Brigham and Women’s Hospital (BWH) gastroenterologists Norton J. Greenberger, MD, and Matthew J. Hamilton, MD, specialize in the diagnosis and treatment of mast cell disorders involving the gastrointestinal tract. An integral part of the Mastocytosis Center at BWH, they collaborate closely with allergists, immunologists, and pathologists to optimize the care of patients and advance the diagnosis and treatment of mast cell disease.
The team characterized the clinical manifestations of mast cell activation syndrome (MCAS) by examining MCAS patients seen at BWH over a three-year period (J Allergy Clin Immunol. 2011 Jul;128(1):147-152.e2.). Patients enrolled in the study had at least four of the signs and symptoms of abdominal pain, diarrhea, flushing, dermatographism, memory and concentration difficulties, or headache. Among the most common symptoms, 94 percent had abdominal pain, 89 percent had flushing, 89 percent had dermatographism, and 72 percent had all three symptoms. Patients in the study went an average of 4.6 years with symptoms and without a diagnosis before coming to BWH for evaluation.
“Recognizing the constellation of signs and symptoms is extremely important in identifying patients with mast cell disease, particularly mast cell activation syndrome which can masquerade as other conditions like irritable bowel syndrome,” said Dr. Greenberger. “While most patients respond very well to treatment, they often suffer for years before receiving a correct diagnosis.”
In conjunction with pathologists in the Center, Dr. Hamilton has established new methods of diagnosing mast cell disorders from gastrointestinal biopsies. The team determined that a diagnosis of systemic mastocytosis, traditionally made through bone marrow biopsy, may be achieved from gastrointestinal biopsies using specialized immunohistochemistry (Am J Surg Pathol. 2014 Jun;38(6):832-43). They are researching similar markers in MCAS and are studying how the phenotype of mast cells in gastrointestinal tissue can be used to determine the relative state of mast cell activation and aid in diagnosis.
“Current testing for patients with mast cell activation syndrome is based on blood and urine tests that have limited accuracy and sensitivity, and the diagnosis is often made only when other disorders have been ruled out,” said Dr. Hamilton. “Being able to make an accurate diagnosis sooner can help to eliminate unnecessary tests and procedures.”
Dr. Hamilton is exploring novel treatments for mast cell patients with persistent or refractory symptoms. The primary treatment for the symptoms of mast cell activation remains the blockade of the mast cell mediators with antihistamines, mast cell stabilizers, and prostaglandin and leukotriene inhibitors
The regimen is maximized to therapeutic effect and tailored to address gastrointestinal symptoms. Additional medications with direct action on the gastrointestinal tract such as budesonide are considered based on the clinical presentation. The use of probiotics and fecal microbiota transplantation are being evaluated as novel treatment modalities in these patients. Finally, dietary intervention including the low histamine diet and FODMAPs diet are offered to patients with particular subsets of gastrointestinal symptoms.
A 37-year-old female health care worker presented with debilitating symptoms that included unexplained fatigue and diarrhea. Despite evaluation with multiple health care providers, there was no working diagnosis. Over a three-year period she underwent extensive laboratory, endoscopy, and imaging studies, including head CT and MRI, abdominal MRI, chest CT, and cardiac stress echocardiography. All results were negative or normal. The patient was seen for a gastroenterology consultation at BWH.
A detailed history of symptoms taken at the patient’s visit to BWH included flushing, headaches, sweats, forgetfulness, abdominal pain and distension, inordinate fatigue, alcohol intolerance, reddened skin following hot showers, and symptoms suggestive of Postural Orthostatic Tachycardia Syndrome (POTS). Her skin showed marked dermatographism with flushing in a mantle distribution upon examination. Initial baseline serum tryptase and 24-hour urine tests for N-methyl histamine and 11-beta prostaglandin F2 levels were normal but the tryptase was subsequently elevated during a period of increased symptoms. The patient was diagnosed with mast cell activation syndrome and was treated with loratidine, ranitidine, singulair, and cromolyn.
At follow-up evaluations while on treatment, the patient has noted no diarrhea and minimal flushing, sweats, and abdominal pain. Her forgetfulness is also greatly reduced and she is back to her job.
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