Lipoid Pneumonia: an Unusual form of Drug Induced Lung Injury

An Unusual form Lung Injury
Meir Krupsky MD
Tel –Aviv Sourasky Medical CTR
Case description
•
•
•
•
a 88 y.o. male
No smoking history
Dancing instructor!!
Past medical history:
– HTN
– No TB contacts
1st admission
• SOB - Inspiratory, productive (whithish) cough,
NO fever - 3 months duration
• Weight loss 10Kg/ year
• Physical examination –rales bilateral bases (more Rt)
• FEV1=88% FEV1/FCV=76% O2 Sat=98%
• Labs:
Hb
WBC
12.3
Plt
13700 Globulin
415K
Creat
1.1
Glucose
101
3.1
Urea
46
LDH
176
Diagnosis
•
•
•
•
•
RLL pneumonia
Treated with ofloxacine
No initial response
Sputum & blood cultures neg.
Follow up CXR > CT recommended
2nd admission –
• Fever, cough, Rt. Chest pain – few days
• Physical exam. – bilateral Decreased respiratory
sounds and diffuse rales
• Continued infiltrate RLL
• Labs:
Hb
12.3
Plt
277K
Creat
1.1
WBC
13900
Globulin
3.9
Urea
33
Glucose
113
Imaging : CXR
Imaging : CT
Imaging : CT
• Rt. Lung base consolidation-homogeous,
GGO, mix alveolar & interstitial opacities
• Interlobular septal thickening
• Crazy- Paving Pattern
Additional testing
• Bronchoscopy – Rt. thickened bronchial
congested & hyperemic mucosa, easy bleed,
No obsrtruction No Mass/Infiltrative tumor
• Biopsies - RLL & RUL
• BAL- RLL
Case description
• a 77 y.o. male
• Past medical history:
–
–
–
–
–
D.M. – Insulin Rx.
CRF- diabetic nephropathy
HTN
Permanent pacemaker d/t C-AVB
CVA – 10 months ago
Medications
•
•
•
•
Insulin
Furosamide
PPI’s
???
1st admission
• Fever without localizing complaints, 3 days duration
• Recent dental treatment
• Physical examination – rales Rt. Lung base
• Labs:
Hb
WBC
12.3
Plt
17800 Globulin
415K
Creat
1.8
Glucose
256
3.5
Urea
56
LDH
176
Imaging : CXR
Diagnosis
• RLL pneumonia
• Treated with amoxycillin/clavulanate &
ofloxacine
• No initial response, blood cultures neg.
• TTE, oral surgeon consultation – no
abnormality
• Slow decrease in temp. – discharged
• Follow up CXR > CT recommended
• CXR - Continued infiltrate RLL
• ESR- 88
• No further evaluation done
2nd admission
• Fever, cough, Rt. Chest pain – few days
• Physical exam. – bilateral Decreased
respiratory sounds and rales
• Labs:
Hb
12.3
Plt
277K
Creat
2.1
WBC
14200
Globulin
4.1
Urea
63
Glucose
163
Imaging : CXR
Imaging : CT
Additional testing
• Pulmonary Function tests – low DLCO, mild combined
restriction & obstruction
• Sputum for culture and Sudan Black staining – negative
• Gallium scan – a Ga. avid pulmonary lesion – bilateral (most
active - RML)
• Bronchoscopy – thickened bronchial mucosa,
No obstruction No tumor
• Biopsies and BAL
Imaging : CT
Histology
• Fragments of lung parenchyma showing:
– Numerous clear droplets
– Intra-alveolar and intersitial macrophages with
vacuolated cytoplasm
– Reactive hyperplasia and septal thickening
– No granulomata
– No malignancy
Diagnosis: Lipoid pneumonia
Lipoid Pneumonia: an Unusual
form of Drug Induced Lung Injury
Lipoid pneumonia (LP)
• the result of foreign body type reaction to the
presence of lipid material within the lung
parenchyma.
• LP can be caused by the deposition of:
– Endogenous lipid material
– aspiration or inhalation of Exogenous lipids
Many types of lipids
• East African countries - a pediatric condition,
force feeding of infants with animal fat.
