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Dermatologic Manifestations of Human Immunodeficiency Virus Infection

      Human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS) have become major health problems in the United States, and patients with manifestations of these diseases are seen by physicians in all areas of medicine. Cutaneous manifestations develop in as many as 92% of HIV-positive persons. Familiarity with these manifestations facilitates early diagnosis and enhances the care of HIV-infected patients. The spectrum of mucocutaneous disorders in these patients includes an acute exanthem, multiple infections, neoplastic processes, and miscellaneous disorders. Herein we review the most common and the most specific dermatologic manifestations associated with HIV infection, which often are atypical, more severe, or less responsive to treatment than the corresponding diseases encountered in non-HIV-infected persons.
      The human immunodeficiency viruses (HIV), types I and II, are distinct human retroviruses that are responsible for the development of the acquired immunodeficiency syndrome (AIDS).
      • Hellinger JA
      • Essex M
      Human immunodeficiency virus and other retroviruses.
      • Centers for Disease Control
      AIDS due to HIV-2 infection—New Jersey.
      These viruses preferentially infect the CD4-positive helper/inducer T lymphocyte and monocyte-macrophage populations; thereby they create a probable reservoir for HIV in the fixed-tissue macrophages and decrease the number and function of helper T cells. The helper/inducer T-cell abnormalities also lead to secondary perturbations in the CD8 cytotoxic/suppressor T lymphocytes, natural killer cells, and B cells. The result is a severe defect in cell-mediated immunity and thus susceptibility to numerous infectious and malignant processes.
      • Hellinger JA
      • Essex M
      Human immunodeficiency virus and other retroviruses.
      • Centers for Disease Control
      AIDS due to HIV-2 infection—New Jersey.
      • Fauci AS
      • Schnittman SM
      • Poli G
      • Koenig S
      • Pantaleo G
      Immunopathogenic mechanisms in human immunodeficiency virus (HIV) infection.
      In the United States, through July 31, 1991, the Centers for Disease Control recorded 186,895 cases of AIDS and 118,411 deaths due to AIDS. These data include 3,199 cases of AIDS among children younger than 13 years of age and 1,677 deaths in this age-group. At least 1 million persons in the United States are infected with HIV; 390,000 to 480,000 cases of AIDS are projected by the end of 1993, of which 285,000 to 340,000 will be fatal.
      • Center for Infectious Diseases, Division of HIV/AIDS
      • Morbidity and Mortality Report Centers for Disease Control
      Current trends in mortality attributable to HIV infection/AIDS—United States, 1981–1990.
      In one study,
      • Coldiron BM
      • Bergstresser PR
      Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus.
      cutaneous manifestations were noted in 92% of HIV-positive persons, and such manifestations may affect almost all patients at some point in the course of their illness. Awareness and recognition of these manifestations may facilitate early diagnosis of HIV infection and enhance patient care. The initial manifestation of mucocutaneous diseases in HIV-infected persons may be typical, but often it will be atypical, more severe, and less responsive to usual treatment regimens than that in non-HIV-infected persons. Herein we review the major dermatologic manifestations of HIV infection and provide representative clinical examples of the most common or specific entities; complete atlas compilations are available for interested readers.
      • Weismann K
      • Petersen CS
      • Søndergaard J
      • Wantzin GL
      • Friedman-Kien AE
      • Penneys NS
      The spectrum of mucocutaneous disorders in HIV-infected persons includes exanthems indicative of acute HIV infection as well as benign and malignant processes encountered in advanced disease. This spectrum can be divided into several major categories: (1) acute exanthems, (2) neoplastic processes, (3) infections, and (4) other (Table 1). Most mucocutaneous disorders manifest in infected persons after the helper T-cell count decreases to less than 100 cells/μl;
      • Center for Infectious Diseases, Division of HIV/AIDS
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      • Lane HC
      Acquired immunodeficiency syndrome.
      however, a recent investigation
      • Coldiron BM
      • Bergstresser PR
      Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus.
      found no significant differences in prevalence or severity of skin disease between asymptomatic patients and those with AIDS-related complex (no longer a part of the classification scheme of the Centers for Disease Control) or AIDS.
      Table 1Cutaneous Manifestations Associated With Human Immunodeficiency Virus (HIV) Infection
      Modified from Fisher and Warner.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      By permission of the International Society of Dermatology: Tropical, Geographic and Ecologic, Inc.
      Acute HIV exanthem
      See text for discussion of this manifestation.
      Neoplastic diseases
       Kaposi's sarcoma
      See text for discussion of this manifestation.
       Lymphoma (B cell, normally)
      See text for discussion of this manifestation.
       Mycosis fungoides
      See text for discussion of this manifestation.
       Squamous cell carcinoma
      See text for discussion of this manifestation.
       Bowenoid papulosis
      See text for discussion of this manifestation.
       Cloacogenic carcinoma
      See text for discussion of this manifestation.
       Basal cell carcinoma
      See text for discussion of this manifestation.
       Melanoma
      See text for discussion of this manifestation.
       Eruptive dysplastic nevi
      See text for discussion of this manifestation.
      Infectious diseases
       Viral infections
        Herpes simplex
      See text for discussion of this manifestation.
        Herpes zoster
      See text for discussion of this manifestation.
        Chickenpox
      See text for discussion of this manifestation.
        Epstein-Barr virus exanthem
      See text for discussion of this manifestation.
        Oral hairy leukoplakia
      See text for discussion of this manifestation.
        Molluscum contagiosum
      See text for discussion of this manifestation.
        Common warts
      See text for discussion of this manifestation.
        Condyloma acuminatum
      See text for discussion of this manifestation.
        Cytomegalovirus exanthem
      See text for discussion of this manifestation.
        Vaccinia
       Bacterial infections
        Abscesses
      See text for discussion of this manifestation.
        Folliculitis
      See text for discussion of this manifestation.
        Impetigo
      See text for discussion of this manifestation.
        Ecthyma
      See text for discussion of this manifestation.
        Cellulitis
      See text for discussion of this manifestation.
        Ulcers
      See text for discussion of this manifestation.
        Scalded skin syndrome
      See text for discussion of this manifestation.
        Mycobacterial infections
      See text for discussion of this manifestation.
        Actinomycosis
        Syphilis
      See text for discussion of this manifestation.
        Bacillary angiomatosis
      See text for discussion of this manifestation.
        Chancroid
      See text for discussion of this manifestation.
        Granuloma inguinale
        Botryomycosis
       Fungal and yeast infections
        Candidiasis
      See text for discussion of this manifestation.
        Dermatophytosis
      See text for discussion of this manifestation.
        Cryptococcosis
      See text for discussion of this manifestation.
        Histoplasmosis
      See text for discussion of this manifestation.
        Sporotrichosis
      See text for discussion of this manifestation.
        Scopulariopsis infection
        Coccidioidomycosis
       Protozoal infections
        Amebiasis cutis
        Cutaneous Pneumocystis carinii
      See text for discussion of this manifestation.
        Toxoplasma gondii
        Acanthamoeba
       Arthropod infections
        Scabies
      See text for discussion of this manifestation.
        Demodex folliculitis
      See text for discussion of this manifestation.
      Miscellaneous dermatoses
       Vascular lesions
        Vasculitis
      See text for discussion of this manifestation.
        Telangiectasia
      See text for discussion of this manifestation.
        Splinter hemorrhages
      See text for discussion of this manifestation.
        Thrombocytopenic purpura
      See text for discussion of this manifestation.
        Hyperalgesic pseudothrombophlebitis syndrome
      See text for discussion of this manifestation.
        Cutis marmorata
       Papulosquamous diseases
        Xerotic (asteatotic) eczema
      See text for discussion of this manifestation.
        Seborrheic dermatitis
      See text for discussion of this manifestation.
        Psoriasis
      See text for discussion of this manifestation.
        Palmoplantar keratoderma and Reiter's syndrome
      See text for discussion of this manifestation.
        Ichthyosis
      See text for discussion of this manifestation.
        Erythroderma
      See text for discussion of this manifestation.
        Pityriasis rosea
        Lichen planus
       Oral diseases
        Angular cheilitis
      See text for discussion of this manifestation.
        Aphthosis
      See text for discussion of this manifestation.
        Gingivitis
      See text for discussion of this manifestation.
       Hair and nail changes
        Thinning of hair
      See text for discussion of this manifestation.
        Alopecia areata
      See text for discussion of this manifestation.
        Telogen effluvium
      See text for discussion of this manifestation.
        Premature graying
      See text for discussion of this manifestation.
        Nail deformities
      See text for discussion of this manifestation.
        Changes in nail color
      See text for discussion of this manifestation.
       Miscellaneous disorders
        Drug-induced eruptions
      See text for discussion of this manifestation.
        Eosinophilic folliculitis
      See text for discussion of this manifestation.
        Pruritus
      See text for discussion of this manifestation.
        Urticaria
        Papular pruritic eruption
      See text for discussion of this manifestation.
        Dermatitis
      See text for discussion of this manifestation.
        Nutritional deficiencies
      See text for discussion of this manifestation.
        Porphyria cutanea tarda
      See text for discussion of this manifestation.
        Granuloma annulare
        Transient acantholytic dyskeratosis (Grover's disease)
        Pyoderma gangrenosum
        Bullous pemphigoid
        Erythema elevatum diutinum
        Vitiligo
        Dermatomyositis
        Calciphylaxis
        Lymphocytoma cutis
        Dermatitis herpetiformis
        Erythema nodosum
        Neutrophilic eccrine hidradenitis
      * See text for discussion of this manifestation.

