What is mastocytosis (Mast Cell Disorder)?

From the Guidelines

Mastocytosis patients should be managed with a multidisciplinary approach, including referral to specialized centers, counseling on signs and symptoms of disease, avoidance of known triggers, and carrying injectable epinephrine for anaphylaxis, as recommended by the NCCN guidelines 1.

Treatment Considerations

The management of mastocytosis involves a comprehensive approach to control symptoms and prevent complications.

• H1 antihistamines like cetirizine (10mg daily) or fexofenadine (180mg daily) can help control itching and flushing.
• H2 blockers such as ranitidine (150mg twice daily) or famotidine (20mg twice daily) address gastrointestinal symptoms.
• Mast cell stabilizers like cromolyn sodium (200mg four times daily) can prevent mast cell degranulation.
• For severe systemic cases, tyrosine kinase inhibitors such as midostaurin (100mg twice daily) may be prescribed, as suggested by the NCCN guidelines 1.

Perioperative Management

Patients with mastocytosis undergoing surgical procedures require careful management to prevent mast cell activation, including the use of perioperative drugs, analgesics, and caution with opioids, as well as being prepared for potential anaphylaxis, as outlined in the NCCN guidelines 1.

Monitoring and Follow-up

Regular monitoring by specialists is essential, as mastocytosis can progress over time, and patients should be educated on the signs and symptoms of disease, as well as the importance of avoiding known triggers, as recommended by the NCCN guidelines 1. The condition results from genetic mutations (particularly KIT D816V) that cause mast cells to proliferate excessively and release inflammatory mediators like histamine, leukotrienes, and prostaglandins, leading to the characteristic symptoms of the disease, as discussed in the NCCN guidelines 1.

From the Research

Definition and Classification of Mastocytosis

• Mastocytosis denotes a wide range of disorders characterized by having abnormal growth and accumulation of mast cells 2.
• It is classified into cutaneous mastocytosis (CM) and systemic mastocytosis (SM), with CM being the most common form of mastocytosis, affecting predominantly children 3.
• Systemic mastocytosis comprises multiple distinct entities in which mast cells infiltrate the skin and/or other organs 3.

Symptoms and Clinical Presentation

• Symptoms of mastocytosis can include flushing, pruritus, nausea, vomiting, abdominal pain, diarrhea, vascular instability, and headache 2.
• Cutaneous mastocytosis symptoms include pruritus, flushing urticaria, and dermatographism, while systemic mastocytosis symptoms include cutaneous symptoms in association with syncope, gastric distress, nausea and vomiting, diarrhea, bone pain, and neuropsychiatric symptoms 3.
• The clinical features of mastocytosis generally divide into cutaneous and systemic manifestations 2.

Diagnosis and Risk Stratification

• The diagnosis of systemic mastocytosis is based on the presence of one major criterion and one minor criterion or three minor criteria 3.
• Major criteria include the presence of multifocal dense infiltrates of > 15 mast cells in bone marrow and/or other extracutaneous organs 3.
• Minor criteria include the presence of elevated serum alpha-tryptase levels > 20 ng/mL, the expression of CD2 and CD25 surface markers in c-kit-positive mast cells from bone marrow or other organs, the presence of a c-kit mutation on bone marrow and/or other tissues mast cells, and the presence of > 25% abnormal spindle-shaped mast cells in bone marrow and/or tissues 3.
• Identification of poor-risk mutations (ie, ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification 4, 5.

Treatment and Management

• Treatment is aimed at avoiding mast cell degranulation, inhibiting the actions of the constitutive mediators released by mast cells and, in severe cases, cytoreductive and polychemotherapeutic agents 2.
• Behavioral intervention includes avoidance of triggers, such as heat, cold, pressure, exercise, sunlight, and strong emotions 2.
• Treatment for released histamine and other inflammatory mediators includes H1 antihistamines, H2 antihistamines, proton pump inhibitors, anti-leukotriene agents, and injectible epinephrine (for possible anaphylaxis) 2.
• High response rates have been seen with small-molecule inhibitors that target mutant-KIT, including midostaurin (Food and Drug Administration approved) or avapritinib (investigational) 4, 5.
• Other options for MC cytoreduction include cladribine or interferon-α, although head-to-head comparisons are lacking 4, 5, 6.