Mast cells (MCs) are physiologically activated by binding of stem cell factor (SCF) to the extracellular domains of the Kit receptor. This binding increases the proliferation and prolongs the survival of normal mature MCs, as well as intensifies the release of mediators. In mastocytosis, somatic mutations of the coding Kit gene cause autocrine dysregulation and lead to constitutive KIT activation even in the absence of its ligand SCF. Clinical symptoms are caused by MC-mediator release and/or infiltration of MCs into tissues. Aberrant KIT activation may result in increased production of MCs in the skin and extracutaneous organs. Depending on the affected organ(s), the disease can be divided into cutaneous mastocytosis (CM), systemic mastocytosis (SM), and localized MC tumors. The updated classification of WHO discriminates between several distinct subvariants of CM and SM. While the prognosis in CM and indolent SM (ISM) is excellent with (almost) normal life expectancy, the prognosis in aggressive SM (ASM) and MC leukemia (MCL) is dismal. The symptoms may comprise urticaria, angioedema, flush, pruritus, abdominal pain, diarrhea, hypotension, syncope, and musculoskeletal pain and are the results of MC infiltration and mediator release into target organs, i.e., the skin, gastrointestinal tract, liver, spleen, lymph nodes, and bone marrow. Mastocytosis differs from a lot of other hematological disorders because its pathology is not only based on the lack of normal function of a specific pathway or of a specific cell type but additionally is a proliferative disease. Currently available treatments of mastocytosis include symptomatic, antimediator and cytoreductive targeted therapies.
The conjunctiva is a common site for the allergic inflammatory response due to it being highly vascularized, having constant exposure to environmental pollutants and allergenic pollens and having a unique conjunctival associated lymphoid tissue. The primary morbidity of anterior surface conjunctival disorders that include allergic conjunctivitis and tear film disorders is associated with its high frequency of involvement rather than its severity, although the more chronic forms can involve the cornea and lead to sight-threatening conditions. Ocular allergy is associated with IgE-mediated mast cell activation in conjunctival tissue leading to the release of pre- The allergic events during AC occur following exposure to allergens mainly pollens, animal dander, and mold spores. Mast cell activation takes place in two phases: an acute phase, occurring within minutes, and a late phase, spanning from 6 to 72 h after exposure. The acute-phase reaction is due to the release of preformed (e.g,
Omalizumab (Xolair), a monoclonal antibody, is a new agent that blocks the allergic cascade at its primary step. This drug offers substantial promise for patients with moderate-to-severe, persistent allergic asthma that is not well controlled. But due to the cost of the drug, limitations on dosage, and available clinical trial data, it is not a first-line therapy. This review discusses how this drug works, which patients will be candidates for it, and the practical aspects of using it. * Dr. Lang has indicated that he has received honoraria from, carried out clinical research with, or served as a consultant for the Abbott, AstraZeneca, Aventis, Genentech/Novartis, GlaxoSmithKline, Merck, Pfizer, and Schering/Key corporations. † Dr. Kavuru has indicated that he has received grant or research support from and serves on the speakers' bureaus of the Genentech/Novartis and GlaxoSmithKline corporations. This paper discusses therapies that are experimental or are not approved by the US Food and Drug Administration for the use under discussion.
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