      ACUTE HIV EXANTHEM

      Primary infection with HIV may lead to sudden onset of an acute retroviral syndrome, which is estimated to occur in a half to two-thirds of infected persons,
      • Weismann K
      • Petersen CS
      • Søndergaard J
      • Wantzin GL
      but symptoms may be minimal and easily misdiagnosed as a nonspecific influenzalike syndrome or infectious mononucleosis. This syndrome can occur 1 to 8 weeks after infection and is self-limited; symptoms and laboratory abnormalities usually subside after 1 to 3 weeks.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Brehmer-Andersson E
      • Torssander J
      The exanthema of acute (primary) HIV infection: identification of a characteristic histopathological picture?.
      • Hulsebosch HJ
      • Claessen FAP
      • van Ginkel CJW
      • Kuiters GRR
      • Goudsmit J
      • Lange JMA
      Human immunodeficiency virus exanthem.
      • Cooper DA
      • Gold J
      • Maclean P
      • Donovan B
      • Finlayson R
      • Barnes TG
      • Michelmore HM
      • Brooke P
      • Penny R
      Acute AIDS retrovirus infection: definition of a clinical illness associated with seroconversion.
      • Tindall B, Barker S, Donovan B, Barnes T, Roberts J, Kronenberg C, Gold J, Penny R, Cooper D, Sydney AIDS Study Group
      Characterization of the acute clinical illness associated with human immunodeficiency virus infection.
      Symptoms may include fever, sweats, malaise, pharyngitis, myalgia, arthralgia, lymphadenopathy, diarrhea, abnormalities of the central nervous system (headache, photophobia, meningitis, and encephalitis), and an exanthem. Transient leukopenia, thrombocytopenia, and an inverted helper-suppressor ratio of T cells may be found.
      In 30 to 50% of patients with primary HIV infection, an associated exanthem and enanthema are present—usually a macular or maculopapular eruption on the trunk, face, and upper extremities.
      • Brehmer-Andersson E
      • Torssander J
      The exanthema of acute (primary) HIV infection: identification of a characteristic histopathological picture?.
      • Hulsebosch HJ
      • Claessen FAP
      • van Ginkel CJW
      • Kuiters GRR
      • Goudsmit J
      • Lange JMA
      Human immunodeficiency virus exanthem.
      • Abrams DI
      Clinical manifestations of HIV infection, including persistent generalized lymphadenopathy and AIDS-related complex.
      Lesions may be maculopapular or roseola-like, scaling and pityriasis rosea-like, or occasionally hemorrhagic or necrotic. Palms and soles may be involved, and the findings resemble secondary syphilis.
      • Brehmer-Andersson E
      • Torssander J
      The exanthema of acute (primary) HIV infection: identification of a characteristic histopathological picture?.
      • Hulsebosch HJ
      • Claessen FAP
      • van Ginkel CJW
      • Kuiters GRR
      • Goudsmit J
      • Lange JMA
      Human immunodeficiency virus exanthem.
      An enanthema, which varies from erythema to frank ulceration and severe dysphagia, is also usually present.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Brehmer-Andersson E
      • Torssander J
      The exanthema of acute (primary) HIV infection: identification of a characteristic histopathological picture?.
      • Hulsebosch HJ
      • Claessen FAP
      • van Ginkel CJW
      • Kuiters GRR
      • Goudsmit J
      • Lange JMA
      Human immunodeficiency virus exanthem.
      Most patients with an acute retroviral syndrome have had the presence of HIV antigen (p24 core antigen) confirmed in the serum during the acute phase, and seroconversion to HIV antibody positivity usually occurs within 1 to 2 months after the onset of symptoms.
      • Brehmer-Andersson E
      • Torssander J
      The exanthema of acute (primary) HIV infection: identification of a characteristic histopathological picture?.
      • Hulsebosch HJ
      • Claessen FAP
      • van Ginkel CJW
      • Kuiters GRR
      • Goudsmit J
      • Lange JMA
      Human immunodeficiency virus exanthem.
      • Gaines H
      • von Sydow M
      • Sönnerborg A
      • Albert J
      • Czajkowski J
      • Pehrson PO
      • Chiodi F
      • Moberg L
      • Fenyö EM
      • Åsjö B
      • Forsgren M
      Antibody response in primary human immunodeficiency virus infection.
      Although nonspecific exanthems occur in most HIV-infected children, an acute exanthem is infrequently diagnosed in such children, presumably because seroconversion frequently occurs in utero in these patients.
      • Prose NS
      HIV infection in children.
      • Nance KV
      • Smith ML
      • Joshi VV
      Cutaneous manifestations of acquired immunodeficiency syndrome in children.

      NEOPLASMS

      In approximately 30 to 40% of patients with AIDS, neoplastic disease develops, and Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma constitute 95% of such disease states.
      • Hiddemann W
      What's new in malignant tumors in acquired immunodeficiency disorders?.
      Neoplasms rarely occur in children with AIDS.
      • Nance KV
      • Smith ML
      • Joshi VV
      Cutaneous manifestations of acquired immunodeficiency syndrome in children.

      Kaposi's Sarcoma.

      KS, the most common neoplasm that occurs in HIV-infected persons,
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Haverkos HV
      • Friedman-Kien AE
      • Drotman DP
      • Morgan WM
      The changing incidence of Kaposi's sarcoma among patients with AIDS.
      • Rabkin CS
      • Biggar RJ
      • Horm JW
      Increasing incidence of cancers associated with the human immunodeficiency virus epidemic.
      develops in 11 to 15% of patients diagnosed with AIDS in the United States.
      • Coldiron BM
      • Bergstresser PR
      Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus.
      • Friedman-Kien AE
      • Saltzman BR
      Clinical manifestations of classical, endemic African, and epidemic AIDS-associated Kaposi's sarcoma.
      Of all cases of AIDS-associated KS (AIDS-KS), 95% have occurred in homosexual men; however, for unclear reasons, the incidence of AIDS-KS has decreased since 1981—from 44% of men with AIDS to less than 20% in 1989.
      • Hiddemann W
      What's new in malignant tumors in acquired immunodeficiency disorders?.
      • Friedman-Kien AE
      • Saltzman BR
      Clinical manifestations of classical, endemic African, and epidemic AIDS-associated Kaposi's sarcoma.
      KS is a tumor of endothelial origin. Hypotheses exist about potential roles of coinfection with cytomegalovirus, endothelial growth factors, genetic predisposition of persons with HLA-DR5, some unidentified infectious agent transmitted by sexual contact, and environmental cofactors.
      • Hiddemann W
      What's new in malignant tumors in acquired immunodeficiency disorders?.
      • Rabkin CS
      • Biggar RJ
      • Horm JW
      Increasing incidence of cancers associated with the human immunodeficiency virus epidemic.
      • Friedman-Kien AE
      • Saltzman BR
      Clinical manifestations of classical, endemic African, and epidemic AIDS-associated Kaposi's sarcoma.
      Lesions of KS can develop at any time during the course of HIV infection, may be widely distributed, and may have varied morphologic features, from the earliest asymptomatic macular stage to indurated papules, plaques, and nodules (Fig. 1). Lesions vary from several millimeters to several centimeters; are round, oval, or irregular; and are pinkish red to violaceous. They tend to be symmetrically distributed along skin tension lines and often enlarge or coalesce.
      • Friedman-Kien AE
      • Saltzman BR
      Clinical manifestations of classical, endemic African, and epidemic AIDS-associated Kaposi's sarcoma.
      • Safai B
      Kaposi's sarcoma and other neoplasms in acquired immunodeficiency syndrome.
      Common sites include the lower extremities, upper trunk, head and neck, hard palate and oropharyngeal mucosa, and occipital and periauricular regions. Lesions occur in patients of all ages.
      Figure thumbnail gr1
      Fig. 1Kaposi's sarcoma of nasal tip in patient with human immunodeficiency virus infection. Note similar lesion on left lower aspect of cheek and seborrheic dermatitis on malar areas.
      AIDS-KS frequently involves lymph nodes and the gastrointestinal tract, lungs, liver, kidney, and spleen. Although more aggressive than the classic type of KS,
      • Hiddemann W
      What's new in malignant tumors in acquired immunodeficiency disorders?.
      • Friedman-Kien AE
      • Saltzman BR
      Clinical manifestations of classical, endemic African, and epidemic AIDS-associated Kaposi's sarcoma.
      • Safai B
      Kaposi's sarcoma and other neoplasms in acquired immunodeficiency syndrome.
      AIDS-KS rarely causes death. Indeed, patients with KS as an initial manifestation of HIV infection have a better prognosis than do those who have opportunistic infections.
      • Friedman-Kien AE
      • Saltzman BR
      Clinical manifestations of classical, endemic African, and epidemic AIDS-associated Kaposi's sarcoma.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      Although AIDS-KS is most often asymptomatic, treatment may be warranted for symptomatic or cosmetically troublesome lesions. Local radiotherapy is effective, although such treatment for oral lesions may result in severe mucositis. Liquid nitrogen cryotherapy, electrocautery, excision, and intralesional administration of vincristine sulfate, vinblastine sulfate, bleomycin, or interferon-α are effective alternatives for selected lesions. Systemic chemotherapy may be considered for disseminated or resistant disease, although it provides palliation only and does not influence overall survival.
      • Hiddemann W
      What's new in malignant tumors in acquired immunodeficiency disorders?.
      • Friedman-Kien AE
      • Saltzman BR
      Clinical manifestations of classical, endemic African, and epidemic AIDS-associated Kaposi's sarcoma.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      Interferon-α may be the treatment of choice when systemic management is necessary.
      • Hiddemann W
      What's new in malignant tumors in acquired immunodeficiency disorders?.
      Chemotherapy may actually further compromise the patient's already impaired immune function. Spontaneous resolution has also occurred.
      In children with AIDS, KS rarely develops (5.6%), and those in whom KS develops often do not have skin lesions but, rather, aggressive systemic lesions with a fulminant course.
      • Nance KV
      • Smith ML
      • Joshi VV
      Cutaneous manifestations of acquired immunodeficiency syndrome in children.
      • Straka BF
      • Whitaker DL
      • Morrison SH
      • Oleske JM
      • Grant-Kels JM
      Cutaneous manifestations of the acquired immunodeficiency syndrome in children.
      The reason for the rarity of KS in children is uncertain; perhaps it is related to the infrequent coinfection of children with cytomegalovirus in comparison with the 90 to 95% frequency of cytomegalovirus infection in adult patients with AIDS.
      • Straka BF
      • Whitaker DL
      • Morrison SH
      • Oleske JM
      • Grant-Kels JM
      Cutaneous manifestations of the acquired immunodeficiency syndrome in children.
      Similarly, other potentially sexually transmitted cofactors would be less likely in the pediatric than in the adult subpopulation.

      Lymphomas.

      HIV infection increases the risk for the development of several neoplasms that may affect the skin—in particular, non-Hodgkin's lymphomas.
      • Haverkos HV
      • Friedman-Kien AE
      • Drotman DP
      • Morgan WM
      The changing incidence of Kaposi's sarcoma among patients with AIDS.
      • Rabkin CS
      • Biggar RJ
      • Horm JW
      Increasing incidence of cancers associated with the human immunodeficiency virus epidemic.
      The incidence is commensurate to that seen in other immunodeficiency states.
      • Myskowski PL
      • Straus DJ
      • Safai B
      Lymphoma and other HIV-associated malignancies.
      In general, any HIV-infected patient with indeterminate or suspicious skin lesions or any patient with risk factors for HIV infection should undergo biopsy for histologic study.
      Lymphoma in HIV-infected patients is most often the B-cell type and is associated with an aggressive disease state; it frequently is diagnosed at an advanced stage, extranodal involvement is common, and response to chemotherapy is poor.
      • Rabkin CS
      • Biggar RJ
      • Horm JW
      Increasing incidence of cancers associated with the human immunodeficiency virus epidemic.
      A third of the patients with HIV-associated lymphoma have persistent generalized lymphadenopathy.
      • Hiddemann W
      What's new in malignant tumors in acquired immunodeficiency disorders?.
      • Safai B
      Kaposi's sarcoma and other neoplasms in acquired immunodeficiency syndrome.
      • Myskowski PL
      • Straus DJ
      • Safai B
      Lymphoma and other HIV-associated malignancies.
      Non-Hodgkin's lymphomas, the second most frequent neoplasm in patients with AIDS (4 to 10%),
      • Hintner H
      • Fritsch P
      Skin neoplasia in the immunodeficient host: the clinical spectrum; Kaposi's sarcoma, lymphoma, skin cancer and melanoma.
      tend to be intermediate or high grade, B-cell type.
      • Prose NS
      HIV infection in children.
      • Rabkin CS
      • Biggar RJ
      • Horm JW
      Increasing incidence of cancers associated with the human immunodeficiency virus epidemic.
      Frequently diagnosed as advanced disease (stage III or IV), these lymphoproliferative states follow the development of KS or opportunistic infections in two-thirds of the patients. The most frequently affected organs include the central nervous system (40%), bone marrow (33%), gastrointestinal tract (17%), and mucous membranes and skin (15%).
      • Lane HC
      Acquired immunodeficiency syndrome.
      • Hiddemann W
      What's new in malignant tumors in acquired immunodeficiency disorders?.
      • Hintner H
      • Fritsch P
      Skin neoplasia in the immunodeficient host: the clinical spectrum; Kaposi's sarcoma, lymphoma, skin cancer and melanoma.
      Cutaneous lesions are usually papules and nodules. Many B-cell lymphomas in HIV-infected patients contain the Epstein-Barr virus genome, which is thought to be an important pathogenetic factor.
      • Hiddemann W
      What's new in malignant tumors in acquired immunodeficiency disorders?.
      • Rabkin CS
      • Biggar RJ
      • Horm JW
      Increasing incidence of cancers associated with the human immunodeficiency virus epidemic.
      • Hintner H
      • Fritsch P
      Skin neoplasia in the immunodeficient host: the clinical spectrum; Kaposi's sarcoma, lymphoma, skin cancer and melanoma.
      The median survival of patients with AIDS and non-Hodgkin's lymphoma is as brief as 5 months; death is often attributed to infection.
      • Hiddemann W
      What's new in malignant tumors in acquired immunodeficiency disorders?.
      • Myskowski PL
      • Straus DJ
      • Safai B
      Lymphoma and other HIV-associated malignancies.
      Thus, less intensive chemotherapy, immunomodulators, or antiretroviral agents may result in a superior outcome in comparison with aggressive intervention.
      • Myskowski PL
      • Straus DJ
      • Safai B
      Lymphoma and other HIV-associated malignancies.
      Hodgkin's disease in HIV-infected persons has a similarly aggressive course; the median survival is 14 months. Death is frequently due to intercurrent opportunistic infection. Skin involvement and noncontiguous spread of the disease are more common in HIV-infected than in noninfected patients.
      • Shaw MT
      • Jacobs SR
      Cutaneous Hodgkin's disease in a patient with human immunodeficiency virus infection.
      Other B-cell malignant processes, including chronic lymphocytic leukemia and multiple myeloma, have been reported in HIV-infected patients,
      • Myskowski PL
      • Straus DJ
      • Safai B
      Lymphoma and other HIV-associated malignancies.
      as have systemic B-cell lymphoma, primary B-cell lymphoma of the brain, and Burkitt-like lymphoma.
      • Safai B
      Kaposi's sarcoma and other neoplasms in acquired immunodeficiency syndrome.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      Mycosis fungoides, a cutaneous T-cell lymphoma, has occurred in several patients with HIV infection;
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      however, it is encountered more frequently in association with infection by the related retrovirus human T-cell lymphotropic virus type I (implicated as the agent that causes the adult T-cell lymphoma-leukemia syndrome).
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Safai B
      Kaposi's sarcoma and other neoplasms in acquired immunodeficiency syndrome.
      Lymphomas in HIV-infected children are extremely rare.
      • Straka BF
      • Whitaker DL
      • Morrison SH
      • Oleske JM
      • Grant-Kels JM
      Cutaneous manifestations of the acquired immunodeficiency syndrome in children.

