Taming severe AD: With studies, literature lacking, experience often guides systemic treatment

December 1, 2009

Few controlled studies are available for the treatment of atopic dermatitis, so physicians must rely on experience.

Key Points

Dallas - With few randomized, controlled studies to guide them, dermatologists often must rely on smaller case series and their own experience when treating severe atopic dermatitis (AD) systemically, an expert says.

In trying to treat severe eczema, "I've found that there's an incredible paucity of good literature examining the use of systemic therapies," says William Abramovits, M.D., professor of dermatology, department of medicine, Baylor University Medical Center, and assistant clinical professor of dermatology, University of Texas Southwestern, Dallas.

Dr. Abramovits defines severe AD cases as those requiring some form of immune modification. "It's clinically severe, hinders quality of life and responds poorly to therapy." Although severe eczema's etiology remains unclear, Dr. Abramovits adds, one theory suggests that filaggrin mutations result in barrier disruption. When this happens, "Antigens are quickly exposed to dendritic cells, triggering a dysregulated immune response. Treatments should address barrier repair."

As for probiotics, "The jury is still out," he says. Conversely, he says that although researchers do not yet know why, children who receive heart transplants before age 1 develop less eczema.

Systemic treatments

Among systemic treatments, he says the best-studied are cyclosporine and azathioprine. Around 40 percent of patients can achieve remission while on azathioprine, Dr. Abramovits says, but many double-blinded, randomized studies show that a similar percentage will fail therapy (Meggitt SJ, Gray JC, Reynolds NJ. Lancet. 2006 Mar 11;367(9513):839-46).

Regarding mycophenolate mofetil (MMF), Dr. Abramovits says, "A retrospective study of 14 patients showed that nine were clear or almost clear (Heller M, Shin HT, Orlow SJ, Schaffer JV. Br J Dermatol. 2007 Jul;157(1):127-132. Epub 2007 May 8)." Similarly, a retrospective study of 20 patients treated with MMF showed that 17 improved. However, four patients in that study developed herpes zoster while on MMF, he adds (Murray MI, Cohen JB. Clin Exp Dermatol. 2007 Jan;32(1):23-27). Conversely, an open-label study involving 10 patients showed a mean self-assessment score in atopic dermatitis (SCORAD) improvement of 68 percent, and cytokines involved in the eczema process, including IgE, decreased in proportion to the clinical response (Neuber K, Schwartz I, Itschert G. Br J Dermatol. 2000 Aug;143(2):385-391).

Cyclosporine is the drug that dermatologists most commonly prescribe for severe eczema, Dr. Abramovits says. "Most of us use it for as short a duration as possible - up to six months." Such treatments require relatively little monitoring, he adds, "But it's very important to check on creatinine and watch for development of hypertension in these patients."

In a meta-analysis involving 602 patients, 40 percent showed clinical improvement with doses of four mg/kg per day, and 44 percent showed clinical improvement with doses of six mg/kg per day (Schmitt J, Schmitt N, Meurer M. J Eur Acad Dermatol Venereol. 2007 May;21(5):606-619. Review).

Additionally, a retrospective study of 15 patients showed that clinical improvement plateaued at 10 weeks of treatment (Lee SS, Tan AW, Giam YC. Ann Acad Med Singapore. 2004 May;33(3):311-313).