Psoriasis sufferers often feel like lepers. The skin is the body's largest organ and when it looks diseased, the evidence is hard to hide.

There are 6.4 million people in the US alone who have this immune disorder that causes affected skin cells to reproduce ten times faster than normal ones, building-up inflamed scaly lesions that shed. It generally does not kill, but engages patient and physician in a day-to-day struggle for near normalcy - for skin that does not itch, hurt, turn red and angry, and leave scales on clothing, furniture, and playgrounds. Twenty percent of those diagnosed are children. A recent survey of adults with the illness disclosed that psoriasis has driven 5 percent to consider suicide. Fifty percent said they would choose a potentially life-threatening therapy if it could clear their skin.

For Alice Gottlieb, MD, PhD, WH Conzen Chair in Clinical Pharmacology and Director of the Clinical Research Center at UMDNJ-Robert Wood Johnson Medical School, her work is truly a labor of love. Her mother, a Holocaust survivor who immigrated to this country in 1948, has spent years battling this other tough adversary, and Gottlieb has personally witnessed its impact. "People are cruel to those who look different," comments the renowned psoriasis specialist.

"Individuals with this disease are embarrassed by their appearance and are frequently discriminated against," she observes. "They are fired, or not promoted. Many pick jobs with low visibility. High school and college athletes are forced off teams. Children are left out of group activities. This is truly a life-changing condition."

Psoriasis was confused with leprosy in biblical times, Gottlieb explains. Now it's understood to be closer to rheumatoid arthritis or inflammatory bowel disease, but scientific discovery and common knowledge are still light years apart. Most people with this disease have had the experience of a handshake refused or a casual swim denied, she says.

There are many types of psoriasis, but the disease is generally described by its severity. Anywhere from 1 to 100 percent of the body can be covered, explains Gottlieb. Roughly 75 percent of affected individuals have mild to moderate disease (covering less than 10 percent of their bodies) and 25 percent have moderate to severe. The first symptoms generally appear between the ages of 14 and 35, but can surface at any age. Men and women are affected equally. The disease can be life-threatening, says the specialist, for women who are pregnant, or for those who are HIV positive, or have other severe immune system disorders.

The disease goes through cycles, flaring up, improving, going into remission and flaring again.

A major breakthrough in understanding psoriasis occurred in the mid '80s, when it was identified as an immune disorder. It is now thought that an immune system response to as yet unknown stimuli activates many T-cells (a type of white blood cell that fights infection and other disease) in the skin. This, in turn, triggers inflammation and excessive skin cell production.

Skin then reacts as if it is wounded. The body's healing process goes into high gear, producing skin cells and pushing them to the surface in two to four days, rather than the normal 28-day cycle. But the skin cannot get rid of the excess cells quickly enough, so they build up and form reddened clumps called plaques. The silvery, dead skin cells that top these clumps are the scales that slough off everywhere.

"If you can eliminate the activated T-cells, you get rid of the evidence of disease," says Gottlieb.

But how does the disease begin? The physician says that in most cases it's not known, although about half have a family history. One third share the disorder with a close relation. A genetic predisposition is often the first step, with other factors triggering its actual onset. (The National Psoriasis Tissue Bank is currently collecting - and making available to researchers - white blood cells from families with a pattern of psoriasis.)

The disease goes through cycles, flaring up, improving, going into remission and then flaring again. Strep infection, stress, skin injury, vaccinations, contact dermatitis from such products as hair coloring, and other unknown factors can trigger the cycle. Often flare-ups are unpredictable.

Mild disease sometimes responds well to medications applied directly to the skin - such as cortico- steroids, vitamin D3 ointments and coal tar. Although this is effective for some of the people some of the time, Gottlieb says that patients are often kept on topical medications long after they stop working.

Step two involves the use of artificial forms of light delivered by a light box, sometimes in combination with drugs. UVB (ultraviolet B) phototherapy is used for milder forms of the disease, and psoralen with UVA (often called PUVA) for more severe cases. Psoralen - a plant derivative applied topically or taken orally - enhances the effect of the ultraviolet light. Although often highly effective, PUVA has been implicated in the development of skin cancers, and in photo-aging.

Severe psoriasis is a beast of a different sort, and requires systemic medicines. This is the beast that researchers are tackling with renewed vigor. "Ten years ago, research on the pathogenesis of psoriasis focused primarily on affected skin cells. Today, its primary focus is the immune system," says Gottlieb.