      Carcinomas.

      Epithelial malignant and premalignant neoplasms, including actinic keratosis, squamous cell carcinoma, bowenoid papulosis, keratoacanthoma, basal cell carcinoma, and cloacogenic carcinoma, have been observed in a wide variety of immunosuppressed patients. Lesions are often multiple, and premalignant lesions may progress rapidly to cancers.
      • Safai B
      Kaposi's sarcoma and other neoplasms in acquired immunodeficiency syndrome.
      • Hintner H
      • Fritsch P
      Skin neoplasia in the immunodeficient host: the clinical spectrum; Kaposi's sarcoma, lymphoma, skin cancer and melanoma.
      Although HIV infection has not been shown to increase the incidence of such neoplasms, they may exhibit aggressive growth behavior and occasionally manifest atypically.
      • Hintner H
      • Fritsch P
      Skin neoplasia in the immunodeficient host: the clinical spectrum; Kaposi's sarcoma, lymphoma, skin cancer and melanoma.
      The appropriate management of any epithelial carcinoma in an HIV-infected patient is complete excision.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      Squamous cell carcinoma usually manifests as a shallow, nonhealing ulcer or erosion that is surrounded by a wide, elevated, indurated border. In HIV-infected patients, the incidence of squamous cell carcinoma is disproportionately high in comparison with basal cell carcinoma. An increased incidence of squamous cell carcinoma of the anus and oral mucosa is found in immunodeficient homosexuals, although the relationship to the immunodeficient state is uncertain.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Hiddemann W
      What's new in malignant tumors in acquired immunodeficiency disorders?.
      • Rabkin CS
      • Biggar RJ
      • Horm JW
      Increasing incidence of cancers associated with the human immunodeficiency virus epidemic.
      • Safai B
      Kaposi's sarcoma and other neoplasms in acquired immunodeficiency syndrome.
      • Daling JR
      • Weiss NS
      • Klopfenstein LL
      • Cochran LE
      • Chow WH
      • Daifuku R
      Correlates of homosexual behavior and the incidence of anal cancer.
      Human papillomavirus genotypes 16, 18, and 33 are strongly associated with the development of anogenital carcinomas.
      Bowenoid papulosis, a papular eruption that resembles genital warts clinically but has histologic features of squamous cell carcinoma in situ, has been associated with multiple human papillomavirus genotypes, especially genotype 16. Lesions may regress spontaneously, but they have developed into frank squamous cell carcinoma in several HIV-infected patients.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      • Rüdlinger R
      • Buchmann P
      HPV 16-positive bowenoid papulosis and squamous-cell carcinoma of the anus in an HIV-positive man.
      • Lever WF
      • Schaumburg-Lever G
      Cloacogenic carcinomas of the anorectum have been identified in homosexual men, whether HIV positive or not, who engage in receptive rectal intercourse and have been associated with an increased incidence of condyloma acuminatum in comparison with that in patients who have other colorectal malignant lesions (Fig. 2). This neoplasm arises from transitional zone mucosa of the anal canal. Patients usually experience rectal bleeding, pain, constipation, or, occasionally, perianal erythema or induration. The neoplasm is highly associated with human papillomavirus genotypes 16, 18, and 33.
      • Myskowski PL
      • Straus DJ
      • Safai B
      Lymphoma and other HIV-associated malignancies.
      Cervical intraepithelial neoplasms have also been found in HIV-infected patients in association with condylomas.
      • Myskowski PL
      • Straus DJ
      • Safai B
      Lymphoma and other HIV-associated malignancies.
      Figure thumbnail gr2
      Fig. 2Cloacogenic carcinoma with erythema and erosion around anus in patient with human immunodeficiency virus infection.
      Basal cell carcinomas are usually small, pearly bordered papules or nodules with telangiectatic vessels and a tendency toward slow enlargement with central ulceration. These common skin cancers have been detected in patients with AIDS and have even metastasized on rare occasions.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      • Myskowski PL
      • Straus DJ
      • Safai B
      Lymphoma and other HIV-associated malignancies.

      Malignant Melanoma.

      Whether the incidence of malignant melanoma is increased in HIV-infected patients is unclear, but melanomas, including multiple primary tumors, have been reported in such patients.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      • Van Ginkel CJW
      • Sang RTL
      • Blaauwgeers JLG
      • Schattenkerk JKME
      • Mooi WJ
      • Hulsebosch HJ
      Multiple primary malignant melanomas in an HIV-positive man.
      • Merkle T
      • Braun-Falco O
      • Fröschl M
      • Ruzicka T
      • Landthaler M
      Malignant melanoma in human immunodeficiency virus type 2 infection (letter to the editor).
      At the time of diagnosis, these tumors tend to be thicker (mean, 2.61-mm depth of invasion)
      • Rivers JK
      • Kopf AW
      • Postel AH
      Malignant melanoma in a man seropositive for the human immunodeficiency virus.
      and to have less inflammatory cell response than do malignant melanomas in non-HIV-infected patients; both features suggest a poor prognosis. Metastatic involvement is common.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      • Hintner H
      • Fritsch P
      Skin neoplasia in the immunodeficient host: the clinical spectrum; Kaposi's sarcoma, lymphoma, skin cancer and melanoma.
      • Rivers JK
      • Kopf AW
      • Postel AH
      Malignant melanoma in a man seropositive for the human immunodeficiency virus.
      • Tindall B
      • Finlayson R
      • Mutimer K
      • Billson FA
      • Munro VF
      • Cooper DA
      Malignant melanoma associated with human immunodeficiency virus infection in three homosexual men.
      Investigators have also described a syndrome of eruptive dysplastic nevi, in which multiple new moles with dysplastic features, clinically and histologically, erupt in patients with no prior history of dysplastic nevi and no family history of melanoma.
      • Duvic M
      • Lowe L
      • Rapini RP
      • Rodriguez S
      • Levy ML
      Eruptive dysplastic nevi associated with human immunodeficiency virus infection.
      These progressive nevi tend to develop with the onset of HIV-related symptoms; thus, obtaining biopsy specimens in HIV-infected persons is important.

      INFECTIONS

      Infections are the largest category of dermatologic manifestations of HIV infection, especially in affected children. They are nondiagnostic but, in some cases, highly suggestive of HIV infection and may be premonitory signs for the development of AIDS. The manifestation of even common infections in immunosuppressed patients may be atypical; responsible microorganisms are more resistant to therapy than in normal control subjects.

      Viral Infections.

      The most common viruses that cause skin lesions in HIV-infected patients are herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, molluscum contagiosum virus, human papillomavirus, and cytomegalovirus.

      Herpes Simplex Virus.

      The incidence of herpes simplex virus infection in HIV-positive patients is increased throughout the course of the disease, particularly after helper T-cell counts decrease to less than 100 cells/μl; the prevalence has been estimated to be as high as 27%.
      • Goodman DS
      • Teplitz ED
      • Wishner A
      • Klein RS
      • Burk PG
      • Hershenbaum E
      Prevalence of cutaneous disease in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.
      In most studies, the incidence is 3 to 6%, and herpes simplex virus is the most common viral infection that produces skin lesions in these patients.
      • Hellinger JA
      • Essex M
      Human immunodeficiency virus and other retroviruses.
      • Coldiron BM
      • Bergstresser PR
      Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus.
      • Sindrup JH
      • Weismann K
      • Petersen CS
      • Rindum J
      • Pedersen C
      • Mathiesen L
      • Worm A-M
      • Kroon S
      • Søndergaard J
      • Wantzin GL
      Skin and oral mucosal changes in patients infected with human immunodeficiency virus.
      The initial manifestation varies from grouped vesicles on the lip or elsewhere that resolve without incident to chronic nonhealing ulcers, particularly in labial or perianal regions (Fig. 3).
      • Goodman DS
      • Teplitz ED
      • Wishner A
      • Klein RS
      • Burk PG
      • Hershenbaum E
      Prevalence of cutaneous disease in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.
      Glossal lesions may manifest as vacciniform white or yellow papules with depressed centers;
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      primary, recurrent, or nonhealing herpetic gingivostomatitis and dehydration may occur, especially among HIV-infected children, in whom the condition tends to be severe.
      • Nance KV
      • Smith ML
      • Joshi VV
      Cutaneous manifestations of acquired immunodeficiency syndrome in children.
      Chronic recalcitrant perianal ulceration in homosexual men represents herpes simplex virus-induced disease until proved otherwise. Herpetic proctitis may occur; it exhibits mild redness and edema but is associated with severe anorectal pain, tenesmus, hematochezia, paresthesias, and urinary retention. Chronic ulceration in other regions, Kaposi's varicelliform eruption, esophageal and tracheobronchial involvement, and systemic dissemination may all occur. After diagnosis by the Tzanck test (demonstration of multinucleate giant cells), biopsy, or culture, acyclovir therapy should be administered. Prolonged or indefinite treatment may be necessary.
      • Goodman DS
      • Teplitz ED
      • Wishner A
      • Klein RS
      • Burk PG
      • Hershenbaum E
      Prevalence of cutaneous disease in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.
      After discontinuation of therapy, recurrences are common, and intravenous administration of acyclovir may be necessary for severe or resistant cases.
      • Straka BF
      • Whitaker DL
      • Morrison SH
      • Oleske JM
      • Grant-Kels JM
      Cutaneous manifestations of the acquired immunodeficiency syndrome in children.
      Occasionally, patients with recurrent or chronic nonhealing herpes simplex virus-induced lesions have been infected with acyclovir-resistant strains of herpes simplex virus. Foscarnet (phosphonoformate) is reported to be effective in such patients; the efficacy of this drug is superior and the toxicity is less frequent in comparison with vidarabine. The relapse rate after treatment, however, remains high.
      • Safrin S
      • Crumpacker C
      • Chatis P
      • Davis R
      • Hafner R
      • Rush J
      • Kessler HA
      • Landry B
      • Mills J
      • other members of the AIDS Clinical Trials Group
      A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome.
      Other potential agents for acyclovir-resistant herpes simplex virus include vidarabine, ganciclovir, and interferon-α.
      • Cohen PR
      • Grossman ME
      Clinical features of human immunodeficiency virus-associated disseminated herpes zoster virus infection—a review of the literature.
      • Erlich KS
      • Mills J
      • Chatis P
      • Mertz GJ
      • Busch DF
      • Follansbee SE
      • Grant RM
      • Crumpacker CS
      Acyclovir-resistant herpes simplex virus infections in patients with the acquired immunodeficiency syndrome.
      Figure thumbnail gr3
      Fig. 3Typical lesions of herpes simplex virus infection, beginning as grouped vesicles on a red base, which then rupture and form crusts as depicted here in patient with human immunodeficiency virus infection.
      Molecular studies have shown that herpesviruses (and perhaps other chronic B-cell stimulants) may activate HIV gene expression through the production of cytokines such as tumor necrosis factor alpha and interleukin 6 by B cells; this process causes active virus expression by infected latent T cells. Thus, B-cell stimulants, such as herpesviruses, may act as cofactors in promoting the development of AIDS.
      • Fauci AS
      • Schnittman SM
      • Poli G
      • Koenig S
      • Pantaleo G
      Immunopathogenic mechanisms in human immunodeficiency virus (HIV) infection.

