Cutaneous manifestations of AIDS

See Table 39-1.

Papulosquamous dermatoses are among the most commonly seen cutaneous manifestations of HIV infection, and these include seborrheic dermatitis (Fig. 39-1) and xerosis. Other common dermatologic conditions include bacterial infections, such as Staphylococcus aureus skin infections. Fungal infections, such as mucocutaneous candidiasis (oropharyngeal and vulvovaginal) and dermatophytosis (tinea pedis, tinea cruris, tinea manuum, and onychomycosis), are also commonly encountered. Frequently seen viral infections include human papilloma virus infections (condyloma acuminata, common and plantar warts), as well as infections with herpes simplex virus, varicella-zoster virus, molluscum contagiosum, and Epstein-Barr virus (oral hairy leukoplakia).

Staphylococcus aureus is the most common cutaneous bacterial pathogen in HIV disease. Cutaneous infections due to S. aureus most commonly present as a superficial folliculitis. Less common manifestations include impetigo, ecthyma, furunculosis, cellulitis, abscesses, and botryomycosis. In addition, S. aureus can secondarily infect underlying primary dermatoses such as eczema, scabies, herpetic ulcers, and Kaposi’s sarcoma, or can colonize intravenous catheter sites. Staphylococcal colonization (carriage) of the nose and flexures (perineal, toe webspaces) is known to increase in HIV disease and may account for the increased incidence of cutaneous infections. As in the general population, infections with community-acquired methicillin-resistant S. aureus (MRSA) are becoming increasingly common.

Table 39-1. Mucocutaneous Diseases Seen in HIV Infection*

Neoplastic Diseases	Infectious Diseases
Kaposi’s sarcoma Lymphoma Squamous cell carcinoma Basal cell carcinoma	Bacterial Staphylococcus aureus infections Syphilis Bacillary angiomatosis Fungal Candida, Penicillium marneffei Dermatophytosis Cryptococcosis Histoplasmosis Viral Human papillomavirus (HPV) Molluscum contagiosum Herpes simplex virus (HSV) Varicella-zoster virus (VZV) Cytomegalovirus (CMV) Epstein-Barr virus Arthropods Scabies
PAPULOSQUAMOUS DISEASES
Seborrheic dermatitis Xerosis/acquired ichthyosis Psoriasis Reiter’s syndrome
MISCELLANEOUS DISEASES
Eosinophilic folliculitis Drug eruptions Hyperpigmentations Photoeruptions Pruritus Lipodystrophy Granuloma annulare Aphthosis

Dover JS, Johnson RA: Cutaneous manifestations of human immunodeficiency virus infection: parts 1 and 2, Arch Dermatol 127:1383–1391, 1549–1558, 1991.

James W, editor: AIDS: a ten-year perspective, Dermatol Clin 9:391–615, 1991.

* Costner M, Cockerell CJ: The changing spectrum of the cutaneous manifestations of HIV disease, Arch Dermatol 134:1290–1292, 1998.

Ahuja D, Albrecht H: HIV and community-acquired MRSA, AIDS Clin Care 21:21–23, 2009.

Kaposi’s sarcoma (KS) or, more specifically, epidemic Kaposi’s sarcoma. In the Swiss HIV Cohort Study, the risk for KS and non–Hodgkin’s lymphoma continued to be at least 20-fold higher among HAART-treated individuals compared with that of the general population. Most cases occurred in homosexual or bisexual men with HIV disease. However, KS has also been reported in HIV-negative homosexual males. Human herpesvirus–8 is associated with epidemic as well as other types of KS.

Chang Y, Cesarman E, Pessin MS, et al: Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma, Science 266:1865–1869, 1994.

Clifford GM, Polesel J, Richenbach M, et al: Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy, J Natl Cancer Inst 97:425–432, 2005.

Schwartz RA, Micali G, Nasca MR, et al: Kaposi sarcoma: a continuing conundrum, J Am Acad Dermatol 59:179–206, 2008.

Epidemic Kaposi’s sarcoma has a widespread, symmetrical distribution of rapidly progressive macules, patches, nodules, plaques, and tumors. Common areas of involvement include the trunk, extremities, face, and oral cavity. Early lesions consist of erythematous macules, patches, or papules that may have a bruiselike halo. They enlarge at different rates and tend to be oval or elongated in shape, following the lines of skin cleavage. The color varies from pink to red, purple, or brown and can easily mimic purpura, hemangiomas, nevi, sarcoidosis, pityriasis rosea, secondary syphilis, lichen planus, basal cell carcinoma, and melanoma. The surface may become scaly, hyperkeratotic, ulcerated, or hemorrhagic.

