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CUTANEOUS SIGNS OF HIV INFECTION

Infection with human immunodeficiency virus (HIV, a small RNA retrovirus) was initially associated with homosexual transmission, but in less than 20 years has become increasingly commonly transmitted by heterosexual contact, materno–fetal transmission, and infection from contaminated blood products (iatrogenic, shared needles in drug abusers, or by accidental occupational needle-stick injury). It causes an acquired defect of cell-mediated immunity, and is associated with a vast number of patterns of cutaneous, genital, and other organ involvement, including a wide range of infections. Some of these may vary according to the route of transmission of HIV, for example Kaposi sarcoma (KS) is most frequent in homosexual transmission.

    HIV infection follows a variable course, with three main phases. After an initial asymptomatic period, there is a phase of rapidly increasing viremia, in which about half of infected individuals will have ‘viral symptoms' and a transient non-specific rash, which is usually macular and which may be associated with oral and palmoplantar lesions. In this phase, infected patients are antibody-negative on enzyme-linked immunosorbent assay (ELISA) tests. Following this, there is a phase that lasts months or years without symptoms; in this phase there is a low level of viremia, mild reduction of CD4 lymphocyte count, and antibodies are present. In the final phase, there is increasing viremia, decreasing CD4 count, and increasing symptoms with increasing tendency to infections and neoplasia such as lymphomas and KS (known as the acquired immune deficiency syndrome, AIDS).

Kaposi sarcoma

Kaposi sarcoma is one of the most specific cutaneous signs of AIDS (Fig.12.64), although a sporadic form known as classic KS also occurs unrelated to HIV infection. Classic KS usually occurs on the feet and lower legs (see Chapter 33). KS is strongly associated with human herpesvirus type 8 (HHV8) infection, and AIDS-related KS is seen predominantly in homosexual patients.

    The skin lesions are typically purplish-colored patches and plaques that may occur at any site and are often subtle initially. Initial involvement of the head and neck is common, and lesions of the palate and other parts of the oral cavity are a notable and useful diagnostic feature. Most lesions occur in patients with known HIV infection, but biopsy for histologic confirmation may be necessary to exclude other diagnoses, such as infections (discussed later). Lesions progress from patches and plaques to become nodules, and may ulcerate or cause secondary lymphedema. Other organs, such as lungs and gastrointestinal tract, may be affected.

    Other neoplastic skin lesions in AIDS include lymphomas, squamous cell carcinoma (which may occur at unusual sites, Fig. 12.65), and other papillomavirus-related cancers.

Figure 12.64 (a–e) Examples of AIDS-related Kaposi sarcoma. Lesions are usually purplish-colored patches and plaques or nodules, but may just resemble bruises or may resemble pyogenic granulomas (e). The palate (a common site) and conjunctivae may be affected as well as the skin.

Figure 12.65 Squamous cell carcinoma in the perianal area of an HIV-positive patient. The marker outlines the radiation port for radiation therapy.

Oral lesions, oral hairy leukoplakia

The oral cavity, especially the palate, is a common site for KS. Oral candidiasis is a common, but not very specific, feature in HIV infection. The combination of median rhomboid glossitis (a candidal infection discussed in Ch.26) together with a corresponding lesion on the hard palate may signify the presence of immunosuppression; it has been termed the thumbprint of AIDS, or the CIT-NIP syndrome (candidal infection of the tongue with non-specific inflammation of the palate).

    Oral hairy leukoplakia is found mainly in homosexual persons, and is probably due to Epstein–Barr virus infection. The lesions are verrucous or reticulate streaky plaques on the sides of the tongue or buccal mucosa, which may resemble lichen planus, candidiasis (which may also be present), or leukoplakia.

Cutaneous infections

Numerous infections occur with increased frequency or severity in HIV infection, especially yeast and viral infections (Figs 12.66 – 12.72). Sexually transmitted infections are common, and genital ulcer diseases appear to increase the risk of HIV transmission. Oral candidiasis is a relatively early sign, which should arouse suspicion in adults without other predisposing causes such as frequent antibiotic use. Herpes simplex virus (HSV) infections may be chronic, severe, and atypical in morphology; chronic perineal HSV is particularly suspicious, although similar atypical patterns of HSV infection also occur in patients with hematologi malignancies. Perineal ulceration may be due to HSV or cytomegalovirus (CMV) infection, although most CMV infection in AIDS is inferred from positive serology; it also affects eyes and central nervous system, or causes disseminated disease. Extensive, often facial, viral warts or molluscum contagiosum may occur; the latter may be difficult to distinguish from cryptococcosis in patients with AIDS. Extensive impetigo or dermatophytosis may occur in some patients, as well as less ordinary infections such as nocardiosis, histoplasmosis, blastomycosis, and coccidiomycosis.