      Varicella-Zoster Virus.

      Varicella-zoster virus infection affects 3 to 4% of HIV-positive patients and may cause severe primary chickenpox (Fig. 4) as well as dermatomal or generalized herpes zoster, occasionally with systemic involvement. In one study, eruptions of varicella occurred in 3.5% of HIV-positive patients, and 3 of 15 patients had atypical poxlike lesions of varicella (not zoster), which were due to a reactivation of varicella-zoster virus infection.
      • Perronne C
      • Lazanas M
      • Leport C
      • Simon F
      • Salmon D
      • Dallot A
      • Vildé J-L
      Varicella in patients infected with the human immunodeficiency virus.
      Figure thumbnail gr4
      Fig. 4Chickenpox with generalized papules, vesicles, and excoriations in various stages of evolution in patient with human immunodeficiency virus infection.
      Herpes zoster is often the initial manifestation of immune dysfunction, and it can precede other symptoms by a mean of 1.5 years.
      • Gulick RM
      • Heath-Chiozzi M
      • Crumpacker CS
      Varicella-zoster virus disease in patients with human immunodeficiency virus infection.
      In children, herpes zoster is prone to dissemination.
      • Nance KV
      • Smith ML
      • Joshi VV
      Cutaneous manifestations of acquired immunodeficiency syndrome in children.
      The usual manifestation is a vesicular, erosive eruption that in HIV-positive patients is characterized by chronicity, multidermatomal distribution, severe pain, and scarring (Fig. 5). Recently, investigators have also described patients with chronic localized or disseminated disease, hyperkeratotic plaques, and confirmed acyclovir resistance, perhaps because of inadequate initial treatment.
      • Disler RS
      • Dover JS
      Chronic localized herpes zoster in the acquired immunodeficiency syndrome (letter to the editor).
      • Hoppenjans WB
      • Bibler MR
      • Orme RL
      • Solinger AM
      Prolonged cutaneous herpes zoster in acquired immunodeficiency syndrome.
      The frequency of postherpetic neuralgia may be high, and herpes zoster in any young patient with appropriate risk factors may indicate HIV infection (which suggests the need for an enzyme-linked immunosorbent assay and a western blot serologic determination).
      Figure thumbnail gr5
      Fig. 5Chronic ulcerative herpes zoster involving perianal and sacral areas in patient with human immunodeficiency virus infection.
      In a study of homosexual men with herpes zoster, investigators estimated that, over time, AIDS would develop in approximately 1% per month
      • Melbye M
      • Grossman RJ
      • Goedert JJ
      • Eyster ME
      • Biggar RJ
      Risk of AIDS after herpes zoster.
      and that the cumulative incidence of AIDS in such men would be 23% within 2 years after the development of herpes zoster and 46% within 4 years.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      Patients with active disease require high-dose orally administered acyclovir, and intravenous treatment is necessary for severe disease.
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      Persistent disease should prompt viral isolation and assessment of viral thymidine kinase activity.
      • Gulick RM
      • Heath-Chiozzi M
      • Crumpacker CS
      Varicella-zoster virus disease in patients with human immunodeficiency virus infection.
      • Disler RS
      • Dover JS
      Chronic localized herpes zoster in the acquired immunodeficiency syndrome (letter to the editor).
      • Hoppenjans WB
      • Bibler MR
      • Orme RL
      • Solinger AM
      Prolonged cutaneous herpes zoster in acquired immunodeficiency syndrome.
      HIV-infected patients with primary varicella may also require intravenously administered acyclovir.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      In addition, immunoglobulin has been administered intravenously in some cases.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Straka BF
      • Whitaker DL
      • Morrison SH
      • Oleske JM
      • Grant-Kels JM
      Cutaneous manifestations of the acquired immunodeficiency syndrome in children.

      Epstein-Barr Virus and Oral Hairy Leukoplakia.

      Epstein-Barr virus, another virus in the herpes family, may act as an HIV cofactor by enhancing the growth capabilities of the virus in lymphocytes, and it is associated with the development of lymphoma in HIV-infected persons.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      Epstein-Barr virus is also the cause of oral hairy leukoplakia, one of the most specific cutaneous manifestations of HIV infection;
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      hairy leukoplakia has been noted only rarely in immunosuppressed persons who are not HIV infected.
      • Resnick L
      • Herbst JS
      • Raab-Traub N
      Oral hairy leukoplakia.
      The exact incidence is uncertain because of frequent confusion with oral candidiasis, but hairy leukoplakia has been identified in all HIV-associated risk groups except infants; it is rare in HIV-infected children.
      • Nance KV
      • Smith ML
      • Joshi VV
      Cutaneous manifestations of acquired immunodeficiency syndrome in children.
      One study showed a 48% probability of the development of AIDS within 16 months and 83% within 31 months of the diagnosis of oral hairy leukoplakia.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      Leukoplakia usually manifests as asymptomatic, adherent, whitish gray plaques that are localized to the lateral aspects of the tongue and that occasionally involve the buccal mucosa (Fig. 6). Actively replicating Epstein-Barr viruses have been found within these lesions and are believed causative, although papillomaviruses and Candida species may be cofactors. The lesion is not premalignant and therefore treatment is not imperative; however, acyclovir, ganciclovir sodium, azidothymidine (AZT, zidovudine), desciclovir, and topically applied tretinoin solution have been associated with temporary regression.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      • Resnick L
      • Herbst JS
      • Raab-Traub N
      Oral hairy leukoplakia.
      Clotrimazole troches, 100 mg daily for several days, may also help.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      Confirmation of the presence of Epstein-Barr virus should be a criterion for the diagnosis of leukoplakia.
      • Resnick L
      • Herbst JS
      • Raab-Traub N
      Oral hairy leukoplakia.
      Figure thumbnail gr6
      Fig. 6Oral hairy leukoplakia with white plaques on lateral surfaces of tongue in patient with human immunodeficiency virus infection.

      Molluscum Contagiosum.

      The characteristic lesions of molluscum contagiosum are waxy, flesh-colored, umbilicated papules that are caused by a poxvirus and generally occur in children or in anogenital areas of adults. In HIV-infected patients and those with AIDS, in whom the incidence is 0.4 to 2% and 8 to 15%, respectively, lesions are usually localized to the anogenital area or the face but may be disseminated and may rapidly enlarge or coalesce into large plaques that can ulcerate
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Sindrup JH
      • Weismann K
      • Petersen CS
      • Rindum J
      • Pedersen C
      • Mathiesen L
      • Worm A-M
      • Kroon S
      • Søndergaard J
      • Wantzin GL
      Skin and oral mucosal changes in patients infected with human immunodeficiency virus.
      • Ficarra G
      • Gaglioti D
      Facial molluscum contagiosum in HIV-infected patients.
      (Fig. 7). Local destruction and excision have been used, but recurrence is common. Molluscum bodies should be demonstrated in the lesions because disseminated histoplasmosis or Cryptococcus in immunosuppressed patients may mimic molluscum contagiosum, in which case fungal stains, fungal serologies, and culture of biopsy specimens are confirmatory.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      Figure thumbnail gr7
      Fig. 7Multiple umbilicated papules of molluscum contagiosum in anogenital area of patient with human immunodeficiency virus infection.

      Common Warts and Condyloma Acuminatum.

      Multiple common, filiform, and flat warts occur with increased frequency in HIV-infected patients, particularly on the face, neck, hands, and feet; treatment is often ineffective.
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      Anogenital warts occur in up to 40% of HIV-positive homosexual men and in 3 to 6% of all HIV-positive patients, and they may develop into large vegetating lesions that are highly resistant to treatment.
      • Coldiron BM
      • Bergstresser PR
      Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus.
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Sindrup JH
      • Weismann K
      • Petersen CS
      • Rindum J
      • Pedersen C
      • Mathiesen L
      • Worm A-M
      • Kroon S
      • Søndergaard J
      • Wantzin GL
      Skin and oral mucosal changes in patients infected with human immunodeficiency virus.
      • McMillan A
      • Bishop PE
      Clinical course of anogenital warts in men infected with human immunodeficiency virus.
      These condylomas are also common within the anal canal in this population. Human papillomavirus types 6 and 11 have frequently been associated with anal condylomas and are present in 72 to 94% of lesions;
      • McMillan A
      • Bishop PE
      Clinical course of anogenital warts in men infected with human immunodeficiency virus.
      • Syrjänen SM
      • von Krogh G
      • Syrjänen KJ
      Anal condylomas in men. 1. Histopathological and virological assessment.
      human papillomavirus types 16, 18, 31, and 33 have also been noted.
      • McMillan A
      • Bishop PE
      Clinical course of anogenital warts in men infected with human immunodeficiency virus.
      One study found anal intraepithelial neoplasms in conjunction with anal condylomas in about 30% of all patients.
      • Syrjänen SM
      • von Krogh G
      • Syrjänen KJ
      Anal condylomas in men. 1. Histopathological and virological assessment.
      Anal intraepithelial neoplasms were found in both HIV-positive and HIV-negative patients in association with human papillomavirus types 6 and 11, in addition to the traditional “high-risk” types 16, 18, 31, and 33.
      • Syrjänen SM
      • von Krogh G
      • Syrjänen KJ
      Anal condylomas in men. 1. Histopathological and virological assessment.
      Topical caustic agents or destructive procedures often fail, as may surgical or laser removal.

      Cytomegalovirus.

      Cutaneous cytomegalovirus infection in HIV-positive patients is uncommon but is associated with a poor prognosis, and patients usually have nonhealing perianal ulceration, which does not diminish after acyclovir therapy.
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      Disseminated cutaneous cytomegalovirus infection may manifest as small, elevated, purpuric, reddish papules and macules that often ulcerate; the Tzanck test may be helpful in the diagnosis, and serologic studies and culture should be done to distinguish cytomegalovirus from herpes simplex and varicella-zoster infection. Chronic, latent, systemic cytomegalovirus infection, present in almost all patients with AIDS, has been successfully treated with ganciclovir.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      • Bryson YJ
      Promising new antiviral drugs.