Disfigurement and pain secondary to edema can occur, especially on the face, genitals, and lower extremities. Koebnerization, or formation of new lesions at sites of trauma, can be seen. Secondary bacterial infection can also occur. Lesions can be arranged in several known patterns, such as a follicular (clustered) pattern (Fig. 39-2), pityriasis rosea–like pattern, or dermatomal pattern.

Therapy of localized disease may be with intralesional vinblastine, radiotherapy, liquid nitrogen cryotherapy, surgical excision, and topical alitretinoin. Treatment of more extensive disease includes α-interferon as well as single- or multiple-agent chemotherapy with vinblastine, vincristine, bleomycin, or liposomal doxorubicin.

Conant M, The International and North American Panretin Gel KS Study Groups: topical alitretinoin gel as treatment for cutaneous lesions of AIDS-related Kaposi’s sarcoma: results of multicenter, double-blind, vehicle-controlled trials, Presented at the 6th Conference on Retroviruses and Opportunistic Infections, Chicago, 1999.

Walmsley S, Northfelt DW, Melosky B, et al: Treatment of AIDS-related cutaneous Kaposi’s sarcoma with topical alitretinoin (9-cis-retinoic acid) gel. Panretin Gel North American Study Group, J Acquir Immune Defic Syndr 22:235–246, 1999.

Although the course of syphilis in most HIV-infected patients is not different from that in a normal host, it may differ in several ways.

Oral hairy leukoplakia, which is predictive for development of AIDS, is primarily seen in HIV-infected patients but also has been described rarely in HIV-negative immunosuppressed organ transplant recipients. It is due to Epstein-Barr virus replication within clinical lesions. Oral hairy leukoplakia occurs primarily on the lateral edges of the tongue as parallel, vertically oriented, white plaques, producing a corrugated appearance (Fig. 39-3A). It can infrequently also involve the dorsal and ventral aspects of the tongue, the buccal or labial mucosa, and the soft palate. The plaque in this condition does not rub off with scraping (unlike candidal thrush) and is usually asymptomatic. Histologically, parakeratosis, acanthosis, and ballooning cells (koilocytes) are seen. In situ Epstein-Barr virus DNA hybridization of lesional scrapings or tissue sections shows positive nuclear staining within epithelial cells. Lesions may respond to acyclovir, zidovudine, podophyllin, tretinoin, or excision but do not respond to anticandidal treatment.

Resnick L, Herbst JS, Raab-Traub N: Oral hairy leukoplakia, J Am Acad Dermatol 22:1278–1282, 1990.

Pseudomembranous candidiasis appears as whitish, cottage-cheese–like or creamy plaques at any site in the oropharynx. These are removable when scraped and may leave a reddish surface. Erythematous candidiasis appears as well-demarcated patches of erythema on the palate or dorsal tongue. Lesions of erythematous candidiasis on the tongue can look smooth and depapillated. Hyperplastic candidiasis appears as a white coating on the dorsum of the tongue that persists with scraping (Fig. 39-3B). Angular cheilitis consists of erythema, cracking, and fissuring of the mouth corners. More than one type of oropharyngeal candidiasis can coexist.

HIV-associated eosinophilic folliculitis is a chronic, pruritic dermatosis of unknown etiology characterized by discrete, erythematous, follicular, urticarial papules on the head and neck, trunk, and proximal extremities (Fig. 39-4). Most cases occur in males, but the disease has been reported in females. Bacterial cultures are negative, and the eruption does not resolve with antistaphylococcal treatment. It is associated with peripheral eosinophilia, an elevated serum IgE level, and advanced HIV infection (CD4 counts lower than 250 cells/mm³). Eosinophilic folliculitis is not specific for HIV infection, as it has rarely been described in association with hematologic malignancies.

Transverse histologic sections are superior to vertical sections in the diagnosis of this disease. Histopathologic findings include a perivascular and perifollicular mixed infiltrate with variable numbers of eosinophils and spongiosis of the follicular infundibulum or sebaceous gland with a mixed infiltrate. Treatment options include potent topical corticosteroids, antihistamines, ultraviolet B phototherapy, itraconazole, oral metronidazole, permethrin cream, and isotretinoin.

Piantanida EW, Turiansky GW, Kenner JR, et al: HIV-associated eosinophilic folliculitis: diagnosis by transverse histologic sections, J Am Acad Dermatol 38:124–126, 1998.

Simpson-Dent SL, Fearfield LA, Staughton RCD: HIV-associated eosinophilic folliculitis: differential diagnosis and management, Sex Transm Infect 75:291–293, 1999.

