Mastocytosis are rare diseases. They affect both children and adults, all ethnic groups regardless of gender.
Mastocytosis is a rare heterogeneous group of disorders characterized by accumulation or abnormal proliferation of mast cells (MC) in one or more organs. Mast cells are part of the cells involved in allergic reactions or IgE-dependent in defending the body against infections and thus have a negative role or beneficial for the body. If the mast cell multiplies in an exaggerated manner (abnormal growth) is then responsible for mastocytosis, whose mechanism is generally associated with the presence of a point mutation and acquired activating receptor called KIT, which is the main receptor growth factor normal mast cell, the stem cell factor or SCF. This mutation, present in more than 85% of patients with systemic mastocytosis, resulting in uncontrolled proliferation of mast cells. This is the release of mediators, including histamine, a phenomenon of mast cell degranulation, leading to the onset of many symptoms vary from one individual to another. Mastocytosis are described as rare and orphan diseases, onset most often sporadic, but sometimes family, and very heterogeneous in their clinical expression, their evolutionary modes and prognosis. The skin is the only tissue involved in cutaneous mastocytosis such as urticaria pigmentosa (UP), skin diseases especially in children and often resolve spontaneously during adolescence. Systemic mastocytosis (SM) are defined by the achievement of one or more organs, including bone marrow, with or without skin. Represent 10 to 30% of mastocytosis and usually occur in adults. They are characterized by abnormal proliferation of mast cells in different organs: bone marrow, bone, mucosa of the gastrointestinal tract and sometimes in severe cases, liver and spleen. They can be clinically stable over time and is known as indolent systemic mastocytosis, or conversely, have a more pejorative clinical course (aggressive systemic mastocytosis). The MS are frequently associated with other hematologic non mast cell disease (leukemia, lymphoma ...). In exceptional cases, we describe an extremely aggressive form, the mast cell leukemia, which is defined by the presence of more than 20% of abnormal mast cells in the bone marrow smear and whose prognosis is now very pejorative. Finally, familial forms of mastocytosis (at-least two cases in one family) are more rare, estimated to date at least ten percent of patients.
The most common symptoms are:
The diagnosis of mastocytosis mainly used histological criteria, the clinical suspicion of mastocytosis was confirmed by histological examination of skin and bone marrow. Colorations as toluidine blue can be used to identify mast cells. In addition, immunocytochemical reactions showing tryptase are useful to confirm the nature of the mast cell infiltrate. Finally, the diagnosis may be supported by immunophenotypic study of MC present in bone marrow. Indeed, the MC normal, and the cells encountered in mastocytosis, expressed so strong antigen CD117, whereas antigens not normally found on the MC may be present in aberrantly on MCs abnormalities, such CD2 and / or the CD25. The extent of mast cell mediators can also help in the diagnosis of mastocytosis. Thus, histamine in serum and urine, blood tryptase, and metabolites of prostaglandin D2 and histamine in urine are high in most cases of MS. An international consensus conference recently defined diagnostic criteria of mastocytosis: Major Criteria. b. Detection of a mutation at codon 816 of c-kit in bone marrow or other extracutaneous organs analyzed c. Detection of mast cells expressing CD117 CD2 and / or CD25 d. Serum tryptase controlled. Symptomatic treatments aimed at reducing adverse effects associated with the production of mediators by mast cells in excess. The main drugs used are H1 and H2 antihistamines. H1 antihistamines are usually effective against the itching and flushing, while H2 blockers are used to treat gastrointestinal disorders. Other molecules, such as corticosteroids, can be used in cases of severe skin symptoms, whereas anticholinergics are administered to treat diarrhea and migraines. Cromolyn sodium is used to treat respiratory symptoms. Shock states associated with massive mast cell degranulation may require the use of adrenaline and resuscitation. Finally, bisphosphonates are to be effective in patients with osteoporosis. The ideal treatment of mastocytosis should specifically inhibit abnormal mast cell proliferation, but this goal has not yet been reached. Interferon-alpha has been used alone or in combination with corticosteroids. Treatment with interferon-alpha achieves clinical improvement in many cases, however, relapse was noted in some patients. Moreover, in patients treated with interferon induces significant side effects that limit its use. Therefore, one can ask the question of how to deal with subjects not responding to interferon and having a progressive disease. For these patients, different treatments have been proposed. Thus, very recently a pilot study using cladribine (2-CdA) was conducted in ten patients with MS associated with severe symptoms. Nine patients have received 6 courses of 2-CdA, inducing a decrease in their clinical signs and level of mast cell mediators. However, none of the patients had been in complete remission. It therefore appears that 2-CdA could be an effective new treatment during severe MS, although the protocol for use of this molecule remains to refine. And interferon-alpha 2-CdA can provide therapeutic benefit in some cases of MS, but these molecules lack specificity. Indeed, they do not aim the molecular abnormality present in most cases of MS, namely the activating mutation of KIT. Thus, new molecules specifically designed to block abnormal tyrosine kinase activity of this mutated receptor could be a promising therapeutic approach. A possible therapeutic strategy in the short term for the specific treatment of mastocytosis in humans could be as follows. These specific inhibitors are being developed by various pharmaceutical companies. Furthermore, Japanese researchers have recently isolated a protein (called "allergine-1") on the surface of murine and human mast cells. In mast cells cultured in vitro, the allergine-1 can block the release of substances from mast cells causing the allergic reaction. In addition, severe allergies affect deficient mice allergine-1. This suggests the possibility of future discovery of a drug inhibiting the production of histamine, which could be useful in symptomatic treatment of some patients with mastocytosis.
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