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OTHER NEW ATOPIC DERMATITIS TREATMENTS

Conventional atopic dermatitis (AD) treatment with corticosteroids, immunosuppressants and other medications is effective in controlling atopic dermatitis symptoms, but they have the potential to produce rather serious side effects. Since atopic dermatitis imposes tremendous social and financial costs on patients, improved drugs that reduce these costs and have fewer side effects are necessary.

Topical calcineurin inhibitors are probably the first milestone in the advancement of atopic dermatitis treatment in 50 years, offering a potentially better alternative to corticosteroids.

Some of the other recent drugs being tested for atopic dermatitis are leukotriene antagonists, monoclonal antibodies, leflunomide, recombinant interferon-gamma and intravenous immunoglobin.

Leukotriene antagonist (LTA)

Leukotrienes are metabolites of arachidonic acid and potent biological inflammatory mediators. They induce bronchoconstriction, mucous hypersecretion and increase airway vascular permeability.

LTA modulating agents have been used with success in asthma, especially in children. In vitro and in vivo data have demonstrated that LTAs may play a key role in atopic dermatitis. Clinical evidence of the use of LTA agents in atopic dermatitis is limited, but initial results have been promising. Improvement of skin symptoms in atopic dermatitis has been reported with leukotriene receptor antagonists.

Satisfactory resolution or control of atopic dermatitis has been reported with oral zafirlukast 20 mg twice daily and oral montelukast 10 mg daily, both LTAs.

Patients have generally shown good tolerance to LTAs. The most common side effects of LTAs are headaches, pharyngitis and transient raised alanine aminotransferase levels in the blood. LTAs may be more effective in atopic dermatitis patients with asthma but further evaluation is necessary.

Monoclonal antibodies

Infliximab, a chimeric monoclonal antibody, binds to a chemical signal called TNF-alpha and blocks its action. TNF-alpha is made by the body to stimulate inflammation. Blcoking TNF-alpha inhibits the migration of leukocytes and the release of inflammatory cytokines into the skin. Patients with atopic dermatitis show high levels of tissue concentrations of TNF-alpha. In a pilot study on 9 patients with atopic dermatitis, unresponsive to conventional treatment, intravenous infliximab showed a good response. However, the response was not maintained when the treatment stopped. Only two patients qualified for the retreatment phase (a second course of infliximab), allowing treatment to continue till the 46th week. However, both these patients later developed atopic dermatitis- like eruptions.

Basiliximab, another chimeric monoclonal antibody produced, largely, similar results in another study on atopic dermatitis patients.

Side effects of treatment with monoclonal antibodies can include reactivation of tuberculosis if someone already has it, infusion reactions, pancytopenia and systemic lupus erythematosus features. The approval of monoclonal antibodies for general use in atopic dermatitis treatment has to await the clinical trials they are undergoing.

Leflunomide

Leflunomide is an immunomodulating drug with anti-inflammatory and immunosuppressive properties, exhibiting an extremely long in vivo half-life. Because T cells and eosinophils play an important role in atopic dermatitis development, and long-term treatment is often required, leflunomide may be effective in severe atopic eczema. It is a well-known treatment in rheumatoid arthritis.

In a study, two patients with severe atopic dermatitis, unresponsive to systemic therapy, achieved stable remission with oral leflunomide. In one patient, the remission was total and in the other partial.

The major side effect of the drug is raised liver function enzymes, occurring in 5% of patients. Leflunomide has the potential to become a second line medication in atopic dermatitis, but more studies are needed to confirm this.

Recombinant interferon-gamma

Patients with atopic dermatitis often have an elevation of serum immunoglobulin (Ig) E levels, depressed cellular immunity, elevated blood eosinophilia, and increased interleukin (IL)-4 productions. In addition, atopic dermatitis patients produce reduced levels of interferon-gamma (an inflammatory signal made by immune system cells in the body) spontaneously and in response to stimuli. These and other immunological findings led to clinical trials with recombinant interferon-gamma in severe unremitting atopic dermatitis patients. Interferon-gamma was expected to correct the immunological imbalances in atopic dermatitis patients by decreasing serum IgE levels, IL-4 levels, restoring immune balance, and thereby leatopic dermatitising to clinical improvement.

Initial studies demonstrated the clinical efficacy of recombinant interferon-gamma. Patients showed significant reductions in severity of erythema, edema, pruritus, dryness, lichenification and body surface area involvement.

Surprisingly, interferon-gamma did not lower serum IgE levels as expected. Instead, decreases were noted in absolute white blood cell and eosinophil counts that tended to correlate with clinical improvement.

The longer studies showed that interferon-gamma is well tolerated by patients. The most common side effect was flu-like symptoms, which was easily treatable. Patients with lowest serum levels of IgE and blood eosinophil seem to be best suited for this treatment. Although it needs subcutaneous administration, it looks like a good treatment for adults with severe atopic dermatitis, unresponsive to other treatments.

Intravenous immunoglobin(IVIg)

IVIgs show various immunomodulatory and anti-inflammatory properties. Although it has been used in autoimmune blistering disorders, how it works is unknown. IVIg has been effective in a few atopic dermatitis cases when large doses with prednisolone were used. In small doses, it was ineffective. Side effects were mild and appeared 30 minutes to an hour after the first infusion and included headaches, chills, fever, nausea and vomiting. Since IVIg is made from a pool of plasma from thousands of donors, it carries a risk of infection if it is not processed properly.