      Bacterial Infections.

      Recurrent or severe chronic bacterial folliculitis, impetigo, and ecthyma may be clues to immunosuppression and are common in HIV-positive patients, especially intravenous drug abusers; 50% of symptomatic HIV-infected persons may also be affected.
      • Becker BA
      • Frieden IJ
      • Odom RB
      • Berger TG
      Atypical plaquelike staphylococcal folliculitis in human immunodeficiency virus-infected persons.
      • Duvic M
      • Johnson TM
      • Rapini RP
      • Freese T
      • Brewton G
      • Rios A
      Acquired immunodeficiency syndrome—associated psoriasis and Reiter's syndrome.
      An early pattern is bullous impetigo of the axilla or groin; subsequently, facial or truncal acneiform folliculitis, furunculosis, or ecthyma develops. An uncommon manifestation is a staphylococcal folliculitis that consists of violaceous plaques (up to 10 cm), superficial pustules, and crusts
      • Becker BA
      • Frieden IJ
      • Odom RB
      • Berger TG
      Atypical plaquelike staphylococcal folliculitis in human immunodeficiency virus-infected persons.
      that occur in the groin, axilla, or scalp. Staphylococcus aureus groups A, C, and G and Streptococcus are the most common causes of folliculitis and furunculosis, but relatively uncommon pathogenic organisms such as S. epidermidis or diphtheroids may be involved.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      These infections may be resistant to treatment; often, prolonged systemic administration of antibiotics is necessary.
      Bacterial cellulitis, abscesses, and ulcers are also common, especially in the perianal areas, frequently attributable to S. aureus; surgical débridement is necessary in some cases.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      Pyomyositis or staphylococcal scalded skin syndrome caused by S. aureus may also occur.
      B-cell immunologic defects have a more prominent role in HIV infection in pediatric patients than in adults; consequently, morbidity and mortality as a result of bacterial infections are higher in this age-group. Investigators have hypothesized that HIV stimulates continuous B-cell activation; subsequently, responsiveness of lymphocytes to specific antigenic stimulation is decreased and therefore antibody response is poor. S. aureus is the most common organism that infects the skin of children with AIDS, in the forms of impetigo, cellulitis, or persistent folliculitis;
      • Nance KV
      • Smith ML
      • Joshi VV
      Cutaneous manifestations of acquired immunodeficiency syndrome in children.
      S. pneumoniae, Haemophilus influenzae type B, and Salmonella cause most outpatient episodes of bacteremia.
      • Straka BF
      • Whitaker DL
      • Morrison SH
      • Oleske JM
      • Grant-Kels JM
      Cutaneous manifestations of the acquired immunodeficiency syndrome in children.
      Several investigators recommended monthly therapy with parenterally administered immunoglobulin, which decreased the incidence of serious bacterial and viral infections in one study group of pediatric patients with AIDS.
      • Straka BF
      • Whitaker DL
      • Morrison SH
      • Oleske JM
      • Grant-Kels JM
      Cutaneous manifestations of the acquired immunodeficiency syndrome in children.

      Mycobacteria.

      Mycobacterial infections in HIV-positive patients may manifest as acneiform papules that mimic folliculitis, indurated crusted plaques, abscesses, or swollen matted lymph nodes with overlying erythema. Rarely, ill-defined macules or ecthymatous lesions are noted. Frequent causative organisms include Mycobacterium avium-intracellulare and M. tuberculosis; rarely, M. kansasii and M. marinum are incriminated.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Abramson C
      Podiatric implications of acquired immunodeficiency syndrome.
      • Barbaro DJ
      • Orcutt VL
      • Coldiron BM
      Mycobacterium avium—Mycobacterium intracellulare infection limited to the skin and lymph nodes in patients with AIDS.
      Disseminated M. avium-intracellulare infection is common in patients with advanced HIV infection; however, cutaneous involvement is rare, although patients who have been taking zidovudine have occasionally had only a localized cutaneous disease that responded well to incision and drainage.
      • Fauci AS
      • Schnittman SM
      • Poli G
      • Koenig S
      • Pantaleo G
      Immunopathogenic mechanisms in human immunodeficiency virus (HIV) infection.
      • Barbaro DJ
      • Orcutt VL
      • Coldiron BM
      Mycobacterium avium—Mycobacterium intracellulare infection limited to the skin and lymph nodes in patients with AIDS.
      Active tuberculosis reportedly affects approximately 10% of all patients with AIDS, particularly intravenous drug users, and at least one extrapulmonary site is involved in more than half of these cases.
      • Fauci AS
      • Schnittman SM
      • Poli G
      • Koenig S
      • Pantaleo G
      Immunopathogenic mechanisms in human immunodeficiency virus (HIV) infection.
      Treatment of mycobacterial infections generally involves combinations of antimycobacterial agents.

      Syphilis.

      Syphilis is common in HIV-infected patients, especially homosexuals, and any stage of syphilis may occur. Syphilitic chancre and other genitoulcerative diseases are risk factors that predispose to HIV infection because of decreased barrier function; syphilis may be the initial manifestation in patients with concurrent HIV positivity.
      • Gregory N
      • Sanchez M
      • Buchness MR
      The spectrum of syphilis in patients with human immunodeficiency virus infection.
      Progression from primary to tertiary syphilis within a few months has been reported, as have recrudescent cutaneous secondary syphilis, neurosyphilis without previously confirmed syphilitic infection, possible syphilitic relapse after bacille Calmette-Guérin vaccination, and recurrent neurosyphilis after administration of standard antibiotic regimens.
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      • Sindrup JH
      • Weismann K
      • Petersen CS
      • Rindum J
      • Pedersen C
      • Mathiesen L
      • Worm A-M
      • Kroon S
      • Søndergaard J
      • Wantzin GL
      Skin and oral mucosal changes in patients infected with human immunodeficiency virus.
      • Gregory N
      • Sanchez M
      • Buchness MR
      The spectrum of syphilis in patients with human immunodeficiency virus infection.
      • Bari MM
      • Shulkin DJ
      • Abell E
      Ulcerative syphilis in acquired immunodeficiency syndrome: a case of precocious tertiary syphilis in a patient infected with human immunodeficiency virus.
      Secondary syphilis may manifest as a generalized maculopapular eruption with or without scaling; palmoplantar vesicles, papules, or macules; hypopigmented axillary macules; and oral erosions. Coexistent lesions of secondary syphilis and tertiary gummas have been described. Precocious tertiary syphilis may also manifest with noduloulcerative lesions and lymphadenopathy.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Gregory N
      • Sanchez M
      • Buchness MR
      The spectrum of syphilis in patients with human immunodeficiency virus infection.
      • Bari MM
      • Shulkin DJ
      • Abell E
      Ulcerative syphilis in acquired immunodeficiency syndrome: a case of precocious tertiary syphilis in a patient infected with human immunodeficiency virus.
      Reservoirs for treponemes have been found in the central nervous system, lymph nodes, aqueous humor, aorta, spinal cord, and liver; all allow possible relapse.
      • Gregory N
      • Sanchez M
      • Buchness MR
      The spectrum of syphilis in patients with human immunodeficiency virus infection.
      Serologic studies may be unreliable because of artifact or true absence of antibody, although Treponema pallidum may be identifiable in tissue biopsy specimens, which therefore become an important aspect of diagnosis.
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      • Gregory N
      • Sanchez M
      • Buchness MR
      The spectrum of syphilis in patients with human immunodeficiency virus infection.
      A patient with HIV infection who is receiving treatment and is persistently seropositive for syphilis represents a management challenge, particularly if intermittent titer increases are verified. In these patients, standard doses of penicillin G benzathine for early syphilis may fail;
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Gregory N
      • Sanchez M
      • Buchness MR
      The spectrum of syphilis in patients with human immunodeficiency virus infection.
      overtreatment could be advocated as a maxim of management.

      Bacillary Angiomatosis.

      The recently described, potentially fatal disease of bacillary angiomatosis has primarily been noted in HIV-infected patients. It is caused by a previously uncharacterized, weakly reactive, gram-negative rickettsia-like organism most closely related to Rochalimaea quintana, the causative agent of trench fever,
      • Relman DA
      • Loutit JS
      • Schmidt TM
      • Falkow S
      • Tompkins LS
      The agent of bacillary angiomatosis: an approach to the identification of uncultured pathogens.
      and to Bartonella bacilliformis, the agent of bartonellosis. The agent of bacillary angiomatosis seems distinct from the incompletely characterized agent of cat-scratch disease, although some patients with bacillary angiomatosis have recently been scratched by a cat.
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      • Cockerell CJ
      • LeBoit PE
      Bacillary angiomatosis: a newly characterized, pseudoneoplastic, infectious, cutaneous vascular disorder.
      • Spach DH
      Bacillary angiomatosis.
      • Szaniawski WK
      • Don PC
      • Bitterman SR
      • Schachner JR
      Epithelioid angiomatosis in patients with AIDS: report of seven cases and review of the literature.
      Patients with bacillary angiomatosis usually have few to many reddish rubbery to firm papules and nodules that resemble pyogenic granulomas. Initially, these are pinpoint, but occasionally they become several centimeters in diameter (Fig. 8). They may be found anywhere on the skin—often on the upper trunk and face and occasionally on the oral, anal, or gastrointestinal mucosa or in visceral organs; several cases of peliosis hepatis have been attributed to the organism that causes bacillary angiomatosis.
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Cockerell CJ
      • LeBoit PE
      Bacillary angiomatosis: a newly characterized, pseudoneoplastic, infectious, cutaneous vascular disorder.
      • Spach DH
      Bacillary angiomatosis.
      • Szaniawski WK
      • Don PC
      • Bitterman SR
      • Schachner JR
      Epithelioid angiomatosis in patients with AIDS: report of seven cases and review of the literature.
      Deep-seated nodules or tumors that involve the subcutaneous tissue may also be noted. Lesions often bleed profusely when traumatized. Organisms are usually seen in biopsy specimens with use of Warthin-Starry stain and electron microscopy. Usually the condition responds to erythromycin therapy (minimum, 4-week treatment period).
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      • Cockerell CJ
      • LeBoit PE
      Bacillary angiomatosis: a newly characterized, pseudoneoplastic, infectious, cutaneous vascular disorder.
      • Spach DH
      Bacillary angiomatosis.
      • Szaniawski WK
      • Don PC
      • Bitterman SR
      • Schachner JR
      Epithelioid angiomatosis in patients with AIDS: report of seven cases and review of the literature.
      Locally destructive measures may be sufficient for one to several lesions.
      Figure thumbnail gr8
      Fig. 8Bacillary angiomatosis in patient with human immunodeficiency virus infection. Note numerous rubbery papules and nodules similar to pyogenic granulomas.
      (Photograph courtesy of Dr. Clay Cockerell, Dallas, Texas.)
      Bacillary angiomatosis may be clinically and histologically similar to KS. Thus, biopsy specimens and special stain confirmation of suspected KS in HIV-infected patients are necessary.
      • Cockerell CJ
      • LeBoit PE
      Bacillary angiomatosis: a newly characterized, pseudoneoplastic, infectious, cutaneous vascular disorder.
      • Walford N
      • Van Der Wouw PA
      • Ten Velden JJAM
      • Hulsebosch HJ
      Epithelioid angiomatosis in the acquired immunodeficiency syndrome: morphology and differential diagnosis.

      Chancroid.

