Mast cell disease

Travis WD, Li CY, Bergstralh EJ, et al Systemic mast cell disease. Analysis of 58 cases and literature review Medicine (Baltimore) 1988 67 345-368 Published erratum appears in Medicine (Baltimore) 1990 69 34. 

Escribano L. Orfao A, Diaz-Agustin B, et al Indolent systemic mast cell disease in adults immunopheno-typic characterization of bone marrow mast cells 46 and its diagnostic implications. Blood 1998 91 2731 -2736. 

Walls, A.F., Roberts, J.A., Godfrey, RC., Church, M.K. and Holgate, S.T. (1990c). Histochemical heterogeneity of human mast cells disease-related differences in mast cells recovered by bronchoalveolar lavage. Int. Arch. Allergy Appl. Immunol. 92, 233-241. 

CML, mast cell disease, renal oncocytoma, renal chromophobe carcinoma, thymic carcinoma, seminoma, gliomas... 

Asboe-Hansen, G. and Kaalund-Jorgensen, O., Systemic mast-cell disease involving skin, liver, bone-marrow, and blood associated with disseminated xanthomata, Acta haematol. 16, 273 (1956). 

Huang TY, Yam LT et al (1987) Radiological features of systemic mast-cell disease. Br J Radiol 60(716) 765-770 Khilnani MT, Wolf BS et al (1962) Roentgen features of carcinoma of the gallbladder on barium-meal examination. Radiology 79 264-273... 

Synthesis. Histamine [51-45-6] 2-(4-imidazolyl)ethylarnine (1) is formed by decarboxylation of histidine by the enzyme L-histidine decarboxylase (Fig. 1). Most histamine is stored preformed in cytoplasmic granules of mast cells and basophils. In humans mast cells are found in the loose connective tissue of all organs, especially around blood and lymphatic vessels and nerves. These cells are most abundant in the organs expressing allergic diseases the skin, respiratory tract, and gastrointestinal tract. 

Adding another layer of complexity to the regulation of mast cell activation levels in vivo is the observation that activated mast cells can respond to, and in some cases produce, a myriad of mediators that may serve to amplify FceRI-induced responses. For example, stem cell factor (SCF), the ligand for KIT, both can enhance FceRI-dependent activation of mouse or human mast cells and, under certain circumstances, can directly induce mast cell degranulation [6, 25, 62]. Thus, elevated SCF levels and/or activating KIT mutations (such as those that occur in mastocytosis) may exacerbate mast cell-driven reactions. Indeed, patients (both adult and children) with extensive skin disease associated with mastocytosis are at increased risk to develop severe anaphylaxis [63]. Moreover, it was recently reported that cases of idiopathic anaphylaxis are... 

Hibbs ML, Tarlinton DM. Armes J. Grail D. Hodgson G, Maghtto R, Stacker SA, Dunn AR Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease. Cell 1995 83 301-311. Nishizumi H, Yamamoto T Impaired tyrosine phosphorylation and Ca + mobiUzation, but not degranulation, in Lyn-deficient bone marrow-derived mast cells. J Immunol 1997 158 2350-2355. 

Mast cells are present in the normal human heart and even more abundant in diseased hearts [ 16-18,25,47]. Within heart tissue, mast cells he between myocytes and are in close contact with blood vessels. They are also found in the coronary adventitia and in the shoulder regions of coronary atheroma [20, 21], The density of cardiac mast cells is higher in patients with dilated and ischemic cardiomyopathy than in accident victims without cardiovascular diseases [25], Importantly, in some of these conditions there is in situ evidence of mast cell activation [16,34],... 

Mast cells express high-affinity IgE Fc receptors (FceRI) on their surface, contain cytoplasmic granules which are major sources of histamine and other inflammatory mediators, and are activated to release and generate these mediators by IgE-dependent and non-IgE-dependent mechanisms [1]. Disturbances either in the release of mast cell mediators or in mast cell proliferation are associated with clonal mast cell disorders including monoclonal mast cell activation syndrome (MMAS) and mastocytosis respectively, which are in turn associated with some cases of anaphylaxis [2], Molecular mechanisms have been identified which may link increased releasability of mast cell mediators and conditions leading to increased mast cell numbers [3]. Patients with mastocytosis have an increased risk to develop anaphylaxis [4, 5] and those with anaphylaxis may suffer from unrecognized mastocytosis or may display incomplete features of the disease [6-8]. 

Mastocytosis is a disorder characterized by increased numbers of mast cells in the skin, bone marrow, gastrointestinal tract, Uver, spleen, and lymph nodes [9,10]. The prevalence is unknown the incidence has been roughly estimated to be 3-7 new patients per million per year [9]. Most cases are sporadic with only a limited number (50-100) of cases with mastocytosis reported to pass from generation to generation [11], Mastocytosis presents at any age, although most cases occur during the first 2 years of life (childhood-onset) or after puberty (adult-onset) [9]. Mastocytosis in childhood often is self-limited and involves only the skin, whereas the course in patients with adult-onset disease is normally chronic and includes systemic involvement. 

In 1995, Nagata et al. [16] identified a point mutation consisting of a substitution of valine for aspartic acid in the catalytic domain of c-kit (D816V) in the peripheral blood of patients with mastocytosis and predominately myelodysplastic features. Subsequently, the same mutation was identified in adult patients with different forms of mastocytosis in tissues where mast cells are abundant, such as bone marrow, skin and spleen [17]. It is now believed that more than 90% of adults with mastocytosis have the D816V mutation, if bone marrow mononuclear cells are examined [17]. In a subset of patients, primarily those with more severe disease, the clone expands sufficiently to be detected in peripheral blood [16]. 

Systemic mastocytosis with an associated clonal hematologic non-mast cell lineage disease (SM-AHNMD)... 

Mastocytosis is recognized in most patients because of the presence of characteristic cutaneous lesions [10]. A positive Darier s sign and/or histological examination of the skin using metachromatic stains, or by immunohistochemistry using antibodies to mast cell tryptase, helps confirm the diagnosis of cutaneous disease. 

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