Systemic mastocytosis

Systemic Mastocytosis Systemic mastocytosis is a condition in which there are excessive mast cells in the bone marrow, reticuloendothelial system, GI system, bones, and skin. In patients with systemic mastocytosis, prostaglandin Dj, released from mast cells in large amounts, has been found to be the major mediator of severe episodes of vasodilation and hypotension this PGD effect is resistant to antihistamines. The addition of aspirin or ketoprofen has provided relief However, aspirin and tNSAIDs can trigger degranulation of mast cells, so blockade with Hj and H histamine receptor antagonists should be established before NSAIDs are initiated. 

Shapiro GG, Metcalfe DD Omalizumab for the treatment of unprovoked anaphylaxis in patients with systemic mastocytosis. J Allergy Clin Immunol 2007 119 1550-1551. 

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. 

Mastocytomas and diffuse cutaneous mastocytosis are further manifestations of cutaneous mastocytosis (CM) [9]. Solitary mastocytomas are common in children. Most are present at birth or develop in infancy. These lesions are flat or mildly elevated, well demarcated, solitary yellowish red-brown plaques or nodules, typically 2-5 cm in diameter. Diffuse cutaneous mastocytosis is a rare disorder characterized by diffuse mast cell infiltration of large areas of the skin that presents in infants in the first year of life. Severe edema and leathery indurations of the skin leads to accentuation of skin folds (pseudo-lichenified skin) and a peau-dbrange-like appearance. Systemic complications include hypotension and gastrointestinal hemorrhage. Infants and young children with considerable mast cell infiltration of the skin sometimes exhibit blister formation in the first 3 years of life. MPCM and other forms of CM have been classified in a consensus nomenclature (table 1) [10]. 

Whereas in children internal organ involvement (systemic mastocytosis, SM) is unusual, MPCM in adults is associated with SM in the majority of cases [10]. WHO criteria for SM consist of the major criterion of multifocal mast cell infiltrates in the bone marrow or other extracutaneous organ(s) and four minor criteria (table 2) [21] 25% or more of mast cells in non-cutaneous biopsy sections with spindle-shaped or abnormal morphology, or... 

Table 2. Criteria for the diagnosis of systemic mastocytosis [adapted from 10]...

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

Hymenoptera venom is a prominent trigger of systemic reactions. Severe and fatal reactions have been described in patients with mastocytosis [9, 30, 31]. In few cases with urticaria pigmentosa and Hymenoptera venom anaphylaxis, no sensitization could be detected by means of skin tests and determination of specific IgE antibodies [32]. However, larger series found evidence that these systemic reactions are normally IgE-mediated insect sting allergies [7,33]. 

Garcia-Montero AC, Jara-Acevedo M. Teodosio C. et al KIT mutation in mast cells and other bone marrow hematopoietic cell hneages in systemic mast cell disorders a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood 2006 108 2366-2372. Daley T, Metcalfe DD, Akin C Association of the Q576R polymorphism in the interleukin-4 receptor a chain with indolent mastocytosis limited to the skin. Blood 2001 98 880-882. 

Horan RF, Austen KF Systemic mastocytosis retrospective review of a decade s clinical experience at the Brigham and Womens Hospital. J Invest Dermatol 1991 96 5S-13S. 

Florian S, Krauth MX, Simonitsch-Klupp I, et al Indolent systemic mastocytosis with elevated serum tryptase, absence of skin lesions, and recurrent severe anaphylactoid episodes. Int Arch Allergy 43 Immunol 2005 136 273-280. 

Gonzalez de Olano D, Alvarez-Xwose I, Esteban-Lopez MI, et al Safety and effectiveness of immunotherapy in patients with indolent systemic mastocytosis present- 44 ing with Hymenoptera venom anaphylaxis. J Allergy Clin Immunol 2008 121 519-526. 

Carter MC, Uzzaman A, Scott LM, et al Pediatric mastocytosis routine anesthetic management for a complex disease. Anesth Analg 2008 107 422-427. Bonadonna R Zanotti R, Caruso B, et al Allergen-specific immunotherapy is safe and effective in patients with systemic mastocytosis and Hymenoptera allergy. J Allergy Clin Immunol 2008 121 256-257. 

Kontou-Fili K High omalizumab dose controls recurrent reactions to venom immimotherapy in indolent systemic mastocytosis. Allergy 2008 63 376-378. 

Recently, BN 52063 has been demonstrated to be effective against mastocytosis [304], a condition which was previously incurable. This suggests that PAF, as well as mast cell degranulation, may have a role in systemic mastocytosis. The injectable (pure) form of BN 52021 is much more powerful than BN 52063. Preliminary clinical investigations have shown a long and intense inhibition of ex vivo PAF-induced platelet aggregation. The injectable form is now under clinical trials in graft rejection, stroke, haemodialysis and shock. 

Sinus problems, hay fever, bronchial asthma, hives, eczema, contact dermatitis, food allergies, and reactions to drugs are all allergic reactions associated with the release of histamine and other autocoids, such as serotonin, leukotrienes, and prostaglandins. Histamine release is frequently associated with various inflammatory states and may be increased in urticarial reactions, mastocytosis, and basophilia. Histamine also acts as a neurotransmitter in the central nervous system (CNS). Upon release from its storage sites, histamine exerts effects ranging from mild irritation and itching to anaphylactic shock and eventual death. 

Histamine is formed by decarboxylation of the amino acid l -histidine, a reaction catalyzed in mammalian tissues by the enzyme histidine decarboxylase. Once formed, histamine is either stored or rapidly inactivated. Very little histamine is excreted unchanged. The major metabolic pathways involve conversion to /V-methylhistamine, methylimidazoleacetic acid, and imidazoleacetic acid (IAA). Certain neoplasms (systemic mastocytosis, urticaria pigmentosa, gastric carcinoid, and occasionally myelogenous leukemia) are associated with increased numbers of mast cells or basophils and with increased excretion of histamine and its metabolites. 

Pardini S, Bosincu L, Bonfigli S, Dore F, Longinotti M. Anaphylactic-like syndrome in systemic mastocytosis treated with alpha-2-interferon. Acta Haematol 1991 85(4) 220. 

There is epidemiologic evidence to suggest an increased prevalence of duodenal ulcers in patients with certain chronic diseases, but the pathophysiologic mechanisms of these associations are uncertain. A strong association exists in patients with systemic mastocytosis, multiple endocrine neoplasia type 1, chronic pulmonary diseases, chronic renal failure, kidney stones, hepatic cirrhosis, and ai-antitrypsin deficiency. An association may exist in patients with cystic fibrosis, chronic pancreatitis, Crohn s disease, coronary artery disease, polycythemia vera, and hyperparathyroidism. 

In patients with systemic mastocytosis who have GI symptoms owing to an excessive number of mast cells in the GI mucosa, an oral preparation of cromolyn (Gastro-crom) is effective in reducing symptoms. The benefits reflect local action rather than systemic absorption cromolyn is poorly absorbed, and only the GI symptoms are improved in the treated patients. 

Omeprazole (20 mg daily for 4 to 8 weeks) is indicated for active duodenal ulcer, GERD, and pathological hypersecretory conditions, snch as Zollinger-Ellison syndrome, mnltiple endocrine adenomas, and systemic mastocytosis. 

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