of familial euthyroid multinodular goiter, they
should be observed for the necessity of thyroid
hormone replacement. Surgical management
(subtotal thyroidectomy) may be considered if
there are signs of structure compression due
to thyroid gland enlargement. Example of compression signs includes a positive Pemberton
sign, including facial flushing and dilation of
cervical veins on lifting the arms over the head,
which indicates obstruction to jugular venous
flow. Other signs and symptoms include dysphagia and vocal cord paralysis due to recurrent laryngeal nerve involvement. For patients
who are not candidate for surgery, radioiodine
ablation may provide palliative relief of any obstructive symptoms. It may reduce the size of
the gland by 30% to 50% (30).
CONCLUSION
Multinodular goiter is a common cause of enlarged thyroid gland usually encountered in
clinical practice by primary care physicians,
endocrinologists, surgeons, and otolaryngologists. The pathogenesis is multifactorial, including genetic, autoimmune and environmental factors. The major environmental influence
is attributable to iodine intake. Other factors
such as age, sex, and cigarette smoking are
known to influence the development of goiter.
Multinodular goiter occurs in geographic areas
with non-iodine deficiency and without family
history. However, family and twin pair studies
in endemic and non-endemic areas clearly
demonstrated a genetic predisposition for goiter development. The approach to the patient
70
with non toxic multinodular goiter should be a
serum TSH measurement to assess functional
thyroid status and ultrasound examination to
evaluate the number, size, and sonographic
features of the nodules and assist in the selection of nodules that may need fine-needle
aspiration biopsy that are the cornerstones in
the diagnostic work-up. Patients with nodules
yielding malignant cytology should be referred
for surgery. Given the lack of reliable markers
to predict biological behavior of nodules with
suspicious cytology, patients with such nodules
are generally advised to have surgery, unless
autonomous function of these nodules can be
confirmed by scintigraphy. Most of these patients, however, will ultimately prove to have
benign follicular tumors. Periodic follow-up
with neck palpation and ultrasound exam is
recommended for all patients. Although familial euthyroid multinodular goiter is scantly described in the literature, this condition should
be searched in patients with goiter even in iodide sufficient areas for early diagnosis, management and avoid future complications.
REFERENCES
1. Palermo GC, Martinez MJ,GonzalezE..et.al. Clinical and thyroid ultrasound evaluation in a asymptomatic adult Puerto Rican
population. Boletin. 2011.1: 26-32
2. Pankow BG, Michalak J, McGee MK: Adult human thyroid
weight. Health Phys, 1985; 49: 1097.
3. Guyton A, Hall J: Textbook of Medical Physiology, 10th Ed,
Philadelphia, W.B. Saunders Company, 2000: 858-65.
4. Hampel R, Gordalla A, Zollner H, Klinke D, Demuth M. Continuous rise of urinary iodine excretion and drop in thyroid gland
size among adolescents in Mecklenburg-West-Pomerania from
1993 to 1997.ExpClinEndocrinol Diabetes2000.108:197–201
5. Hampel R, Beyersdorf-Radeck B, Below H, Demuth M, Seelig
K. Urinary iodine levels within normal range in German schoolage children. Med Klin. 2001.96:125–128
6. Hegedus L, Bonnema SJ, Bennedbek FN. Management of
simple nodular goiter: current status and fature perspectives.
Endocr Reviews 24:102-132, 2003.
7. Tunbridge WM, Evered DC, Hall R, et al .The spectrum of
thyroid disease in a community: the Whickham survey. ClinEndocrinol 1997. 7:481–493.
8. Vander JB, Gaston EA, Dawber TR. Significance ofsolitary
non-toxic thyroid nodules. N Engl J Med. 1954.251:970–973.
9. Rallison ML, Dobyns BM, Meikle AW, et al. Natural history of thyroid abnormalities: prevalence, incidence,
and
regression
of
thyroid
diseases
in
adolescents and young adults. Am J Med.1991. 91:363-370.
10. Marine D: Etiology and prevention of simple goiter. Medicine.1924 3:453.
11. Taylor S: The evolution of nodular goiter. J ClinEndocrinolMetab1953.13:1232.
12. Franklyn JA. Lack of consensus in Europe in the management of multinodular goiter. Clin Endocrinol.2000. (Oxf) 53:3-4.
