Generality
Mastocytosis is a disease characterized by the accumulation of mast cells in different organs and tissues of the body. Once accumulated, these immune cells release significant amounts of histamine.
The histamine produced by mast cells has numerous consequences, sometimes even very serious. The symptoms of the disease are however various and depend on the type of mastocytosis.
Diagnosis requires careful testing and specific tests. Once the type of mastocytosis has been identified, the most appropriate therapeutic path can be planned; therapeutic pathway that does not allow the recovery of the disease, but only improves the symptomatology.
What is mastocytosis?
Mastocytosis is a rare pathological condition characterized by excessive accumulation of mast cells in some organs and tissues of the body.
WHAT ARE MASTOCYTES?
Mast cells, or mastecells, are a group of cells belonging to the immune system, which defend the body against pathogens and other types of threats.
When the human body is attacked by germs (viruses or bacteria), the mast cells begin to release, in the blood vessels, a nitrogenous chemical compound, called histamine . Within the mast cells this substance is enclosed in intracellular granules together with other elements; not surprisingly, the histamine release process is known as mast cell degranulation.
Histamine is a vasodilator, so its release increases the permeability of blood vessels, with which it comes into contact. Greater vascular permeability, in a certain point, favors the influx of other immune cells, having a very specific role: attacking and removing infesting pathogens from the body.
This process is part of that very particular defense mechanism, called inflammation .
What happens when the mast cells do not work properly?
Figure: a mast cell containing histamine granules (in purple).
Sometimes, it may happen that mast cells trigger a massive release of histamine even when the body encounters harmless elements, such as pollens and non-infectious agents. The resulting inflammatory process has no purpose, as there are no germs to attack, but it still has effects and causes: skin redness, skin swelling, difficulty breathing, itching and rhinitis .
This aberrant mechanism is the basis of allergic reactions (or allergies ), and when it becomes particularly intense it is called anaphylaxis .
TYPES OF MASTOCYTOSIS AND EPIDEMIOLOGY
Two types of mastocytosis have been recognized:
- Cutaneous mastocytosis . The symptoms affect only the skin, because this is where the mast cells accumulate; it usually affects children, so much so that it takes the alternative name of pediatric mastocytosis . Among the two types of existing mastocytosis, it is the most common form, although it should be noted that it is, however, a fairly rare disease. In fact, it affects one person in 1000.
- Systemic mastocytosis . The accumulation of mast cells can occur in every body part, therefore skin, any organ (liver, spleen, bone marrow etc.) and bones. It is a very rare disorder, which affects adults the most. According to Anglo-Saxon statistics, one person every 150, 000 becomes ill with systemic mastocytosis.
Causes
The accumulation of mast cells, in various parts of the body, causes an intense release of histamine and other chemical mediators (also contained in mast cells); the latter, together with histamine, are the architects of all the typical symptoms of mastocytosis.
WHAT IS IT FOR?
The cause or causes, which trigger the appearance of mastocytosis, have not yet been fully clarified. The only thing certain is that, at the origin of the disorder, there is a genetic error . This certainty derives from the fact that the DNA of people with mastocytosis presents a mutation in the c-KIT gene .
MUTATION OF THE GENE C-KIT: HEREDITARY OR SPONTANEOUS?
The researchers, after years of studies, have come to the conclusion that a part of the mastocytosis patients inherits the c-KIT gene mutated by the parents, while another part develops the genetic mutation spontaneously and without a reason (for now) explainable .
Symptoms and Complications
Cutaneous mastocytosis presents symptoms and signs different from those typical of systemic mastocytosis. Therefore, the symptomatology depends, exclusively, on the type of mastocytosis that is in progress.
CUTANEOUS MASTOCYTOSIS
As can be guessed from the name itself, the most characteristic symptom of cutaneous mastocytosis is the appearance of lesions and abnormalities on the skin.
These skin lesions can be:
- Small areas of different colored leather. These are also called macules .
- Small stable skin reliefs. They are also called papules .
- Reliefs of the skin of considerable size and red. These are the so-called nodules .
- Extended raised areas of leather, noticeable only by touch. These are also identified with the term plaques .
- Blisters, or subcutaneous fluid collections.
Figure: cutaneous mastocytosis, in a teenager
The lesions, as a rule, appear only on the trunk and have a color that can vary from yellow-light brown to intense red-brown. Their dimensions are extremely variable: they can measure a millimeter in diameter, but also several centimeters.
Moreover, their number is also variable: some patients show only one / two lesions, others show a thousand.
Finally, the affected areas of skin develop swelling, itching and skin redness .
SYSTEMIC MASTOCYTOSIS
The presence of an exaggerated number of mast cells in different organs and tissues of the body can cause a very high number of disorders, such as:
- Stomach pain, caused by continuous peptic ulcers . Peptic ulcers are the natural consequence of the excessive release of histamine in the stomach.
