Mastocytosis is due to the accumulation in tissues of certain white blood cells, mast cells, and their unregulated activation. This rare disease most often affects the skin but can also affect other organs and cause a wide variety of symptoms. As with any rare disease, there is an expert center to diagnose mastocytosis and take care of patients, and inform them and their families about this disease: CEREMAST is located in Ile-de-Europe but it is at the heart of a network of 24 competence centers spread across the entire territory.
What are the symptoms of mastocytosis? Do we know the causes? How is this disease diagnosed? And above all, what are the treatments for mastocytosis? Find out what we know about this rare disease.
What is mastocytosis?
Mastocytosis is a rare sickness which affects 1 in 7700 to 1 in 10400 people in Europe.
It results from the accumulation of mast cells in the tissues, but above all from the absence of regulation of their activation. Mast cells are cells of the immune system produced by the bone marrow. They are found in many tissues, particularly in the skin, lungs and mucous membranes of the intestine. These cells intervene in the event of intrusion of a pathogen into the body: the mast cells then release mediators (histamine, tryptase, heparin, etc.) involved in inflammatory and allergic reactions. In the case of mastocytosis, the accumulation of mast cells and the absence of regulation of their activation lead to the excessive release of these mediators, the effects of which are responsible for various local or remote reactions.
On distingue two main types of mastocytosis : the cutaneous mastocytosisby far the most important (90% of cases) which affects the skin, and the systemic mastocytosis, much rarer (10% of cases), which can affect all organs. The average age at diagnosis of mastocytosis is 60 years, but this disease can also affect children: if necessary, they almost exclusively develop the cutaneous form, unlike adults who tend to develop the systemic form.
In addition to the form of the disease, the main difference between adults and children is the evolution of mastocytosis: while that of children regresses largely, even completely, during adolescence, the disease is chronic when It manifests itself in adulthood. It often manifests itself in flare-ups, the frequency of which varies from one patient to another and for the same patient. It can remain asymptomatic for several years before manifesting itself.
The causes of mastocytosis
The exact causes of mastocytosis are not known. In the vast majority of cases, it is an acquired disease, which is therefore very rarely hereditary, and which is characterized by the appearance, during life, of a mutation in the c-Kit gene. This gene encodes the synthesis of a receptor present on the surface of mast cells, which plays an essential role in the development of these cells. It is this genetic mutation which leads to the permanent and uncontrolled activation of the c-Kit receptor, and therefore the excessive release of the mediators causing mastocytosis. Therefore, mastocytosis is by no means a contagious disease.
What are the symptoms of mastocytosis?
Symptoms of cutaneous mastocytosis may be related to the accumulation of mast cells in the skin or the uncontrolled release of mediators (referred to as symptoms of mast cell activation or SAMA), or both.
- By far the most common symptom ispigmentary urticaria which manifests itself as small red-brown spots, slightly raised, located mainly on the trunk, the extremities of the limbs and the head. If they swell and redden upon friction, this is the “Darier sign” characteristic of the disease;
- Much more rarely, cutaneous mastocytosis causes the dilation of the capillaries – we speak of Persistent eruptive macular telangiectasia or TMEP;
- The diffuse skin form results in thickening and reddish discoloration of the skin;
- The papulo-nodular form exists only in the child, often from birth; it manifests itself by the appearance of a mastocytomean often single mass of one to a few centimeters in diameter, and of variable color (dark red, yellowish brown, dark brown);
- The release of mediators systematically causes itching and flushs similar to hot flashes which lead to a redness face and upper torso.
If its symptoms suggest an allergy, mastocytosis is distinguished by its chronic rather than episodic nature. Furthermore, the mechanism that leads to the release of mediators differs since in mastocytosis, unlike allergy, this release is autonomous and does not respond to exposure to allergens.
Systemic mastocytosis only exists in adults. There are 3 forms:
- The indolent systemic mastocytosis (MSI) : by far the most common, it represents 80% of cases in adults. In addition to the skin involvement, almost always present (90% of cases), it is characterized by an infiltration of abnormal mast cells into other organs such as the digestive tract, the liver, the spleen or the bone. The affected organs continue to function normally, and the only symptoms, when they exist, are those linked to mast cell activation;
- The latent systemic mastocytosis (LSM) or smouldering systemic mastocytosis (MSS): uncommon, it is characterized by a greater infiltration of abnormal mast cells into other organs, which results in an increase in their volume and an increase in the level of tryptase in the blood. Here again, the main symptoms are linked to mast cell activation;
- Even rarer, the aggressive systemic mastocytosis. In this form, the infiltration of the organs is such that their functioning is impaired, leading to “failure”: liver failure if the liver is affected, renal failure if it is the kidney, or even heart failure if it is the heart. . Urgent treatment is necessary because the vital prognosis is still engaged.
Whatever its form, systemic mastocytosis can be associated with a non-mast cell hematological disease (MS-AHNMD) such as myelodysplastic syndrome (qualitative defect in the production of blood cells by the bone marrow) or myeloproliferative syndrome (excess production of the marrow bone).
Symptoms related to mast cell activation can affect all organs. Varying in type and intensity between two individuals, they can also vary over time within the same individual. They are not very specific, which can complicate and delay the diagnosis of mastocytosis:
- At the digestive levelsystemic mastocytosis can cause pain, transit disorders (diarrhea, constipation), nausea, vomiting, bloating, flatulence;
- At the cardiovascular levelmastocytosis can manifest itself as palpitations, discomfort with sometimes a drop in blood pressure, or even anaphylactic shock or angioedema which are life-threatening emergencies;
- At the musculoskeletal levelit can cause joint, bone, muscle and/or tendon pain;
- At the pulmonary and ENT levelthe symptoms of systemic mastocytosis range from a simple cough to the feeling of a blocked nose, including itchy and watery eyes;
- Systemic mastocytosis can also affect the urogenital system and lead to frequent urination (>6/d), burning sensations when urinating, and libido disorders;
- Finally, mastocytosis can be the cause of neuropsychological disorders such as headaches, dizziness, memory and concentration problems but also mood disorders (sadness, irritability, anxiety, excessive emotionality).
How to make the diagnosis of mastocytosis?
The diagnosis of mastocytosis is not always easy to make, both because of the rarity of this disease – which is therefore not always well known to doctors – and because its nonspecific symptoms are common to many people. number of other diseases, and that they are not systematically present and of the same intensity in all patients.
However, some elements may prompt the search for mastocytosis, such as the intensity and repetition of symptoms. The existence of osteoporosis before the age of 60 should also be a warning.
- In childrenthe diagnosis of mastocytosis is generally based on a simple examination of the skin, the latter being sufficient to highlight the skin lesions characteristic of cutaneous mastocytosis.
- In adultsa suspicion of mastocytosis on clinical examination must be confirmed by bone marrow biopsy to determine the density of mast cells and determine the stage of the disease. It is estimated that the diagnosis of mastocytosis is probable beyond 15 aggregated mast cells. But for it to be confirmed, the analyzed sample must also present at least one other criterion such as the presence of more than 25% of atypically shaped mast cells, the existence of a mutation on the KIT gene or even a abnormally high level of tryptase (>20 ng/ml) in the blood.
In case of doubt, a urine and plasma dosage mast cell mediators and their metabolites may be prescribed, along with a bone scan and gastrointestinal evaluation.
Additional examinations may be necessary to better characterize the disease and its complications…