American Foundation for AIDS Research, July 2003
Jeff Getty

Psoriasis has proved to be one of the most dramatic and intractable skin ailments experienced by people with HIV. It commonly appears first on the knees and elbows as itchy or burning inflamed reddish patches that become covered with silvery gray scales or plaque. In more severe cases, the malady can spread to 20% or more of the skin surface and be quite uncomfortable. Psoriasis is not caused by a contagious agent, though skin injury, including that caused by infections, can trigger an episode. Systemic infections as well as certain drugs represent environmental stress factors that can spark psoriasis, too.

The plaque is composed of an overgrowth of skin cells that rapidly mature and move to the surface, where they die and leave a scaly surface on top of the eruption. Psoriasis is usually a mild-to-moderate condition but can become severe and may be accompanied by psoriatic arthritis.

About 3% of Americans have psoriasis. Dermatology and HIV specialists agree that the prevalence of psoriasis among those with HIV is likely similar to or just slightly higher than in the general population. They also find that HIV can aggravate psoriasis. HIV-positive individuals with exacerbated psoriasis are prone to developing new systemic infections. Such psoriasis-induced infections, rare in persons with psoriasis alone, can trigger still more extensive psoriasis flare-ups.

When patients develop moderate to severe psoriasis, quality of life deteriorates. According to the National Psoriasis Foundation, afflicted individuals have described problems with employment, sexual activity and suicidal thoughts. The Foundation reported that 81% of psoriasis survey respondents felt embarrassed by the disease and most thought the treatments to be ineffective. Some 54% reported depression and many reported sleep disorders.

Most doctors agree that good antiviral coverage is the best treatment for psoriasis and other HIV-related skin problems. Effective use of HAART does not guarantee psoriasis will magically vanish, and standard treatments for normal psoriasis may or may not produce results in HIV patients.

HIV-related psoriasis is compounded by the fact that there are only a few doctors in the country that specialize in this area. Most AIDS care providers have little experience dealing with the condition. Patients are commonly prescribed some type of topical cortisone or a Vitamin D analog to reduce inflammation and then referred to a dermatologist with little or no training in HIV. Often the overworked dermatologists have little time to see these patients, and only prescribe the same run-of-the-mill ointments and creams. Ultraviolet light therapy three or more times weekly has become the automatic backup when topical treatments fail to reduce the inflammation on their own. Topical and oral retinoids are employed to reduce skin cell maturation and proliferation.

A last resort is high potency immune-inhibiting therapy with cyclosporin or methotrexate. Hydroxyurea is considered a safer substitute in persons with HIV. It inhibits DNA production and already is sometimes used to boost the anti-HIV potency of ddI and other nucleoside analogs. (See box for an HIV-associated psoriasis treatment algorithm.)

These therapies all have significant toxicities, which are enhanced in persons with HIV. Since such persons already face a mountain of disease- and drug-related problems, psoriasis can be quite devastating. Unless a well-informed dermatologist is available, HIV-related psoriasis could become part of a downward spiral of disease progression.

The Psoriatic Paradox
No one knows the exact cause of psoriasis. Most authorities ascribe the cause of psoriasis to overactive T-lymphocytes, whose inflammatory secretions (cytokines) increase skin cell growth in a manner that parallels wound healing. But HIV kills CD4+ T-lymphocytes, which stimulate the other main kind of T-lymphocytes, the CD8+ killer cells. In a review of the association between HIV and psoriasis, specialist Eleanor Mallon (Imperial College School of Medicine, London) concluded, "It is paradoxical that, while drugs that target T-lymphocytes are effective in psoriasis (e.g., cyclosporin), the condition should be exacerbated by HIV infection." (See E Mallon and CB Bunker, "HIV-Associated Psoriasis" in AIDS Patient Care and STDs, May 2000, pages 239-C46).

Although persons with HIV have depleted CD4 cell populations, their immune systems are overactive in many respects. Dr. John Fung, a leading transplant surgeon at the University of Pittsburgh, observed that recent HIV-positive organ transplant recipients required greater -C not smaller -C levels of immunosuppressive drugs to block organ rejection. Dermatitis, folliculitis, joint pain and arthritis all are common inflammatory symptoms associated with HIV infection.

Dr. Marcus Conant, a dermatologist and pioneer HIV specialist in San Francisco, recalled that in the early days of AIDS when antiviral medications were lacking, psoriasis was common in HIV populations, suggesting that untreated HIV patients may have a higher incidence of psoriasis. Research published in the 1980s about HIV and psoriasis indicated that patients were dying within a year or so of their psoriasis outbreaks. Reiter's syndrome and arthritic conditions were also diagnosed in untreated HIV patients in the eighties and were more common before HAART.

