What is mastocytosis?
Mast cells are found in the bone marrow and other tissues in our body, including the skin and mucous membranes, and play an important role in immune defense and allergic reactions. Numerous mediators, such as histamine and tryptase, are released after activation of mast cells, stimulating the immune system. More than sixty such mediators are known to occur in a mast cell.
Mastocytosis is characterized by an increase in mast cells, which can accumulate in the skin or in other organs such as the bone marrow, gastrointestinal tract, spleen, liver or lymph nodes.
Causes
Although a genetic alteration of the KIT gene is detectable in more than 90% of patients with mastocytosis, it is not a hereditary disease because this mutation is acquired during a patient's lifetime. It is not yet known exactly why this is the case. The KIT gene is responsible for the correct structure and function of the KIT receptor, a so-called tyrosine kinase receptor, which drives the proliferation of mast cells. Due to the mutation of the KIT gene, the tyrosine kinase receptor is activated in an uncontrolled manner, which leads to a deregulated proliferation of mast cells as well as to the overactivation of certain signaling pathways in the mast cells
Symptoms
Patients with mastocytosis can experience various symptoms due to the proliferation and activation of mast cells, followed by the release of mediators. The overactive mast cells can also be triggered by bee and wasp venom, cold and heat, contrast media, emotional stress, and many other factors. This may then lead to symptoms such as redness and swelling of the skin lesions, itching, discomfort, headaches, abdominal cramps, diarrhea, bone pain, or restrictions to the point of loss of consciousness. The latter is called anaphylactic shock. Some patients also develop osteoporosis, anemia, an enlarged spleen, or suffer from weight loss. However, both the activating factors and the reactions to them are different in every patient with mastocytosis.
Forms of mastocytosis
There are different forms of mastocytosis. If the proliferation of mast cells is limited to the skin and causes symptoms only there, it is referred to as cutaneous mastocytosis. This often occurs in children. In cutaneous mastocytosis, brown-red patches appear on the skin that may turn into itchy wheals when rubbed. This reaction of the skin lesions, known as Darier's sign, is typical of mastocytosis.
If, on the other hand, there is an accumulation of mast cells in the bone marrow or other organs, we speak of systemic mastocytosis. This affects the entire body and occurs more frequently in adults. The skin may also be affected, but does not have to be. The non-advanced variants of systemic mastocytosis occur frequently, in about 75% of cases. A distinction is made here between bone marrow mastocytosis, indolent systemic mastocytosis, and smoldering systemic mastocytosis. More rarely, in about 25% of patients, advanced forms of systemic mastocytosis occur, such as systemic mastocytosis with associated hematologic or myelopoietic neoplasia, aggressive systemic mastocytosis, or mast cell leukemia. In the advanced forms, the pronounced accumulation of mast cells leads to functional impairment of the affected organs, e.g. anemia in the case of bone marrow involvement or weight loss if the intestinal wall is affected.
Diagnosis
Since mastocytoses are rare and the symptoms are very diverse and non-specific, their diagnosis is often delayed. Depending on the organs affected, the collaboration of several medical disciplines is necessary to make an exact diagnosis and thus enable adequate therapy. As a rule, the tryptase in the serum is measured with a blood test. The tryptase level is typically elevated in mastocytosis, but in rare cases it can also be normal.
If systemic mastocytosis is suspected, a bone marrow examination should be performed to assess the proportion of mast cells in the bone marrow, their appearance and their cell surface characteristics. Genetic testing should be used to detect the typical mutation in the KIT gene. If systemic mastocytosis is present, further investigations may be necessary, e.g. bone densitometry, as mastocytosis may be associated with reduced bone density or even osteoporosis, or an ultrasound examination of the abdomen, as the liver and spleen may be enlarged.
Treatment
In cutaneous mastocytosis and the non-advanced forms of systemic mastocytosis, the main therapeutic goal is to control the mediator-caused symptoms. For this purpose the individual triggers of mast cell activation should be known and avoided. There are several medication options available, such as histamine H1 blockers, histamine H2 blockers, and cromoglicic acid.
In the advanced forms of systemic mastocytosis, most cases are treated with targeted therapies, e.g. tyrosine kinase inhibitors, as well as chemotherapy and stem cell transplantation.
To avoid the risk of anaphylactic shock, it is crucial that all adult patients, in addition to an emergency pass, always carry an adrenaline auto-injector and an emergency kit consisting of two tablets of a histamine H1 blocker and two tablets of cortisone (each 50 mg prednisolone). For children, this recommendation applies only in the case of more severe mastocytosis.
If insect venom allergy has been detected in patients with mastocytosis, life-long allergen-specific immunotherapy with bee or wasp venom is advised.