      Chancroid, a sexually transmitted disease caused by H. ducreyi, manifests as one to several tender, soft genital ulcers, often with an undermined border and associated inguinal lymphadenitis, which can give rise to inguinal abscesses termed “buboes.” Chancroid has become endemic in southern Florida and New York City, and studies in East Africa have shown chancroid to be the major risk factor for heterosexual transmission of HIV-1 in East Africa (presumably due to egress or entry of virions through ulcerated skin).
      • Ronald AR
      • Plummer FA
      Chancroid and granuloma inguinale.
      Chancroidlike ulcers may occur in herpes simplex infections or syphilis, and cultures for herpes simplex virus as well as dark-field examination should be performed in suspected cases of chancroid. The diagnosis of chancroid is confirmed by culture of ulcer exudate, and it is treated with trimethoprim-sulfamethoxazole, amoxicillin-clavulanic acid, ceftriaxone sodium, or ciprofloxacin.
      • Ronald AR
      • Plummer FA
      Chancroid and granuloma inguinale.

      Fungal and Yeast Infections.

      Candidiasis.

      Candidiasis and Pneumocystis carinii pneumonia are the most frequent opportunistic infections in HIV-positive patients, in whom the prevalence of mucocutaneous candidiasis has been estimated to be 37 to 47%.
      • Coldiron BM
      • Bergstresser PR
      Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus.
      • Goodman DS
      • Teplitz ED
      • Wishner A
      • Klein RS
      • Burk PG
      • Hershenbaum E
      Prevalence of cutaneous disease in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.
      In one study, 50% of patients with both unexplained oral candidiasis and risk factors for AIDS experienced multiple subsequent opportunistic infections.
      • Lane HC
      Acquired immunodeficiency syndrome.
      In 42% of one group of patients with oral candidiasis, full-blown AIDS developed within a 42-week follow-up period in comparison with only 6% who did not have oral candidiasis.
      • Plettenberg A
      • Reisinger E
      • Lenzner U
      • Listemann H
      • Ernst M
      • Kern P
      • Dietrich M
      • Meigel W
      Oral candidosis in HIV-infected patients: prognostic value and correlation with immunological parameters.
      Infection seems to correlate with the immune status of the patient; it often occurs when helper T-cell counts are less than 400 cells/μl, increases when they are less than 100 cells/μl, and becomes intractable when they are less than 10 cells/μl.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      • Plettenberg A
      • Reisinger E
      • Lenzner U
      • Listemann H
      • Ernst M
      • Kern P
      • Dietrich M
      • Meigel W
      Oral candidosis in HIV-infected patients: prognostic value and correlation with immunological parameters.
      The initial manifestation of candidiasis varies from small and large, pseudomembranous, white plaques on the oral mucosa to deep erosions on the tongue and thick plaques in the posterior aspect of the pharynx (Fig. 9). Severe dysphagia may accompany esophageal candidiasis. Diffuse candidiasis of the gastrointestinal tract, anus, and vagina may occur and is difficult to treat. Candidal onychodystrophy may be refractory to therapy and generally correlates with an absolute helper T-cell count of less than 100 cells/μl.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      An extensive diffuse diaper-type dermatitis may be seen in children and involves both the trunk and the extremities;
      • Nance KV
      • Smith ML
      • Joshi VV
      Cutaneous manifestations of acquired immunodeficiency syndrome in children.
      cutaneous candidiasis may also be generalized in adults (Fig. 10). Systemic candidiasis may involve any organ, including the brain and liver. Potassium hydroxide smear reveals typical pseudohyphae and yeast forms from cutaneous plaques.
      Figure thumbnail gr9
      Fig. 9Oral candidiasis with white plaques on tongue and buccal mucosa in patient with human immunodeficiency virus infection. A potassium hydroxide smear revealed pseudohyphae.
      Figure thumbnail gr10
      Fig. 10Generalized cutaneous candidiasis, revealing typical red and hemorrhagic macules and papules in patient with human immunodeficiency virus infection.
      Initial treatment involves topically applied antifungal agents such as nystatin (mouthwash or tablets), clotrimazole troches, or miconazole nitrate, although continuous use is often necessary. In these cases or those resistant to topically administered therapy, systemically administered ketoconazole is useful and may also be needed continuously; careful monitoring of liver enzymes is necessary.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      Ketoconazole may interfere with the metabolism of rifampin and other drugs that the HIV-infected patient may be required to take. Orally administered fluconazole has been effective for oral candidiasis in several studies and was more effective than ketoconazole in one, in which the incidence of side effects was similar.
      • Winkelman WJ
      The Fifth International Conference on AIDS: the scientific and social challenge.
      Clotrimazole may also be effective. With any agent, the recurrence rate is high after discontinuation of treatment.
      In one study, a conspicuous absence of candidiasis was noted in patients with AIDS who were receiving 200 mg of zidovudine every 4 hours. Improvement of immunologic surveillance and increasing helper T-cell counts probably explain this response.
      • Burns S
      Podiatric manifestations of AIDS.

      Dermatophytosis.

      Dermatophytosis has been found in approximately 20% of HIV-infected patients
      • Coldiron BM
      • Bergstresser PR
      Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus.
      • Sindrup JH
      • Weismann K
      • Petersen CS
      • Rindum J
      • Pedersen C
      • Mathiesen L
      • Worm A-M
      • Kroon S
      • Søndergaard J
      • Wantzin GL
      Skin and oral mucosal changes in patients infected with human immunodeficiency virus.
      and may manifest as tinea corporis, cruris, faciei, pedis, manuum, or unguium.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      A severe widespread dermatophytosis may also be seen, particularly in children. Involved areas are usually erythematous, scaly, and pruritic (Fig. 11). Dermatophytosis may resemble palmoplantar keratoderma with diffuse thickening of the skin of the palms or soles; infection of the nail or paronychia, usually spared by dermatophytes, occurs more commonly in HIV-infected than in noninfected patients.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      Usually, these infections are caused by Trichophyton rubrum, and potassium hydroxide smears for hyphae and culture are recommended for diagnosis. Lesions are often resistant to topically applied imidazole antifungal agents, and systemically administered griseofulvin or ketoconazole is often the drug of choice (if treatment is warranted). Recurrences are common.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      Figure thumbnail gr11
      Fig. 11Discrete and confluent annular plaques of tinea corporis, with characteristic peripheral erythema and scale, in patient with human immunodeficiency virus infection.
      Tinea versicolor infection, caused by the yeastlike fungus Pityrosporum orbiculare, is common and may be seen early in the course of HIV infection when helper T-cell counts are more than 300 cells/μl. Patchy or extensive areas of fine scale and hypopigmentation are present, and irregular acanthosis may be noted when helper T-cell counts decrease to less than 100 cells/μl. Infection is usually resistant to topically applied agents, such as selenium sulfide, miconazole, or clotrimazole; systemically administered ketoconazole may be efficacious, but recurrent infection is common.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).

      Cryptococcosis.

      Cryptococcosis has been reported to occur in 2 to 9% of patients with AIDS.
      • Azon-Masoliver A
      • Gonzalez-Clemente J
      • Pedrol E
      • Lecha M
      • Mensa J
      • Mascaro JM
      Herpetiform and mollusca contagiosa-like cutaneous cryptococcosis in a patient with AIDS.
      • Ricchi E
      • Manfredi R
      • Scarani P
      • Costigliola P
      • Chiodo F
      Cutaneous cryptococcosis and AIDS.
      • Picon L
      • Vaillant L
      • Duong T
      • Lorette G
      • Bacq Y
      • Besnier JM
      • Choutet P
      Cutaneous cryptococcosis resembling molluscum contagiosum: a first manifestation of AIDS.
      • Eng RHK
      • Bishburg E
      • Smith SM
      • Kapila R
      Cryptococcal infections in patients with acquired immune deficiency syndrome.
      • Zuger A
      • Louie E
      • Holzman RS
      • Simberkoff MS
      • Rahal JJ
      Cryptococcal disease in patients with the acquired immunodeficiency syndrome: diagnostic features and outcome of treatment.
      Incidence estimates for cutaneous spread vary from none to 10 to 15%,
      • Picon L
      • Vaillant L
      • Duong T
      • Lorette G
      • Bacq Y
      • Besnier JM
      • Choutet P
      Cutaneous cryptococcosis resembling molluscum contagiosum: a first manifestation of AIDS.
      • Zuger A
      • Louie E
      • Holzman RS
      • Simberkoff MS
      • Rahal JJ
      Cryptococcal disease in patients with the acquired immunodeficiency syndrome: diagnostic features and outcome of treatment.
      and involvement is almost always associated with disseminated disease, although cutaneous manifestations have occasionally preceded systemic signs of infection.
      • Ricchi E
      • Manfredi R
      • Scarani P
      • Costigliola P
      • Chiodo F
      Cutaneous cryptococcosis and AIDS.
      • Picon L
      • Vaillant L
      • Duong T
      • Lorette G
      • Bacq Y
      • Besnier JM
      • Choutet P
      Cutaneous cryptococcosis resembling molluscum contagiosum: a first manifestation of AIDS.
      Skin lesions may be polymorphic, including nodules, abscesses, papules, pustules, herpetiform papulovesicles, vegetating plaques, and deep ulcers (Fig. 12).
      • Azon-Masoliver A
      • Gonzalez-Clemente J
      • Pedrol E
      • Lecha M
      • Mensa J
      • Mascaro JM
      Herpetiform and mollusca contagiosa-like cutaneous cryptococcosis in a patient with AIDS.
      • Ricchi E
      • Manfredi R
      • Scarani P
      • Costigliola P
      • Chiodo F
      Cutaneous cryptococcosis and AIDS.
      • Picon L
      • Vaillant L
      • Duong T
      • Lorette G
      • Bacq Y
      • Besnier JM
      • Choutet P
      Cutaneous cryptococcosis resembling molluscum contagiosum: a first manifestation of AIDS.
      Multiple flesh-colored to reddish, dome-shaped, translucent 1- to 4-mm papules that resemble molluscum contagiosum are common manifestations;
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      • Azon-Masoliver A
      • Gonzalez-Clemente J
      • Pedrol E
      • Lecha M
      • Mensa J
      • Mascaro JM
      Herpetiform and mollusca contagiosa-like cutaneous cryptococcosis in a patient with AIDS.
      • Ricchi E
      • Manfredi R
      • Scarani P
      • Costigliola P
      • Chiodo F
      Cutaneous cryptococcosis and AIDS.
      • Picon L
      • Vaillant L
      • Duong T
      • Lorette G
      • Bacq Y
      • Besnier JM
      • Choutet P
      Cutaneous cryptococcosis resembling molluscum contagiosum: a first manifestation of AIDS.
      exclusion of cryptococcosis necessitates biopsy of molluscoid growths.
      Figure thumbnail gr12
      Fig. 12Cutaneous cryptococcosis, shown as a large, dry, noninflammatory crusted ulcer. Culture is necessary for diagnosis.
      Methenamine silver and mucicarmine stains of histologic specimens are helpful in identifying the Cryptococcus organisms.
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      Once the diagnosis has been made, investigation for systemic involvement, including analysis of cerebrospinal fluid, serum, urine, sputum, and prostatic secretions, should be undertaken.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      Early use of systemically administered antifungal agents may be lifesaving in these patients, although relapses occur in more than 50%,
      • Mares M
      • Sartori MT
      • Carretta M
      • Bertaggia A
      • Girolami A
      Rhinophyma-like cryptococcal infection as an early manifestation of AIDS in a hemophilia B patient.
      The combination of amphotericin B and flucytosine is often used.
      • Picon L
      • Vaillant L
      • Duong T
      • Lorette G
      • Bacq Y
      • Besnier JM
      • Choutet P
      Cutaneous cryptococcosis resembling molluscum contagiosum: a first manifestation of AIDS.
      • Zuger A
      • Louie E
      • Holzman RS
      • Simberkoff MS
      • Rahal JJ
      Cryptococcal disease in patients with the acquired immunodeficiency syndrome: diagnostic features and outcome of treatment.
      • Mares M
      • Sartori MT
      • Carretta M
      • Bertaggia A
      • Girolami A
      Rhinophyma-like cryptococcal infection as an early manifestation of AIDS in a hemophilia B patient.
      Maintenance treatment has been suggested for prevention of relapse.
      • Zuger A
      • Louie E
      • Holzman RS
      • Simberkoff MS
      • Rahal JJ
      Cryptococcal disease in patients with the acquired immunodeficiency syndrome: diagnostic features and outcome of treatment.
      • Mares M
      • Sartori MT
      • Carretta M
      • Bertaggia A
      • Girolami A
      Rhinophyma-like cryptococcal infection as an early manifestation of AIDS in a hemophilia B patient.

