Treatment of recalcitrant atopic dermatitis with omalizumab
ABSTRACT 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.
- SourceAvailable from: Marianna Kulka
Allergic Diseases - Highlights in the Clinic, Mechanisms and Treatment, 03/2012; , ISBN: 978-953-51-0227-4
- "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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- "In the two positive studies, doses corresponding to recommended, according to individual weight and IgE level, were used except for a 13-year-old child with a serum IgE level of 6120 IU/mL who was treated with a 450 mg dose. The level of total IgE appeared a critical factor, considering that the three patients in the unsuccessful study had a mean starting level of 17.600 IU/mlL(Krathen et al 2006) compared with a mean level of 3600 IU/mL in the pediatric study (Lane et al 2006), and of 1060 IU/mL in the study on adults and children (Vigo et al 2006). However, the available data on omalizumab in AD cannot indicate the optimal level of IgE for predicting a positive response to treatment and, as noted by the authors of the studies, well-designed controlled trials are needed to explore such issue, comparing patients with different IgE levels. "
ABSTRACT: IgE antibodies are a pivotal factor in pathophysiology of allergic diseases, and the possibility of reducing their level by anti-IgE has long been envisioned. Following several attempts, an effective biologic agent was obtained with the recombinant humanized mono-clonal antibody (rhuMAb)-E25, known as omalizumab. A number of controlled clinical trials demonstrated its efficacy and safety in the treatment of severe allergic asthma uncontrolled by standard drug treatment with maximal recommended doses, and treatment with omalizumab is currently included in international guidelines on asthma management. Other studies reported a clear effectiveness also in allergic rhinitis, but the cost of the anti-IgE treatment suggests its use in patients with rhinitis concomitant with asthma. Other indications to be further investigated are skin disorders such as atopic dermatitis and IgE-mediated urticaria, as well as adverse reactions to foods, with a particularly important role in preventing food-induced anaphylaxis. Finally, there are data indicating the usefulness of omalizumab when used in combination with allergen specific immunotherapy, in terms of reducing the adverse reactions to treatment and increasing the clinical efficacy.Targets & therapy 04/2008; 2(1):67-73. DOI:10.2147/BTT.S1800
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ABSTRACT: Actions of antiallergic drugs depend on their ability to inhibit a particular stage of allergic reaction and to control symptoms of allergic inflammation. Drugs effective in early stage of allergic reaction prevent allergic cascade by acting on dendritic cells, by means of DNA-based therapies resulting both in down-regulation of T-helper cell type 2 (Th2) cytokine profile release and immunoglobulin E (IgE) production, or by blocking IgE mediated activation of mastocytes and basophiles using monoclonal anti-IgE antibodies. Adhesion molecules and cytokines are also a potential target for therapeutic intervention in allergy. The relationship between drug concentration and pharmacologic response or effect is the essence of clinical pharmacology and the major mechanism of this relationships is that drugs or chemicals bind to or interact with macromolecules on cell surfaces (receptors) or in the cytoplasm to produce the effect. After receptor binding, the drug can activate and/or intensify a normal physiologic function and is termed an agonist, such as b2-receptor agonists and corticosteroids or can inhibit any intrinsic activity by competing for endogenous regulatory substances at the receptor and are called antagonists, such as antihistamines and anticholinergics. Through molecular biology techniques, most of the receptors for b2-agonists, corticosteroids, H1 antihistamines, anticholinergics, antileukotrienes (montelukast, pranlukast, zafirlukast) as well as enzyme inhibitors (methylxanthines, zileuton), which are of interest for asthma and allergy treatment, have been identified and described, and much is still being learned about their molecular activity and interactions.