• Far Eastern countries - Squalene (shark liver)
• Animal fat more reactive than vegetable or
mineral oils
LP in developed nations
• Oily foods (ketogenic diet associated LP)
• Vaporized lipids inhaled during metal processing.
• The most frequent cause for LP : the medicinal use
of mineral oil (paraffin) – usually as a laxative
agent.
Paraffin oil
• A mixture of liquid saturated hydrocarbons
obtained from petroleum.
• When administered orally it is only
negligibly absorbed
• Common side effects :
– rectal seepage
– anal irritation.
• Aspiration > > > LP
Usage associated with LP
• Laxative
• Nasal drops
• Fire Eaters
‫אסון גשר המכבייה ה‪15-‬‬
Incidence of LP
• unknown.
• autopsy series : an incidence of about 1% .
• clinically diagnosed LP appears to be rare.
• The only national survey of LP
• Based on a survey of medical departments.
• 1981 to 1993
• only 44 cases of LP
• This would represent a prevalence of less
that 1:107 inhabitants.
• ¾ - associated with paraffin oil
Common findings
•
•
•
•
•
•
•
•
•
Mean age 61
M=F
Long exposure (mean 9.5 years)
Only 60% symptomatic
Fever, cough, weight loss
Occasional - chest pain, hemoptysis
Labs: ESR, leucocytosis (20%)
PFT – mostly DLCO, Restriction
Imaging – hypodense, peripheral sparing
Radiological - CT - finding in
Exogenous Lipoid Pneumonia
J Thorac Imaging. 2003; 18(4): 217-24
BaronSE, Haramati LB, Rivera VT
Albert Einstein College of Medicine, NY, USA
•
•
•
•
•
•
•
Consolidation
Ground glass opacities
Linear/nodular opacities
Masses
Fat attenuation
Pleural effusion
Lower lobes involvement
• “Crazy-paving” pattern ***
Radiological - CT - finding in
Exogenous Lipoid Pneumonia
J Thorac Imaging. 2003; 18(4): 217-24
BaronSE, Haramati LB, Rivera VT
Albert Einstein College of Medicine, NY, USA
• Consolidation and lower lobe involvement
in acute and chronic LP
• Pleural effusion and improvement on followup CT in acute LP
• Pulmonary masses and progression on followup CT in chronic LP
“Crazy-Paving” pattern at
thin-section CT of the lungs
Radiographics. 2003; 23(6): 1509-19
Rossi SE et al
• Scattered or diffuse ground - glass
attenuation with superimposed interlobular
thickning and intralobular lines.
•
•
•
•
•
•
Pneumocystis carinii pneumonia
Mucinous bronchioloalveolar carcinoma
Pulmonary alveolar proteinosis
Nonspecific interstitial pneumonia
Exogenous lipoid pneumonia
Pulmonary hemorrhagic syndromes
Radiological finding in
chronic exogenous lipoid pneumonia
Treatment of LP
•
???
– Severe anecdotal cases:
• Whole lung lavage
• Corticosteroids
– Milder cases:
• Corticosteroids
• Avoidance of further exposure without specific therapy
Natural history of LP - ????
• two deaths unrelated to the lipid pneumonia.
• In the 32 cases in which the oil was discontinued:
– 5 patients deteriorated (despite corticosteroid therapy in
one case)
– 27 patients remained stable/ improved regardless of
concomitant treatment
Imaging follow-up
•
•
•
•
3 complete cures (14%)
6 improvements (29%)
10 stable courses (48%)
2 deteriorations(10%)
Main lessons
• Paraffin should not be administered
to patients at risk:
– G-E reflux
– Neurological abnormality
• Not all febrile infiltrates are pneumonia
• Search for atypical features
• The importance of radiological
evaluation and follow up
ExLP- Exogenous Lipoid Pneumonia
•
Most Elderly –late 7-8th decade
•
Infants and mentally retarded
•
Impaired swallowing mechanism: neurological and esophageal disorders.