- Enlarged liver ( hepatomegaly ) and subsequent jaundice . All this causes a sense of apathy
- Enlarged spleen ( splenomegaly ) and consequent abdominal pain
- Joint pain
- Enlarged lymph nodes
- Sense of weakness
- Extreme fatigue, even in doing less burdensome activities
- Mood swings, such as irritability and sudden confusion, and amnesia
- Loss of appetite
- Weight loss
- Osteoporosis and bone pain.
- Need to urinate often
Furthermore, systemic mastocytosis is also characterized by the appearance of:
- Repeated hot flushes . This is a different feeling than that caused by intense sweating.
- Palpitations, or irregular heartbeat.
- Stunning . The patient feels severe dizziness .
- Hypotension, or drop in blood pressure, with all its consequences (blurred vision, fainting, general malaise, etc.).
- Headache, shortness of breath, chest pain, nausea and diarrhea.
These symptoms, in particular hot flashes, palpitations and confusion, appear suddenly, in the form of attacks lasting 15-30 minutes. After this time, they gradually disappear, only to reappear later.
Attacks are very often following physical exertion, the intake of certain drugs (aspirin or antibiotics), emotional stress, the ingestion of particular foods and spices, alcohol intake and infectious diseases such as flu and cold.
Subtypes of systemic mastocytosis
Based on severity and affected organs and tissues, three different subtypes of systemic mastocytosis could be distinguished. These are indolent systemic mastocytosis, aggressive systemic mastocytosis and systemic mastocytosis associated with a blood disease . In 90% of cases, those suffering from systemic mastocytosis are affected by the indolent form, which is characterized by a moderate and variable symptomatology.
anaphylaxis
Individuals with mastocytosis, both systemic and cutaneous, are protagonists, more than healthy people, of episodes of anaphylaxis . Anaphylaxis, as we have seen, is an allergic reaction caused by a reckless release and without any reason for histamine, by the mast cells.
The reason for this increased predisposition is probably due to the massive presence of mast cells in various tissues and organs.
Typical symptoms of anaphylaxis
- Breathing difficulties
- Swelling of the eyes, lips, hands and other areas of the body
- Itching of the skin and a rash of vegetables
- Strange metallic taste in the mouth
- Eyes reddened, itchy and inflamed
- Heart rate changes
- Sudden sense of anxiety
- Hypotension
- Sense of vomiting and diarrhea
- Temperature
Diagnosis
Cutaneous mastocytosis and systemic mastocytosis each have their own symptoms, consequently they are diagnosed with different tests and examinations.
CUTANEOUS MASTOCYTOSIS
Cutaneous mastocytosis causes, as seen, evident cutaneous signs (or lesions).
Therefore, first, we begin with an objective examination, during which the doctor (usually a dermatologist ) analyzes the appearance and the size of the lesions. These are important characteristics, because they are typical of cutaneous mastocytosis: the reddened appearance of the skin of the trunk and the sensation of itching in the affected area.
The second step consists in a biopsy, which establishes, in a definitive way, what the marks on the skin are due to, detected by the physical examination. The biopsy involves the microscopic collection and analysis of a small sample of pathological skin tissue (ie affected by papules, nodules, etc.). If, from the observation under the microscope, it emerges that the sample contains a very high number of mast cells, then it is cutaneous mastocytosis.
SYSTEMIC MASTOCYTOSIS
To establish the correct diagnosis of systemic mastocytosis, the following 5 tests should be used in sequence:
- Complete blood count . This is the count of all the cells and other elements present in the blood. It requires the taking, from a vein of the arm, of a blood sample and its accurate analysis. If, at the conclusion of the tests, a strangely low level of blood cells emerges, it could mean that there is an excessive presence of mast cells in the bone marrow (NB: the bone marrow is the organ that produces blood cells).
- Analysis of tryptase levels in the blood . Tryptase is an enzyme found only within mast cells, specifically in granules. Therefore, if there is a high amount of tryptase in an individual's blood, it means that there is almost certainly a high number of circulating mast cells. Quantification of tryptase levels is obtained with a particular blood test.
- Abdominal ultrasound . It is a non-invasive radiological examination, which provides clear images of the internal organs of the body. In patients with suspected systemic mastocytosis (blood count and analysis of positive tryptase levels), it is performed to see if the liver and spleen are enlarged.
- DEXA (dual energy X-ray absorptiometry) . It is an X-ray examination, which allows the measurement of calcium levels in an individual's bones. In the case of systemic mastocytosis, the bones are poor in calcium and subject to osteoporosis, as they are "infested" by an excessive number of mast cells, which produce substances with corrosive effects.
