Mastocytosis is a disease characterized by the presence in too many of a kind of white blood cells in the tissues, mast cells. The latter can give manifestations on the skin but also in the deep organs and sometimes formidable generalized reactions.

Mastocytosis is a rare disease characterized by an excess of mast cells in the skin and / or other organs.

Mast cells are white blood cells playing a role in inflammation and allergy, because they deliver mediators such as heparin, histamine, cytokines (such as TNF α) to the tissues, etc. which cause the tissues to swell , dilate blood vessels …

The clinical manifestations of mastocytosis are linked, on the one hand, to the accumulation of mast cells in the tissues and, on the other hand, to the effects of the mediators they release, responsible for inflammatory manifestations and allergic appearance.

These manifestations are classified according to the organs affected:

• Cutaneous mastocytosis: pigmentary urticaria, dermographism, redness
• Systemic mastocytosis: blood manifestations (anemia, increase or decrease in white blood cells, increase or decrease in platelets, malignant blood diseases, etc.), neurological manifestations (headaches, syncope, dizziness, convulsions, anxiety, depression, dementia, etc.), manifestations cardiovascular (palpitations, hypotension, etc.), respiratory impairment such as interstitial fibrosis or laryngeal involvement causing respiratory disorders, in particular difficulty in breathing, etc.
• Digestive mastocytosis: abdominal pain, diarrhea, nausea and vomiting …
• Bone mastocytosis: bone and joint pain

Causes of mastocytosis

Mutations in the c-Kit gene located on chromosome 4 are found in many mastocytoses. These mutations cause the production of Kit protein which stimulates proliferation of mast cells.

Who is affected by mastocytosis?

Mastocytosis is a disease that can occur at any age, without gender predisposition.

Diagnosis of mastocytosis

The diagnosis of mastocytosis requires performing a skin biopsy (on an area not previously traumatized in order to avoid degranulation of mast cells which would make their recognition more difficult and without adrenaline in local anesthetic or after cold anesthesia) in order to evidence of a mast cell infiltrate in the dermis with a density greater than 15 cells per field at magnification 40.

The doctor may ask for a blood test of tryptase: the normal level is less than 5 ng / ml, patients with cutaneous mastocytosis often have a level lower than 20 ng / ml while those with systemic mastocytosis often have a level higher than 20 ng / ml. Furthermore, the presence of a level greater than 75 ng / ml would be systematically associated with the presence of the disease.

Evolution and possible complications of mastocytosis

Cutaneous mastocytosis progresses by congestive attacks with redness and swelling of the plaques.

In deep or profuse cutaneous mastocytosis, the manifestations can be serious (respiratory disorders, osteoarticular damage, etc.).

In children, mastocytosis is often benign and often regresses within a few years.

In adults, on the other hand, we often fear systemic and reactional damage or even an evolution towards malignant diseases:

• myeloproliferative or myelodysplastic syndromes (lymphomas, acute or chronic leukemias, etc.).
• aggressive mastocytosis, gradually invading all organs
• mast cell leukemia: fortunately exceptional, it is the malignant form of mastocytosis invading the bone marrow and the blood.

Cutaneous mastocytosis

• Pigmented urticaria is the most common form of the cutaneous manifestations of mastocytosis, causing small swellings of the skin of a reddish-brown color, the friction of which accentuates the swelling and reddening, especially in children (i.e. Darier’s sign). Urticaria pigmentosa resolves spontaneously at puberty in more than 50% of cases.
• Mastocytomas are more common in infants: they are balls embedded in the skin of a pinkish-brown color, the friction of which accentuates the swelling and reddening (Darier’s sign). Mast cell tumors have a good prognosis and usually resolve spontaneously within a few years.
• Telangiectasia macularis eruptiva perstans is a rare form of mastocytosis occurring more in adults, causing small red patches covered with telangiectasias (small red-purplish vessels) on the trunk, often accompanied by deep signs.

Deep mastocytosis

Many organs can be invaded by mast cells or the target of manifestations linked to mast cells, most often in addition to skin damage (pigmentary urticaria, diffuse cutaneous mastocytosis, etc.).

• Blood mastocytosis: anemia, increase or decrease in white blood cells, increase or decrease in platelets, malignant blood diseases …
• Neurological mastocytosis: headaches, syncope, dizziness, convulsions, anxiety, depression, dementia …
• Cardiorespiratory mastocytosis: palpitations, hypotension, interstitial fibrosis, laryngeal involvement …
• Digestive mastocytosis: abdominal pain, diarrhea, nausea and vomiting …
• Bone mastocytosis: bone and joint pain

Reaction events

These are manifestations related to the release of mediators by mast cells under the influence of external factors, most often

• drugs (anesthetics of the curare or opioid family, aspirin, anti-inflammatory drugs, codeine, morphines, polymyxin B, hydralazine, amphotericin B, quinine, scopolamine, reserpine, pilocarpine, macromolecules, etc.)
• foods (peanuts, citrus fruits, fish and shellfish, fermented cheeses, fermented and alcoholic drinks, smoked foods, tomatoes, spinach, bananas, spices, strawberries, etc.),
• physical (local trauma and friction, stress and emotions, temperature variation during baths, or efforts, snake bites or hymenoptera stings, surgical interventions, etc.)