    An important infection that occurs mainly in immunocompromised patients, especially those with AIDS, is bacillary angiomatosis. This is mainly due to Bartonella henselae , the cause of cat scratch disease. Its importance, apart from the close association with AIDS, is that it causes skin nodules that may resemble KS. It may also cause fever, weight loss, malaise, lymphadenopathy, and lesions of lung, brain, heart, and bone marrow in disseminated infection. Thus it may be confused with advanced-stage AIDS unless a biopsy is taken. The distinction is critical, as bacillary angiomatosis usually responds to treatment with erythromycin or azalide antibiotics.

    Severe and extensive seborrheic dermatitis is a particular feature of HIV infection. This is due to Pityrosporum yeasts, although there is some argument about whether this is quite the same as seborrheic dermatitis in HIV-negative individuals. Extensive pityriasis versicolor is also frequent.

Figure 12.66 Giant molluscum contagiosum of the scalp in a patient infected with HIV.

Figure 12.67 Molluscum contagiosum in a patient infected with HIV.

Figure 12.68 (a,b) Perianal herpes simplex infection in patients infected with HIV.

Figure 12.69 Cytomegalovirus infection in a patient infected with HIV.

Figure 12.70 Herpes zoster in a woman with AIDS. Although this looks like localized herpes simplex, the patient had several scattered lesions and zoster was confirmed by virologic testing.

Figure 12.71 Proximal white onychomycosis is a fungal infection that occurs by invasion into the proximal nail fold and growth under the nail plate. It is strongly associated with HIV infection.

Figure 12.72 Superficial white onychomycosis affects the surface of the nail plate. It is a relatively uncommon pattern of fungal nail disease in immunocompetent individuals.

Miscellaneous

Acquired ichthyosis in young adults is suspicious of HIV infection (Fig.12.73), but other diagnoses such as lymphoma must be considered. Psoriasis in HIV-positive patients may be severe and therapy-resistant, and there is an increased frequency of Reiter syndrome (discussed in Ch. 33). Severe acne may occur, but infection must be excluded as a cause of acneiform eruption.

    Folliculitis is common in HIV infection. It may be due to infections (bacteria, Pityrosporum , or other yeasts), but a particularly itchy, sterile folliculitis may also occur. In some such cases, there is marked tissue eosinophilia (HIV-associated eosinophilic folliculitis, Figs 12.74 and 12.75). The papular pruritic eruption of HIV is probably part of this spectrum of follicular lesions. This is relatively resistant to all therapies,
but may respond to UVB radiation, isotretinoin, or pentoxifylline. Scabies should be excluded, especially if eosinophilia is a feature.

    Drug reactions are particularly common and severe in HIV infection, especially to co-trimoxazole (trimethoprim–sulfamethoxazole). Some drugs used primarily for HIV also cause reactions, such as nail pigmentation due to zidovudine, and penile ulcers due to foscarnet.

    Elongated eyelashes have been described in several reports as a feature of AIDS. Elevated porphyrin levels, and less commonly porphyria cutanea tarda, occur with increased frequency in HIV infection.

Figure 12.73 Ichthyosis may occur due to HIV infection. Clinically, it resembles a rather severe version of the relatively common and benign autosomal dominant type of ichthyosis.

Figure 12.74 Eosinophilic folliculitis showing scattered lesions on the trunk.

Figure 12.75 Eosinophilic folliculitis, the non-specific, close-up morphology showing a tiny pustule with much surrounding erythema.

Treatment

Treatment of HIV and AIDS is a constantly changing field. It incorporates components of antiretroviral treatment, prophylaxis and treatment of infections, treatment of complications such as KS, and general supportive measures. Antiretroviral treatment regimens are complex and have serious side effects, so need to be carefully considered. Current guidelines suggest that treatment should be offered to all those with symptoms due to HIV infection, and usually to those with a CD4 T-cell count below 0.35 ¥ 10 9 /L or with viral load, measured as the HIV RNA concentration, of more than 55000 copies/mL. Viral load is a predictor of prognosis, and also (as the half-life is short) is a useful indicator of therapeutic response to antiretroviral infection. It is expected that viral load will be <50 copies/mL at 4–6 months after starting treatment. It is now common to use highly active antiretroviral therapy (HAART), which consists of triple therapy with two nucleoside reverse transcriptase inhibitors (NRTIs) and a protease inhibitor (PI) for asymptomatic disease, or with two NRTIs and a non-nucleoside reverse transcriptase inhibitor (NNRTI), or two NRTIs and one or two PIs (depending on the agent) for established disease. Side effects of HAART include lactic acidosis, hyperglycemia, lipodystrophy, hyperlipidemia, osteopenia, and rashes including severe Stevens–Johnson syndrome and toxic epidermal necrolysis.

    Treatments for KS include systemic antiviral therapy for the underlying HIV infection; local treatments such as radiotherapy, cryotherapy, or laser treatment; and systemic treatments with interferon or chemotherapeutic agents such as doxorubicin.

    Infections are treated with appropriate antimicrobials, but courses of treatment may require high doses and prolonged therapy. Resistant organisms may also be a feature, for example aciclovir-resistant HSV is relatively common in patients with HIV but rare in other situations.

PRACTICE POINTS

White/Cox: Diseases of the Skin, 2ed.(c) 2006, Elsevier Inc. All rights reserved.