What is the best course of action for a patient with a suspected mast cell disorder, presenting with shiny, almost metallic-looking light brown stools for months, normal fecal qualitative fat, and normal elastase levels?

Evaluation and Management of Shiny Metallic-Looking Stools in Suspected Mast Cell Disorder

The shiny, metallic-appearing light brown stools in this patient with suspected mast cell disorder most likely represent bile acid malabsorption or altered bile metabolism related to mast cell mediator effects on the gastrointestinal tract, and the patient should be evaluated with baseline serum tryptase, symptom-triggered tryptase testing, and consideration of oral cromolyn sodium for gastrointestinal symptom management.

Understanding the Clinical Presentation

The shiny, almost metallic appearance of stools typically indicates excess fat or bile acids, but with normal fecal qualitative fat and elastase, this suggests:

• Bile acid malabsorption is the most likely explanation, as mast cell mediators (particularly histamine and prostaglandins) can accelerate intestinal transit and impair bile acid reabsorption in the terminal ileum 1, 2
• Mast cell mediator-induced diarrhea commonly presents with loose, frequent stools that may have unusual appearance due to rapid transit and altered bile metabolism 3
• The normal pancreatic elastase excludes exocrine pancreatic insufficiency as the cause 4

Diagnostic Approach

Essential Mast Cell Testing

• Obtain baseline serum tryptase when the patient is completely asymptomatic to establish their personal reference value 4, 5
• Collect acute serum tryptase 1-4 hours after symptom onset during episodes of diarrhea or other systemic symptoms 4, 5
• Diagnostic threshold: An increase of ≥20% above baseline PLUS an absolute increase of ≥2 ng/mL confirms mast cell activation 4, 5
• If baseline tryptase is persistently >20 ng/mL, bone marrow biopsy is indicated to evaluate for systemic mastocytosis 4

Additional Testing to Consider

• 24-hour urine collection for N-methylhistamine, leukotriene E4, and 11β-prostaglandin F2α if serum tryptase testing is negative or difficult to obtain during symptomatic episodes 5
• Peripheral blood KIT D816V mutation testing using highly sensitive allele-specific oligonucleotide quantitative PCR to identify clonal mast cell activation syndrome 4, 5
• Evaluate for associated conditions: Measure postural vital signs with active stand test (heart rate increase ≥30 beats/min within 10 minutes) to screen for POTS, which commonly coexists with mast cell disorders 4

What NOT to Test

• Do NOT routinely count mast cells on endoscopic biopsies for isolated GI symptoms without evidence of generalized mast cell disorder, as the threshold distinguishing normal from abnormal is debated and overlap with normal patients is too great to be clinically useful 4, 6
• Avoid plasma or urine histamine levels, as N-methylhistamine is more reliable 5
• Do NOT test heparin or chromogranin A, as these are not validated markers for mast cell activation 5

Treatment Strategy

First-Line Therapy for GI Symptoms

• Oral cromolyn sodium 200 mg four times daily is FDA-approved for mastocytosis and has demonstrated improvement in diarrhea, abdominal pain, nausea, and vomiting in clinical trials 7
• Clinical improvement typically occurs within 2-6 weeks of treatment initiation 7
• Add H1 antihistamines (cetirizine or fexofenadine) at 2-4 times standard FDA-approved doses 5, 8
• Add H2 antihistamines (famotidine) to enhance symptom control by blocking additional histamine pathways 5, 8

Second-Line Options

• Leukotriene antagonists (montelukast or zileuton) if urinary leukotriene E4 is elevated or inadequate response to antihistamines 5, 8
• Consider aspirin therapy if urinary 11β-prostaglandin F2α is elevated, but use with caution due to risk of paradoxical mast cell activation 5, 8

When to Refer

• Refer to allergy specialist or mast cell disease research center if diagnosis is supported through clinical and/or laboratory features 4, 5
• Refer to gastroenterology if symptoms remain refractory to first-line mast cell-targeted therapy for evaluation of other causes of diarrhea 4

Critical Pitfalls to Avoid

• Do not assume functional GI disorder without first evaluating for mast cell activation, as GI symptoms are among the most frequent and debilitating manifestations of mast cell disorders 1, 2, 3
• Do not delay treatment while waiting for definitive diagnosis, as empiric trial of cromolyn sodium and antihistamines is safe and may provide rapid symptom relief 7
• Do not perform extensive endoscopic evaluation solely to count mast cells, as this has poor diagnostic utility for mast cell activation syndrome 4, 6
• Recognize that normal tryptase does not exclude mast cell activation syndrome, as serum tryptase may be <20 ng/mL or only transiently elevated 4, 5