TREATMENT ISSUES: The Gay Men's Health Crisis Newsletter of Experimental AIDS Therapies - Volume 7, Number 6 -- July 1993
John Chism

In HIV-infected people, skin disorders caused by viruses are common. This article reviews viral skin diseases in AIDS and emphasizes that early detection and treatment are the best course of action.

MOLLUSCUM CONTAGIOSUM

Molluscum contagiosum is caused by a pox virus. Molluscum are benign, pimple-like lesions which occur in both children and adults; the primary sites of involvement for adults are the face, buttocks and genitals. In appearance, molluscum are smooth translucent bumps, sometimes flesh-colored, sometimes yellowish or pearly. The lesions have a sack-like core of viral material. They may cause mild discomfort and cosmetic frustration, but are neither acutely painful nor life-threatening.

Molluscum is believed to be transmitted by both sexual and nonsexual routes, although epidemiological data are inconclusive. Since molluscum usually goes away on its own in healthy people, those with it often do not see a doctor. Furthermore, molluscum is not reported to public health authorities like other sexually transmitted diseases. Before AIDS, molluscum was primarily regarded as a childhood disease transmitted through ordinary child's play.

Strong indirect evidence from studies of prostitutes and those attending STD clinics supports the belief that molluscum is transmitted sexually.(1) Other reports suggest that it may be spread by nonsexual routes such as baths, swimming pools, sharing towels, and contact with infected family members. Nonsexual transmission is uncommon in North America and Europe, though, except among children. The limited epidemiologic data which do exist indicate that reported molluscum infections have increased eleven-fold since 1966,(2) are five times more likely to occur in men than women, and two to four times more frequent in whites than blacks.

In HIV-infected people, molluscum lesions can number in the hundreds or thousands, (3) which is uncharacteristic of molluscum in those uninfected with HIV. In uninfected people, or those with few lesions, molluscum is treated by physical destruction of each lesion. Several techniques are used, although none has been evaluated in controlled studies. Scraping or scooping the lesion off the skin through minor surgery is a common method. Cryotherapy, freezing the lesion with liquid nitrogen, is another method of direct physical destruction. Often, the affected area is treated with chemicals (such as phenol, silver nitrate, trichloroacetic acid, or iodine) or cauterization after physical removal of the lesion.

However, physical removal of each lesion-is often impractical in people with AIDS because multiple lesions may cover the face or genital areas. When surgical techniques are impractical, there are no effective drugs to treat and cure molluscum in people with AIDS. Topical treatment with podophyllin, canthraradin, retin-A, silver nitrate, phenol, or trichloroacetic acid may be effective to a very limited degree. Systemic treatment with oral isoprinosine, a purported immunomodulator available in some buyers' clubs, does not appear effective for molluscum, despite encouraging preliminary results from Sweden.

HERPES SIMPLEX VIRUS

Herpes Simplex Virus (HSV) can produce recurrent, painful lesions on the genitals, anus, mouth, and face in people with HIV. HSV is sexually transmitted. It enters the body through broken skin or the mucosa. Although serologic tests are available to determine if you have been infected by HSV, the vast majority of people with AIDS are already infected. HSV infections have a fundamental connection to AIDS: chronic HSV lesions on the skin and mucosa are an AIDS-defining diagnosis and HSV genital lesions are believed to be a risk factor for subsequent or concurrent HIV infection.(4)

Once HSV enters the body, it remains latent in the nervous system for the life of the individual. Periodically, HSV may reactivate and produce painful lesions which can last several weeks. The lesions are blister-like ulcers on outer layers of reddened skin or mucosa.

The lesions can be extremely painful. HIV-infected people have a much higher rate of HSV recurrences; often HSV outbreaks may become chronic. Additionally, HSV lesions in HIV-infected people can grow much larger than those in healthy people. A lesion can grow to cover the entire buttocks, for example, or two thirds of a patient's face.(5) Sometimes the entire body is covered with small ulcers.(6) Although HSV skin lesions are not life-threatening, the pain and suffering they cause can be substantial. (HSV can also cause life-threatening infections of the brain, lungs, and GI tract.)

Acyclovir (Zovirax, Burroughs Wellcome) is an effective, approved therapy to treat and prevent HSV lesions. The drug comes in several forms: the topical, cream form is used for milder outbreaks and the pill or intravenous forms are used for more severe illness. Many people with HIV are placed on chronic, suppressive oral acyclovir therapy to prevent HSV outbreaks. Recently, HSV strains resistant to acyclovir have emerged. In these cases, foscarnet (Foscavir, Astra) is an effective, but more toxic, alternative. Foscarnet is given intravenously. In addition, research is underway to find better treatment options for HSV and acyclovir-resistant HSV.

HERPES ZOSTER: "SHINGLES"

Shingles is another viral skin disorder that occurs in HIV-positive people. It is caused by the Varicella Zoster Virus (VZV), the herpes virus responsible for childhood chicken pox. After a childhood episode of chicken pox, VZV is not eliminated from the body. It remains latent for years in the nervous system. Although VZV remains in the body through adulthood, most adults never experience a reactivation of the virus. However, reactivation occurs in approximately 10 to 20 percent of adults who had childhood chicken pox.

Reactivation of latent VZV is more common in HIV-positive people. A small number go on to experience three or more outbreaks of shingles. Early detection and treatment of shingles often resolve the problem in a matter of days, but delays in treatment can extend treatment to more than three weeks, and increase the likelihood of residual pain.

