INTRODUCTION
Atopic Dermatitis (AD), or eczema, is a chronic inflammatory skin disease that is a significant cause of morbidity, quality-of-life impairment, and health-care costs. It is seen more commonly in children but a recent population-based study of US adults found the prevalence of adult eczema to be 10.2%.1 It follows a relapsing and remitting course. Known precipitants of AD are heat, stress, hormones, and infection.2 It has been suggested that AD is a cutaneous manifestation of an autoimmune disorder or atopic diathesis that may also present as asthma and allergic rhinitis.
The majority of patients with AD can achieve clinical improvement with conventional topical therapies, phototherapy, and emollient use.3 However, there is a subset of patients for which these therapies are unable to control the disease. In these cases, systemic immunomodulators are used in both children and adults. The most common include: cyclosporine, methotrexate, mycophenolate mofetil (MMF) and azathioprine, however none of these are FDA approved for the treatment of atopic dermatitis.4,5 This report summarizes the evidence for use of MMF in the treatment of AD for both children and adults.
Immunopathophysiology of Atopic Dermatitis
Atopic Dermatitis is thought to be predominantly mediated by helper T-cell subtype 2 (Th-2) and Th-22 immune responses.6 The Th-2 cytokines IL-4, IL-5, and IL-13 stimulate immunoglobulin E-dependent reactions that activate mast cells and eosinophils. It has been observed that many patients with AD have elevated total immunoglobulin E (IgE) levels. Additionally, the level of IgE present appears to correlate with disease severity.7 This Th-2 immune pathway is implicated in allergic diseases. Significantly increased Th-22 cells, which produce IL-22, are also found in AD skin lesions that also positively correlate with disease severity.8
Subsequent studies have demonstrated increased Th-17 cells within acute AD skin lesions. The percentage of Th-17 cells in the peripheral blood also correlates with clinical severity.9 These cells produce IL-17, IL-22 and interferon-gamma and are involved in the regulation of antimicrobial peptides in keratinocytes. Patients with AD have a reduction of these peptides which is thought to be one of the reasons for their increased susceptibility to skin infections.10
Severe Atopic Dermatitis
Severe AD refers to the presence of widespread dermatitis that significantly interferes with daily activities and quality of life of the affected patient and family. In the vast majority it can be controlled with topical treatments along with avoidance of known trigger factors. In persistent severe disease more aggressive systemic therapy is warranted. It includes phototherapy, systemic immunosuppressants and emerging biologic treatments. Examples of the established effective immunosuppressant therapies are methotrexate, cyclosporine, azathioprine, and MMF.3
Mycophenolate Mofetil
MMF is a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH) preventing de novo purine synthesis.11 Moreover, MMF is a potent inhibitor of the type II isoform of IMPDH, which is expressed in activated B and T cells.12 Therefore, MMF selectively inhibits B and T lymphocyte proliferation as they lack a purine salvage pathway and rely solely on de novo purine synthesis. MMF is used in the management of patients with organ transplants, but is now frequently used off-label in the treatment of some autoimmune diseases.13
The first use of MMF for refractory AD was described in 1999.14 Since then, multiple studies in both children and adults have
