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Cutaneous manifestations of HIV infection

By Dr. Amira Abulfotooh
Lecturer of dermatology, venereology & Andrology.
HIV is an Icosahedral (20 sided), enveloped, single-stranded RNA virus belonging to the genus
Lentivirus within the family Retroviridae.
HIV has substantial genetic variability due to:

the high error rate and recombinogenicity of its reverse transcriptase

the very rapid turnover of the virus in infected individuals.
Retroviruses have a single-stranded RNA genome that serves as the template for the synthesis of
viral DNA, reversing the normal flow of genetic information and giving retroviruses their name.
AIDS Definition in HIV-infected individual
Any HIV-infected individual with a CD4+ T cell count of <200/L has AIDS by definition,
regardless of the presence of symptoms or opportunistic diseases.
Transmission of the Virus
Sexual intercourse: Anal and vaginal; Blood transfusion; Contaminated needles; Mother to child:
In utero, at birth, breast milk; Organ/tissue donation
CDC 1992 classification system for HIV disease:
Group I: Primary HIV
Group II: Asymptomatic infection
Group III: Persistent generalized lymphadenopathy
Group IV: Symptomatic infection
Group IVA: HIV wasting syndrome (AIDS) and constitutional disease
Group IVB: HIV encephalopathy (AIDS) and neurological disease
Group IVC1: Major opportunistic infections specified as AIDS- defining
Croup IVC2: Minor opportunistic infections
Group IVD: Cancers specified as disease defining
Group IVE: Other conditions
Cutaneous manifestations of HIV infection
I- Infectious HIV-related cutaneous disorders
A-Viral Infections
1-Exanthem of primary HIV infection (acute retroviral syndrome)
The earliest cutaneous manifestation of primary HIV infection
Lasts 45 days and is typically generalized, with most pronounced involvement on the face and
trunk, often sparing the distal extremities.

2- Herpes simplex virus (HSV)

In relatively immunocompetent HIV-infected individuals: Oral, labial and genital HSV
infections are typical in appearance, severity & recurrence rates.

In cases with significant immune suppression: Chronic, non-healing, deep ulcerations, favor
the perianal region, genitalia and tongue, more frequent recurrences.
3- Varicella zoster virus (VZV)

Primary varicella: Ranges from a typical course to fatal pulmonary involvement

Herpes zoster: patients have 715 times greater relative risk of developing herpes zoster,
Predictive of progression to more severe immune suppression, especially if associated with fever
Presentation: Classic dermatomal eruption, multidermatomal, ulcerative, chronic, verrucous
and/or widely disseminated with systemic involvement
Bacterial super infection, acyclovir resistance, therapeutic failure, and multiple recurrences.
4-Poxvirus(Molluscum contagiosum)
Affects HIV patients with significantly reduced CD4+ cell counts

They may be: Classic dome-shaped umbilicated papules, or larger (>1 cm), coalescent and
disfiguring lesions that are often resistant to treatment
Although any part of the body can be affected, the lesions favor the face, neck and intertriginous
areas.
5-Human papillomavirus (HPV)
HIV Tat protein upregulates the expression of HPV.
Lesions may be extensive, with multiple verrucae on the face, limbs and genitalia that coalesce
into large plaques.
HIV patients are at higher risk of developing cervical intraepithelial neoplasia (CIN) and anal
intraepithelial neoplasia (AIN).

Institution of ART does not:
Result in clearance of warts
Prevent high-grade CIN or AIN from progressing to cancer
6- EpsteinBarr virus (EBV)

Oral hairy leukoplakia: Represents an early sign of HIV infection, corrugated white plaques
with hair-like projections along the lateral aspect of the tongue, that develops in up to 25% of
HIV-infected individuals
It is not associated with malignant degeneration, but predicts disease progression if ART is not
administered
Treatment: is usually not necessary, topical or oral antiviral agents, podophyllin resin or gentian
violet can be of benefit. Antiretroviral therapy may also lead to regression of the plaques.

