Cutaneous manifestations of human immunodeficiency virus infection

Clinical Skills
Cutaneous manifestations
of human immunodeficiency
virus infection
Asha Rajeev, Claire Fuller
Abstract
Human immunodeficiency virus (HIV) infection continues to be a major challenge to medical science
worldwide. Diseases of the skin and mucous membranes were among the first recognised clinical
manifestations of acquired immunodeficiency syndrome (AIDS) in the early 1980s.There is no skin
condition reported so far that is specific for HIV infection but some, like Kaposi’s sarcoma and eosinophilic
folliculitis, are strongly suggestive. Skin diseases which usually are self-limited or tend to run a milder course
may become chronic, with frequent relapses and resistance to treatment. Drug resistance has added
problems in management with profound effects on health economy. Recognising HIV-related skin diseases
may lead to early diagnosis and initiation of antiretroviral therapy and the role of histopathology and
microbiology in the diagnostic process should not be underestimated.
Relevance of the article
As of June 2010, there have been 26,262
people with a diagnosis of AIDS in the
United Kingdom and 19,457 people
diagnosed with HIV have died (Health
Protection Agency Centre for Infections,
2010). Basic knowledge about cutaneous
manifestations of HIV is mandatory for
health professionals as the skin lesions are
more frequently encountered in our dayto-day practice. Diseases such as refractory
candidiasis, bacillary angiomatosis, Kaposi’s
sarcoma and multi-dermatomal herpes
zoster should alert us to look into factors
causing immunosuppression, HIV being the
first to come to mind. Some skin diseases
give a clue with regards to the progression
of HIV to AIDS.The most important
fact about HIV in terms of diagnosis is
that common skin diseases have unusual
presentations.This article aims to give
an overview of the skin manifestations
of HIV/AIDS, including clinical features,
investigations and management.
Cutaneous signs of primary HIV infection:
Pathophysiology
HIV produces cellular immune deficiency
characterised by depletion of T-Helper
Dr Asha Rajeev is Speciality Doctor,
Dermatology, and Dr Claire Fuller is Consultant
Dermatologist, Kent and Canterbury Hospital
12
cells (CD4) cells. Most infections and
neoplasms of the skin are facilitated by the
loss of CD4 cells. Primary HIV infection
is usually asymptomatic. Some patients
develop a maculopapular rash associated
with a flu-like syndrome. Mucosal lesions in
the form of erosions have been reported.
The symptoms resolve on their own
and are often not identified as part of
primary HIV infection unless the patient is
considered to be at high risk of acquiring
HIV. In the early asymptomatic stage of
HIV disease, no signs of infection other
than lymphadenopathy are present and it
can last 10 years or longer. With the onset
of immunosuppression, common disorders
with atypical clinical features are seen.
Mucocutaneous manifestations of established
HIV infections
Viral infections:
Herpes simplex (HSV)
Early in the HIV epidemic, chronic
persistent infection with HSV was
recognised in patients with advanced
HIV disease. Now it is one of the AIDSdefining illnesses as per the Centre
for Disease Control (CDC) criteria
(Centre for Disease Control, 1992).
Herpes simplex infection is usually a
self-limiting viral infection affecting the
oral or genital mucosa. As HIV infection
progresses, HSV becomes persistent
and progressive. Perianal and perioral
ulcers could be large and severely painful.
In paediatric patients, herpes simplex
stomatitis may become chronic and
ulcerative. Periungual infection is another
characteristic manifestation of HSV-2
infection in an HIV-infected patient; all
paronychial lesions should be cultured
for HSV (Glickel, 1988). Giemsa stained
Tzanck smear from the edge of the ulcer
when positive for multinucleated giant
cells gives a rapid diagnosis. A biopsy
sample with a portion of it sent for viral
culture may be needed in some cases for
a diagnosis.
Oral acyclovir is very effective in
most cases and may need intermittent or
chronic suppressive therapy. Famciclovir
and Valaciclovir are alternatives. Acyclovirresistant strains are treated with
Foscarnet.
