Systemic mastocytosis is characterized by hyperplasia of mast cells that, in most cases, it is benign and no tendency to neoplastic progression. Since human mast cells originate from pluripotent bone marrow cells (CD34 +), migrating in the form of mononuclear precursors positive for c-kit and stained metachromatic and subsequently undergo proliferation and maturation prostate specific hyperplasia is generally detectable only in the bone marrow and normal peripheral distribution sites, such as skin, gastrointestinal mucosa, liver and spleen. Mastocytosis can affect all ages and slightly higher incidence in males. The prevalence of systemic mastocytosis is still unknown and the existence of a familiarity has not been demonstrated.

Classification, pathophysiology and clinical manifestations

A recent attempt at classification of systemic mastocytosis requires the existence of four forms:

Indolent type with skin manifestations, circulatory collapse, peptic ulcers, malabsorption, skeletal lesions, hepatosplenomegaly or lymphadenopathy. This form, known as benign or indolent "is by far the more common and does not appear to change the normal life expectancy. When asked about a diagnosis of benign systemic mastocytosis, the evaluation of the patient must be especially careful, since the clinical findings may indicate the onset of possible complications and influence the therapeutic course.

Type II Associated with hematological disorders is of a nature that myelodysplastic myeloproliferative. This type of systemic mastocytosis is associated with hematologic disorders, in the sense that the underlying disease by dismielopoiesi a frank leukemia.

Type III Aggressive, either by itself or as mastocytosis with eosinophilia, lymphadenopathy. In this form there is a large aggressive systemic mast cell proliferation in some parenchymatous organs such as liver, spleen and lymph nodes in some subjects is also a marked eosinophilia. The prognosis of this form is unfavorable.

Type IV Leukemia Mastocytosis, is the rarest form, but its course is invariably fatal.

Signs and symptoms.

In systemic mastocytosis type II and IV there is a point mutation of the tyrosine kinase c-kit, respectively, in leukocytes and mast cells. Mastocytosis in type I and III there is an excessive production of mast cells in microanibiente of c-kit ligand (stem cell factor) that in the type III may represent an autocrine mechanism. The clinical manifestations of systemic mastocytosis characterized by a complication of leukemia are caused by tissue infiltration by a large population of mast cells or the tissue response to this mass, and by the release of chemical mediators with effects both locally and systemically. The symptoms induced by chemical mediators are itching, flushing of the face (flushing) palpitations, circulatory collapse, cramping abdominal pain and recurrent headache. The cell hyperplasia occurs in the skin with the appearance of small reddish maculopapular (urticaria pigmentosa) and determines the onset of bone pain and malabsorption. The fibrotic lesions induced by mast cells are restricted to the liver, spleen and bone marrow and are likely related to the functional characteristics of mast cells developed in those organs, which are different from those of mast cells that develop in sites not affected by fibrosis such as skin or gastrointestinal tissue. However, studies performed with immunofluorescence techniques on bone marrow and skin lesions have shown the existence of a single phenotype with cell epitopes by tryptase, and carboxypeptidase from chimasi A.
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Urticaria pigmentosa skin lesions respond to trauma with itching and erythema (Darier's sign). The incidence of these injuries is estimated to be approximately 90% in indolent systemic form. About 1% of patients with systemic mastocytosis has skin lesions similar to latte-colored spots and areas of erythematous patches with telangiectasia (persistent erythematous macular telangiectasia). At the level of the upper gastrointestinal tract, the histamine-dependent hypersecretion (with subsequent development of gastritis and peptic ulcer) is the most common clinical problem. In the lower gastrointestinal tract the onset of diarrhea and abdominal pain are attributable to the increased motility caused by mediators released from mast cells, and these symptoms may be aggravated by malabsorption resulting in malnutrition and osteomalacia. Periportal fibrosis due to infiltration of mast cells and eosinophils may sometimes give rise to portal hypertension and ascites. In some patients, flushing and circulatory collapse are associated with recurrent idiosyncrasy against non-steroidal anti-inflammatory drugs, even when administered at low doses. The nature of neuropsychiatric disorders most obvious is the decrease in short-term memory and the onset of a migraine-like headache. Patients with any form of systemic mastocytosis may show an exacerbation of clinical symptoms after ingestion of alcohol, consumption of narcotic drugs that can interact with mast cells and recruitment of non-steroidal anti-inflammatory drugs.

Diagnosis

Although in most cases the diagnosis can be suspected on the basis of the history and physical examination, diagnostic confirmation requires running some laboratory tests and histological examination. The 24-hour urine collection for determination of histamine, its metabolites and PGD2 delL3 the diagnostic approach is a less invasive alternative (although the positivity rate is lower, is represented by the assay of plasma histamine or neutral protease produced by mast cells and tryptase. Further investigations must be based on the type of clinical manifestation may be the scan of the hip, in performing an endoscopy or radiography or computed tomography (CT) scan of the upper gastrointestinal tract and small intestine, and in a neuropsychiatric evaluation with EEG in the presence of urticaria pigmentosa histological examination is essential but the diagnosis of systemic mastocytosis requires that more organs are involved, in most cases, therefore, diagnostic confirmation can only be achieved through a marrow biopsy.

Therapy

The treatment of systemic mastocytosis depends on the predominant clinical manifestations: shows the anti-H1 antihistamines for the itching and flushing, the anfistaminici anti-H2 or proton pump inhibitors for gastric acid hypersecretion, the cromolyn sodium oral for diarrhea and abdominal pain and anti-inflammatory drugs for the flushing associated with cardiovascular collapse, where a failed conventional therapy with antihistamines and anti-anti-H1 H2. The administration of systemic glucocorticoid appears to decrease the malabsorption. The headaches are usually treated with the usual drugs used for migraine. To alleviate the vasomotor reactions was employed ketotifen in patients who can not tolerate NSAIDs and in patients with intractable bone pain or headaches. The effectiveness of interferon in systemic mastocytosis is controversial and it may depend on the difficulty of administering an adequate dose in some patients, because of side effects. Chemotherapy is not indicated in patients with mastocytosis benign and does not appear to prolong the life expectancy of patients with mastocytosis with leukemia, it is rather useful in the form associated with haematological disorders and aggressive systemic mastocytosis.

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