Chapter Title Cutaneous Manifestations of HIV Infection Carrie L. Kovarik, MD Addy Kekitiinwa, MB, ChB Heidi Schwarzwald, MD, MPH Objectives Table 1. Cutaneous manifestations of HIV 1. Review the most common cutaneous Cause Manifestations manifestations of human immunodeficiency Neoplasia Kaposi sarcoma virus (HIV) infection. Lymphoma 2. Describe the methods of diagnosis and treatment Squamous cell carcinoma for each cutaneous disease. Infectious Herpes zoster Herpes simplex virus infections Superficial fungal infections Key Points Angular cheilitis 1. Cutaneous lesions are often the first Chancroid manifestation of HIV noted by patients and Cryptococcus Histoplasmosis health professionals. Human papillomavirus (verruca vulgaris, 2. Cutaneous lesions occur frequently in both adults verruca plana, condyloma) and children infected with HIV. Impetigo 3. Diagnosis of several mucocutaneous diseases Lymphogranuloma venereum in the setting of HIV will allow appropriate Molluscum contagiosum treatment and prevention of complications. Syphilis Furunculosis 4. Prompt diagnosis and treatment of cutaneous Folliculitis manifestations can prevent complications and Pyomyositis improve quality of life for HIV-infected persons. Other Pruritic papular eruption Seborrheic dermatitis Overview Drug eruption Vasculitis Many people with human immunodeficiency virus Psoriasis (HIV) infection develop cutaneous lesions. The risk of Hyperpigmentation developing cutaneous manifestations increases with Photodermatitis disease progression. As immunosuppression increases, Atopic Dermatitis patients may develop multiple skin diseases at once, Hair changes atypical-appearing skin lesions, or diseases that are refractory to standard treatment. Skin conditions that have been associated with HIV infection are listed in Clinical staging is useful in the initial assessment of a Table 1. patient, at the time the patient enters into long-term HIV care, and for monitoring a patient’s disease progression. Once HIV infection has been confirmed, the diagnosis of The clinical stage of a patient has been shown to be certain mucocutaneous conditions in children (Table 2) related to survival, prognosis, and disease progression. and adults (Table 3) can be used to clinically stage the As shown in Tables 2 and 3, the skin examination plays a patient. The World Health Organization (WHO) clinically significant role in the clinical staging process of patients stages patients as having HIV that is asymptomatic (stage with HIV. Also, the diagnosis of these cutaneous diseases 1) or with mild symptoms (stage 2), advanced symptoms may lead to the early testing and diagnosis of HIV in (stage 3), or severe symptoms (stage 4). children and adults if recognized with other signs and symptoms of HIV infection. 173 173 HIV Curriculum for the Health Professional This module focuses on many of the most common and/or significant cutaneous manifestations of HIV; however, other sections cover several mucocutaneous manifestations in depth. To avoid duplication, we will mention them here only briefly. Viral Skin Disease Cutaneous Infection with Herpes Simplex Virus Herpes simplex virus (HSV) infection most commonly causes disease in the oral or anogenital region; however, widespread disease may be seen in immunocompromised patients (Figure 1). In adults, a relationship has been + Figure 1. Herpes Simplex Confirmed herpes simplex virus infection on the nose and observed between decreased CD4 cheek of an HIV-infected man. This patient also had similar ulcers on the genitals. lymphocyte counts and an increased incidence of cutaneous HSV. In children, herpes gingivostomatitis can be so severe that it leads to progressive, and painful orolabial, genital, or anorectal poor nutrition and dehydration (Figure 2). Chronic HSV lesions and is one of the criteria for severely symptomatic infection (present for >1 month) may manifest as severe, (WHO Clinical Stage 4) HIV infection (Figure 3). Table 2. Criteria for recognizing HIV-related mucocutaneous clinical events in children (younger than 15 years)* Clinical Event Clinical Diagnosis Definitive Diagnosis Clinical Stage 2 Pruritic papular Papular lesions with intense pruritus. Clinical diagnosis, exclude other causes, such eruptions as drug eruptions, atopic dermatitis, scabies. Fungal nail Fungal paronychia (painful, red, and swollen nail bed) or Clinical diagnosis, microscopic demonstration infections onycholysis (painless separation of the nail from the nail bed). of fungal hyphae, or culture of the nail. Proximal white subungual onycho mycosis is uncommon without immunodeficiency. Angular cheilitis Splits or cracks at the angles of the mouth, usually with Clinical diagnosis or response to