Herpes zoster
Herpes zoster is common in HIV patients
and may be multi-dermatomal, bullous,
necrotic and haemorrhagic. A young
patient with recurrent or disseminated
zoster and no other contributing factor
to suggest immunosuppression will need
investigation to rule out HIV. Chronic
varicella zoster virus (VZV) infections
associated with HIV begin as vesicles and
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systemically are a feature of this
opportunistic infection caused by
Bartonella. They appear as redviolaceous papules similar to pyogenic
granuloma and tend to bleed profusely.
Differential diagnosis includes pyogenic
granuloma, angioma, Kaposi’s sarcoma
and disseminated cryptococcosis.
Systemic involvement is common and
can be fatal. Early diagnosis using silver
stains is important as the organism is
difficult to culture and responds well to
erythromycin and doxycycline. Unlike
Kaposi’s sarcoma, another vascular lesion
seen in AIDS, BA does not respond to
radiotherapy.
progress into necrotic, non-healing ulcers
(Erdal et al, 2009). Dissemination of VZV
in HIV is fortunately uncommon (Cohen,
Grossman, 1989). VZV does disseminate
more commonly than HSV and hence
all disseminated herpetiform eruptions
should be considered VZV unless proved
otherwise and high-dose acyclovir should
be given. Since VZV is less sensitive to
acyclovir than HSV, four times higher
dosage is needed. Some authors believe
intravenous treatment is better than oral
(Pahwa et al, 1988), especially when the
eye is involved.
Molluscum contagiosum (MC)
The MC virus is a DNA virus causing
small papules with central depression,
often self-limiting and common in children.
MC occurs in approximately 10-20%
of HIV-infected persons (Schwartz,
Myskowski, 1992). Often large, disfiguring
lesions are seen, which can only be
differentiated by histology. They can appear
on the face, neck, eyelids and scalp, which
is not a common site for molluscum
in adults. The lesions can get inflamed
and there may be associated dermatitis.
Treatment is mainly cosmetic with
cryotherapy and curettage and cautery.
Human papilloma virus
Widespread and treatment-unresponsive
warts can be seen on the perianal region,
face and oral mucosa. HPV is closely
linked to sexually transmitted cancers, the
most common being cervical cancer and
anorectal carcinoma. There is increased
risk of intra-epithelial carcinoma even
with HPV types not usually associated
with malignancy. Regular screening of
patients with HIV helps in early detection.
Presence of external warts should prompt
an internal examination, including smears
and colposcopy in women and anoscopy
in men. Management is similar to that in
immunocompetent individuals, except
that multiple attempts are needed and
treatment resistant lesions should be
surgically removed and sent for histology.
Cytomegalovirus (CMV)
CMV, another DNA virus, can cause
persistent perineal ulceration. Herpes virus
infection might be present concurrently.
Diagnosing CMV cutaneous infection
is important as it is considered a poor
prognostic sign in HIV (Erdal et al, 2009).
Figure 1. Human papilloma virus: genital warts.
Bacterial infections:
Staphylococcus aureus
Staphylococcal infections are the
most common bacterial infection in
HIV patients. Folliculitis, abscesses and
furuncles, as well secondary infection of
eczema, scabies and ulcers are frequently
seen. In patients with bacteraemia,
Staph aureus is a common cause.
HPV is closely linked
to sexually transmitted
cancers, the most common
being cervical cancer and
anorectal carcinoma.
The risk factors include intravenous
catheter use, intravenous drug use
and trauma. Impetigo and folliculitis
may be recurrent and persistent in
HIV disease, particularly in children.
Folliculitis caused by Staphylococci can
be severely pruritic and often mistaken
for other itchy skin conditions. Gram
stain and culture confirms the diagnosis
and appropriate treatment can be given
at the earliest. Nasal mupirocin, topical
antibacterial washes, hydrogen peroxide/
benzyl peroxide washes/creams all help
elimination of bacteria and may prevent
relapses.
