New approaches described for common and uncommon dermatologic disorders

National report - Recent literature has suggested some new approaches to treatment for cutaneous diseases associated with rheumatologic disorders, according to Jeffrey P. Callen, M.D., professor of medicine (dermatology) and chief of the division of dermatology at the University of Louisville, Louisville, Ky.

Pyoderma gangrenosum. Results of a randomized, controlled study undertaken by Griffiths et al support considering the use of infliximab to treat pyoderma gangrenosum. Thirty patients were initially randomized to infliximab or placebo, then evaluated after two weeks. Six of 13 infliximab-treated patients had improved.

"Some people are touting infliximab as a new wonder drug for pyoderma gangrenosum, and this study demonstrated it had a statistically valid difference relative to placebo at two weeks. However, at the endpoint evaluation in this study, one-third of patients were still nonresponders," Dr. Callen tells Dermatology Times.

Patients were also allowed to continue with their conventional therapy. Two patients developed serious systemic side effects consisting of new onset congestive heart failure and fatal staphylococcal septicemia. Dr. Callen also had a patient treated with infliximab for pyoderma gangrenosum who developed an episode of staphylococcal septicemia but with a favorable outcome.

"In the spectrum of treatments for pyoderma gangrenosum, I believe infliximab should follow after more traditional therapy with immunosuppressives but may be an appropriate option to try before IV immunoglobulin or thalidomide," he says.

Cutaneous dermatomyositis. Efficacy of mycophenolate mofetil for the treatment of cutaneous dermatomyositis was described in two recent papers. An open-label retrospective analysis authored by Dr. Callen and colleagues reported that response was achieved in 10 of 12 patients with refractory disease. The other paper appeared in the neurology literature and reported that mycophenolate mofetil had a steroid-sparing effect in six of 10 patients who were being treated with high-dose corticosteroid therapy.

Adverse effects

Some significant adverse events were encountered in both series. One patient in Dr. Callen's group developed a CNS B-cell lymphoma that cleared after mycophenolate mofetil was stopped, and another patient had a sterile pyuria with treatment-limiting hepatic enzyme elevation. In the other paper, three patients developed opportunistic infections of which one was fatal.

"I suspect the latter risk may be related to the fact that these patients were on high-dose corticosteroids," Dr. Callen says.

"Methotrexate remains my treatment of choice for cutaneous dermatomyositis, but I would consider mycophenolate mofetil as a second-line intervention," Dr. Callen notes.

Cutaneous LE. Although there are no randomized, double-blind placebo-controlled trials evaluating thalidomide for the treatment of cutaneous LE, results from a number of open-label trials suggest it can be very effective. Neuropathy is the major treatment-limiting toxicity, but it can be addressed with careful dosing.

"I don't order nerve conduction studies at baseline or during treatment because I think they tend to confuse more than inform. However, I treat with a low dose of thalidomide, 50 mg at bedtime, and then decrease the frequency of administration to every other day or every third day once the disease is controlled. With such a low dose, the risk of neuropathy is decreased significantly and is possibly negligible," Dr. Callen says.

Benefit of methotrexate treatment for cutaneous LE has also been reported recently. In an open-label study published in 2005, the authors described good results administering methotrexate concomitantly with folic acid, although treatment cessation was followed by relapse.

"Interestingly, existing lymphopenia was also reversed with methotrexate treatment, suggesting it removed the immunologic cause of the lymphopenia," Dr. Callen says.