What is the best course of action for a patient with elevated tryptase levels and eye symptoms, potentially indicating a mast cell disorder or severe allergic reaction?

Management of Elevated Tryptase with Eye Symptoms

If you have a patient with elevated tryptase and eye symptoms, immediately assess whether this represents acute mast cell activation requiring emergency treatment, or chronic mast cell disease requiring diagnostic workup—the presence of ocular involvement alongside elevated tryptase strongly suggests active mast cell degranulation affecting multiple organ systems. 1, 2

Immediate Clinical Assessment

Determine Timing and Acuity

• If tryptase was measured during or within 1-4 hours of acute eye symptoms (conjunctival injection, periorbital edema, tearing, pruritus), this represents acute mast cell degranulation requiring immediate anaphylaxis management. 3
• Eye symptoms combined with any other organ system involvement (cutaneous flushing/urticaria, respiratory distress, cardiovascular instability, gastrointestinal cramping) constitute systemic anaphylaxis requiring emergent treatment. 1
• Tryptase levels in tear fluid are elevated during active ocular allergic reactions and directly correlate with conjunctival mast cell activation. 2

Emergency Management Protocol (if acute presentation)

• Administer intramuscular epinephrine 0.01 mg/kg immediately into the anterolateral thigh as first-line treatment. 3
• Establish large-bore IV access and administer rapid fluid boluses with normal saline or lactated Ringer's at 5-10 mL/kg in the first 5 minutes, then 20 mL/kg boluses as needed. 3
• Remove all potential causative agents including IV colloids, latex, chlorhexidine, and any recently administered medications. 1
• Administer chlorphenamine 10 mg IV (adult dose) and hydrocortisone 200 mg IV (adult dose). 1
• Obtain three timed blood samples for mast cell tryptase: initial sample as soon as feasible after resuscitation starts, second at 1-2 hours after symptom onset, and third at 24 hours or in convalescence. 1, 3

Diagnostic Workup for Non-Acute Presentations

Establish True Baseline Tryptase

• Repeat tryptase measurement at least 24 hours after complete resolution of all symptoms to obtain a true baseline, as acute measurements may reflect recent mast cell degranulation even without recognized symptoms. 1, 3
• If baseline tryptase remains >20 ng/mL when completely asymptomatic, this meets a minor diagnostic criterion for systemic mastocytosis and mandates bone marrow evaluation. 1, 3, 4
• If baseline tryptase is >200 ng/mL, this indicates high mast cell burden requiring urgent hematology referral and possible hospitalization, as it strongly suggests advanced systemic mastocytosis or mast cell leukemia. 1, 4

Systematic Assessment for Mast Cell Mediator Release

• Examine skin thoroughly for urticaria pigmentosa or mastocytosis lesions; positive Darier's sign (wheal formation with stroking) occurs in 89-94% of cutaneous mastocytosis cases. 1
• Document gastrointestinal symptoms: diarrhea, abdominal cramping, nausea, vomiting, bloating. 1, 3
• Assess cardiovascular symptoms: hypotension, tachycardia, syncope, palpitations, vasomotor instability. 1, 3
• Review for respiratory symptoms: bronchospasm, wheezing, throat swelling. 1
• Specifically inquire about history of severe anaphylaxis to Hymenoptera stings, as this is strongly associated with underlying mastocytosis. 3

Mandatory Bone Marrow Evaluation (if baseline tryptase >20 ng/mL)

• Bone marrow aspiration and core biopsy with immunohistochemistry for CD117, CD25, and CD2 expression on mast cells, KIT D816V mutation testing, and flow cytometry to assess mast cell immunophenotype. 1, 3
• The European Competence Network on Mastocytosis recommends bone marrow examination when serum tryptase is >15 ng/mL and/or KIT D816V mutation is detected. 4
• Evaluation for associated hematologic neoplasms is necessary, as they are present in up to 71% of advanced cases. 3

Consider Hereditary Alpha-Tryptasemia

• Approximately 4-6% of the general population carry germline TPSAB1-α copy number gains, resulting in elevated baseline tryptase without systemic mastocytosis. 1
• Symptomatic individuals with baseline serum tryptase exceeding 6.5 ng/mL should be considered for tryptase genotyping to screen for hereditary alpha-tryptasemia. 5
• Hereditary alpha-tryptasemia is associated with flushing, pruritus, dysautonomia, gastrointestinal symptoms, chronic pain, and joint hypermobility. 1

Long-Term Management and Symptom Control

Antimediator Therapy for Ocular and Systemic Symptoms

• H1 antihistamines for urticaria, pruritus, flushing, and ocular symptoms (conjunctival injection, tearing, itching). 1, 3
• H2 antihistamines for gastrointestinal symptoms and as adjunctive therapy for cutaneous symptoms. 1, 3
• Cromolyn sodium inhibits mast cell degranulation and may provide benefit for both ocular and gastrointestinal symptoms; approximately 8% is absorbed after administration with rapid excretion. 6
• Leukotriene receptor antagonists as adjunctive therapy for symptom control. 1, 3

Mandatory Safety Measures

• All patients with confirmed elevated baseline tryptase require two epinephrine auto-injectors to carry at all times, even if currently asymptomatic. 1, 3
• Provide Medic Alert identification documenting elevated tryptase and anaphylaxis risk. 1, 3
• Educate on avoiding mast cell degranulation triggers: extreme temperatures, physical trauma to skin, alcohol, NSAIDs, opioids (especially codeine/morphine), certain antibiotics, contrast media, stress, vigorous exercise, hot water exposure. 3

Perioperative Precautions

• If surgery is required, notify the anesthesia team of elevated tryptase; use fentanyl or sufentanil rather than morphine or meperidine, avoid ketorolac, and have emergency anaphylaxis protocols ready. 3
• Obtain baseline coagulation studies before procedures. 3
• Subjects with clonal mast cell disorders are at higher risk of severe reactions with either specific or non-specific triggers during anesthesia. 7

Ongoing Monitoring Strategy

• Annual tryptase monitoring is recommended to assess disease burden in patients with confirmed systemic mastocytosis. 1, 3
• Establish multidisciplinary care with allergy/immunology and hematology for ongoing symptom management and disease monitoring. 1
• Instruct the patient to maintain a detailed diary documenting episodic symptoms, timing, potential exposures, and activities to identify previously unrecognized triggers. 1

Critical Pitfalls to Avoid

• Do not assume normal tryptase excludes anaphylaxis—anaphylaxis can occur through basophil or complement activation pathways without tryptase elevation. 3
• Do not rely on a single elevated tryptase measurement; obtain both acute and baseline values separated by >24 hours to calculate the diagnostic ratio. 3
• More than 50% of patients with non-mastocytosis conditions (urticaria, angioedema, anaphylactic reactions) can have baseline tryptase levels >20 μg/L, necessitating thorough diagnostic workup including bone marrow biopsy. 8
• The ratio of total tryptase to beta-tryptase can distinguish mastocytosis from acute anaphylaxis: ratio ≤10 suggests anaphylaxis without mastocytosis, while ≥20 suggests systemic mastocytosis. 1