Atopic dermatitis is a common diagnosis that presents a therapeutic challenge. Although multiple therapeutic modalities exist, there is no single monotherapy that has proven exceptional in ameliorating the symptoms of this disease. Current topical and systemic therapeutic options offer benefit but carry varying degrees of adverse effects that often limit their application. We present 3 patients with severe, recalcitrant atopic dermatitis successfully treated with omalizumab.
"The ability of some IgEs to bind to multivalent autoantigens such as HRF or DNA raised the possibility that mast cells and basophils can be activated by interacting with such an autoantigen via FcεRI-bound IgE. Given the importance of IgE in the pathogenesis of AD, asthma and other allergic diseases30-33 and preferential IgE reactivity with autoantigens in AD,34 we measured levels of IgE that reacted with dsDNA, ssDNA, β-galactosidase, and LPS in sera of AD patients. AD patients had significantly higher serum levels of ssDNA-reactive and β-galactosidase-reactive IgE than healthy controls (Fig. 4A and 4C). "
[Show abstract][Hide abstract] ABSTRACT: Monomeric IgE molecules, when bound to the high-affinity receptor, exhibit a vast heterogeneity in their ability to induce survival promotion and cytokine production in mast cells. At one end of this spectrum, highly cytokinergic (HC) IgEs can induce potent survival promotion, degranulation, cytokine production, migration, etc., whereas at the other end, poorly cytokinergic (PC) IgEs can do so inefficiently. In this study, we investigated whether IgEs recognize autoantigens and whether IgEs' binding of autoantigens correlates with difference s in HC versus PC properties.
Enzyme-linked immunosorbent assays were performed to test whether IgEs bind antigens. Histamine-releasing factor in human sera was quantified by western blotting. Cultured mast cells derived from human cord blood were used to test the effects of human sera on cytokine production.
Most (7/8) of mouse monoclonal HC IgEs exhibited polyreactivity to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), β-galactosidase, thyroglobulin and/or histamine-releasing factor. By contrast, mouse PC IgEs failed to react with these antigens. A human monoclonal HC IgE also showed polyreactivity to histamine-releasing factor, dsDNA and ssDNA. Interestingly, sera from atopic dermatitis patients showed increased reactivity to ssDNA and β-galactosidase and increased levels of histamine-releasing factor. Some atopic dermatitis patients, but not healthy individuals, had substantial serum levels of HRF-reactive IgE. Sera from atopic dermatitis patients with high titers of DNA-reactive IgE could induce several fold more IL-8 secretion in human mast cells than sera from healthy individuals.
The results show that most HC, but not PC, IgEs exhibit polyreactivity to autoantigens, supporting the autoimmune mechanism in the pathogenesis of atopic dermatitis.
"The monoclonal antibody Omalizumab binds free IgE and inhibits IgE binding to the high-affinity IgE-receptor. As Omalizumab is licensed for severe bronchial asthma, there is clinical experience from co-treatment of concomitant AD in addition to some smaller case series56,57. The Omalizumab dosing regimen of the published AD cases is highly variable, the results are incoherent, and the overall efficacy appears low. "
[Show abstract][Hide abstract] ABSTRACT: Atopic eczema, also known as atopic dermatitis, is a frequent, highly pruritic, chronic skin disease, which is typically running in flares. The traditional treatment mainly consists of the reactive application of topical anti-inflammatory agents such as topical corticosteroids and topical calcineurin inhibitors. The short term benefit of this approach is well known, but long term remission between flares is difficult to achieve. Therefore, innovative long-term treatment strategies targeting flare prevention and skin barrier stabilization are needed. We and others have shown that normal looking, non-lesional skin of atopic dermatitis patients is immunobiologially not normal but characterized by an invisible inflammation and barrier defect. This has led to the novel concept of proactive therapy, which is defined as long-term, low-dose intermittent application of anti-inflammatory therapy to the previously affected skin, together with an ongoing emollient treatment of unaffected skin. This review article describes the most important long-term treatment options for atopic dermatitis, which includes emollient therapy, the novel concept of proactive treatment, the different ultraviolet light modalities and a selection of systemic immunosuppressive drugs and biologics. Current trial data, licensed indications, off-label use and relevant side effects of the different treatment modalities are summarized.
Annals of Dermatology 08/2012; 24(3):253-60. DOI:10.5021/ad.2012.24.3.253 · 1.39 Impact Factor
"It binds free IgE but not IgE bound to FcεRI on masts cells, so in this way it sequesters free IgE without activating bound IgE and causing mast cell degranulation (Presta et al., 1993). Omalizumab has been approved by the FDA for use in severe recalcitrant asthma (Strunk & Bloomberg, 2006) and has been investigated for severe cases of atopic dermatitis with positive results (Lane et al., 2006). "
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