Clinical Approach to MCAS Diagnosis and Cutaneous Mastocytosis
Diagnosis and Treatment of MCAS (Part 3 of 3)
Response to treatment in MCAS
Finally, an integral component in the diagnosis of MCAS is documenting a response to therapeutics which target MC mediators (Table 4) [1]. For instance, if anti-histamines, do not alleviate the patient’s rash or pruritus, the diagnosis of urticaria itself needs to be questioned. H2- blockers or cromolyn should help reduce MC-related GI symptoms. Anti leukotriene agents (receptor antagonists, 5-LO inhibitors) and H2-blockers may be added if inadequate symptom control with H1-inhibition alone. In cases where symptom control remains insufficient, systemic treatment options may be considered. Inhibition of mast cell activation and mast cell cytoreduction therapies include tyrosine kinase inhibitors (imatinib, midostaurin, avapritinib), cladribine, corticosteroids, hydroxyurea, chemotherapy, interferon-α, and even hematopoietic stem cell transplant. Imatinib has a limited role in systemic mastocytosis (SM) treatment, as it targets the minority of patients without the D816V mutation. Midostaurin and avapritinib are both highly selective for D816V-mutated KIT, and both are now FDA-approved for the treatment of aggressive systemic mastocytosis (ASM). Avapritinib has been FDA-approved for the treatment of advanced SM since June 2021 and is the only drug FDA-approved for indolent systemic mastocytosis (ISM).
Table 4: Pharmacotherapy for mast-cell derived symptoms [2, 3, 10, 11, 13]
Organ | Symptoms | Mediators | Treatment/Management |
Pulmonary Upper airway
Lower airway | Sneezing Rhinorrhea Nasal congestion Conjunctivitis Stridor Dyspnea Chest tightness Wheezing Hypoxia | Histamine PDG2 PAF Cysteinyl LTs | -H1 anti-histamines (oral, nasal) -Corticosteroids (nasal, inhaled) -Inhaled epinephrine -Anti-leukotrienes -Omalizumab |
Mucocutaneous | Angioedema Urticaria Flushing Pruritis | Histamine PDG2 PAF Cysteinyl LTs | -H1 and H2 anti histamines -Ketotifen -Rupatadine -Aspirin, NSAIDs -Omalizumab |
Gastrointestinal (GI) | Nausea Emesis Diarrhea Abdominal cramping | Histamine PAF Cysteinyl LTs | -H2 anti-histamines -Cromolyn (oral) -Corticosteroids |
Cardiovascular (CV) | Dizziness Lightheadedness (Pre)syncope Hypotension | Histamine PGD2 PAF Cysteinyl LTs | -If emergency, see treatment below -H1 and H2 anti histamines -Anti-leukotrienes -Omalizumab -Venom immunotherapy, if applicable |
Anaphylaxis (≥ 2 organ systems, hypotension following exposure to known allergen [32]) | See above – also, reports of uterine contractions | Histamine PGD2 PAF Cysteinyl LTs | Dependent upon symptoms: -Epinephrine (IM, gtt) -IV fluids -Oxygen -Albuterol, ipratropium, racemic epinephrine -Position (supine with legs elevated, L decubitus if pregnant – caution with resuming upright position [empty vena cava]) [33] -Glucagon (if on beta blocker and non responsive to epinephrine, IVF; caution re: airway as this can cause emesis)
-May consider beta-2 agonists to treat uterine contractions, NSAIDs for prevention of future uterine contractions (as long as no concern NSAID-related symptoms worsening) [34] |