We're hiring ! Join us and make a difference in our hospitals
Mastocytoses
Mastocytoses
Definition and symptoms
Mastocytoses are a group of diseases characterised by the abnormal proliferation of mast cells as a result of an acquired activating mutation of the CKIT gene (D816V), and their accumulation in various organs: the skin (mainly), haematopoietic organs (bone marrow, liver, spleen), the digestive tract and bones. They are also characterised by the autonomous, unregulated activation of mutated mast cells, which causes their excessive degranulation (release of mast-cell mediators contained in the mast-cell granules).
Symptoms of mast-cell activation (MCAS) may affect all organs and include: flushing (episodes of redness), itching, anaphylactic shock, malaise, various digestive disorders (diarrhoea, pain, food intolerances), various types of pain, particularly skeletal pain and headaches, fatigue, sleep and mood disorders, rhinitis and shortness of breath.
Mastocytosis is a rare disease, affecting approximately 1 in 150,000 patients per year.
Types
Mastocytosis is referred to as cutaneous when there is no excess of mast cells in organs other than the skin. This form is by far the most common in children.
From birth or during the first weeks of life, a child may develop one or more skin lesions corresponding either to urticaria pigmentosa or mastocytomas. These lesions are particularly reactive to friction or sudden changes in temperature, which may cause blisters to appear and trigger symptoms of mast-cell activation (diarrhoea, malaise, etc.). Mastocytosis in children may regress completely during adolescence. However, the exact frequency of this spontaneous remission remains to be determined (50% of cases or more?).
When mastocytosis is diagnosed in an adult, it is always considered systemic; the disease is chronic, and no treatment is considered capable of curing it. However, mastocytosis in adults is most often indolent.
The most common form in adults (80% of cases) is Indolent Systemic Mastocytosis (ISM). Skin involvement is common, in the form of urticaria pigmentosa or telangiectasias (TMEP). Infiltration of organs other than the skin causes neither enlargement nor dysfunction of these organs. Most symptoms result from MCAS, which may sometimes cause significant functional impairment (for example, in cases of recurrent anaphylactic shock, urgent diarrhoea, disabling pain, repeated flushing with post-episode fatigue, cognitive and mood disorders). Quality of life may therefore be severely impaired in some patients, while other patients remain asymptomatic. In this form, screening for bone demineralisation (30% of patients) is essential in order to initiate bone-forming treatment if necessary and prevent vertebral fractures. These patients’ survival is not threatened. Outpatient follow-up takes place annually.
The remaining 20% of patients have an aggressive form of mastocytosis (primarily aggressive systemic mastocytosis, and much more rarely mast-cell leukaemia or mast-cell sarcoma), with or without an associated non-mast-cell clonal haematological disorder (mainly myelodysplasia). They are managed in a haematology inpatient setting. Their survival is rapidly threatened by dysfunction of at least one organ massively infiltrated by mast cells: liver failure, bone-marrow failure, cachexia due to digestive malabsorption or hypersplenism. MCAS is rare or absent. Cytoreductive treatment must be initiated urgently.
How is mastocytosis treated?
There is no curative treatment for mastocytosis. The therapeutic objective depends on the type of mastocytosis.
In most cases, the disease is indolent. The therapeutic objective is to improve patients’ quality of life if it has deteriorated. Treatment includes strict avoidance of any factor identified as triggering mast-cell degranulation (food, medication, hymenoptera sting, excessively strenuous physical activity or extremely high or low temperatures), as well as symptomatic treatment (antihistamines). If, after at least 6 months of optimal and properly administered symptomatic treatment (maximum doses and good adherence to the prescription), the impairment remains too disabling, long-term cytoreductive treatment may be considered. In patients with a history of anaphylactic shock, an adrenaline auto-injector must be carried at all times.
In the rarer aggressive form of mastocytosis, the primary objective is to reduce the mast-cell infiltration that is suffocating the organs. Cytoreductive medicines (cladribine-based chemotherapy and tyrosine kinase inhibitors) are essential for this purpose and must be started as soon as possible.