Residency · Residency · Dermatology

Cutaneous Manifestations of HIV/AIDS

Overview

Skin disease affects over 90 percent of HIV-infected individuals during the course of illness and often provides the earliest clinical clue to underlying immunosuppression. The spectrum of cutaneous manifestations correlates with CD4+ T-cell count and viral load. Recognizing these skin findings enables earlier diagnosis of HIV and guides assessment of immune status and disease progression.

Skin Findings by CD4 Count

CD4 >500 cells/microL (Early HIV)

In early HIV infection, skin findings include acute retroviral syndrome (morbilliform exanthem), seborrheic dermatitis (which may be the first sign), herpes zoster (particularly multidermatomal or recurrent), oral hairy leukoplakia, psoriasis (new onset or flare), and pruritic papular eruption.

CD4 200-500 cells/microL (Moderate Immunosuppression)

With moderate immunosuppression, patients develop severe seborrheic dermatitis, widespread and large molluscum contagiosum, recalcitrant and numerous warts, oral candidiasis (thrush), Kaposi sarcoma, prurigo nodularis, and xerosis with acquired ichthyosis.

CD4 <200 cells/microL (AIDS-Defining)

Advanced immunosuppression brings aggressive Kaposi sarcoma, disseminated deep fungal infections (cryptococcosis, histoplasmosis, coccidioidomycosis), bacillary angiomatosis, eosinophilic folliculitis, crusted (Norwegian) scabies, chronic herpes simplex ulcers persisting more than one month, disseminated molluscum contagiosum with giant lesions, and CMV skin ulcers.

Infectious Conditions

Kaposi Sarcoma (KS)

Kaposi sarcoma, caused by HHV-8 (KSHV), is the most common malignancy in AIDS, though its incidence is declining with ART. It presents as violaceous patches, plaques, and nodules that are non-blanching, distributed on the face (particularly the nose tip), oral mucosa, trunk, and lower extremities. Lymphedema from lymphatic involvement is common, and the disease can involve the lungs, GI tract, and lymph nodes. Histology reveals spindle cell proliferation forming slit-like vascular spaces with extravasated RBCs, positive for HHV-8 LANA immunostain. ART is the primary therapy, as immune reconstitution often leads to regression. Local treatments include radiation, cryotherapy, intralesional vinblastine, and alitretinoin gel, while systemic options for advanced disease include liposomal doxorubicin and paclitaxel.

Bacillary Angiomatosis

Bacillary angiomatosis is caused by Bartonella henselae or B. quintana and presents as a vascular proliferative lesion mimicking KS or pyogenic granuloma. Red-purple papules and nodules are friable and bleed easily. The condition can involve the liver (peliosis hepatis) and spleen, typically occurring at CD4 counts below 100. Histologically, it shows lobular vascular proliferation with neutrophils and amphophilic granular material (bacterial clumps visualized with Warthin-Starry stain). The key distinction from KS is the presence of neutrophils, positive Warthin-Starry staining, and negative HHV-8. Treatment consists of prolonged erythromycin or doxycycline for three or more months.

Oral Hairy Leukoplakia

Oral hairy leukoplakia is EBV-induced and pathognomonic for HIV, though not AIDS-defining. It presents as white, corrugated, "hairy" plaques on the lateral tongue that cannot be scraped off, distinguishing it from thrush. It is often asymptomatic and usually does not require treatment, resolving with ART; antivirals (acyclovir) or podophyllin can be used if symptomatic.

Molluscum Contagiosum (Disseminated)

Molluscum contagiosum in HIV is widespread with large lesions exceeding 1 cm ("giant molluscum"), often facial. Facial molluscum in an adult should raise suspicion for HIV. It may mimic cryptococcosis or histoplasmosis. Treatment centers on ART for immune reconstitution leading to clearance, with cryotherapy and curettage for individual lesions.

Herpes Simplex (Chronic Ulcerative)

Chronic herpes simplex ulcers persisting more than one month are AIDS-defining. They present as non-healing ulcers with vegetative or verrucous borders and can become acyclovir-resistant through thymidine kinase mutations. Treatment includes valacyclovir or acyclovir, with IV foscarnet for resistant strains.

Deep Fungal Infections

Cryptococcosis presents as umbilicated papules mimicking molluscum, especially on the face, caused by Cryptococcus neoformans and diagnosed with India ink and serum/CSF CrAg. Histoplasmosis causes disseminated papules, nodules, and ulcers that may mimic molluscum. Coccidioidomycosis presents as verrucous nodules, papules, and draining sinuses. Penicilliosis (talaromycosis), caused by Talaromyces marneffei and endemic to Southeast Asia, presents with umbilicated papules.

Crusted (Norwegian) Scabies

Crusted scabies results from massive Sarcoptes scabiei infestation due to impaired immunity, presenting as thick, crusted, hyperkeratotic plaques containing thousands to millions of mites. It is often misdiagnosed as psoriasis or eczema and is extremely contagious compared to classic scabies (which involves approximately 10 to 15 mites). Treatment requires combination oral ivermectin plus topical permethrin, often needing multiple cycles, with treatment of all contacts.

Inflammatory Conditions

Eosinophilic Folliculitis

Eosinophilic folliculitis presents as intensely pruritic, sterile, follicular papules and pustules in a seborrheic distribution (head, neck, upper trunk), typically at CD4 counts below 250. Histology shows an eosinophilic infiltrate around the follicular infundibulum. The differential includes bacterial folliculitis, Pityrosporum folliculitis, and acne. Treatment includes ART, topical corticosteroids, phototherapy (UVB), itraconazole, and antihistamines.