Too Much BLyS
These theories have led to current psoriasis treatments such as cortisone and ultraviolet phototherapy. Acitretin (Soriatane) is a standard systemic retinoid for severe psoriasis. It is often is used in conjunction with ultraviolet light, reducing the doses and side effects of both therapies while increasing overall effectiveness. The effect is synergistic, with the UV therapy inhibiting lymphocyte activation and the retinoid reducing skin cell proliferation.

Alefacept (Amevive), a new drug from Massachusetts-based Biogen, has been approved for people who need something more than topical psoriasis therapy. Amevive lowers the number and activity of memory/effector T-lymphocytes. These CD4+ and CD8+ T-cells are the quick-acting cells stored from past immune reactions. They are the most numerous type detected in psoriasis lesions. In alefacept trials, 14% to 21% of recipients largely resolved their chronic psoriasis after a 12-week course of treatment. Another 38% to 42% experienced major improvement, compared with 10% to 18% in the placebo arm. The effect remained for at least 12 weeks post-dosing.

The most common reason for discontinuing alefacept is a severe depletion in CD4 cells. The drug is not recommended for people with below normal CD4 counts, the characteristic condition of HIV infection. It is not known if alefacept is safe for HIV-positive patients, even those receiving successful anti-HIV therapy, because Biogen has conducted no trials in such populations.

Studies continue on inhibiting lymphocyte activation with Embrel and Remicade, two blockers of tumor necrosis factor (TNF) that are already on the market for other uses. Meanwhile, immunologist Michael McCune (University of California, San Francisco) suspects that some new and undiscovered factor might be the common cause of several HIV-associated inflammatory diseases.

McCune's suspicions arise from a paper published a paper last summer by William Stohl (University of Southern California). Stohl identified a new tumor necrosis factor in arthritis, lupus and HIV patients. The factor, B lymphocyte simulator (BLyS) was present in high levels in half of the HIV patients enrolled in the study. Stohl observed that patients with high HIV levels also had more BLyS in their blood. This mystery factor could be related to the skin disorders that affect people with HIV.

An anti-BLyS biological drug has been developed and is being given to lupus patients to test for safety. The research is still quite early, but McCune and Stohl wonder if this drug might help people failing anti-HIV treatment. So far, the drug has shown safety in animals and in the first human lupus study. A request for funding an AIDS pilot study has yet to be approved.

The National Psoriasis Foundation has published a helpful handbook for psoriasis diagnosis and treatment, "Psoriasis: Treatment Options and Patient Management." This handbook was the outcome of a consensus meeting held in March 2002 on the latest understanding of the disease. It can be obtained by contacting the National Psoriasis Foundation (800-723-9166). The handbook discusses different types of psoriasis, including HIV-related psoriasis, along with likely treatment strategies.

My Journey to the Skin Boutique
I first became aware of my psoriasis problem last spring when a few itchy, flaking patches of skin erupted into large annular sores that began to take over huge portions of my back, trunk, arms and legs. My initial onset was so severe that my doctor and I decided to use prednisone to stop the onslaught. This worked, and I later weaned off the prednisone, only to have the psoriasis slowly return to its former severity. A dermatologist then prescribed the usual cortisone creams and ointments. These had little or no effect.

At this point, I moved from the Bay Area to southern California and began seeing a new physician. He referred me to a dermatologist who ran a huge skin-care center in the desert south of Los Angeles.

I drove to the skin "boutique" and was amazed to find a large building with an enormous waiting room full of black leather couches. On the couches sat mostly senior citizens with a wide range of skin problems, but mostly in search of Botox. I was taken into an exam room where I was shown how an ultraviolet (UV) machine worked, and I signed up for 30 sessions. At this point, the doctor told me that psoriasis was caused by T-cells attacking the skin. When I asked her which T-cells, she said she did not know, but that it was definitely T-cells that caused the disease. I did not attempt to introduce the psoriasis pathogenesis debate at this time.

My first treatment began when I took off all my clothing and stepped into a machine the size of an English phone booth. It was full of UV lights, which were switched on for only one minute. I wore special UV-blocking glasses and had sunscreen on my nose, face and ears. As bright blue lights hummed, I closed my eyes for fear of blindness. Then I stepped out and got dressed.

Convinced that the exercise had been useless, I began checking out and noticed an older gentleman next to me. He was plunking down $600 for his Botox injections. The man's face looked quite round and puffy, as if a swarm of bees had stung it. I recall thinking to myself that surely this was southern California at its height.

After two weeks of phototherapy, my psoriasis began clearing up for the first time in a year. Almost 70% of it disappeared, and soon the doctor began advising a maintenance dose of twice a week, which is my current regimen.

I was initially shocked by the excess vanity of the patients at the skin center, as well as by the concept of the skin boutique. I now realize that much of the money from the vanity treatments likely helps support research and buys equipment for the more serious psoriasis and skin cancer conditions treated there. I do not believe that such a center could survive on HMO dollars alone. So ultimately, I think that the skin boutique approach might not be such a bad idea.
- JG

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