B-Bacterial Infections
1- Staphylococcus aureus
The most common bacterial pathogen in patients infected with HIV
Impetigo, folliculitis, furunculosis and cellulitis
generally respond to treatment with
antibiotics, but unusual presentations may be refractory to therapy.
Soft tissue infections with methicillin-resistant S. aureus (MRSA) is over six fold higher in HIVinfected individuals
2-Bacillary angiomatosis
Caused by Gram-negative bacilli in the genus Bartonella
Lesions of variable size and shape may be seen, including red to purple vascular-appearing
papules or nodules and ulcers. The number of lesions ranges from one to more than hundreds
Treatment: Macrolides or tetracyclines for a minimum of 2 months
If left untreated
death from pulmonary or hepatic failure
3- Mycobacteria
Cutaneous tuberculosis can develop during advanced stages of HIV infection. Other
mycobacteria may also produce the skin lesions, which are erythematous papules and nodules,
ulcers, verrucous plaques and deep nodules.
Pruritus is generally absent and patients may be febrile.
Treatment is with antimycobacterial medications as well as the use of ART
4- Syphilis
Classic papulosquamous secondary lesions are often seen,
-Unusual presentations may be observed: A noduloulcerative form, Papular eruptions that mimic
molluscum contagiosum, Syphilitic palmoplantar keratoderma.
-Lues maligna: an aggressive, widespread variant of secondary syphilis with a prodrome of
fever, headaches and myalgia followed by an eruption of papulopustular or necrotic lesions.
CNS involvement occurs more frequently and with greater severity
Neurosyphilis should be considered in HIV-infected patients with neurologic symptoms.
All patients with HIV infection should be tested for syphilis, and vice versa.
C- Fungal Infections
1- Candidiasis
The most frequently encountered fungal infection.
Clinically: Candidiasis of the oropharynx, Perlche with painful fissures at the oral commissures,
Persistent candidal infections of intertriginous zones, Chronic paronychia, onychodystrophy,
Refractory vaginal candidiasis, Disseminated candidiasis which may end fatally in HIV.
2- Dermatophytoses

Cutaneous involvement can be: atypical in appearance, more widespread, resistant to therapy.
Spread of interdigital tinea pedis onto the dorsal foot, Majocchi granuloma anw white
onychomycosis may occur
3- Systemic fungal infections
Disseminated disease can occur in HIV patients, when CD4+ counts are <250 cells/mm3
Clinically: pustules, crusted papules, papulonodules, verrucous plaques and mucocutaneous
ulcerations.
4- Pneumocystis jiroveci
Pneumocystis pneumonia is the most frequent form of infection.
Disseminated cutaneous P. jiroveci infection is extremely rare and may appear as: molluscum
contagiosum-like papules, bluish cellulitic plaques, deeply seated abscesses in the external
auditory canal or nares.
Standard therapy such as intravenous trimethoprimsulfamethoxazole or pentamidine is given.
D- Parasitic Infections
Ectoparasitic Infestations
1- Scabies
The most common ectoparasitic skin infestation in HIV-infected patients.
Severe infestation may develop as a consequence of diminished cell-mediated immunity.
-Cutaneous lesions: vary from the classic crusted papules to pruritic dermatitis to keratotic and
crusted plaques which may or may not be pruritic. Burrows are less apparent in HIV patients.
-The ears, face and scalp (sites not usually affected in immunocompetent adults) are commonly
involved in immunosuppressed patients.
-In crusted (Norwegian) scabies, hyperkeratotic lesions may be generalized with subungual
debris and marked nail thickening due to an extraordinary mite load
-Secondary infection with bacteremia and fatal septicemia has been reported.
II- NON-INFECTIOUS HIV-RELATED CUTANEOUS DISORDERS
A- Papulosquamous Disorders
1- Seborrheic dermatitis
Seborrheic dermatitis is the most common skin disorder to affect HIV infected individuals
Clinically: erythema and yellowish, greasy scale on the scalp and face, the central chest and
inguinal creases.
HIV is suspected in the following cases: Exuberant facial plaques, a sudden onset, acute
worsening of seborrheic dermatitis.
The disease may be more difficult to control with conventional therapy
2- Psoriasis

Clinical presentation tends to be more severe, and tends to worsen with declining immune status
Rapid onset of eruptive psoriasis can serve as a clue to an underlying HIV infection
3- Other papulosquamous dermatoses
Generalized xerosis, acquired ichthyosis, atopic dermatitis and pityriasis rubra pilaris.
B- Non-infectious papular pruritic disorders
1- Papular pruritic eruption of AIDS
Characterized by marked pruritus and involvement of the extremities > the trunk or face. Lesions
are symmetrically distributed, non-follicular papules, often with secondary changes.
May represent an exaggerated response to arthropod antigens.
2- Eosinophilic folliculitis
One of the most characteristic and common pruritic dermatoses associated with HIV.
Clinically: excoriated follicular papules and rare intact pustules found primarily on the face and
upper trunk.
It is an exaggerated reaction to Malassezia yeast or other organisms.
Cultures are negative, peripheral eosinophilia may be present. May prove recalcitrant to therapy
C- Hair and Nail Disorders
1-Alopecia
-Due to infectious etiologies: severe tinea capitis or secondary syphilis, or serious systemic
infections can trigger telogen effluvium.
-Due to non-infectious etiologies: In association with nucleoside analogue treatment

