How is mast cell inflammation managed?

Management of Mast Cell Inflammation

Start with H1 antihistamines as first-line therapy, add H2 antihistamines for gastrointestinal symptoms, prescribe an epinephrine autoinjector for all patients, and use oral cromolyn sodium for refractory gastrointestinal manifestations. 1, 2, 3

First-Line Pharmacotherapy

H1 Antihistamines

• Begin with nonsedating H1 antihistamines such as cetirizine or fexofenadine to control pruritus, flushing, urticaria, and tachycardia 1, 2, 3
• Doses may need to be increased to 2-4 times the standard FDA-approved levels for adequate symptom control, though high doses require monitoring for cardiotoxicity 2, 3
• Sedating options (diphenhydramine, hydroxyzine, cyproheptadine) are available but carry risks of cognitive decline, particularly in elderly patients, and impaired driving ability 1, 3
• Ketotifen, available as a compounded medication, can treat dermatologic, gastrointestinal, and neuropsychiatric symptoms 1

H2 Antihistamines

• Add H2 blockers (ranitidine or famotidine) when gastrointestinal symptoms persist despite H1 antihistamines alone 1, 2, 3
• Combined H1 and H2 therapy is particularly effective for severe pruritus, wheal formation, and cardiovascular symptoms when monotherapy fails 2, 3
• H2 antihistamines prevent histamine-mediated acid secretion and blunt vasoactive effects of histamine 1

Second-Line Therapies

Oral Cromolyn Sodium

• Use oral cromolyn predominantly for gastrointestinal symptoms including abdominal bloating, diarrhea, cramps, nausea, and vomiting 1, 3, 4
• Start at the lowest dose and gradually increase to 200 mg four times daily (before each meal and at bedtime) 1
• Counsel patients that onset of action is delayed; continue for at least 1 month before assessing efficacy 1
• Benefits may extend to neuropsychiatric manifestations and pruritus when applied topically 1, 3
• Only 0.28-0.50% of the oral dose is absorbed systemically, with the remainder excreted in feces 4

Leukotriene Modifiers

• Add montelukast, zafirlukast, or zileuton when urinary LTE4 levels are elevated 1, 3
• These agents work best in conjunction with H1 antihistamines and are most efficacious for dermatologic symptoms 1
• Particularly useful for bronchospasm or gastrointestinal symptoms 3

Aspirin

• Use aspirin to attenuate refractory flushing and hypotensive episodes associated with prostaglandin D2 secretion 1, 3
• Must be introduced in a controlled clinical setting due to risk of triggering mast cell degranulation 1
• Contraindicated in patients with allergic reactions to NSAIDs 3

Emergency Management

Epinephrine

• Every patient with mast cell inflammation must be prescribed an epinephrine autoinjector 2, 3
• Administer intramuscularly in a recumbent (supine) position immediately for hypotension, wheezing, laryngeal edema, cyanosis, or anaphylaxis 2, 3
• Patients with recurrent hypotensive episodes should be trained to assume supine position immediately 3
• Transport to emergency department while maintaining supine position after epinephrine use 3

Acute Bronchospasm

• Albuterol via nebulizer or metered-dose inhaler treats acute bronchospasm 3

Advanced Therapies for Refractory Cases

Omalizumab (Anti-IgE)

• Consider omalizumab for cases resistant to mediator-targeted therapies 1
• Reduces severity and frequency of allergic reactions and prevents spontaneous anaphylaxis episodes 1
• Particularly beneficial in preventing emergency department visits and lost work time despite high cost 1

Glucocorticosteroids

• Systemic steroids may help some patients but should be tapered as quickly as possible to limit adverse effects 1
• Long-term steroid use should be avoided 3

Cytoreductive Therapies

• Reserve for patients with clonal mast cell activation syndrome in advanced systemic mastocytosis with symptoms refractory to antimediator therapy 1
• Options include interferon-alpha (associated with flu-like symptoms, depression, hypothyroidism, autoimmune disorders) and cladribine (increased infection risk) 1
• Midostaurin, a multikinase inhibitor approved for advanced systemic mastocytosis, can replace interferon-alpha and cladribine 1
• Starting dose is 100 mg twice daily with food; nausea controlled with ondansetron 30-60 minutes before dosing 1