antifungal surrounding erythema, and not attributable to nutritional therapy. deficiency. Extensive wart Characteristic warty skin lesions. Variants include flat, Clinical or histologic diagnosis. virus infection plantar, papular, and genital. More than 5% or body surface area or disfiguring. Extensive molluscum Characteristic skin lesions: small flesh-colored, pearly or Clinical or histologic diagnosis. contagiosum pink, dome-shaped or umbilicated papules. May have surrounding redness. More than 5% or body surface area or disfiguring. Recurrent oral Current event plus at least one previous episode in the Clinical diagnosis. ulceration past 6 mo. Aphthous ulceration, typically with a halo of inflammation and yellow–gray pseudomembrane. Herpes zoster Painful rash with fluid-filled blisters, dermatomal distribution, Clinical diagnosis, microscopic diagnosis can be hemorrhagic on erythematous background, and can with Tzanck smear, or culture. become large and confluent. Should not cross the midline. Can become disseminated. Continued on next page 174 Cutaneous Manifestations of HIV Infection Table 2. Criteria for recognizing HIV-related mucocutaneous clinical events in children (younger than 15 years)* (concluded) Clinical Event Clinical Diagnosis Definitive Diagnosis Clinical Stage 3 Oral candidiasis Persistent or recurrent, creamy white to yellow, soft Clinical, microscopic, or culture diagnosis. plaques that can be scraped off, or red patches on the tongue, palate or lining on the mouth, usually painful or tender (erythematous form). Oral hairy leukoplakia Fine, small linear patches on lateral borders of the tongue, Clinical diagnosis. Acute necrotizing generally bilateral, that do not scrape off. ulcerative gingivitis Severe pain, ulcerated gingival papillae, loosening of teeth, Clinical diagnosis. or stomatitis, or spontaneous bleeding, bad odor, and rapid loss or bone acute necrotizing or soft tissue. ulcerative periodontitis Clinical Stage 4 Chronic herpes Severe and progressive painful orolabial, genital, or Clinical diagnosis, microscopic diagnosis simplex infection anorectal, lesions caused by HSV and present for >1 mo. with Tzanck smear, or culture. (HSV) Extrapulmonary Systemic illness, usually with prolonged fever, night sweats, Positive microscopy showing acid-fast bacilli tuberculosis and weight loss. Clinical features of organs involved, such or culture of Mycobacterium tuberculosis as sterile pyuria, pericarditis, ascites, pleural effusion, from blood or other relevant specimen/tissue meningitis, arthritis, orchitis, or skin lesions. except sputum or bronchoalveolar lavage. Biopsy and histology. Kaposi sarcoma Typical appearance in skin or oropharynx of persistent, Clinical diagnosis, may need histologic initially flat, patches with a pink or purple color. May confirmation. develop into plaques, nodules, or tumors. Disseminated fungal Wide range of clinical presentations in the skin, including Histology, antigen detection, and/or culture infection (cryptococ- papules, nodules, and ulcerations. is needed. cosis, histoplasmosis, coccidioidomycosis) Disseminated Wide range of clinical presentations in the skin, including Nonspecific clinical symptoms (weight loss, mycobacterial papules, nodules, and ulcerations. fever, anemia) plus culture of atypical infection, other than mycobacterial species from tissue other tuberculosis than lung. *Adapted from 2006 WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. HSV cutaneous disease presents as small grouped vesicles (or blisters) with redness on the surrounding skin. The spread of HSV infection to other areas of the skin is common and occurs through autoinoculation or sexual contact. The typical clinical course of HSV infection includes the rupture of the blisters over the course of a week, with subsequent healing in 2 weeks; however, this course can be significantly prolonged in the immunocompromised host. The diagnosis of HSV infection can be reached through clinical examination, Figure 2. Herpes Simplex Figure 3. Large ulceration on the upper lip due microscopic identification of virally Herpes simplex virus inrection in an HIV- to herpes simplex virus infection. This patient’s infected girl. Chronic or progressive herpes ulcer had been present for more than 3 months. infected keratinocytes from the blister skin lesions are observed occasionally in cavity with a Tzanck stain, viral culture, HIV-infected children. 175 HIV Curriculum for the Health Professional Table 3. Criteria for recognizing HIV-related mucocutaneous clinical events in adults and adolescents (15 years and older)* Clinical Event Clinical Diagnosis Definitive Diagnosis Clinical Stage 2 Pruritic papular eruptions See Table 2. See Table 2.