An Emerging Disease Cluster Links POTS, MCAS and Hypermobility to Severe GI Symptoms
Oct. 11, 2024 - Eden McCleskeyWhat do hypermobility spectrum disorders (HSD), postural orthostatic tachycardia syndrome (POTS) and mast cell activation syndrome (MCAS) have in common?
Until recently, physicians would be hard-pressed to come up with an answer, but a new study by Dr. Eamonn Quigley, chief of Gastroenterology at Houston Methodist Hospital, suggests that severe gastrointestinal symptoms and a similar patient profile may link the diverse diagnoses.
The cluster of seemingly unrelated systemic diseases has recently emerged as a significant contributor to debilitating gastrointestinal issues, including intractable nausea, vomiting, reflux, constipation and gastroparesis, especially among young women aged 20-40.
"This is a very striking phenomenon," said Dr. Quigley. "Within the past few years, gastroenterologists have been seeing more and more patients with various combinations of these disorders presenting with GI symptoms that are, in some cases, so extreme that they're unable to tolerate a normal diet and must rely on tube feeding or total parenteral nutrition."
The new study, published in the journal Gastroenterology & Hepatology in August, focuses on a cohort of 26 young adult females treated at Houston Methodist Hospital over the past five years.
The patients exhibited striking similarities in clinical presentation, including significant overlap in their diagnoses of HSD, POTS and MCAS. Despite extensive diagnostic testing, endoscopic imaging and routine laboratory studies failed to reveal any underlying abnormalities to explain their severe GI symptoms, highlighting the elusive nature of these disorders.
Notably, 73% of the patients were diagnosed with POTS, a disorder marked by an abnormal increase in heart rate upon standing, and 27% were diagnosed with joint hypermobility syndrome, a condition where joints extend beyond normal limits. A small percentage also had MCAS, a condition characterized by inappropriate mast cell activation that leads to a variety of systemic symptoms, including GI disturbances. In many cases, these conditions coexisted, complicating both diagnosis and treatment.
"Individually, none of these syndromes are new, but the recent trend of their co-occurrence alongside severe GI symptoms is unprecedented," explained Dr. Quigley. "Suddenly, almost out of nowhere, this collection of conditions has begun to show up in gastroenterology clinics across the nation, so we figured it was time to take a deeper look at why this might be occurring."
Delving into the potential mechanisms linking these conditions to GI symptoms, Dr. Quigley and his co-authors Drs. Oscar Noble and Usman Ansari suggest that the connective tissue abnormalities seen in hypermobility disorders may extend to the gut, contributing to motility issues and visceral hypersensitivity.
In patients with POTS, dysautonomia — a malfunction of the autonomic nervous system — could also impair GI motility. Additionally, the researchers suggest that mast cell activation may trigger inflammation and hypersensitivity in the GI tract.
Psychiatric comorbidities were also common among the patients, with anxiety present in 46% and depression in 23%. These mental health conditions may exacerbate the perception of GI symptoms, adding another layer of complexity to the management of these patients.
The study raises several questions, including why this cluster of conditions is being observed now.
"You could say that perhaps gastroenterologists are not used to dealing with connective tissue or cardiovascular disorders, so maybe we weren't trained to recognize these issues before now," Dr. Quigley said. "There may be some truth to that, but I don't think it explains the sudden jump in cases."
Quigley and his team are exploring potential links between these conditions, but so far, no definitive answer has been found.
"We believe there's some other factor we're missing — maybe a genetic or immunological factor common to all of them," Dr. Quigley said. "Some autoimmune and biochemical mechanisms are being investigated, but further research is necessary to fully understand the shared pathophysiology."
Until then, the researchers aim to raise awareness within the gastroenterology community about this emerging disease cluster and its challenging management.
"This paper highlights the urgent need for consensus on the diagnostic criteria for these syndromes, as well as more research into their shared pathophysiology," Dr. Quigley said.
Among the cohort examined in the study, management of GI symptoms proved challenging. Approximately half of the patients required supplemental nutrition due to their inability to tolerate oral intake, and 23% relied on total parenteral nutrition. Various interventions were attempted, including pyloric botulinum toxin injections and gastric electrical stimulation, but these provided limited relief.
None of the patients in the study experienced complete symptom resolution, underscoring the need for more effective treatment strategies.