13. Bignell GR, Canzian F, Shayeghi M, et al. Familial no toxic
multinodular thyroid goiter locus maps to chromosome 14q but
does not account for familial nonmedullary thyroid cancer.The
American Journal of Human Genetics.1997.61:1123–1130.
14. Mortensen JD, Woolner JB, Bennett WA. Gross and microscopic findings in clinically normal thyroid glands. 1955. JClinEndocrinolMetab15:1270–1280.
15. Greig WR, Boyle JA, Duncan A, et al. Genetic and nongenetic factors in simplegoitre formation: evidence from a twin
study. Q J 1967. Med 36:175–188.
16. Medeiros-Neto GA, Stanbury JB (1966) Particulate iodoprotein in abnormal thyroid glands. J ClinEndocrinolMetab .1966.
26:23–32
17. Rapoport B, Niepomniszcze H, Bigazzi M, et al.Studies on
the pathogenesis of poor thyroglobuliniodination in non-toxic
multinodular goiter.1972. J ClinEndocrinol Metab 34:822–830.
18. DeGroot LJ, Larsen PR, Reffetof S.et.al..The Thyroid and its
Disease. Chicago. John Wiley and Sons, 1984:756- 831.
19. Ieiri T, Cochaux P, Targovnik HM, et al. A 30 splice site mutation in the thyroglobulin gene responsible for congenital goiter
withhypothyroidism. 1991. J Clin Invest 88:1901–1905.
20. Derwahl M, Studer H: Nodular goiter and goiter nodules:
Where iodine deficiency falls short of explaining the facts. ExpClinEndocrinol Diabetes 109:250-60, 2001.
21. Studer H, Peter HJ, Gerber H: Natural heterogeneity of
thyroid cells: The basis for understanding thyroid function and
nodular growth. Endocr Rev 10:125, 1989.
22. Peter JH, Gerber, Studer H.et al. Pathogenesis of heterogeneity in human multinodular goiter. J Clin Invest 76:1992, 1985.
23. Medeiros-Neto G and Knobel M. iodine deficiency disorders.
In: deGroot LJ, Jameson JL, eds. Endocrinology 6th Ed. Chapter 88. New York, Elsevier, 2010.
24. Knobel M & Medeiros-Neto G: An outline of inherited disorders of the thyroid hormone generating system. Thyroid; 13:771801, 2003.
25. Rubio IGS, Medeiros-Neto G. Mutations of the thyroglobulin
gene and its relevance to thyroid disorders.CurrOpinEndocrinol
Diabetes Obes. 16(5):373-8, 2009.
26. Pendred V: Deaf-mutism and goitre. Lancet2; 1896,Vol 148
(issue 3808): 532.
27. Pearce JM: Pendred's syndrome; Eur. Neurol; 2007,Vol. 58
(No. 3): 189–90.
28. Sheffield VC, Kraiem Z, Beck JC, et al.: Pendred syndrome
maps to chromosome 7q21-34 and is caused by an intrinsic
defect in thyroid iodine organification; Nat. Genet.12 (Issue 4):
424–6.
29. Reardon W, Coffey R, Phelps PD, et al: Pendred syndrome-100 years of underascertainment? QJM, 1997, (Issue 7):
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30. Gardner D, Shoback D: Greenspan’s Basic & Clinical Endocrinology. 9th Ed., New York, McGraw-Hill, 2011: 209-11.
71
RESUMEN
El bocio no tóxico es un agrandamiento nodular difuso de la glándula del tiroides que no resulta de
un proceso inflamatorio o neoplásico y no está asociado con una
función anormal del tiroides. Tipos
familiares de bocio en áreas no
conocidas en demostrar deficiencia de iodo son menos comunes.
El bocio eutiroideo ocurre endémicamente y esporádicamente. Sin
embargo, no todos los individuos
de la misma región de deficiencia
de iodo desarrollan un bocio y la
suplementación de iodo no previene el desarrollo de bocio en todos
los pacientes tratados. La etiología
de bocio eutiroideo es por lo tanto
no completamente entendida. Se
asume que el desarrollo del bocio
depende en varias interacciones
entre factores genéticos y ambientales. Presentamos un repaso de
la fisiología del tiroides importante
para reconocer el bocio multinodular familiar eutiroideo.
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de Puerto Rico
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