•
Consistent use of Oils :mineral, animal, vegetable oils in laxatives, nasal drops, mout
spray, oral lubricants, insecticides or traditional folk remedies, occupational fire hazar
of fire eaters (maccabia 1997)
•
The irritation causing agent enters the lung: Aspiration, inhalation or ionized
vegetable - radiopaque medium for lymphangiography, bronchography etc.
•
Vegetable oils, mostly expectorated, residual oils leads to ExLP
•
Mineral oil - Liquid petroleum or paraffin, mixture of long chain saturated
hydrocarbons.
ExLP- Exogenous Lipoid Pneumonia
•
Lung irritation - Diffuse parenchymal reaction
- localized masses / parafinnomas
•
Animal fat is the most harmful to lung tissue – hydrolized by (pulmonary) lipase
into FFA > > severe inflammatory reaction & tissue necrosis. Observed in infants
with ExLP, cultural practice of forced feedings of animal fat (Ghee).
•
ExLP 3 stages: 1. Toxic agitation of capillary endothelium - alveolar
exudative damage
2. Macrophages (alveolar & interstitial) activation - oil
phagocytosis & degradation
3. Fibrointerstitial and granulomatous reactions
•
High lipid content (animal) repress phagocytosis leaving the lymphocytes as the
main cells responsible for fat removal.
•
Histology - Fat-laden macrophages and prominant pleural lymphocytes, easily
mistaken as lymphocytic carcinomatosis.
Questions?
Paraffin:
Yes or No?
(and maybe some answers…)
EnLP- Endogenous Lipoid Pneumonia
(Golden pneumonitis / Cholesterol pneumonitis)
• Collection of intrinsic lipids in the lungs
• Chronic bronchial obstruction/Obstructive pneumonitis: foreign
bodies, tumors
Bronchiolitis obliterans ( chemotherapy/ radiotherapy - release of
lipids in alveoli )
• Pulmonary alveolar proteinosis, repetitive fungal pneumonia, Fat
embolism, Lipid storage diseases: Gaucher’s, Niemann-Pick and
Disseminated lipogranulomatosis
• Normal lung chemically analyzed- fat content 8.63/100g of dry tissue
19% is cholesterol ( percentage marked increase in smokers)
EnLP- Endogenous Lipoid Pneumonia
(Golden pneumonitis / Cholesterol pneumonitis)
• EnLP- Link to Lung Cancer (in resected lungs of 33/147
patients with lung cancer)
18% in Adeno-ca, 31% in Squamous cell ca.
• Lung parenchyma distal to obstructive tumor.
Transbronchial dissemination of breakdown products of
NSCLC cells, including mucin, could contribute to the spread
of non- obstructive component of EnLP.
• Histology of coexisting NSCLC & EnLP (lipids) similar to
coexisting Pulmonary alveolar proteinosis
(surfactant=lipids & protein) & NSCLC (Squamous cell ca
& Large cell ca)
EnLP - NSCLC
EnLP- Lung Cancer
Type I - obstructive LP
Type II & III – Non- obstructive LP
Transbronchial dissemination of:
* Cancer cells breakdown products ( mucin)
* Retained epithelial secretions
* Vessels leakage in prolonged hypoxia
LP & PET
Take Home message
Lipoid pneumonia (LP)
•
Old man & Lung infiltrate & Fever & ESR & WBC is not Sine qua non – Infective Pneumonia
•
ExLP and EnLP – two different entities.
•
In contradistinction to ExLP- External Oils :mineral, animal, vegetable oils , EnLP- Obstructive
pneumonitis
•
Unlike ExLP, the accumulation of lipid-rich cellular debris in EnLP does not manifest
radiologically as lipid- containing opacities
•
Gallium scan – ExLP avid pulmonary lesion
•
Several entities (Infections, lipid storage, PAP) are considered within the spectrum of EnLP.
•
EnLP confirmed diagnosis is histopathologic - imaging vary
•
EnLP Link to NSCLC (Type I , II & III)
•
PET-FDG scan - ExLP avid pulmonary lesion