Symptoms, Diagnosis, and Treatment of Mastocytosis

Mastocytosis is a mouthful. Hearing that you or your loved one has a medical condition you have never heard of can be frightening. Mastocytosis can also be called mast cell disease. Mast cells are a type of white blood cell part of your immune system. They are related to the basophil and are involved in allergies and anaphylaxis (a severe allergic reaction).

Essentially, mast cells attract other immune cells to areas of tissue when needed by releasing chemicals. When an excessive number of mast cells gather together in tissues, it is called mastocytosis. When the mast cells collect in the skin only it is called cutaneous mastocytosis. When it occurs in multiple organs it is called systemic mastocytosis. Systemic mastocytosis is considered a myeloproliferative neoplasm.

Risks, Signs, and Symptoms of Mastocytosis

Because mastocytosis is such a rare disorder it is unknown how many people have it. Males and females seem to be equally affected. In children, most cases are cutaneous while in adults systemic mastocytosis is more common.

Because mastocytosis can occur in multiple organs, the presenting symptoms can vary greatly. Most of the symptoms occur when mast cells release histamine and other chemicals.

Skin findings are the most common and include:

• Rash: There are several types of rash in mastocytosis. Sometimes it can be tan/brown areas that look like freckles. Other times it looks like red spots on the skin.
• Itching (pruritus): The rash may itch particularly when irritated (rubbed/scratched) or when exposed to a sudden change in temperature (like hot water in the shower). 
• Flushing (red, warm skin)
• Blisters

Other symptoms reflect the organ with areas of mast cell infiltration. Gastrointestinal symptoms are common and include abdominal pain, nausea, vomiting, and diarrhea. Involvement of the muscles and bones may present with pain or osteopenia/osteoporosis (decreased bone strength). Allergic reactions and anaphylactic reactions can also occur with low blood pressure (hypotension), syncope (fainting), fatigue (tiredness), shortness of breath, wheezing or swelling of eyes, lips, tongue or throat. Not all patients have these symptoms.

What Can Trigger Symptoms in Mastocytosis? 

People with mastocytosis don't have symptoms all of the time. Sometimes symptoms are triggered by other things.

• Medications: pain medications (morphine, codeine), non-steroidal anti-inflammatory medications (NSAIDs, like ibuprofen), vancomycin (an antibiotic) or muscle relaxants
• Exercise
• Rubbing skin, particularly the rash associated with mastocytosis
• Extreme temperature changes
• Spicy foods
• Alcohol
• Infections
• Surgery
• Bites and stings from bees, wasps, yellow jackets, hornets, ants, jellyfish or snakes
• Emotional stress

Diagnosis of Mastocytosis

Diagnosis of mastocytosis is predominantly focused on biopsies of the area affected (skin, bone marrow, gastrointestinal tract, etc). Because the symptoms can vary greatly making the diagnosis can be challenging.

The World Health Organization (WHO) has published criteria for the diagnosis of mastocytosis which is reviewed below.

Cutaneous Mastocytosis: Symptoms and skin biopsy are consistent with cutaneous mastocytosis and there are no features consistent with systemic mastocytosis.

Systemic Mastocytosis: Must have either the major criterion, or at least 3 of the 4 minor criteria.

Major criterion: 

• On biopsy (either from bone marrow or affected organ) there must be multiple areas of mast cell infiltration (defined as ≥15 mast cells).

Minor criteria:

• On biopsy (either bone marrow or affected organ): More than 25 percent of the mast cells in the infiltrate are atypical (do not look like normal mast cells)
• Detecting a genetic mutation associated with mastocytosis in blood, bone marrow or other tissue (KIT gene).
• Mast cells in biopsy express some additional markers (CD2 and/or CD25) that normal mast cells do not.
• Tryptase (an enzyme that breaks down the protein found in mast cells) that is more than 20 ng/mL. These levels are usually extremely high in mast cell leukemia, a cancerous form of mast cell disease.

Treatments 

Similar to other similar conditions, the severity of disease determines the treatment needed. General treatment measures are similar for cutaneous and systemic mastocytosis.

1. Avoid triggers reviewed above.
2. Being prepared for anaphylaxis (severe allergic reaction). This includes having epinephrine injections available at home for emergent treatment if needed.
3. Preventative treatment when known triggers are unavoidable. This would include prednisone and anti-histamines (like diphenhydramine) before trigger exposures like vaccines and surgery.
4. Immunotherapy: Immunotherapy, also known as allergy shots for stinging insects like bees, wasps, and ants may be used.
5. Antihistamines: Because symptoms are related to histamine release from mast cells, it is not surprising that your physician may prescribe medications called antihistamines. These would include medications used to treat allergies or itching like cetirizine and hydroxyzine. Other medications include cimetidine, which is more commonly used to treat gastroesophageal reflux.
6. Cromolyn: Cromolyn is an oral medication used to treat gastrointestinal symptoms like abdominal pain and diarrhea triggered by mast cell release of histamine. Sometimes the medication may be compounded into an ointment for skin lesions.
7. Antileukotriene medications: Antileukotriene medications like montelukast and zileuton may be used if symptoms are not controlled with antihistamines.
8. Aspirin: Aspirin can be used to treat flushing of the skin.
9. Tyrosine Kinase Inhibitors (TKI): The KIT gene affected codes for a protein called a tyrosine kinase. The mutation found in mastocytosis increases mast cell accumulation in tissues. Medications called tyrosine kinase inhibitors might be helpful. The most well studied TKI, imatinib, is not effective in mastocytosis. Another TKI, midostaurin, is currently being studied in mastocytosis.
10. Chemotherapy: More aggressive forms of mastocytosis may require treatment with chemotherapy like hydroxyurea and cladribine.

Mastocytosis can be a challenging disorder to understand. You may need multiple specialty physicians to reach the diagnosis and optimize your treatment.