Atopic dermatitis is a common, chronic, relapsing cutaneous disease with typical cellular and humoral immunologic abnormalities that can result in significant physical and psychological morbidity to the patient.
Atopic dermatitis typically begins in childhood and can often persist through adolescence into adulthood. Although there are a variety of treatments for
atopic dermatitis, many patients' symptoms do not improve or they have adverse reactions to medications, requiring the search for other, effective therapeutic agents. A number of inflammatory and immunological abnormalities have long been noted in patients with
atopic dermatitis. Although great strides have been made in understanding the causes, the complex pathophysiology of
atopic dermatitis is still not completely understood. Most notably, 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 production. In addition, peripheral blood mononuclear cells of patients with
atopic dermatitis produce reduced levels of
interferon-gamma spontaneously and in response to stimuli. Due to this constellation of features,
atopic dermatitis was initially viewed as a prototypical type 2 helper T lymphocyte (T(h2)) disease. These immunological findings led to a number of clinical trials with recombinant
interferon-gamma in patients who had severe, unremitting
atopic dermatitis. Treatment with recombinant
interferon-gamma was postulated to be able to correct the immunological imbalances in patients with
atopic dermatitis by decreasing serum
IgE levels,
IL-4 levels, restoring immune balance, and thereby leading to clinical improvement. Initial open-label studies, a double-blind placebo trial, and long-term open-label studies have demonstrated the clinical efficacy and tolerability of recombinant
interferon-gamma in a subset of patients with severe, unremitting
atopic dermatitis. Patients receiving treatment often had marked decreases in severity of clinical parameters:
erythema,
edema/indurations,
pruritus, excoriations, dryness, lichenification and associated reduction in total body surface area involvement. Surprisingly, treatment with recombinant
interferon-gamma did not lower serum
IgE levels refuting the hypothesized mechanism by which
interferon-gamma would bring about clinical improvement in patients with
atopic dermatitis. Instead, decreases were noted in absolute white blood cell and eosinophil counts that tended to correlate with clinical improvement. Although the exact mechanism by which recombinant
interferon-gamma brings about clinical changes in patients with
atopic dermatitis is unknown, recombinant
interferon-gamma should be considered a possible
therapy for patients with
atopic dermatitis.