Association between topical calcineruin inhibitors, skin cancer?

August 1, 2006

Philadelphia - Atopic dermatitis is a chronic or chronically recurring, usually pruritic and clinically variable skin disease associated with atopy.

Philadelphia - Atopic dermatitis is a chronic or chronically recurring, usually pruritic and clinically variable skin disease associated with atopy.

Mainstay treatments for this skin affliction, which, depending on symptom severity, ranges from systemic and topical corticosteroids, fatty creams and ointments, antihistamines, phototherapy, as well as regulation of diet.

Dr. Margolis and his team of researchers conducted a case-control study to investigate whether those patients who used topical calcineurin inhibitors in the past few years were more likely than those patients with other dermatologic diseases to develop nonmelanoma skin cancer. Between 2002 and 2005 using the ambulatory care population of patients seen at large academic dermatology practices, Dr. Margolis randomly selected 1,000 cases of patients with histologically confirmed nonmelanoma skin cancer, and compared them to 4,000 randomly selected control patients who were suffering from inflammatory dermatitis. All exposure data were obtained from the patients in the study using a self-administered questionnaire.

Out of the total number of patients surveyed, 70.7 percent responded and 25.7 percent reported exposure to topical calcineurin inhibitors. Topical calcineurin inhibitor exposure was 14.4 percent for the nonmelanoma skin cancer cases and 30.7 percent for the control patients with inflammatory disease.

When comparing those patients with nonmelanoma skin cancer and those without, results showed that the unadjusted odds ratio was 0.38 and the adjusted (age, gender, previous nonmelanoma skin cancer and history of atopic dermatitis) was 0.54.

"We saw that the prevalence of topical calcineurin inhibitor exposure was less in our patients with nonmelanoma skin cancer than in the control patients. Nearly the same unadjusted and adjusted effect estimates were seen if only those patients with a history of atopic dermatitis were included in the analysis, and if nonmelanoma skin cancers were separated into basal cell carcinomas and squamous cell carcinomas," Dr. Margolis says.

Dr. Margolis also noticed that if the exposure of the topical calcineurin inhibitors was limited only to pimecrolimus, then the adjusted effect was 0.66, and if limited only to tacrolimus, the adjusted effect sank to 0.43. Also, the apparent protective effect of these topical calcineurin inhibitors increased with the use of an increasing number of tubes.

Dr. Margolis says, "From these results, the use of topical calcineurin inhibitors is not associated with an increased risk of nonmelanoma skin cancer. In fact, a protective effect may be present, which demonstrates a dose and potency response."

Tacrolimus is an immunosuppressive drug and its original sole use was to prevent organ transplant rejection, given orally or by injection. Pimecrolimus is very similar to tacrolimus in its immune modulating and anti-inflammatory properties. Pimecrolimus is approved for the short-term and long-term treatment of atopic dermatitis in patients that are more than 3 months of age. In general, both medications are used in those patients who respond poorly to conventional therapies (emollients, topical and oral corticosteroids, antibiotics and phototherapy), and/or are suffering from side effects from conventional therapy.