Seborrheic Dermatitis (Severe)

Seborrheic dermatitis may be the earliest cutaneous manifestation of HIV. It is more widespread, inflammatory, and treatment-resistant than in immunocompetent individuals and can involve unusual locations such as the trunk and extremities. Severity correlates inversely with CD4 count. Sudden onset of severe SD in a young adult should prompt HIV testing. Treatment includes topical antifungals (ketoconazole), mild topical corticosteroids, and ART.

Psoriasis

HIV-associated psoriasis is often explosive in onset, severe, and treatment-resistant. Paradoxically, psoriasis is T-cell mediated yet worsens with T-cell depletion, suggesting that CD8+ cells and innate immunity may be key drivers. It may present as severe erythrodermic or pustular forms. ART often improves psoriasis, and phototherapy (NB-UVB) and acitretin are used, while immunosuppressants are avoided if possible. TNF inhibitors and IL-17/IL-23 inhibitors may be used cautiously with ART in select cases.

Pruritic Papular Eruption (PPE)

PPE presents as chronic, pruritic, follicular and extrafollicular papules on the trunk and extremities, very common in tropical and resource-limited settings. It represents a hypersensitivity to insect bites in the setting of immune dysregulation, typically at CD4 counts below 200. Treatment includes ART, antihistamines, topical corticosteroids, and phototherapy.

Drug Eruptions

HIV-infected individuals have an increased frequency of drug reactions. TMP-SMX causes a morbilliform eruption in up to 50 percent of HIV-positive patients (compared to 3 to 5 percent in immunocompetent individuals). Nevirapine carries SJS/TEN risk. Abacavir requires HLA-B*5701 testing before prescribing, as a positive result is an absolute contraindication due to the risk of life-threatening hypersensitivity. Antiretrovirals can cause lipodystrophy and metabolic syndrome.

Immune Reconstitution Inflammatory Syndrome (IRIS)

IRIS involves paradoxical worsening of skin conditions after ART initiation, caused by the recovering immune system mounting an exaggerated response to latent infections and antigens. It occurs within weeks to months of ART initiation, especially with rapid CD4 recovery. Common IRIS-related skin conditions include herpes zoster flare, Kaposi sarcoma flare (paradoxical worsening before improvement), inflammation of molluscum and warts, and mycobacterial abscess formation. Management involves continuing ART, treating the specific condition, and using corticosteroids in severe cases.

Neoplasms

Beyond Kaposi sarcoma, neoplasms in HIV include non-Hodgkin lymphoma (primary cutaneous), cervical and anal SCC (HPV-related, with screening via anal Pap smear recommended), increased SCC risk, and possibly increased melanoma risk (though this is debated).

<image>Clinical photograph panel of HIV-associated skin findings: (A) Kaposi sarcoma showing violaceous patches and nodules on the leg, (B) bacillary angiomatosis with red friable vascular papules, (C) eosinophilic folliculitis with pruritic follicular papules on the face and neck, (D) disseminated molluscum contagiosum with numerous large umbilicated papules on the face of an adult. Show on diverse skin tones.</image>

<image>Diagram correlating CD4+ T-cell count with cutaneous manifestations of HIV/AIDS. Show a vertical axis with CD4 levels (>500, 200-500, <200, <100) and corresponding skin conditions at each level, arranged from early/mild (seborrheic dermatitis, herpes zoster) to advanced/severe (KS, bacillary angiomatosis, disseminated deep fungal infections, crusted scabies). Use color coding to distinguish infectious, inflammatory, and neoplastic categories.</image>

<image>Histopathology comparison of vascular proliferations in HIV: Kaposi sarcoma (spindle cells with slit-like vascular spaces, extravasated RBCs, HHV-8 LANA+) vs. bacillary angiomatosis (lobular capillary proliferation with neutrophils and granular amphophilic bacterial clumps on Warthin-Starry stain). Label distinguishing features clearly.</image>

Key Clinical Pearls

Facial molluscum contagiosum in an adult should prompt HIV testing, as this presentation is almost exclusively seen in immunosuppressed individuals. Bacillary angiomatosis is clinically identical to Kaposi sarcoma but is caused by Bartonella and is curable with antibiotics, so vascular lesions in HIV patients should always be biopsied to distinguish these entities. Severe, refractory seborrheic dermatitis in a young adult may be the earliest cutaneous sign of HIV infection. Herpes zoster in a patient under 50 years, especially if multidermatomal or recurrent, should trigger HIV risk assessment and testing. HLA-B*5701 must be checked before prescribing abacavir, and a positive result is an absolute contraindication due to the risk of life-threatening hypersensitivity. IRIS can cause paradoxical worsening of skin conditions after ART initiation, but ART should be continued and the specific condition managed; antiretroviral therapy should not be discontinued.

References

• Cedeno-Laurent F, Gomez-Flores M, Mendez N, et al. New insights into HIV-1-primary skin disorders. J Int AIDS Soc. 2011;14:5.
• Schwartz RA, Micali G, Nasca MR, Scuderi L. Kaposi sarcoma: a continuing conundrum. J Am Acad Dermatol. 2008;59(2):179-206.
• Rigopoulos D, Paparizos V, Katsambas A. Cutaneous markers of HIV infection. Clin Dermatol. 2004;22(6):487-498.
• Hengge UR, Ruzicka T, Tyring SK, et al. Update on Kaposi's sarcoma and other HHV8 associated diseases. Lancet Infect Dis. 2002;2(5):281-292.

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