Mastocytosis: Causes, Symptoms, Diagnosis, Treatment

Mastocytosis - infiltration of mast cells of the skin and other tissues and organs. Symptoms are mainly due to the release of mediators, and among them there are itching, redness, dyspepsia due to gastric hypersecretion. The diagnosis is based on a skin biopsy, a red bone marrow or both. Treatment consists in prescribing antihistamines and controlling any underlying disease.

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Causes of the mastocytosis

The etiology is unknown, but may concern the mutation of genes encoding the tyrosine kinase receptor (c-kit) of mast cells in some patients. There may be hyperproduction of the stem cell factor, which is a ligand for this receptor.

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Pathogenesis

Mastocytosis is a group of diseases characterized by proliferation of mast cells and infiltration of skin and other organs. Pathogenesis is mainly based on the release of mast cell mediators, including histamine, heparin, leukotrienes, various cytokines of inflammation. Histamine is the cause of many symptoms, including symptoms from the stomach, but other mediators contribute. Significant infiltration of the organ leads to its dysfunction. Among the substances that trigger the release of mediators, physical contact, physical activity, alcohol, NSAIDs, opioids, bites of stinging insects or food are isolated.

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Symptoms of the mastocytosis

Often there is itching of the skin. Stroking or rubbing the skin lesions is the cause of urticaria and erythema around the lesion (Darier symptom); this reaction differs from dermographism, in which changes are observed on normal skin.

Systemic symptoms are very diverse. The most frequent cases of fever; Anaphylactoid reactions with syncope and shock are severe. Other symptoms include epigastric pain due to peptic ulcer, nausea, vomiting, chronic diarrhea, arthralgia, bone pain, neuropsychiatric changes (irritability, depression, mood lability). Infiltration of the liver and spleen can lead to portal hypertension followed by ascites.

Forms

Mastocytosis can be cutaneous or systemic.

Cutaneous mastocytosis usually occurs in children. Most patients have pigmentary urticaria (urticaria), local or diffuse orange-pink (salmon) or a brown maculopapular skin rash, which is the result of multiple small clusters of mast cells. Rareer forms are diffuse cutaneous mastocytosis, which is manifested by the infiltration of the skin by mast cells without discrete lesions, and mastocytoma with large single clusters of mast cells.

Systemic mastocytosis is more common in adults and is characterized by multifocal lesions of the bone marrow; often involve other organs, including skin, lymph nodes, liver, spleen, GIT. Systemic mastocytosis is classified as follows: painless, without organ dysfunction and with good prognosis; mastocytosis associated with other hematologic disorders (eg, myeloproliferative disorders, myelodysplasia, lymphoma); aggressive mastocytosis characterized by considerable organ dysfunction; mast cell leukemia with more than 20% of mast cells in the bone marrow smear, no skin lesions, multiple organ damage and poor prognosis.

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Diagnostics of the mastocytosis

Presumptive diagnosis is made on the basis of clinical signs. Similar symptoms can be observed with anaphylaxis, pheochromocytoma, carcinoid syndrome, Zollinger-Ellison syndrome. The diagnosis is confirmed by a biopsy of the areas of the affected skin and sometimes the bone marrow. Patients with symptoms of peptic ulcer to exclude the Zollinger-Ellison syndrome measured the level of plasma gastrin; In patients with febrile fever, excretion of 5-hydroxyindole acetate (5-HIAA, 5-hydroxyindoleacetic acid) is measured to exclude carcinoid. The level of mediators of mast cells and their metabolites can be increased in blood plasma and urine, but their detection does not allow a final diagnosis.

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Treatment of the mastocytosis

Mastocytosis of the skin. As symptomatic therapy, H2-blockers are effective. Children with mastocytosis of the skin do not require additional treatment, since most such cases are cured on their own. Adults with this form of mastocytosis appoint psoralen and ultraviolet irradiation or locally glucocorticoids 1 or 2 times a day. Mastocytoma is usually independently re-developed and does not require treatment. In children, the cutaneous form rarely progresses to the systemic one, but in adults such cases can be observed.

Systemic mastocytosis. All patients are prescribed H1- and H2-blockers. Aspirin helps in case of fever, but can increase the production of leukotrienes, thus contributing to the development of symptoms associated with the mast cells themselves; It is not prescribed to children because of the high risk of developing Reye's syndrome. To prevent degranulation of mast cells, 200 mg of cromolin is administered intravenously 4 times a day [100 mg 4 times a day for children 2 to 12 years old, but not exceeding the dose of 40 mg / (kg-day)]. There are no treatments available to reduce the number of mast cells in the tissues. You can use ketotifen 2-4 mg orally 2 times a day, but it is not always effective.

In patients with severe forms, interferon a2b 4 million units subcutaneously once a week with a maximum dose of 3 million units per day is prescribed for the relief of bone marrow symptoms. Glucocorticoids may be prescribed (for example, prednisolone 40-60 mg orally once a day for 2-3 weeks). In severe forms, the quality of life can improve splenectomy.

Cytotoxic drugs (daunomycin, etoposide, 6-mercaptopurine) can be used in the treatment of mast cell leukemia, but their effectiveness has not been proven. The possibility of using imatinide (tyrosine kinase receptor inhibitor) for the treatment of patients with c-kit mutations is being studied.