- Bone marrow collection and analysis . The bone marrow is found in the most internal areas of some bones. Therefore, the collection of one of its samples requires a syringe with a very long needle and a small local anesthetic, to be practiced where the needle is to be threaded.
Treatment
Although there is no cure for mastocytosis, it is possible to use a therapy aimed at improving symptoms.
This therapy depends on two factors: the type of mastocytosis, whether cutaneous or systemic, and the severity of the symptoms .
It is based almost exclusively on the administration of various types of drugs, some more effective and powerful than others.
CORTICOSTEROIDS FOR TOPICAL USE
Topical corticosteroids are available in the form of creams, ointments and ointments. They are used by subjects with moderate cutaneous mastocytosis. Their action consists in preventing the release of histamine, anticipating, in fact, the triggering of the subsequent inflammatory process.
The side effects, caused by topical corticosteroids, are:
- Skin thinning and striae on the skin
- Skin discoloration
- Ease of the treated area to develop hematomas
To best limit the side effects, it is advisable to apply the drug exclusively where there are skin lesions.
ANTIHISTAMINES
Antihistamines, as can be guessed from their name, block the effects of histamine.
They are administered both in the case of cutaneous mastocytosis, and in the case of indolent systemic mastocytosis and serve for the treatment of skin itching and redness.
Possible side effects are: headache, dry mouth and dry nose. All three pass very quickly.
SODIUM CHROMOGLICATE
Sodium cromoglicate is a drug used, usually, to treat allergic reactions triggered by certain foods and those that cause itchy eyes and rhinitis. Its therapeutic action is linked to the ability to reduce the amount of substances released by mast cells.
The symptoms, on which it seems to have the greatest effect, are: joint pain, sense of weakness, headache and itching.
PUVA
PUVA consists in the administration of a particular drug, called psoralen, and in the subsequent exposure of the patient to type A ultraviolet rays ( UVA light ). Psoralen increases the sensitivity of the skin to the effects of UVA light, which helps to remove skin lesions.
PUVA is a treatment that, if it is used for long periods of time, could cause skin tumors . For this reason, it is practiced only in cases of severe cutaneous mastocytosis and for a limited number of sessions.
CORTICOSTEROIDS IN TABLETS
Corticosteroids in tablets are given to patients with mastocytosis who suffer from very intense itching and / or severe bone pain.
The side effects are different and, in some cases, even very serious; therefore it is good not to abuse it.
Some side effects of corticosteroids in tablets:
- Weight gain
- Water retention
- Increased appetite
- Hypertension
- Irritability
BIPOSPHONATES AND SOCCER SUPPLEMENTS
Bisphosphonates, associated with calcium-based supplements, are administered to patients with mastocytosis affected by osteoporosis. Their effect, in fact, is to slow down the destruction of bone tissue and favor the opposite process, that is construction.
ANTAGONISTS OF H2 RECEPTORS
H2 receptor blockers are indicated for the treatment of stomach pains due to peptic ulcers. In fact, they act by blocking the excessive release of histamine in the stomach caused by the presence of a large number of mast cells in the body.
DRUGS FOR THE CARE OF SERIOUS SYSTEMIC MASTOCYTOSIS
Aggressive systemic mastocytosis and the so-called systemic mastocytosis associated with a blood disease are treated with a series of drugs, with more or less positive effects.
In detail, all possible medicines are:
- Alpha interferon . Designed for the treatment of tumors, it has also been found to have a positive impact on severe mastocytosis. It is given by injection and, at the first administration, since the body is not yet used, it can cause flu-like symptoms, high fever and joint pain.
- Imatinib . Administered in tablets, it blocks the production mechanism of mast cells. It does not always provide the desired results and makes the patient, who uses it, more susceptible to infections.
- Nilotinib and dasatinib . Patients who do not respond to imatinib are made to take them. Like the latter, they block the production of mast cells and make the patient more susceptible to infections.
- Cladribine . Originally designated for the treatment of leukemias, it was found to have beneficial effects even among patients with mastocytosis. It is given by infusion and works by suppressing the immune system. It makes the patient more susceptible to infections.
Symptoms of an ongoing infection:
- High body temperature
- Headache
- Muscle pains
- Diarrhea
- Feeling tired
In addition to these remedies, in the case of systemic mastocytosis associated with a blood disease, it is also necessary to treat the associated blood disorder. The latter may be acute leukemia, chronic leukemia, lymphoma or multiple myeloma .
For further information: Medications for the treatment of Mastocytosis »
Prognosis
Cutaneous mastocytosis tends to improve over time, so much so that many patients, when they reach puberty, recover completely.
Systemic mastocytosis, on the other hand, is an incurable disease, which, in less severe cases (indolent mastocytosis), only affects the quality of life of patients, while in more severe cases (aggressive mastocytosis and mastocytosis associated with a blood disease) it can also affect the patient's life expectancy.
