What is the appropriate management for a patient presenting with fatigue, blurred vision, and elevated tryptase levels?

Management of Discrete Symptoms: Fatigue, Blurred Vision, and Elevated Tryptase

The priority is to determine whether the elevated tryptase represents a baseline elevation requiring diagnostic workup for systemic mastocytosis versus acute mast cell activation, while simultaneously evaluating common causes of fatigue and blurred vision that are unrelated to tryptase elevation. 1

Critical Initial Distinction

Elevated tryptase measured during an asymptomatic period does not constitute acute mast cell activation and should not be treated as anaphylaxis. 1 The key question is: when was the tryptase measured relative to symptoms?

• If tryptase was measured during or within 1-4 hours of acute systemic symptoms (hypotension, bronchospasm, urticaria affecting multiple organ systems), this represents acute mast cell degranulation requiring emergency anaphylaxis protocols 2
• If tryptase was measured when the patient was asymptomatic or only experiencing fatigue and blurred vision, this represents baseline tryptase requiring diagnostic evaluation for underlying mast cell disorders 1, 2

Baseline Tryptase Interpretation and Workup

A baseline tryptase >20 ng/mL is a minor diagnostic criterion for systemic mastocytosis and mandates bone marrow evaluation. 1, 2

Tryptase Level Stratification:

• Tryptase 8-20 ng/mL: May indicate hereditary alpha-tryptasemia (affects 5-7% of population), requires clinical correlation and genetic testing consideration 1
• Tryptase >20 ng/mL: Meets minor criterion for systemic mastocytosis; bone marrow aspiration and biopsy with immunohistochemistry (CD117, CD25, CD2) and KIT D816V mutation testing is mandatory 2
• Tryptase >200 ng/mL: Indicates high mast cell burden requiring urgent hematology referral and possible hospitalization; strongly suggests advanced systemic mastocytosis or mast cell leukemia 3, 2

Required Diagnostic Evaluation:

• Thorough skin examination for urticaria pigmentosa, mastocytomas, or positive Darier's sign (wheal formation with stroking) 1, 3
• 24-hour urine histamine metabolites to evaluate for ongoing mast cell activation 1
• Complete blood count with differential to assess for associated hematologic disorders 4
• Review for risk factors: history of severe anaphylaxis to insect stings, unexplained osteoporosis, hepatosplenomegaly 2

Addressing Fatigue and Blurred Vision

Elevated baseline tryptase alone should not be assumed to explain fatigue, and common causes of fatigue must be evaluated independently of tryptase level. 1

Common Causes to Evaluate:

• Anemia, thyroid dysfunction, diabetes mellitus (which could also explain blurred vision), vitamin deficiencies, sleep disorders, depression 1
• Blurred vision specifically requires ophthalmologic evaluation to rule out refractive errors, cataracts, diabetic retinopathy, or other ocular pathology unrelated to mast cell disorders 1
• Fatigue in systemic mastocytosis, when present, typically occurs with other mast cell mediator symptoms (flushing, pruritus, gastrointestinal distress, cardiovascular instability) 3

Management Based on Diagnosis

If Hereditary Alpha-Tryptasemia (Tryptase 8-20 ng/mL):

• Prescribe epinephrine auto-injectors for potential severe reactions 1
• Provide trigger avoidance education (temperature extremes, alcohol, certain medications, physical stimuli) 3
• Educate on recognition of mast cell activation symptoms requiring emergency treatment 1

If Systemic Mastocytosis Confirmed (Tryptase >20 ng/mL with bone marrow criteria):

• Antimediator therapy: H1 antihistamines (cetirizine, loratadine), H2 antihistamines (ranitidine, famotidine), and leukotriene inhibitors (montelukast) 1, 2
• Cromolyn sodium for gastrointestinal symptoms 3
• Mandatory epinephrine auto-injectors and Medic Alert identification 2
• Trigger avoidance counseling (hot water, alcohol, NSAIDs, opioids, physical/emotional stress) 3
• Referral to hematologist for disease monitoring and consideration of cytoreductive therapy if advanced disease 1, 2

If Mast Cell Activation Syndrome (requires acute tryptase elevation >20% + 2 μg/L above baseline on ≥2 occasions with multi-organ symptoms):

• Similar antimediator therapy as systemic mastocytosis 1
• Epinephrine auto-injectors 1
• Aggressive trigger identification and avoidance 3

Critical Pitfalls to Avoid

• Never treat asymptomatic tryptase elevation with epinephrine or emergency anaphylaxis protocols 1
• Do not assume normal tryptase excludes anaphylaxis—anaphylaxis can occur through basophil or complement activation pathways without tryptase elevation 2
• Do not rely on single elevated tryptase measurement—obtain both acute (if symptoms occur) and baseline values separated by >24 hours to calculate the diagnostic ratio 2
• Do not attribute all symptoms to tryptase elevation—fatigue and blurred vision require independent evaluation for common medical causes 1

Monitoring and Follow-Up

• Patients with baseline tryptase >20 ng/mL or confirmed systemic mastocytosis require hematology referral 1
• Annual monitoring of tryptase levels to assess disease burden in diagnosed systemic mastocytosis 1
• Serial tryptase measurements during any future acute systemic symptoms: initial sample as soon as feasible, second at 1-2 hours after symptom onset, third at 24 hours or in convalescence 3, 2