They are like

• congestive flare-ups of skin lesions,
• itching,
• dermographism (when lightly rubbed the skin, it swells and pink on the rubbed areas, you can even write or draw on the skin)
• general signs (headache, redness, digestive pain, diarrhea, nausea, palpitations, hypotension or even cardiovascular shock, breathing difficulties, etc.).

Risk factors

Mastocytosis is a rare but not exceptional disease which most often occurs without predisposition of sex, at any age.

Our doctor’s opinion

The prognosis is very different depending on the age and the organs affected. The mastocytosis of the child, often very anxiety-provoking for the parents, is fortunately generally benign, confined to the skin and spontaneously regressive, whereas the mastocytosis of the adult is often accompanied by deep signs.

The treatment of mastocytosis is poorly codified and is based more on experience than on scientific studies with a high level of evidence. Besides the treatment, the preventive measures of congestive manifestations must however always be well known to the patient and his entourage.

Mastocytosis cannot be prevented.

However, we can limit the triggers of congestive attacks

Physical factors

• Local trauma and friction
• Stress and emotions
• Temperature variation (baths, efforts)
• Snake bites or Hymenoptera stings
• Surgeries

Food

Peanuts, citrus fruits, fish and shellfish, fermented cheeses, fermented and alcoholic drinks, smoked foods, tomatoes, spinach, bananas, spices, strawberries …

pharmaceuticals

Anesthetics of the family of curare or opiates, aspirin, anti-inflammatory drugs, codeine, morphines, polymyxin B, hydralazine, amphotericin B, quinine, scopolamine, reserpine, pilocarpine, macromolecules … In addition, beta-blockers are contraindicated because they decrease the effectiveness of adrenaline

Treatment of mastocytosis involves preventing and treating reactive manifestations.

Prevention of reaction flare-ups

Limitation of physical factors

• friction of the skin, especially when washing infants or children;
• local burns or trauma
• Hymenoptera stings (bees, wasps, etc.)

Avoid histaminoliberating foods

Peanuts, citrus fruits, fish and shellfish, fermented cheeses, fermented and alcoholic drinks, smoked foods, tomatoes, spinach, bananas, spices, strawberries …

Avoid certain medications

• General anesthesias are often the cause of severe reaction flare-ups. It is therefore always necessary to warn the anesthetist who will avoid curares and opiates and will prescribe antihistamines before the operation.
• if iodinated contrast medium is injected before an x-ray or CT scan, antihistamines should also be prescribed
• the other contraindicated drugs are: aspirin, anti-inflammatory drugs, codeine, morphines, polymyxin B, hydralazine, amphotericin B, quinine, scopolamine, reserpine, pilocarpine, macromolecules … and beta-blockers (by reducing the effectiveness of adrenaline)

Treatment of reaction surges

Anti histaminiques

Antihistamines block receptors for histamine, one of the mediators released by mast cells. They reduce allergic symptoms (itching, swelling of the skin, etc.) but do not modify mast cell proliferation.

Anti H1 antihistamines (Aerius ® (desloratadine), Clarityne ® (loratadine), Kestin ®, Telfast ®, Tinset ®, Virlix ® (cetirizine), Xyzall ® (levocetirizine), Zyrtec ® (cetirizine) …) are often associated with anti-H2 (ranitidine, famotidine, cimetidine)

Anti dégranulants

These are molecules that limit mast cell degranulation (disodium cromoglycate and ketotifen)

Choc

The onset of anaphylactic shock is based on the emergency injection of epinephrine.

Treatment of small numbers of mast cell tumors

Single lesion

In the event of a solitary mastocytoma, surgical excision is proposed in the event of functional discomfort.

Pigmentary urticaria

• Cortisone cream: it is mainly used on urticaria pigmentosa
• Ultra Violets: the doctor delivers Ultra-Violets in the cabin three times a week (UV therapy) because UV rays reduce the number of mast cells and their synthesis of mediators.

Treatments for systemic mastocytosis

Many treatments have been tried: Interferon, 2-CdA (Cladribine®), imatinib mesylate (Glivec®), bisphosphonates, chlorambucil, etc.