The classic symptom of shingles begins as a slight sunburn-like feeling on the skin, often around the upper torso, upper arms, or face, which progresses within a day or two to a painful outbreak of reddened skin and fluid-fulled red sores. The pattern of the outbreak on the skin may delineate the track of the affected nerve. In HIV-negative people, the outbreak is usually confined to a small area of the body and often affects just one side of the body. In HIV-positive people, the outbreak can affect both sides and be much more extensive. HIV-related shingles is extremely painful. While skin manifestations of VZV are not life-threatening, the virus can involve the eye, resulting in blindness. Also, VZV can spread to the lungs or the central nervous system, although this is rare.(7)

Treatment for shingles is oral or intravenous acyclovir. Axsair or Zostrix creams can be applied topically to alleviate pain and infection with bacteria.(8) Intravenous foscarnet can be used in acyclovir-resistant VZV. Furthermore, experimental drugs, most notably Bv-ara-U and 882C, have shown preliminary success against VZV.

HAIRY LEUKOPLAKIA

Oral hairy leukoplakia (OHL), once thought unique to HIV-positive people, occurs in other patients who are immune-suppressed, such as renal transplant patients. The disease was discovered in 1984 and manifests itself as white, plaque-like growths on the sides of the tongue or raised lesions with a corrugated texture.(9) The tongue isn't the only site of occurrence, but it is the most common. OHL can also occur in other parts of the oral mucosa, but it is never found on other mucous membranes outside the mouth. Although the exact cause of OHL is not yet determined, the Epstein-Barr Virus (EBV), another herpes virus, plays a critical role. The presence of EBV in a OHL lesion is a requirement for diagnostic purposes. However, diagnosis of EBV in OHL lesions requires in situ hybridization, a technique not routinely available.

While OHL is not life-threatening, nearly all patients with HIV who come down with it are likely to develop other AIDS-related symptoms later.(10) There is controversy among treating physicians whether to treat OHL. Since OHL is usually painless and not life-threatening, patients often request treatment for cosmetic reasons. Systemic antiviral treatment with acyclovir or ganciclovir has been suggested. Often physicians are reluctant to begin systemic antiviral treatment for OHL alone. Other reports suggest the use of topical treatment, such as retin-A and podophyllin in cases where systemic antiviral therapy is unwarranted.(11)

GENITAL WARTS

There are at least 50 related Human Papilloma Viruses, three groups of which lead to various diseases of the genital area. HPV 6 and 11 cause anal and genital warts; HPV 16 and 18 are highly associated with invasive cervical cancer; HPV 31, 33, and 35 have a lower, but still significant, connection to cervical cancer. [Editor's note: See Treatment Issues Vol. 6, No. 7, the special issue on women and AIDS, for a review of HPV.] (12)

HPV genital warts can occur on virtually any part of the vagina, penis, or anus, and are usually visible, cone-like, flesh-colored growths. Warts can also grow inside the vagina, anus, or urethra, making detection more difficult. Genital warts may also be subclinical that is, they are invisible until painted with acetic acid. Individuals with subclinical warts are infectious, despite the absence of obvious growths. Therefore, individuals who have had sex with someone with genital warts should be examined by a physician, even if they have no obvious signs of infection.

Genital warts are treated by surgical removal, topical treatment, or by local injections of alpha-interferon. HIV-infected people often have multiple warts, making surgical removal difficult. Therefore, alpha-interferon injections are increasingly common. However, warts can recur despite treatment. Optimal treatment to prevent or reduce recurrences in HIV-infected people has not yet been defined.

CONCLUSION

While many viral skin disorders common in HIV-infected people are not ordinarily life-threatening, they can cause significant pain, illness, and cosmetic frustration. In some cases, viral skin diseases can spread to infect other parts of the body, possibly resulting in life-threatening conditions, like HSV encephalitis. The early detection, prophylaxis, and treatment of skin diseases is clearly the best approach to take.

REFERENCES

1. Postlethwaite R. Archives of Environmental Health. 1970. 21:432.

2. Becker TM, et al. Sexually Transmitted Disease. 1986.13:18.

3. Stone MS, Lynch PJ. in Principles and Practice of Dermatology. Editors: W. Mitchell Sams Jr and Peter J. Lynch. Churchill Livingstone. 1990.

4. Holmberg SD, Stewart JA, et al. JAMA. 1988, 259(7):1048-51.

5. Cockerell CJ. in AIDS and Other Manifestations of HIV Infection. Editor: Gary P. Wormser. Raven Press. 1992.

6. Corey L. in Sexually Transmitted Agents. Editors: Holmes KK, et al. McGraw-Hill. 1990.

7. Cockerell CJ. in AIDS and Other Manifestations of HIV Infections. Editor: Gary P. Wormser. Raven Press. 1992.

8. Seattle Treatment Education Project. Skin Manifestations Associated with HIV Infection. [chart].

9. Greenspan D, et al. Lancet. 1984;2:331-4

10. Greenspan JS, Greenspan D. in AIDS and Other Manifestations of HIV Infection. Editor: Gary P. Wormser. Raven Press. 1992.

11. Greenspan JS, Greenspan D. Oral Surgery, Oral Medicine, Oral Pathology. 1989; 67:396-403.

12. Shah KV. in Sexually Transmitted Agents. Editors: Holmes KK, et al. McGraw-Hill. 1990.

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