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© 2006 SAGE Publications Skin Lesions: Mirror Images of Oral Lesion InfectionsPresented at the Fifth World Workshop on Oral Health and Disease in AIDS, Phuket, Thailand, July 6–9, 2004, sponsored by Prince of Songkla University, Thailand, the International Association for Dental Research, the World Health Organization, the NIDCR/National Institutes of Health, USA, and the University of California-San Francisco Oral AIDS Center.
The Thai Red Cross AIDS Research Centre, 104 Rajdumri Road, Pathumwan, Bangkok 10330, Thailand; nittaya.p{at}chula.ac.th
Skin lesions can be the presenting signs for HIV disease and are among the most prevalent manifestations throughout the course of HIV disease. Correlation of skin diseases and HIV disease staging has long been recognized and used to guide medical management in resource-limited settings. The purpose of this paper is to give a review of common skin infections presented in HIV-infected patients. Common skin infections presenting in HIV-infected patients include viral, fungal, mycobacterial, and bacterial infections, along with skin infestation. Key diagnostic points correlate with certain HIV disease staging for many skin diseases. These can help facilitate appropriate diagnosis and referral by health care personnel when treating HIV-infected patients who have skin lesions. Knowledge of common skin manifestations found in HIV-infected patients is essential for all health care personnel who work in the HIV field. Most skin infections presenting in HIV-infected patients can be treated effectively if the correct diagnosis and appropriate referral are made promptly.
Key Words: Oral • infections • HIV • skin
Skin manifestations are among the most frequent problems encountered by up to 95% of people living with HIV/AIDS. Some skin diseases can be the first presenting signs of HIV disease that bring patients into the medical care system. Skin infections consist of the majority of all skin manifestations in HIV-infected patients. Local impairments of the skin barrier—such as skin dryness, symptoms of itching with or without rashes, which usually leads to the itch-scratch cycle—and many skin-inflammatory diseases can occur early in the course of HIV disease. In general, the more advanced the HIV disease is, the more atypical, more protracted, and more resistant to conventional treatment the course of skin infections will be. Viral, bacterial, and fungal pathogens are common causes of skin infections in HIV-infected patients. In addition, infestation by the mite Sarcoptes scabiei is also frequently seen and can cause confusion with other skin-infectious and -inflammatory diseases. Not unlike certain oral manifestations in HIV-infected patients, some skin manifestations, including skin infections, are frequently used as indicators for patients’ immunological status, especially in the setting where testing for CD4+ cell count and HIV-1 RNA viral load cannot be performed regularly. The use of Highly Active Antiretroviral Therapy (HAART) has significant impact on the incidence of many skin diseases, with decreasing prevalence of most. However, some skin diseases—i.e., herpes zoster, eosinophilic folliculitis, mycobacterial skin infections, and cutaneous sarcoidosis—are gradually becoming recognized as signs of immune recovery. The spectrum of skin diseases seen in the future will be changed, with more malignancies expected as HIV-infected patients have longer life expectancy. Both melanoma and non-melanoma skin cancers, as seen in the general population in certain settings, are expected to increase in HIV-positive long-term survivors, even though melanoma is rare in Asian countries.
The Table
Viral infections Human papillomavirus (HPV) HIV-infected patients tend to be infected with more HPV types, including oncogenic types. HPV infection has also been shown to facilitate HIV gene expression (Gage et al., 2000). Frequent manifestations of HPV infection include multiple common warts on the hands (Fig. 1  ), facial warts, intra-oral warts, and anogenital warts (condyloma acuminata). Although intra-epithelial neoplasia of mucosal surfaces can develop more frequently in HIV-infected patients, even without the HPV types usually associated with malignancy, the role of HPV in non-melanoma skin cancers is still unclear (Maurer et al., 1997; Harwood et al., 1999). Extensive disease can often be seen when the CD4 cell count is lower than 500 cells/mm3. Treatment includes cryotherapy, CO2 laser surgery, electrocautery, podophyllin, and 5% imiquimod cream. HPV infection refractory to conventional topical treatments and recurrence can usually be anticipated.
Herpes simplex virus (HSV) HSV infection is extremely common in HIV-infected patients. HSV lesions can also be a significant risk factor for the acquisition and transmission of HIV (Hook et al., 1992). HSV can also activate and promote replication of HIV (Mole et al., 1997). With advanced HIV disease, HSV can manifest itself as very painful, persistent, progressive, clean-based ulcers (Fig. 2 ). Sometimes HSV can also present with atypical deep ulcers, verrucous or vegetative erosions, or folliculitis. Chronic ulcerating HSV lesions that last for more than one month constitute an AIDS-defining illness in HIV-positive individuals. Extensive lesions are usually seen when the CD4 cell count is lower than 50 cells/mm3. Treatment includes 7–14 days of oral acyclovir, 200–400 mg five times daily. Newer anti-herpetic agents—valacyclovir, which provides better absorption, and famciclovir, which provides longer half-life—can also be used. However, although these agents can be taken in a more convenient dose, two or three times daily, they come with much higher cost. Chronic antiviral suppressive therapy can be considered for cases with frequent relapses.