Molluscum contagiosum, a poxvirus infection, is seen in approximately 8% to 18% of patients with symptomatic HIV disease and AIDS. Although molluscum lesions often appear as dome-shaped, flesh-colored umbilicated papules, they can have an unusual appearance, involve atypical sites, and be widespread.

In HIV disease, molluscum lesions tend to occur on the face, trunk, intertriginous areas, and buttocks as well as in the genital area. Beard area lesions are commonly seen, and these are probably spread by shaving. Lesions can be large (>1 cm, giant molluscum) or hyperkeratotic; can simulate skin cancers, common and genital warts, and keratoacanthomas; and can become confluent. Lesions can also involve the follicular epithelium with sparing of the interfollicular epithelium. Molluscum lesions can be associated with a localized chronic dermatitis surrounding a centrally located lesion (molluscum dermatitis). With progressive immune dysfunction, lesions increase in number and become diffuse. Disseminated cryptococcosis, histoplasmosis, and Penicillium marneffei infection can mimic facial molluscum contagiosum.

Mastrolorenzo A, Urbano FG, Salimbeni L, et al: Atypical molluscum contagiosum infection in an HIV-infected patient, Int J Dermatol 37:378–380, 1998.

Treatment options include liquid nitrogen cryotherapy, curettage, electrodesiccation, trichloroacetic acid, topical wart preparations, laser ablation, tretinoin, topical fluorouracil and imiquimod, and topical or intravenous cidofovir. However, treatment of widespread lesions in advanced HIV disease is problematic, as lesions are numerous and tend to recur.

Buckley R, Smith K: Topical imiquimod therapy for chronic giant molluscum contagiosum in a patient with advanced human immunodeficiency virus I disease, Arch Dermatol 135:1167–1169, 1999.

The prevalence of human papillomavirus (HPV) infections is increased in HIV disease, including verruca vulgaris (common warts) and condyloma acuminata (genital warts). Lesions can be numerous, large, confluent, and resistant to standard treatment with increasing immunodeficiency. Condyloma acuminata occur in the genital and perianal areas, where it is associated with receptive anal intercourse. In HIV disease, the incidence of HPV-associated intraepithelial neoplasia of the cervix and of the anus in homosexual men is increased. Resolution of recalcitrant hand warts temporally related to protease inhibitor–containing antiretroviral therapy has been reported.

Spach DH, Colven R: Resolution of recalcitrant hand warts in an HIV-infected patient treated with potent antiretroviral therapy, J Am Acad Dermatol 40:818–821, 1999.

Primary infection with the varicella-zoster virus (VZV, chickenpox) in HIV disease may be associated with complications such as pneumonia, encephalitis, hepatitis, profuse eruptions, and even death. Reactivation of latent VZV infection is increased in HIV disease. Reactivation usually manifests itself as a typical unidermatomal eruption, but with advanced immunodeficiency, multidermatomal and disseminated eruptions can occur. These eruptions may be vesiculobullous, hemorrhagic, necrotic, or poxlike and may be very painful. Chronic, painful verrucous and ecthymatous (poxlike) lesions can occur and appear as hyperkeratotic warty nodules and necrotic ulcerations, respectively.

Weinburg JM, Mysliwiec A, Turiansky GW, et al: Viral folliculitis: atypical presentations of herpes simplex, herpes zoster, and molluscum contagiosum, Arch Dermatol 133:983–986, 1997.

Various photosensitive dermatoses have been described in HIV disease, and these include porphyria cutanea tarda (PCT), lichenoid photoeruptions, and chronic actinic dermatitis. Photosensitivity may, in fact, be the presenting sign of HIV infection.

Most cases of PCT in HIV infection are acquired and many are associated with historical or serologic evidence of hepatitis B or C infection, as well as with elevated transaminase levels and history of alcohol abuse. Patients present with blisters, erosions, crusting, scarring, and increased skin fragility on the face and dorsal hands. In one study, urinary and stool porphyrin excretion patterns classic for PCT occurred in hepatitis C–positive AIDS patients without any clinical evidence of porphyria.

Lichenoid photoeruptions in HIV infection occur most often in black individuals with advanced HIV disease and may be associated with photosensitizing drug use. Patients present with pruritic, violaceous plaques that begin on the face, neck, dorsal hands, and arms. The plaques may become hyperpigmented, hypopigmented, or depigmented and may extend to non–sun-exposed sites. Histopathologic features are primarily those of lichenoid drug eruption or hypertrophic lichen planus, but some patients have findings of lichen nitidus. Patients may improve or clear with discontinuation of a photosensitizing drug, sun avoidance, and sunscreen use.