Bacillary angiomatosis (BA)
Vascular tumours that can disseminate
Syphilis
Syphilis has made a reappearance in
the HIV era, as it frequently co-exists
with HIV. Syphilitic ulcers are believed
to increase HIV transmission. Even
though most cases are typical, atypical
features include painful chancre, absent
or abnormally high antibody titres,
necrotising lesions and rapid progression
into tertiary or neurosyphilis. For latent
syphilis of longer than one year or of
unknown duration, CSF examination
is recommended for all HIV-infected
patients. Penicillin still remains the drug
of choice for the treatment of syphilis.
Mycobacteria
Systemic infections with Mycobacterium
tuberculosis and atypical mycobacteria
are a frequent problem in HIV disease
and AIDS.The skin manifestations of
Mycobacterium avium complex are not
characteristic and can present as crusted
ulcers, inflammatory nodules and scaly
plaques. Localised lesions resembling the
linear ascending pattern of sporotrichosis is
rare. Other mycobacteria which cause skin
lesions are M. kansasi and M. haemophilum.
Unless special stains for AFB are
ordered, misdiagnosis may result. Atypical
mycobacteria should be suspected when
smears for Acid fast bacilli (AFB) are
positive, yet standard AFB cultures are
negative.Treatment includes clarithromycin,
doxycycline and clofazimine.
Fungal infections:
Superficial fungal infections
Candida, dermatophytes and tinea
versicolor are the usual fungi causing
superficial fungal infections. Treatment
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et al, 1986). Scabies mites can cause
Norwegian (crusted) scabies with
immunosuppression and this can be
easily confused with psoriasis and severe
dermatitis. Unlike ordinary scabies, the
host is infested by millions of mites and
is highly contagious. Topical treatments
by themselves won’t be effective and
oral ivermectin is needed.
Regional Dermatology Training Centre, Moshi Tanzania
Demodicosis
Demodicosis caused by Demodex
folliculorum, a normal hair follicle
resident mite, appears as an itchy,
papular eruption affecting head, neck,
trunk and arms. Permethrin may help
get rid of the problem.
Skin tumours in HIV
Figure 2. Kaposi’s sarcoma (KS) was the first reported malignancy associated with HIV infection.
resistant candidiasis in the form of
thrush, ulcers, erosions, hyperplastic
plaques and angular chelitis should raise
the suspicion of HIV if no other cause
for immunosuppression can be found.
Trichophyton rubrum can cause tinea
capitis in adults. Nail involvement with
dermatophytes results in proximal white
onychomycosis, which is the pattern
usually seen with HIV. Tinea versicolor
can often be resistant and extensive
with HIV. Malassezia folliculitis produces
multiple follicular centred papules on the
face, chest and upper extremities and
is often pruritic. Candida and tinea can
be diagnosed by potassium hydroxide
examination of scales or material from
the pustules. Usual topical treatment
in the form of nystatin or imidazoles
is usually effective. Persistent lesion on
the groins should alert to a possible
alternative diagnosis of flexural psoriasis/
seborrhoeic dermatitis.
Deep mycoses
Histoplasma, Cryptococcus, North
American blastomycosis and
coccidiodomycosis all cause extensive
and unusual manifestations when
associated with HIV. Mostly deep
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Scabies in HIV-infected
persons usually presents
with the typical involvement
of skin folds, genitalia and
finger webs.
mycoses are diagnosed by histology.
Granulomas are seen and special stains
can identify the organism. Clinical
differential diagnosis matters most in
selecting special stains. There should be
a low threshold to biopsy lesions and
send one sample for bacteriology and
fungal culture. Cutaneous cryptococcosis
can resemble molluscum contagiosum.
Amphotericin B and Itraconazole are
the usual antifungals used to treat
systemic mycoses.
Arthropod infestations:
Scabies
Scabies in HIV-infected persons usually
presents with the typical involvement
of skin folds, genitalia and finger webs.