Varicella zoster virus (VZV) Usually, VZV is the cause of varicella or chicken pox, in children, and the cause of herpes zoster or shingles, in elderly people. In HIV-infected individuals, VZV can be the cause of varicella, even in adults, and can cause manifestations more severe than in normal children. Chronic verrucous or vegetative nodules can develop on the original sites of varicella lesions (Fig. 3 ). Herpes zoster in young, sexually active adults is also one of the common presenting features of HIV. Dermatomal vesiculopustular lesions, preceded by localized itching, tenderness, or burning pain, are the hallmark. In late-stage HIV disease, multi-dermatomal herpes zoster (sometimes with widespread dissemination) is often seen. Post-herpetic neuralgia is more common in HIV-infected patients. Herpes zoster may develop a few months after initiation of HAART, when the CD4 count rises to 300–500 cells/mm3 as a sign of immune reconstitution (Aldeen et al., 1998). Treatment includes 10–14 days of oral acyclovir, 800 mg five times daily, along with the use of Burow’s solution wet compression.
Fungal infections Candidiasis Cutaneous candidiasis is not more common in HIV-infected patients than in patients in general. When present, the manifestation is not different from that in normal patients and includes well-demarcated, erythematous, moist patches with satellite pustules on inter-triginous areas such as axillae, infra-mammary folds, and groins, especially in the obese patient. Treatment includes a four-week course of topical antifungal creams and keeping the affected areas dry.
Deep or systemic fungal infections
Oral lesions of histoplasmosis can be found as oral nodules or ulcers. In a large study in Argentina, about 3% of HIV patients were diagnosed with oral histoplasmosis, compared with 0.07% in controls (Hernandez et al., 2004). Palate, gingiva, and oropharynx were the most frequent locations. The importance of including histoplasmosis in the differential diagnosis of ulcerated oral lesions in immunocompromised patients is evident. Histoplasmosis, in addition, often has even more variable skin manifestations, such as psoriaform plaque, exanthem, vasculitis, or erythema multiforme-like lesions. Histoplasmosis skin lesions have been extensively studied histologically, and have showed intravascular mononuclear cells containing parasitized organisms and variable vascular luminal obliteration, which might explain the clinical presentation of vasculitis or erythema multiforme-like lesions (Kramdial et al., 2002). Treatment includes systemic antifungal agents (amphotericin, itraconazole, fluconazole) followed by secondary prophylaxis.
Mycobacterial infections
Oral tuberculous lesions, even in HIV, are uncommon but have increased in prevalence. They usually present as ulceration of the tongue or palate (Feller et al., 2005)
Viral infections Molluscum contagiosum can give the picture of pink or skin-colored, pearly papules with central umbilication (Fig. 6 ). The presentation is so typical that the name has frequently been referred to as ‘molluscum-like lesions’ when similar lesions are seen in patients with systemic fungal infections. In advanced HIV disease, lesions can be very large and sometimes reach 20 cm, called ‘giant molluscum’ (Fig. 7). Extensive lesions can be seen when the CD4 cell count falls below 50 cells/mm3. These lesions can be easily auto-inoculated, especially for facial lesions, if the patient continues shaving. Treatment includes curettage, electrocautery, cryosurgery, topical retinoic acid, and 5% imiquimod cream.
Fungal infections Dermatophyte infection is very common in the general population, and the extent of the increase in HIV infection is unclear. The manifestations can be very extensive and have unusual morphologies. However, dermatophytosis has a low morbidity and no associated mortality. There are many names for dermatophytosis, depending on which anatomical site is affected. Tinea pedis (foot), tinea cruris (groins), Majocchi’s granuloma (hair follicle), and onychomycosis (nail) are common examples. The typical presentation is pruritic, annular, erythematous, scaling plaques with central clearing (Fig. 8 ). In advanced HIV disease, the central clearing may be absent, and patients can have widespread dermatophytosis. Fungal nail infection most commonly presents as ‘distal subungual onychomycosis’, because the weakest part that facilitates fungal entry is the area under the distal part of the nail plate (Fig. 9). Although distal subungual onychomycosis is still the most common form of fungal nail infection seen in HIV-infected patients, the fungus can sometimes invade the HIV-infected patient’s nail from the proximal part of the nail plate and cause ‘proximal subungual onychomycosis’ (Odom, 1994) (Fig. 10). This unique form can be seen only in HIV-infected patients. Trichophyton rubrum is the most frequently encountered fungal pathogen in dermatophytosis. Treatment of limited infection includes four weeks of topical antifungal cream. For extensive infection or infection of soles, palms, scalp, or nails, prolonged systemic antifungal agents (itraconazole, terbinafine) are needed. Use of antifungal shampoo to affected areas can reduce the spread of lesions.
Bacterial infections Staphylococcus aureus is the most common skin and systemic bacterial pathogen in HIV-infected patients. Around 50% of HIV-infected patients show chronic staphylococcus nasal carriage (Ganesh et al., 1989). In addition, systemic neutropenia, functional neutrophil defect, and impaired skin barrier are reasons for frequent and recurrent bacterial skin infections. Treatment includes oral antibiotics (penicillin and cephalosporin groups). Topical mupirocin ointment applied nasally once daily for 7 days can reduce the frequency of recurrences.
Infestation
Not only can skin lesions be among the first presenting signs of HIV infection, but also they can frequently be the only visible sign of systemic infections or diseases. Skin lesions can harm HIV-infected patients both physically and mentally, since they are so obvious and easily recognized by the public as HIV stigmata. Skin infections in HIV-infected patients, not different from infections of other organ systems, can be caused by bacterial, viral, and fungal pathogens. Fortunately, most skin infections presenting in HIV-infected patients can be diagnosed easily and treated promptly. Knowledge of common skin manifestations found in HIV-infected patients is essential for all health care personnel who work in the HIV field.
Advances in Dental Research, Vol. 19, No. 1,
69-72 (2006)
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Abstract
Introduction