Chronic actinic dermatitis has been described in markedly immunosuppressed patients and presents as a chronic pruritic and idiopathic eczematous dermatitis in a photodistribution. Phototesting shows increased sensitivity to ultraviolet B. Histologic findings demonstrate eczematous, lymphoma-like, and psoriasiform changes.

O’Connor WJ, Murphy GM, Darby C, et al: Porphyrin abnormalities in acquired immunodeficiency syndrome, Arch Dermatol 132:1443–1447, 1996.

A recent study of 34 consecutive HIV-positive patients with a clinical and histologic diagnosis of granuloma annulare revealed that the generalized form of granuloma annulare was a more common clinical pattern than the localized form of granuloma annulare. In this study, two patients with localized granuloma annulare had perforating lesions, both clinically and histologically. Although granuloma annulare can occur in all stages of HIV infection, it is slightly more common in patients with AIDS. Generalized granuloma annulare lesions appear as multiple, discrete, skin-colored dermal papules distributed on the trunk and extremities. Localized granuloma annulare lesions present as solitary or few discrete papules or annular plaques on one area of the body. The histologic findings of HIV-associated granuloma annulare are similar to those of non–HIV-infected individuals. There are no known cases of diabetes mellitus reported in association with HIV and granuloma annulare.

Toro JR, Chu P, Yen T-S B, et al: Granuloma annulare and human immunodeficiency virus infection, Arch Dermatol 135:1341–1346, 1999.

A syndrome of lipodystrophic changes is temporally associated mainly with use of protease inhibitors, and possibly with nucleoside reverse transcriptase inhibitors. It is characterized by enlargement of the dorsocervical fat pad (“buffalo hump”), breast hypertrophy, visceral abdominal fat accumulation (“crix belly,” “protease paunch”) (Fig. 39-5), peripheral fat wasting with prominence of the superficial veins, and loss of fat in the buccal, temporal, and buttocks areas. Lipodystrophic changes have been associated with hypertriglyceridemia, hypercholesterolemia, hyperglycemia, insulin resistance, and hyperinsulinemia. Evidence of associated Cushing’s syndrome or disease is lacking. Lipodystrophic changes have occasionally been reported in patients not taking protease inhibitors. Histologic findings in patients with lipoatrophy include atrophy of the subcutaneous fat, fat lobules with variably sized and often large adipocytes, prominent capillary vascular proliferation, and focal lymphocytic infiltrate and lipogranuloma formation. The exact mechanism involved in these changes is not clear. In addition, antiretroviral therapy has recently been temporally associated with symptomatic angiolipomatosis. Also, painful periungual inflammation (paronychia) of the fingernails and toenails has been reported with use of indinavir and lamivudine. Cutaneous side effects have been described with enfuvirtide (Fuzeon, T-20) use. This drug is a member of a new class of HAART known as fusion inhibitors and is administered subcutaneously. Reported skin side effects are very common and include erythema, induration, nodules, and cysts at the injection sites (Fig. 39-6A,B).

Dank JP, Colven R: Protease inhibitor-associated angiolipomatosis, J Am Acad Dermatol 42:129–131, 2000.

James J, Carruthers A, Carruthers J: HIV-associated facial lipoatrophy, Dermatol Surg 28:979–986, 2002.

Lalezari JP, Henry K, O’Hearn M, et al: Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America, N Engl J Med 348:2175–2185, 2003.

Ward HA, Russo GG, Shrum J: Cutaneous manifestations of antiretroviral therapy, J Am Acad Dermatol 46:284–293, 2002.

Immune restoration syndrome (IRS) is also known as immune reconstitution syndrome, immune reactivation syndrome, and immune reconstitution inflammatory syndrome. It consists of the paradoxical recrudescence of quiescent disease or the appearance of new internal and cutaneous diseases that are temporally associated within weeks to months of HAART initiation. New or recurrent skin disease may consist of initial or recurrent herpes zoster, eosinophilic folliculitis, erythema nodosum with pulmonary sarcoidosis with or without cutaneous sarcoidosis, extensive cytomegalovirus ulceration, reactions to prior tattoos, disseminated cutaneous M. avium complex infection, alopecia universalis and Graves’ disease, and leprosy complicated by type 1 reactional state. The IRS is attributed to the immunologic recovery produced by HAART, with restoration of pathogen-specific immunity.

Hirsch HH, Kaufmann G, Sendi P, et al: Immune reconstitution in HIV-infected patients, CID 38:1159–1166, 2004.