      Histoplasmosis.

      Cutaneous histoplasmosis may occur in HIV-infected patients in association with symptomatic primary pulmonary or disseminated histoplasmosis—especially in endemic areas of the United States, such as the Ohio River valley where up to 90% of the population has evidence of prior pulmonary infection.
      • Greenberg RG
      • Berger TG
      Progressive disseminated histoplasmosis in acquired immune deficiency syndrome: presentation as a steroid-responsive dermatosis.
      Histoplasmosis has also been associated with cave exploration and with residence in the Caribbean, Central or South America, and Cuba.
      • Mandell W
      • Goldberg DM
      • Neu HC
      Histoplasmosis in patients with the acquired immune deficiency syndrome.
      In a recent review, Cohen and associates
      • Cohen PR
      • Bank DE
      • Silvers DN
      • Grossman ME
      Cutaneous lesions of disseminated histoplasmosis in human immunodeficiency virus-infected patients.
      identified 239 HIV-infected patients with disseminated histoplasmosis in reports through December 1989, of whom 11% had cutaneous lesions. The actual incidence of skin lesions in patients with disseminated histoplasmosis may be higher because of the nonspecific nature of the lesions.
      • Cohen PR
      • Bank DE
      • Silvers DN
      • Grossman ME
      Cutaneous lesions of disseminated histoplasmosis in human immunodeficiency virus-infected patients.
      • Johnson PC
      • Khardori N
      • Najjar AF
      • Butt F
      • Mansell PWA
      • Sarosi GA
      Progressive disseminated histoplasmosis in patients with acquired immunodeficiency syndrome.
      Initial manifestations vary, including shallow crusted ulcers, pustules, psoriasiform papules, papulonecrotic plaques, a cellulitis-like eruption, perianal ulceration, mild diffuse dermatitis, a disseminated maculopapular eruption, and widespread 2- to 6-mm pink to red papules with mild folliculitis.
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      • Greenberg RG
      • Berger TG
      Progressive disseminated histoplasmosis in acquired immune deficiency syndrome: presentation as a steroid-responsive dermatosis.
      • Hazelhurst JA
      • Vismer HF
      Histoplasmosis presenting with unusual skin lesions in acquired immunodeficiency syndrome (AIDS).
      • Lindgren AM
      • Fallon JD
      • Horan RF
      Psoriasiform papules in the acquired immunodeficiency syndrome.
      Crushed-tissue preparation, special stains for fungi, and culture of skin and bone marrow specimens will usually provide the diagnosis.
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Mandell W
      • Goldberg DM
      • Neu HC
      Histoplasmosis in patients with the acquired immune deficiency syndrome.
      • Cohen PR
      • Bank DE
      • Silvers DN
      • Grossman ME
      Cutaneous lesions of disseminated histoplasmosis in human immunodeficiency virus-infected patients.
      • Johnson PC
      • Khardori N
      • Najjar AF
      • Butt F
      • Mansell PWA
      • Sarosi GA
      Progressive disseminated histoplasmosis in patients with acquired immunodeficiency syndrome.
      Histoplasma capsulatum complement-fixation titers may or may not be positive in these patients.
      • Mandell W
      • Goldberg DM
      • Neu HC
      Histoplasmosis in patients with the acquired immune deficiency syndrome.
      Amphotericin B does not permanently cure histoplasmosis in patients with AIDS, and relapses necessitate long-term antimycotic therapy.
      • Greenberg RG
      • Berger TG
      Progressive disseminated histoplasmosis in acquired immune deficiency syndrome: presentation as a steroid-responsive dermatosis.
      • Johnson PC
      • Khardori N
      • Najjar AF
      • Butt F
      • Mansell PWA
      • Sarosi GA
      Progressive disseminated histoplasmosis in patients with acquired immunodeficiency syndrome.
      Long-term treatment with ketoconazole has been reported to decrease the rate of relapse.
      • Greenberg RG
      • Berger TG
      Progressive disseminated histoplasmosis in acquired immune deficiency syndrome: presentation as a steroid-responsive dermatosis.
      • Cohen PR
      • Bank DE
      • Silvers DN
      • Grossman ME
      Cutaneous lesions of disseminated histoplasmosis in human immunodeficiency virus-infected patients.
      • Johnson PC
      • Khardori N
      • Najjar AF
      • Butt F
      • Mansell PWA
      • Sarosi GA
      Progressive disseminated histoplasmosis in patients with acquired immunodeficiency syndrome.

      Sporotrichosis.

      Systemic sporotrichosis, caused by Sporothrix schenckii, is uncommon in HIV-infected patients but has been seen with no history of exposure to soil or plants. Unifocal or multifocal systemic sporotrichosis, asymptomatic pulmonary sporotrichosis, or primary cutaneous inoculation sporotrichosis may occur. In HIV-positive patients, the portal of entry is usually the lungs; hematogenous dissemination occurs subsequently. Skin lesions are uncommon but may consist of widespread, enlarging, erythematous and violaceous nodules that ulcerate and leave crusted necrotic centers.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Shaw JC
      • Levinson W
      • Montanaro A
      Sporotrichosis in the acquired immunodeficiency syndrome.
      Involvement of the synovium, periosteum, and bone, which is seen in up to 80% of patients with disseminated sporotrichosis, leads to chronic erosive arthritis and osteomyelitis.
      • Shaw JC
      • Levinson W
      • Montanaro A
      Sporotrichosis in the acquired immunodeficiency syndrome.
      • Sindrup JH
      • Lisby G
      • Weismann K
      • Wantzin GL
      Skin manifestations in AIDS, HIV infection, and AIDS-related complex.
      The use of appropriate fungal stains and cultures for skin biopsy specimens facilitates diagnosis.
      Amphotericin B is the treatment of choice for disseminated sporotrichosis, and maintenance doses may be necessary. Orally administered flucytosine may help, although renal toxicity is often a limiting factor.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Shaw JC
      • Levinson W
      • Montanaro A
      Sporotrichosis in the acquired immunodeficiency syndrome.
      In some cases of cutaneous disease, ketoconazole may be effective. In one report, supersaturated potassium iodide was beneficial but not curative.
      • Shaw JC
      • Levinson W
      • Montanaro A
      Sporotrichosis in the acquired immunodeficiency syndrome.
      Despite all drug therapy, patients may die of disseminated sporotrichosis.

      Protozoal Infections.

      Cutaneous P. carinii infection is rare but may be associated with P. carinii pneumonia or disseminated disease. Nonspecific nodular lesions that involve the external auditory canal, presumably resulting from middle ear infections, have been described.
      • Schinella RA
      • Breda SD
      • Hammerschlag PE
      Otic infection due to Pneumocystis carinii in an apparently healthy man with antibody to the human immunodeficiency virus.
      • Coulman CU
      • Greene I
      • Archibald RWR
      Cutaneous pneumocystosis.
      In a recent study, two patients had nonspecific macules or molluscum contagiosum-like papules on the trunk or head and neck.
      • Hennessey NP
      • Parro EL
      • Cockerell CJ
      Cutaneous Pneumocystis carinii infection in patients with acquired immunodeficiency syndrome.
      Intravenously administered trimethoprim-sulfamethoxazole or pentamidine has been efficacious.
      • Schinella RA
      • Breda SD
      • Hammerschlag PE
      Otic infection due to Pneumocystis carinii in an apparently healthy man with antibody to the human immunodeficiency virus.
      • Coulman CU
      • Greene I
      • Archibald RWR
      Cutaneous pneumocystosis.
      • Hennessey NP
      • Parro EL
      • Cockerell CJ
      Cutaneous Pneumocystis carinii infection in patients with acquired immunodeficiency syndrome.

      Arthropod Infections.

      Infection with Sarcoptes scabiei in HIV-infected patients usually results in a more severe and generalized eruption than in uninfected hosts. The typical extremely itchy red papules may be found in the intertriginous areas (Fig. 13), wrists, and finger web spaces, but they may also develop on the face and scalp, areas usually spared in non-HIV-infected adults. Lesions usually heal with use of gamma benzene hexachloride (1% lindane) topically applied to the entire body for 8 to 12 hours; shampoo may also be used.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      • Jucowics P
      • Ramon ME
      • Don PC
      • Stone RK
      • Bamji M
      Norwegian scabies in an infant with acquired immunodeficiency syndrome.
      Figure thumbnail gr13
      Fig. 13Diffuse pruritic papular eruption of scabies, with excoriations and inguinal accentuation, in patient with human immunodeficiency virus infection. Although patient's fingers were involved, they lacked the telltale linear burrows.
      Norwegian scabies, a rare variant, has been described in adult and pediatric patients with AIDS, usually as their clinical status deteriorates. Patients with this variant have hyperkeratotic and scaly crusted plaques on an erythematous base, primarily on the neck, scalp, and trunk. These patients harbor thousands of mites.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      This variant is highly contagious, and in one report, an infant infected 21 health-care workers despite routine scabies isolation precautions.
      • Jucowics P
      • Ramon ME
      • Don PC
      • Stone RK
      • Bamji M
      Norwegian scabies in an infant with acquired immunodeficiency syndrome.
      Gamma benzene hexachloride is usually effective for this variant, but repeated applications may be necessary. Postscabietic dermatitis, after successful therapy, may be a problem in patients with AIDS; sometimes it persists for several months (until all residual foreign antigens of the organisms and ova are eliminated).
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      Scabies infestation should be a consideration in any patient with an unexplained pruritic eruption or dermatitis. It can be diagnosed by finding the mite, ova, or fecal material in scrapings from a lesion.

      MISCELLANEOUS DERMATOSES

      Vascular Lesions.

      Vasculitis in HIV-infected patients may be classified in two broad categories: (1) systemic vasculitis, including periarteritis nodosa-like disease and granulomatous angiitis, and (2) cutaneous leukocytoclastic or necrotizing vasculitis.
      • Chren M-M
      • Silverman RA
      • Sorensen RU
      • Elmets CA
      Leukocytoclastic vasculitis in a patient infected with human immunodeficiency virus.
      Purpura attributed to leukocytoclastic vasculitis has been reported in patients with P. carinii pneumonia and cytomegalovirus pneumonitis. Bright fluorescence was noted with use of high-titer anti-HIV serum in the vessels of one of these patients.
      • Chren M-M
      • Silverman RA
      • Sorensen RU
      • Elmets CA
      Leukocytoclastic vasculitis in a patient infected with human immunodeficiency virus.
      Telangiectasia has been associated with the complete spectrum of HIV disease. A characteristic manifestation involves telangiectases in a crescent-shaped distribution over the upper chest, shoulder, and clavicular areas, often in conjunction with a mild diffuse erythema.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      Telangiectases of the hands and ankles, angiomas on the ears, and splinter hemorrhages of the nail beds also have been reported.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      Diffuse petechiae attributed to thrombocytopenia may be seen in advanced disease; thrombocytopenic purpura in patients with AIDS may be idiopathic or attributable to cytomegalovirus infection.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      Febrile patients with swelling, erythema, and tenderness of the lower extremities and indurated cords along the course of superficial veins have been described; however, these conditions are not due to deep venous thromboses but rather to KS that involves lymph nodes, with resultant edema. This has been termed the “hyperalgesic pseudothrombophlebitis syndrome.”
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      • Burns S
      Podiatric manifestations of AIDS.
      Anticoagulation is unnecessary in these cases, but the KS must be treated.