The infestation may become more
widespread and refractory to treatment
and spares the characteristic areas with
advanced immunosuppression (Sadick
Kaposi’s sarcoma
Kaposi’s sarcoma (KS) was the first
reported malignancy associated with
HIV infection and is caused by Human
Herpes Virus 8. It is a multifocal, vascular
tumour affecting the skin, lymph nodes
and viscera. One form of Kaposi’s
sarcoma is endemic in the African
subcontinent. The type associated with
HIV/AIDS can be localised or systemic.
Lesions present with red, purple or
brown macules, nodules or plaques
affecting trunk, legs, face and oral cavity.
While taking a biopsy, precautions such
as avoiding foot and lower leg lesions,
waiting at least 5 minutes after injecting
the anaesthetic with adrenaline, and
suturing minimises the risk of bleeding
(Maurer, Berger, 1998). Therapy aims at
controlling the symptoms and includes
antiretroviral treatment, radiation, alpha
interferon or chemotherapy.
Other skin tumours
Lymphomas can produce skin nodules.
An increase in multiple squamous
cell carcinoma, metastatic basal cell
carcinoma and aggressive malignant
melanoma has been repor ted.
Children with AIDS have a higher
risk of developing leiomyosarcoma
(smooth muscle sarcoma) although
the incidence is low. Since the
introduction of Highly Active
Antiretroviral Therapy (HAART),
the incidence of non-AIDS defining
cutaneous cancers like basal cell
carcinoma among HIV-infected
individuals has exceeded that of
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Appeel ad
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Regional Dermatology Training Centre, Moshi Tanzania
secondary to pityrosporum folliculitis,
demodicosis, scabies, hypersensitivity
to insect bites and prurigo. Xerosis of
the skin, which is common in HIV, also
contributes to itchy skin. Asteatotic
eczema needs topical steroids and
emollients for control.
Regional Dermatology Training Centre, Moshi Tanzania
Figure 3. Fixed drug eruption: drug reactions are common when starting new medication.
Figure 4. Toxic epidermal necrolysis, a severe drug reaction, can occur in HIV patients.
AIDS-defining cancers like KS (Erdal
et al, 2009).
Papulosquamous disorders
Seborrhoeic dermatitis as an early
skin manifestation of HIV is seen in
83% of patients and is the commonest
dermatosis associated with HIV.
Lesions may be widespread, atypical,
inflammatory and hyperkeratotic. Some
cases may progress to erythroderma
(Erdal et al, 2009). Treatment includes
topical antifungals combined with topical
corticosteroid and regular emollients.
Phototherapy and oral antifungals may
be needed for resistant cases.
16
Psoriasis could manifest for the first
time with HIV or the pre-existing
psoriasis could flare up and can turn
erythrodermic/pustular. Reiter’s disease
can present with its classical triad of
urethritis, conjunctivitis and arthritis and
often could be an early manifestation.
The incidence is approximately 250 fold
higher in HIV positive patients when
compared with the normal population
(Penneys, 1995).
Pruritus in HIV
Pruritus is a common complaint in
patients with advanced HIV disease.
It can occur as primary pruritus or
Eosinophilic folliculitis
EF is a non-infectious eosinophilic
infiltration of hair follicles. The three
variants include classic eosinophilic
pustular folliculitis, immunosuppressionassociated EF (mostly HIV related)
and infancy associated EF (Nervi et
al, 2006). The male-to-female ratio
is 5:1. Eosinophilic folliculitis, which
is considered a distinct marker of
advanced HIV, manifests as severely
itchy follicular and non-follicular
urticarial papules and sterile pustules
involving the face, upper trunk and
proximal extremities. Treatments
including isotretinoin (Annam et
al, 2010), phototherapy, dapsone
and topical steroids are used in the
management of this condition, but with
limited efficacy.
Drug reactions
Early drug reactions also should be
thought of when eliciting the history
from a patient with HIV and pruritus.
Drug reactions are common within
7-12 days of starting a new medication
but can occur months later as the
patient’s immune status improves.
The most common pattern is a
maculopapular rash and the usual culprit
is sulphonamides. Severe drug reactions
include Stevens Johnson’s syndrome,
toxic epidermal necrolysis (TEN) and
acute generalised exanthematous
pustulosis (AGEP), which can be lifethreatening due to fluid and electrolyte
imbalance and secondary infection.
