What is the treatment for mast cell syndrome?

Treatment of Mast Cell Activation Syndrome

Begin treatment with H1 antihistamines as first-line therapy, add H2 antihistamines for gastrointestinal symptoms, prescribe an epinephrine autoinjector for all patients, and implement strict trigger avoidance. 1, 2

First-Line Pharmacologic Management

H1 Antihistamines

• Start with nonsedating H1 antihistamines (cetirizine, loratadine, fexofenadine) as the foundation of therapy to control flushing, pruritus, tachycardia, and dermatologic manifestations 1, 2
• Doses may need to be increased to 2-4 times the standard FDA-approved dose for adequate symptom control, though high doses require cardiac monitoring for potential cardiotoxicity 1, 2
• Sedating H1 antihistamines (diphenhydramine, hydroxyzine) are alternatives but carry risk of drowsiness, impaired driving ability, and cognitive decline particularly in elderly patients 1
• These medications work prophylactically rather than acutely—once symptoms appear, it is too late to block histamine already bound to receptors 1

H2 Antihistamines

• Add H2 antihistamines (famotidine, ranitidine) when gastrointestinal symptoms persist despite H1 antihistamine monotherapy 1, 2, 3
• Combined H1 and H2 therapy is particularly effective for severe pruritus and wheal formation when monotherapy fails 2
• H2 blockers also help attenuate cardiovascular symptoms when used alongside H1 antihistamines 1

Mast Cell Stabilizers

• Oral cromolyn sodium reduces abdominal bloating, diarrhea, and cramps, with potential benefit extending to neuropsychiatric manifestations 1, 4
• Use divided dosing with weekly upward titration to the target dose to improve tolerance and adherence 1
• FDA-approved specifically for mastocytosis with documented improvement in diarrhea, flushing, headaches, vomiting, urticaria, abdominal pain, nausea, and itching 4

Emergency Management

Epinephrine Autoinjector

• Every patient with mast cell activation syndrome must be prescribed an epinephrine autoinjector with caregiver training in its use 2
• Administer intramuscularly in a recumbent position immediately for hypotension, wheezing, laryngeal edema, cyanotic episodes, or recurrent anaphylactic attacks 2
• Patients with history of systemic anaphylaxis or airway angioedema require this device with clear instructions on when and how to use it 1

Acute Episode Management

• Position patients supine as soon as possible during hypotensive episodes, using bedpan for diarrhea and emesis basin after rolling to side or abdomen 1
• Inhaled bronchodilators (albuterol via nebulizer or metered-dose inhaler) treat bronchospasm symptoms 1
• Discontinue suspected triggering drugs or agents, provide fluid resuscitation, and use intravenous epinephrine for severe reactions 1

Second-Line and Adjunctive Therapies

Leukotriene Modifiers

• Montelukast or zileuton may reduce bronchospasm or gastrointestinal symptoms, particularly if urinary LTE4 levels are elevated 1
• These agents are not well-studied but can be considered when first-line therapies are insufficient 1

Aspirin

• Consider aspirin to reduce flushing and hypotension in patients with increased urinary 11β-PGF2α levels 1
• Contraindicated in patients with allergic or adverse reactions to nonsteroidal anti-inflammatory drugs 1
• Clinical improvement may require dosing up to 650 mg twice daily as tolerated, but use with caution 1

Corticosteroids

• Reserve steroid tapers or bursts for refractory signs or symptoms at initial oral dosage of 0.5 mg/kg/day, followed by slow taper over 1-3 months 1
• Consider 50 mg prednisone at 13 hours, 7 hours, and 1 hour before radiologic or invasive procedures when mast cell activation has been problematic 1
• Steroid side effects limit enthusiasm for long-term use 1

Alternative Antihistamines

• Doxepin, a potent H1 and H2 antihistamine with tricyclic antidepressant activity, may reduce central nervous system manifestations but carries risk of drowsiness, cognitive decline in elderly, and increased suicidal tendencies in children and young adults with depression 1
• Cyproheptadine, a sedating H1 antihistamine with anticholinergic and antiserotonergic activities, may help gastrointestinal symptoms 1

Biologic Therapy

• Omalizumab has case reports showing prevention of anaphylactic episodes in some patients with MCAS or in those who cannot otherwise tolerate needed insect venom immunotherapy 1

Trigger Avoidance and Environmental Control

Temperature Management

• Mast cells are activated by hot temperatures and to a lesser extent cold temperatures 2
• Rational use of baths, showers, swimming pools, and air conditioning can decrease symptoms and reduce need for antihistamines 2

Psychological and Pain Management

• Avoid anxiety and stress as they trigger mast cell activation 2
• Control pain as it also triggers mast cell activation, with safer opioid options including fentanyl and remifentanil 2
• Avoid codeine and morphine, but do not withhold analgesics since pain itself is a trigger 1

Perioperative Considerations

• Safer anesthetic agents include propofol for induction, sevoflurane or isoflurane for inhalation, fentanyl or remifentanil for analgesia, and lidocaine or bupivacaine for local anesthesia 1
• Avoid muscle relaxants atracurium and mivacurium (rocuronium and vecuronium may be safer) and succinylcholine 1

Advanced Therapies for Refractory Disease

Cytoreductive Therapy

• Midostaurin at 100 mg twice daily with food is indicated for patients with clonal mast cell syndromes requiring reduction in mast cell numbers to prevent severe symptoms or disease progression 1
• Monitor for hematologic toxicities with dose adjustments based on ANC and platelet counts 1
• Interferon-alfa can be considered for severe cases during pregnancy refractory to conventional therapy 1

Critical Pitfalls to Avoid

• MCAS is substantially overdiagnosed—do not diagnose based solely on nonspecific symptoms, single organ system involvement, or symptoms without documented mediator elevation 5
• Cognitive decline has been reported for H1 blockers with anticholinergic effects, especially worrisome in elderly populations 1
• Antihistamines work prophylactically, not acutely, so consistent daily dosing is essential rather than as-needed use 1
• Diagnosis requires episodic symptoms affecting at least two organ systems, documented mediator elevation on at least two occasions, and clinical response to mast cell-targeted therapies 5