Trigger Avoidance

Environmental and Physical Triggers

• Identify and avoid temperature extremes (hot temperatures more than cold), mechanical irritation, and alcohol 1, 2, 3
• Rational use of baths, showers, swimming pools, and air conditioning decreases symptoms and reduces antihistamine requirements 2

Medication Triggers

• Avoid aspirin (unless specifically prescribed for prostaglandin D2-mediated symptoms), radiocontrast agents, and specific anesthetic agents 3
• For insect venom sensitivity with history of systemic anaphylaxis, lifelong venom immunotherapy is recommended 3

Psychological Triggers

• Avoid anxiety and stress, as they trigger mast cell activation 2
• Control pain with safer opioid options including fentanyl and remifentanil 1, 2

Perioperative Management

Preoperative Preparation

• Multidisciplinary management involving surgical, anesthesia, and perioperative medical teams is essential 1, 3
• Pre-anesthetic treatment with anxiolytics (benzodiazepines), H1 and H2 antihistamines, and possibly corticosteroids 1, 3

Safer Anesthetic Agents

• Use propofol for induction; sevoflurane or isoflurane for inhalation 1, 3
• Analgesics: fentanyl or remifentanil 1, 3
• Local anesthetics: lidocaine, bupivacaine 1, 3
• Skin antiseptics: povidone-iodine 1

Agents to Avoid

• Avoid muscle relaxants atracurium and mivacurium (rocuronium and vecuronium may be safer) and succinylcholine 1, 3
• Exercise caution with opiates (codeine, morphine), but do not withhold analgesics as pain triggers mast cell activation 1

Acute Perioperative Reactions

• Discontinue suspected drug or anesthetic agent, provide fluid resuscitation, and administer intravenous epinephrine for severe reactions 1
• Use corticosteroids and antihistamines (H1 and H2 blockers) as adjuncts 1
• Check serum tryptase within 30-120 minutes of symptom onset and measure baseline level after full recovery 1

Pregnancy Management

Multidisciplinary Approach

• Management requires high-risk obstetrics, anesthesia, and allergy specialists 1, 3
• A diagnosis of systemic mastocytosis does not appear to affect fertility 1

Medication Safety

• Focus on trigger avoidance, prophylactic antihistamines, as-needed corticosteroids, and epinephrine for anaphylaxis 1, 3
• For severe cases refractory to conventional therapy, interferon-alfa can be considered 1
• Do not use cladribine or tyrosine kinase inhibitors (imatinib, midostaurin) during pregnancy 1

Treatment Monitoring and Tailoring

Mediator-Directed Therapy

• Tailor therapeutic intervention to elevated mediator levels: leukotriene antagonists for increased urinary LTE4, aspirin for increased urinary prostaglandin metabolites 1, 3
• This approach optimizes symptom control by targeting the specific mediators driving each patient's manifestations 1, 3

Education and Communication

• Educate parents, caregivers, pediatricians, teachers, school nurses, and daycare workers about diagnosis, treatment, and potential risks 2
• Communication directly improves quality of life 2

Prognosis

• Patients with indolent systemic mastocytosis generally have normal life expectancy 1, 3
• In children, symptoms usually improve significantly after the first 6-18 months, with many experiencing spontaneous resolution with age 2
• Some patients with clonal mast cell activation syndrome can progress to systemic mastocytosis, most likely indolent systemic mastocytosis 1, 3

Common Pitfalls

• Avoid eliminating drug additives by compounding, as this is not supported by evidence from chronic urticaria studies 3
• Monitor for cognitive decline with sedating antihistamines, especially in elderly patients 1, 3
• Do not withhold analgesics perioperatively despite mast cell concerns, as pain itself triggers activation 1