Leukotriene inhibitors boost atopic dermatitis treatment

Victoria, British Columbia - Leukotriene antagonists may be beneficial when added to the armamentarium of treatments for atopic dermatitis (AD), says a study presented at the annual meeting of the Canadian Dermatology Association.

Dr. Ron Vender, associate clinical professor of medicine at McMaster University in Hamilton, Ontario, Canada, and head of the service of dermatology at St. Joseph's Healthcare System, conducted a review of seven clinical studies, performed between 1998 and 2002, to examine the clinical evidence that warrants the prescription of leukotriene inhibitors as an adjunctive therapy to treat AD.

AD has been classified as falling into two classes: mixed AD (cases associated with respiratory allergies) and "pure" AD. Pure AD has both intrinsic and extrinsic variants. In the extrinsic type, interleukin-4 is secreted by T-cells isolated from spontaneous lesions, and skin-derived T-lymphocytes express more IL-13. Because of the different immuno-pathogenesis, antileukotriene agents may be appropriate as a treatment in this subgroup of the condition, explains Dr. Vender.

"It's important to have more than one method to treat atopic dermatitis," says Dr. Vender. "We know that leukotriene antagonists have been found to be useful in asthma. Their mechanism is blocking a key receptor and therefore decreasing inflammation."

The condition is characterized by intense pruritus, as well as exacerbations and remissions. About 80 percent of children with AD eventually develop allergic rhinitis or asthma, and together these three diseases are referred to as the "atopic triad."

As a class of agents, leukotrienes are important pro-inflammatory mediators, capable of inducing airway smooth-muscle constriction, airway hyper-responsiveness, eosinophil migration, vascular permeability, edema and chemotaxis.

An exaggerated inflammatory response, characterized by a rise in IgE and eosinophilia to environmental triggers, including irritants and allergens, is common to both AD and asthma.

Dr. Vender and Dr. J. Rackal note that four randomized, controlled trials, including a total of 75 subjects (three of the trials represented a total of 43 subjects) found significant improvement in AD using zafirlukast or montelukast. The randomized trials ranged from six to 12 weeks in duration.

The literature also contained three case series that included 13 patients. Patients in those series experienced alleviation of symptoms of AD, particularly pruritus, as well as no adverse events. All trials and case series involved either zafirlukast or montelukast.

Interestingly, leukotriene receptors have also been studied as a treatment for chronic urticaria. As is the case with AD, there is pharmacological plausibility of leukotriene receptor antagonists in treating chronic idiopathic urticaria and chronic urticaria. Moreover, when cysLTs mediate asthma and allergic rhinitis, and when the cysLT receptors are antagonized, symptoms resolve. Similarly, the same process would help resolve AD. Genetic studies have indicated common chromosomal linkages between AD and asthma, according to Dr. Vender.

The alleviation of symptoms of AD will likely lead to improvement in sleep and overall quality of life, according to Dr. Vender.

"We need to conduct longer-term, placebo-controlled studies with larger samples to both provide greater understanding of leukotrienes in the pathogenesis of AD and to verify the efficacy of leukotriene inhibitors in atopic dermatitis," he says. "The research would also help us to determine the best timing and dosing for the treatment of AD."