      Papulosquamous Disease.

      The papulosquamous dermatoses associated with AIDS represent the complete spectrum of disease from mild disorders such as xerosis generalisata to severe psoriasis, Reiter's syndrome, and ichthyosis.

      Xerotic (Asteatotic) Eczema.

      A “generalized dry skin syndrome,” xerotic eczema is one of the most common scaling dermatoses among HIV-positive patients; it occurs in 5 to 20% of such patients. This condition is often severely pruritic and resistant to antihistamines.
      • Coldiron BM
      • Bergstresser PR
      Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus.
      • Sindrup JH
      • Weismann K
      • Petersen CS
      • Rindum J
      • Pedersen C
      • Mathiesen L
      • Worm A-M
      • Kroon S
      • Søndergaard J
      • Wantzin GL
      Skin and oral mucosal changes in patients infected with human immunodeficiency virus.
      • Sadick NS
      • McNutt NS
      • Kaplan MH
      Papulosquamous dermatoses of AIDS.
      The pruritus may be disproportionate to the clinically obvious xerosis, which often manifests as fine branlike scaling with occasional discrete thickened patches.
      • Sadick NS
      • McNutt NS
      • Kaplan MH
      Papulosquamous dermatoses of AIDS.
      The eruption has occurred when helper T-cell counts are less than 400 cells/μl and often may precede other papulosquamous disorders.
      • Sadick NS
      • McNutt NS
      • Kaplan MH
      Papulosquamous dermatoses of AIDS.
      Other itchy, scaling dermatoses such as scabies and fungal infections must be excluded, and treatment of the underlying xerosis includes use of emollients that contain urea and lactic acid, H1 antihistamines, and supersaturated fatty acid soaks.
      • Sadick NS
      • McNutt NS
      • Kaplan MH
      Papulosquamous dermatoses of AIDS.
      A frequent association of xerosis, seborrheic dermatitis, and erythroderma (generalized red skin) with the development of dementia and spinal cord disease has been noted in patients with AIDS. This finding has led to speculation that the neurologic disease and these proliferative disorders could result from the same mechanism.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).

      Seborrheic Dermatitis.

      Seborrheic dermatitis is one of the most common noninfectious skin manifestations of HIV-infected patients; the reported prevalence is 20 to 80% in comparison with 5 to 12% in non-HIV-infected patients.
      • Coldiron BM
      • Bergstresser PR
      Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus.
      • Kaplan MH
      • Sadick N
      • McNutt NS
      • Meltzer M
      • Sarngadharan MG
      • Pahwa S
      Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).
      • Goodman DS
      • Teplitz ED
      • Wishner A
      • Klein RS
      • Burk PG
      • Hershenbaum E
      Prevalence of cutaneous disease in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.
      • Sindrup JH
      • Weismann K
      • Petersen CS
      • Rindum J
      • Pedersen C
      • Mathiesen L
      • Worm A-M
      • Kroon S
      • Søndergaard J
      • Wantzin GL
      Skin and oral mucosal changes in patients infected with human immunodeficiency virus.
      • Sadick NS
      • McNutt NS
      • Kaplan MH
      Papulosquamous dermatoses of AIDS.
      • Arnett FC
      • Reveille JD
      • Duvic M
      Psoriasis and psoriatic arthritis associated with human immunodeficiency virus infection.
      Seborrheic dermatitis is characterized by pinkish-to-red, scaly, occasionally greasy patches and plaques over the malar areas, eyebrows, scalp, and chest; occasionally, the axillary, groin, and genital areas may be involved. Inflammation may be intense, and areas of hypopigmentation or hyperpigmentation may occur within the inflammatory patches and plaques.
      • Sadick NS
      • McNutt NS
      • Kaplan MH
      Papulosquamous dermatoses of AIDS.
      The eruption may generalize with occasional progression to erythroderma, and plaques may resemble psoriasis clinically.
      • Sadick NS
      • McNutt NS
      • Kaplan MH
      Papulosquamous dermatoses of AIDS.
      The severity and extent of disease and resistance to topically applied corticosteroids separate this entity from the common type of seborrheic dermatitis; histologic differences have also been noted.
      • Cockerell CJ
      Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects.
      • Cockerell CJ
      • Friedman-Kien AE
      Skin manifestations of HIV infection.
      • Goodman DS
      • Teplitz ED
      • Wishner A
      • Klein RS
      • Burk PG
      • Hershenbaum E
      Prevalence of cutaneous disease in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.
      • Groisser D
      • Bottone EJ
      • Lebwohl M
      Association of Pityrosporum orbiculare (Malassezia furfur) with seborrheic dermatitis in patients with acquired immunodeficiency syndrome (AIDS).
      The severity often correlates with the degree of immunosuppression.
      • Sadick NS
      • McNutt NS
      • Kaplan MH
      Papulosquamous dermatoses of AIDS.
      Seborrheic dermatitis may be the initial manifestation of HIV infection and may predate the diagnosis of AIDS by up to 2 years.
      • Sadick NS
      • McNutt NS
      • Kaplan MH
      Papulosquamous dermatoses of AIDS.
      The yeastlike fungus P. orbiculare has been associated with seborrheic dermatitis in both HIV-positive and uninfected patients, and topically or orally applied ketoconazole has been helpful for many patients.
      • Groisser D
      • Bottone EJ
      • Lebwohl M
      Association of Pityrosporum orbiculare (Malassezia furfur) with seborrheic dermatitis in patients with acquired immunodeficiency syndrome (AIDS).
      Additional therapy may include topically applied coal tar, selenium sulfide and salicylic acid shampoos, and low- and medium-potency corticosteroid creams and solutions. Control generally deteriorates in conjunction with progressive depletion of helper T cells.
      • Sadick NS
      • McNutt NS
      • Kaplan MH
      Papulosquamous dermatoses of AIDS.

      Psoriasis.

      Psoriasis affects approximately 1 to 2% of the general population and has been noted in 1.3 to 5% of the HIV-infected population; one study found psoriasiform lesions in 20% of HIV-infected persons.
      • Coldiron BM
      • Bergstresser PR
      Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus.
      • Sindrup JH
      • Weismann K
      • Petersen CS
      • Rindum J
      • Pedersen C
      • Mathiesen L
      • Worm A-M
      • Kroon S
      • Søndergaard J
      • Wantzin GL
      Skin and oral mucosal changes in patients infected with human immunodeficiency virus.
      • Duvic M
      • Johnson TM
      • Rapini RP
      • Freese T
      • Brewton G
      • Rios A
      Acquired immunodeficiency syndrome—associated psoriasis and Reiter's syndrome.
      • Sindrup JH
      • Lisby G
      • Weismann K
      • Wantzin GL
      Skin manifestations in AIDS, HIV infection, and AIDS-related complex.
      • Sadick NS
      • McNutt NS
      • Kaplan MH
      Papulosquamous dermatoses of AIDS.
      • Winchester R
      • Brancato L
      • Itescu S
      • Skovron ML
      • Solomon G
      Implications from the occurrence of Reiter's syndrome and related disorders in association with advanced HIV infection.
      Usually, the severity of psoriasis is greatest in HIV-infected persons.
      • Duvic M
      • Johnson TM
      • Rapini RP
      • Freese T
      • Brewton G
      • Rios A
      Acquired immunodeficiency syndrome—associated psoriasis and Reiter's syndrome.
      Psoriasis may be the initial sign of HIV infection and has been considered a poor prognostic indicator.
      • Duvic M
      • Johnson TM
      • Rapini RP
      • Freese T
      • Brewton G
      • Rios A
      Acquired immunodeficiency syndrome—associated psoriasis and Reiter's syndrome.
      • Harawi SJ
      • Ghossein RA
      • Kurban RS
      • Kurban AK
      Cutaneous diseases associated with HIV infection.
      The sudden onset of previously undiagnosed psoriasis or the acute worsening of preexistent disease may indicate HIV infection in patients with appropriate risk factors.
      • Duvic M
      • Johnson TM
      • Rapini RP
      • Freese T
      • Brewton G
      • Rios A
      Acquired immunodeficiency syndrome—associated psoriasis and Reiter's syndrome.
      • Harawi SJ
      • Ghossein RA
      • Kurban RS
      • Kurban AK
      Cutaneous diseases associated with HIV infection.
      Mild to severe disease has been reported among HIV-positive patients, and two clinical patterns have been described. One pattern shows discrete guttate (droplike) or large plaques, and the other is a more diffuse psoriasiform dermatitis, often associated with palmoplantar keratoderma or thickening, which culminates in generalized disease.
      • Sadick NS
      • McNutt NS
      • Kaplan MH
      Papulosquamous dermatoses of AIDS.
      The distribution may be atypical; primary involvement of the groin, axillae, and scalp is termed “inverse psoriasis.”
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      Cultures for staphylococcal, streptococcal, and yeast infection should be considered in these patients because coexistent infection may worsen the psoriasis.
      • Duvic M
      • Johnson TM
      • Rapini RP
      • Freese T
      • Brewton G
      • Rios A
      Acquired immunodeficiency syndrome—associated psoriasis and Reiter's syndrome.
      • Sadick NS
      • McNutt NS
      • Kaplan MH
      Papulosquamous dermatoses of AIDS.
      • Harawi SJ
      • Ghossein RA
      • Kurban RS
      • Kurban AK
      Cutaneous diseases associated with HIV infection.
      Investigators have hypothesized that papulosquamous disease occurs in HIV-infected patients as a spectrum from seborrheic dermatitis to psoriasis vulgaris to pustular psoriasis and Reiter's syndrome. At least for psoriasis, the underlying cause may be in the activity of CD8 cytotoxic/suppressor T cells, perhaps in response to dysfunctional or infected Langerhans cells.
      • Duvic M
      • Johnson TM
      • Rapini RP
      • Freese T
      • Brewton G
      • Rios A
      Acquired immunodeficiency syndrome—associated psoriasis and Reiter's syndrome.
      • Sadick NS
      • McNutt NS
      • Kaplan MH
      Papulosquamous dermatoses of AIDS.
      • Winchester R
      • Brancato L
      • Itescu S
      • Skovron ML
      • Solomon G
      Implications from the occurrence of Reiter's syndrome and related disorders in association with advanced HIV infection.
      • Harawi SJ
      • Ghossein RA
      • Kurban RS
      • Kurban AK
      Cutaneous diseases associated with HIV infection.
      Management of HIV-related psoriasis may be difficult because of additional treatment-related immunosuppression, and lesions may be refractory because of underlying immunoincompetence. Methotrexate therapy should generally be avoided in these patients. Corticosteroids, ultraviolet-B phototherapy, ultraviolet-A phototherapy with psoralen, and cyclosporine all create some degree of immunosuppression and must be used with caution, if at all. Ultraviolet light therapy has been associated with the new onset of KS in some of these patients.
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      Etretinate may be effective, but it can complicate the situation because presumed side effects, such as headache and increased hepatic enzyme values, could instead be the result of occult infection. Therefore, use of etretinate necessitates close monitoring. Orally administered zidovudine helps heal psoriatic lesions in some patients,
      • Fisher BK
      • Warner LC
      Cutaneous manifestations of the acquired immunodeficiency syndrome: update 1987.
      • Duvic M
      • Johnson TM
      • Rapini RP
      • Freese T
      • Brewton G
      • Rios A
      Acquired immunodeficiency syndrome—associated psoriasis and Reiter's syndrome.