Treatment includes stopping the
medication and supportive care.
Intravenous immunoglobulin may be
beneficial in severe cases when started
early in the course of the reaction.
Pruritic papular eruption
Pruritic papular eruption (PPE) of
HIV presents as symmetrical, diffuse,
multiple discrete scratched red bumps
affecting mostly the extremities and
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trunk. The mucous membranes, palms
and web spaces are spared. The cause is
unknown and, according to Boonchai et
al (1999), 81.25% of patients with PPE
have immunosuppression. Some authors
consider it as an exaggerated insect bite
reaction. It is three times more common
when the CD 4 lymphocyte count is
less than 200×109/L.Treatment includes
topical steroids, emollients, topical
tacrolimus, oral antihistamines and
phototherapy. Recurrence is common.
Oral lesions in HIV
Oral lesions are seen in almost the
whole course of HIV, starting from
primary stage into advanced HIV/AIDS.
Some lesions such as oropharyngeal
candidiasis, especially treatment-resistant
ones and frequently relapsing ones,
should raise the suspicion of HIV if no
other predisposing factors are present.
Oesophageal involvement is often seen
and presents as painful swallowing.
Systemic antifungal treatment is needed.
Oral hairy leucoplakia is a distinctive
lesion seen as asymptomatic, ribbed
plaques along the lateral borders of
the tongue and is caused by Epstein
Barr Virus. Oral hairy leucoplakia
has no malignant potential, but may
be the initial sign of progressive
immunosuppression. Oral acyclovir
800mg five times daily until lesions clear,
followed by minimal suppressive dose,
may be considered (Rico et al, 1997).
White plaques are often confused with
candidiasis and lichen planus. Aphthous
ulcers in HIV tend to be larger and
more extensive, involving the pharynx,
tongue and lips, causing dysphagia and
rapid weight loss.
Hair disorders in HIV
Diffuse alopecia or alopecia areata can
be associated with HIV and it could be
inflammatory and permanent. Indinavir, a
protease inhibitor used to treat HIV, can
cause generalised alopecia. Elongation
of eye lashes and straightening and
softening of scalp hair may be observed.
Nail disorders in HIV
Beau’s lines and pallor of the nail beds
could be a manifestation of any long
standing illness. Zidovudine causes
longitudinal, transverse or diffuse hyper
pigmentation of the nails. HIV infection
in itself without treatment can also
cause pigmentation of the nails. Nail
involvement with dermatophytes results
in proximal white onychomycosis which
is the pattern usually seen with HIV
(Erdal et al, 2009).
Indian J Dermatol Venereol Leprol 76(3):
259-62
The value of biopsy in diagnosis
Cohen PR, Grossman ME (1989) Clinical
features of human immunodeficiency
virus-associated disseminated herpes
zoster — a review of the literature. Clin
Exp Dermatol 14(4): 273-276
As already mentioned, the average
HIV-infected individual has at least two
synchronous skin conditions; several
biopsies may be needed to avoid
oversight (Osbourne et al, 2003).
There should be a low threshold
for biopsy including histopathology
and microbiology. More importantly,
Dermatologists play a
major role in diagnosing and
managing drug reactions,
enabling the patient to
have life-long, effective viral
suppression.
knowledge about the conditions matters
most, as differential diagnosis given
by the clinician helps the pathologist
to do special stains and arrive at an
appropriate diagnosis.
Conclusion
HIV-infected persons commonly have
cutaneous abnormalities. Most of the
conditions are the usual ones we
see in our day-to-day practice, but a
bit or grossly different in the clinical
presentation. Progression from HIV to
AIDS takes an average of 10 years and
being aware of the skin manifestations
helps to monitor the progression of
HIV. Dermatologists play a major role in
diagnosing and managing drug reactions,
enabling the patient to have life-long,
effective viral suppression.
Acknowledgements
The photographs are used by kind
permission of RDTC Moshi Tanzania
and Professor Ben Naafs, Consultant
Dermatologist. DN
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