A random urine test panel aids in diagnosing mast cell activation syndrome (MCAS), a complex condition often misdiagnosed due to overlapping symptoms. The panel improves access, speeds up diagnosis, and enables individualized treatment by detecting key mast cell mediators.
Patients often aren’t aware they have mast cell activation syndrome (MCAS), a condition that presents with hives, shortness of breath, vomiting, diarrhea, and other anaphylactic symptoms, and can be life-threatening. Mast cells are white blood cells that play a crucial role in our immune system. With this condition, mast cells mistakenly alert your immune system that something is wrong.
“Patients with MCAS experience recurrent episodes, often described as ‘spells’, that resemble anaphylaxis,” says Patrick Vanderboom, Ph.D., M.S., a consultant in Mayo Clinic’s Division of Clinical Biochemistry and Immunology. “These episodes are unpredictable and are caused by the release of mast cell mediators.”
Because symptoms usually involve more than one organ system, MCAS can imitate other diseases, which means affected patients can experience lengthy diagnostic delays while seeing various specialists to try to find answers. Adding to its diagnostic complexity, this syndrome falls into three categorizations: primary MCAS, when there’s a clonal proliferation of mast cells (or KIT mutation); secondary MCAS, which is from an underlying disorder causing mast cell activation; and idiopathic MCAS, a classification when the other two criteria (primary and secondary) are not met.
Further, traditional testing for MCAS activation, which measures tryptase (an enzyme found within mast cells) levels in serum, has limitations: blood must be collected by a trained professional within one to four hours after the suspected episode.
To mitigate life-threatening diagnostic delays, Mayo Clinic has introduced a commercially available random urine panel (Mayo ID: MCMRU) that measures mast cell mediators. The panel includes three biomarkers that indicate if mast cells have been activated: N-methylhistamine (NMH); leukotriene E4 (LTE4); and 2,3-Dinor-11beta-prostaglandin F2 alpha (2,3 BPG) (Mayo IDs: NMHR, RLTE4, 23BPT, respectively).
“One of the nice things about this random urine panel is Dr. (Joseph) Butterfield and Dr. (Dayne) Volker have championed them as mail-in tests,” says Dr. Vanderboom. “For many, it can be difficult to get a blood draw immediately after experiencing an episode. For patients who live in rural areas, obtaining serum within this short time window is a challenge. Collecting urine at home after a spell is much more convenient and has really helped our physicians provide timely diagnoses for these patients.”
“With a challenging disease state to diagnose, such as mass activation syndrome, these urine mast cell mediators can help provide a bridge to potentially help better diagnose patients with the disease."
— Dayne Voelker, M.D.
An adjunct test to help tailor treatments
The random urine test panel can also be used as an adjunct diagnostic test in scenarios where acute and baseline serum tryptase measurements cannot be readily attained.
“It still allows providers to measure potential mast cell mediator products without having to do an invasive blood draw,” says Dayne Voelker, M.D., an allergist-immunologist, who specializes in mast cell diseases at Mayo. “So it offers these other biomarkers and also helps with potential individualized treatment recommendations based off of test results. With a challenging disease state to diagnose, such as mass activation syndrome, these urine mast cell mediators can help provide a bridge to potentially help better diagnose patients with the disease.”
If one of these mast cell mediators is elevated in a urine sample, there are targeted therapies such as antihistamines or different leukotriene antagonists or prostaglandin inhibitors that can specifically target one of these elevated mediators. Because MCAS has many symptoms and presentations that involve different organ systems, it’s important that treatment be individualized for each patient. Dr. Voelker continues, “These mediators have been shown to be elevated not only in mass cell activation but in other conditions like nasal polyposis, and in patients with chronic hives. So, if one of those products is high, we can do tailored therapy and then provide more individualized treatment for these patients as well.”
Urine Mediator Testing
Urine mediator testing offers a simplified, noninvasive approach to diagnosing mast cell activation syndrome (MCAS). Unlike serum tryptase testing – which requires precise timing and may yield inconclusive results – urine testing allows for stable, reliable measurement of validated mediators from randomly collected samples. This method complements traditional diagnostics and helps guide treatment decisions.
A feedback loop between lab and clinic
The random urine-based mast cell mediator tests, for which Dr. Vanderboom is a specialist, are run in Mayo’s Clinical Mass Spectrometry Laboratory. Another reason this panel is a much-needed diagnostic tool is that traditional tryptase testing can have limitations.
“Harmonizing test results across labs is difficult for any analyte really, but proteins like tryptase can be especially tricky,” says Dr. Vanderboom. “In addition, approximately 5% of the population carries extra copies of alpha-tryptase, resulting in a benign condition known as hereditary alpha-tryptasemia. These patients have elevated baseline levels of tryptase, which can complicate the interpretation of this test.”
Another challenge is that allergists often do not have the expertise to facilitate a diagnostic workup of patients with symptoms not readily explainable by a mast cell activation process. But Mayo Clinic is well-equipped to offer this random urine test panel and to diagnose the syndrome.
“I think Mayo as an institution has done a lot of the clinical studies that demonstrate the utility of this panel, and that feedback has come to us as a lab,” says Dr. Vanderboom. “We've incorporated as much of that information as we can to improve the tests, for example.”
Dr. Voelker adds his perspective: “We have experts in the field of mast cell disorders, including mast cell activation syndrome as well as mastocytosis. So I think our clinical experience, along with the laboratory capabilities, uniquely sets us up as one of the few centers in the country to readily diagnose mast cell activation syndrome and to provide optimal treatment for these patients.”
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