In fact, this dramatic directional switch was due to a serendipitous finding. Patients taking the immunosuppressive drug, cyclosporine, to thwart organ transplant rejection reported that their psoriasis improved, an observation that kicked off a new chapter in research and treatment. Gottlieb says that the drug clears psoriasis 90 percent of the time, but that patients must be closely monitored and limited to one year of treatment because the powerful immunosuppressant can cause kidney malfunction, as well as other serious problems.

There are other potent and effective psoriasis drugs, but all have toxic side effects and can be used only with frequent monitoring by a physician and only for limited time periods. Many were originally developed for other conditions. Among the arsenal of medications are the vitamin A-derived retinoids such as acitretin , the drug methotrexate, often used for cancer therapy, and the sickle cell anemia medication hydroxyurea.

What was once a wasteland of drug development has now opened onto a future that looks far sunnier. Researchers such as Gottlieb and her team at the medical school's Clinical Research Center develop and test new compounds aimed at interrupting the damaging sequence of steps of an immune system gone awry. And they seem to be making some progress.

Just ask Brad Clawson, a 40-year-old park ranger at the Delaware Water Gap. Diagnosed with a mild case of psoriasis at the age of 22, he says the disease began to encompass his entire body about 12 years ago. (There is no evidence of the disease on his face.)

He has tried various topical therapies, as well as PUVA and two systemic medications, methotrexate and etretinate. He stopped using PUVA because it required him to make twice weekly trips to his physician's office for treatments - time that he could not take away from his job. The two systemic drugs worked well for him, but after short periods were discontinued because they caused abnormal blood tests. A couple of years ago, he went back to the topicals "just to keep the psoriasis bearable."

He says that his sleep is often affected by the severe itching, that he is self-conscious and is often questioned about his "bad case of poison ivy." But when he explains that he has psoriasis, "people often know what I'm talking about because someone in their family has it, too," he says.

When Clawson is away from home, he travels with a hand-held vacuum cleaner to pick up the scales. "Sometimes when I take off my shirt, it looks like snow falling," he describes.

All in all, though, he feels lucky - he had already graduated from college when the disease hit. He says that for those on athletic teams and in communal living situations, it's much harder.

His brother's psoriasis began at age 18, and affects both his face and hands. At 44, he's still unmarried. "He handles it well," says Clawson. "But let's just say that if he didn't have it, his life would be different than what it is." Both their father and a grandfather had mild cases of the disease, although no one else in their large family has been affected.

Clawson has been participating in the clinical trial of a new therapy, which is designed to inhibit T-cell activation and migration into the skin. He will come to the Clinical Research Center in New Brunswick every Tuesday for a total of three months - a drive that takes him three hours round-trip on his day off. There he receives the treatment and is closely monitored by the team.

The team at the Clinical Research Center at Robert Wood Johnson Medical School.

Left to right, Top row: Charles Oh, MD, Carolyn Hayes, Lori Reitberg, RN, Shelia Evans.
Middle row: Claudia Van Saders, RN, Joyce Morin, LNHA, FACHE, Alice B. Gottlieb, MD, PhD, Patricia Romano, RN, Ann Marie Lozano, RN, BSN, Annette Berenguer, Amelia Sherr, RN, BSN.
Front row: Galina Solodkina, MD.

"It's kind of scary to do a study of a drug that's not yet approved," he says. "I worry about the side effects and the long-term effects of the drug. I also think that maybe I'm taking potentially life-threatening medications to control a problem that is basically cosmetic.

"But I have three children, and I would do almost anything to help provide research knowledge," he states. "There are also days where I would do almost anything to control my own disease."

Gottlieb, who speaks eloquently about the plight of her patients, also serves as their advocate with the FDA. "We give patients three months on a new drug and they start to feel good. Then we have to take it away, and they worsen again. On the other hand, the test drugs are often administered in such low dosages that they have no effect. Essentially, we're asking people to stop taking a standard medicine that at least is keeping them stable, and then offering them something less effective. In these patients, we need to escalate the doses of the study drugs."

Her bench research focuses on "getting under the skin" to witness the step-by-step process that results in psoriasis lesions, and somehow, to interrupt that process at a crucial step. But for now, she tackles each patient's case as the unique entity it is.

Gottlieb walks into the room to examine Clawson on day 28 of the clinical trial he's enrolled in. She looks pleased. "You're looking a lot better, blue eyes," she says. "How are you feeling?"

"I'm feeling much better," he says quietly. "My hands and stomach are clearing." He holds out his hands for her to see. Then he looks up at her and his smile lights up the room. "That's why I'm here," she says, taking his hand.

For information on psoriasis drug trials at the Clinical Research Center at UMDNJ-Robert Wood Johnson Medical School, call Amelia Sherr, RN, BSN, at 732-418-8474.