Mastocytosis: when mast cells accumulate

Mastocytosis: When Mast Cells Accumulate

Mastocytosis is a rare condition where the body produces too many mast cells, which then accumulate in the skin, bone marrow, or internal organs. Mast cells are part of the immune system and contain histamine and other signalling substances normally released during allergic reactions. When there are too many mast cells, or when they are too easily triggered, reactions occur without an allergic explanation. Symptoms can affect anything from the skin to the gastrointestinal tract, heart, and circulatory system.

The disease exists in both a mild form, primarily affecting the skin, and a more severe systemic form involving internal organs. In adults, the systemic form predominates, while in children, the cutaneous form is most common and often resolves with age.

What are the symptoms?

The range of symptoms varies greatly. The most common complaints include:

• Redness and flushing over the face, neck, and chest
• Itchy skin, often without a visible rash, and brownish spots (urticaria pigmentosa) that swell when scratched (Darier's sign)
• Abdominal pain, diarrhoea, nausea, bloating
• Heartburn and ulcer-like discomfort
• Palpitations, dizziness, or sudden drops in blood pressure
• Allergy-like reactions to insect stings, contrast agents, opioids, NSAIDs, or anaesthesia
• Bone pain, particularly in the hips and back, and in severe cases, osteoporosis with fractures
• Fatigue, brain fog, and difficulty concentrating

Many describe symptoms occurring in waves, triggered by heat, alcohol, stress, spicy food, physical exertion, or medication. Anaphylaxis without a known allergen is a serious presenting symptom and should always raise suspicion of mast cell disease.

Why does it happen?

In the vast majority of adults with systemic mastocytosis, a mutation in the KIT gene (D816V) is found, which makes mast cells overactive and prolongs their lifespan. The mutation is acquired, not inherited, and leads to the accumulation of mast cells, particularly in the bone marrow, but also in the gastrointestinal tract, liver, spleen, and lymph nodes.

The disease is classified by its extent and aggressiveness:

• Cutaneous mastocytosis: only the skin is affected, most common in children
• Indolent systemic mastocytosis (ISM): the most common adult form, slow-progressing, not life-shortening
• Smouldering systemic mastocytosis: an intermediate level with a higher mast cell burden
• Aggressive systemic mastocytosis, mast cell leukaemia, and associated haematological disorders: rare, severe forms

Gastrointestinal symptoms are common in the systemic forms and can be the predominant complaint.

How is it diagnosed?

Diagnosis relies on a combination of factors:

1. Blood test for serum tryptase. A persistently elevated value above 20 ng/mL is a minor diagnostic criterion, not proof on its own. It can also be raised in hereditary alpha-tryptasaemia and other conditions, so it is interpreted together with the other investigations.
2. Bone marrow biopsy with special stains for tryptase, CD117, CD25, and CD2, as well as molecular testing for KIT D816V. This is the reference standard in adults suspected of having the systemic form.
3. Skin biopsy for visible changes.
4. DEXA scan to assess bone density.
5. Gastroscopy and colonoscopy with biopsies may be considered for prominent gastrointestinal symptoms to differentiate from conditions like eosinophilic gastroenteritis or microscopic colitis.

It is not uncommon for the diagnosis to be made only after several years of unexplained symptoms. If you experience repeated unexplained anaphylactic episodes or an unexplained elevated tryptase level, you should be referred to a specialist department.

Treatment

Treatment is symptomatic for most patients. The goal is to reduce mast cell degranulation and prevent severe reactions.

Trigger avoidance is key:

• Know your personal triggers (heat, alcohol, spicy food, exertion, stress)
• Carry an adrenaline auto-injector if you have experienced severe reactions
• Always inform your anaesthetist, surgeon, and dentist before procedures and contrast examinations

Symptom-controlled medication:

• Antihistamines (H1) taken around the clock for itching, flushing, and urticaria
• H2 blockers or PPIs for stomach acid and reflux
• Sodium cromoglicate can alleviate gastrointestinal symptoms
• Montelukast for asthma-like symptoms or flushing
• Aspirin may be used cautiously for flushing under specialist guidance

Bones: Vitamin D, calcium, and bisphosphonates for osteoporosis.

For aggressive forms, targeted treatment with tyrosine kinase inhibitors such as midostaurin or avapritinib is used to inhibit the mutated KIT receptor. These are specialist treatments managed by a haematology department.

When should you see a doctor?

Contact your GP if you have:

• Repeated unexplained anaphylactic episodes, especially after insect stings
• Chronic itching and brownish spots that swell when scratched
• Recurrent abdominal pain, diarrhoea, and flushing without explanation
• Symptoms of low blood pressure or fainting without a cardiac explanation
• Unexplained bone loss or fractures without significant trauma

Call 112 for severe anaphylaxis: difficulty breathing, swelling of the face or throat, a sudden drop in blood pressure, or collapse. If you have been prescribed an adrenaline auto-injector, use it immediately according to your personal instructions.

Frequently Asked Questions

Is mastocytosis an allergy? No, it is a disease of the mast cells themselves. They are overactive or too numerous. The reactions resemble allergies but occur without an external allergen.

Is it hereditary? The KIT D816V mutation is acquired, not hereditary, and family clustering is rare. Children with cutaneous mastocytosis usually have parents without the condition.

Can it be cured? Indolent systemic mastocytosis cannot be cured but can be well-controlled with trigger avoidance and symptomatic medication. Life expectancy is normal or near-normal. Aggressive forms require targeted medication.

What about pregnancy and childbirth? Most women manage pregnancy well with good planning. The anaesthetist must be informed, and the medication list reviewed. Refer to a specialist department early.

What about vaccination? Standard vaccinations can generally be given. Pre-treatment with antihistamines and observation may be relevant for known strong reactions.

Sources

1. Valent P, Akin C, Hartmann K, et al. Updated diagnostic criteria and classification of mast cell disorders: A consensus proposal. Hemasphere. 2021;5(11):e646. PubMed
2. Gotlib J, Castells M, Elberink HO, et al. Avapritinib versus best available therapy in advanced systemic mastocytosis. Nat Med. 2021;27(12):2183-2191.
3. Sundhed.dk. Mastocytose (lægehåndbogen).
4. Pardanani A. Systemic mastocytosis in adults: 2023 update on diagnosis, risk stratification and management. Am J Hematol. 2023;98(7):1097-1116. PubMed

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This article provides general information and is not a substitute for medical consultation. Please contact your GP if you experience symptoms.