The hair in HIV patients may: Spontaneously straighten and become softer and silkier, or
Become lusterless and dull. Sudden graying of the hair may also occur.
Hair regrowth has also been observed after initiating zidovudine therapy
Trichomegaly of the eyelashes (prolonged anagen phase) has also been noted in AIDS patients
and those receiving interferon- and zidovudine.
2- Nail disorders
Proximal subungual onychomycosis, is often a reflection of immunosuppression.
Chronic candidiasis with paronychia and nail ridging
Beaus lines, psoriatic nail pitting and onycholysis may also be seen.
Patients receiving zidovudine may develop hyperpigmentation of the nail plates as a reflection of
increased melanin within melanocytes and dermal melanophages.
Protease inhibitors, especially indinavir
paronychia and ingrown toenails.
D- Vasculitis

E-Photosensitivity Reactions
1-UV light hypersensitivity
2-Chronic actinic dermatitis
F- Metabolic Changes: HIV/ART-associated lipodystrophy
Lipodystrophy syndrome describes clinical and metabolic changes associated with antiretroviral
therapy and HIV.
Clinicaly: Abdominal lipoaccumulation, gynecomasty, fat accumulation in the neck and
lipoatrophy in the face, or limbs
Metabolic changes: Insulin resistance, pathological glucose tolerance, hyperlipidemia, and low
HDL
Mechanism of drug induced lipoatrophy (Stavudine and zidovudine):
-Mitochondrial toxicity.
-impaired differentiation and increased apoptosis of adipocytes
-increased lipolysis and decreased lipogenesis;
Management:
-For lipoatrophy injections with fillers
-Diet and exercise have some positive effects on lipoaccumulation.
-Localized fat accumulation
excision or liposuction
-Hyperlipidemia
statins or fibrates (drug interactions)
-Change to tenofovir or abacavir should be considered in cases of drug induced lipoatrophy.
III- NEOPLASTIC HIV-RELATED CUTANEOUS DISORDERS
1-Squamous and Basal Cell Carcinomas
HIV-infected individuals have a three- to five fold higher risk of developing these skin cancers,
Appear at a younger age and are more often multifocal on the trunk and extremities
Cutaneous SCCs in HIV-infected individuals have a high risk of recurrence and metastasis.
BCCs do not behave more aggressively in patients with HIV infection .
HPV infection (in particular, high-risk genital and genus beta types) increases the risk of
anogenital, oral, digital cutaneous SCCs
2-Lymphomas
Clinically: Pink to violaceous papules and nodules, often ulcerate and may simulate panniculitis.
Differences from lymphomas in the general population:
-Mostly non-Hodgkin B-cell type of high or intermediate grade, occurring at a younger age of
onset, with more advanced stages. Extranodal involvement (especially of the CNS, intestine and
skin) at presentation and associated with EBV infection in >50% of cases
3-Kaposi Sarcoma
Most closely associated with HIV infection. The etiologic agent, human herpes virus type 8

Clinically: lesions vary from small violaceous papules to large plaques to ulcerated nodules.
-The upper body is typically involved, often along skin lines in a pityriasis rosea-like pattern and
at sites of local trauma. Lesions also develop on the face, in particular the nose, and on oral
mucosal surfaces, including the gingiva and hard palate.
-Internal involvement is common in HIV-related KS, most often affecting the lymph nodes
(potentially leading to lymphedema), gastrointestinal tract and lungs.

Treatment
Local destruction, e.g. cryotherapy, Topical alitretinoin (9-cis-retinoic acid) gel,
Superficial radiotherapy,(contraindicated for oral lesions
severe radiation-associated mucosal
ulcers and stomatitis.) Intralesional vinblastine or interferon, and intravenous liposomally
encapsulated doxorubicin, daunorubicin or paclitaxel.
TREATMENT
1- Reverse transcriptase inhibitors:
a- Nucleoside/nucleotide reverse transcriptase inhibitors: Zidovudine, Lamivudine, Tenofovir
b-Non-nucleoside reverse transcriptase inhibitors: Efavirenz, Nevirapine
2- Protease inhibitors: Indinavir, Saquinavir, Ritonavir
3- Fusion inhibitor: Enfuvirtide
4- CC-chemokine receptor 5 (CCR5) inhibitor: Maraviroc
5- Integrase inhibitor: Raltegravir
Combinations