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Small Intestinal Bacterial Overgrowth Is Common in Mast Cell Activation Syndrome: 1194

Small Intestinal Bacterial Overgrowth in Mast Cell Activation Syndrome
Small Intestinal Bacterial Overgrowth in Mast Cell Activation Syndrome
Leonard Weinstock, MD, Jill Brook, MS, Zahid Kaleem, MD, Lawrence Afrin, MD, Gerhart Molderings, MD
Leonard Weinstock, MD, Jill Brook, MS, Zahid Kaleem, MD, Lawrence Afrin, MD, Gerhart Molderings, MD
Specialists in Gastroenterology, St. Louis, Missouri, Hematology/Oncology, Mt. Kisco, New York,
Specialists in Gastroenterology, St. Louis, Missouri, Hematology/Oncology, Mt. Kisco, New York, University Hospital Bonn, Bonn, Germany
University Hospital Bonn, Bonn, Germany
Mast cell activation syndrome (MCAS) often
presents with gastrointestinal symptoms (Sx)
and patients may be misdiagnosed with
functional syndromes including irritable bowel
syndrome (IBS). Small intestinal bacterial
overgrowth (SIBO) can be associated with IBS.
We determined if SIBO was associated with
MCAS is a common disorder of uncontrolled
mast cell (MC) activation with multi-systemic
inflammatory and allergic symptoms. The most
common Sx are fatigue, myalgia, conjunctivitis,
rhinitis, tinnitus, hives, itching, nausea, heartburn,
dyspnea, near syncope, headache, chills, and
edema. All organ systems can be involved.
Printed by
Pts with refractory abd. pain, bloat, change bowels
All evaluated for MCAS and SIBO
MCAS Dx: MC activation Sx in ≥2 organs plus:
o ≥1 elevation of MC blood and/or urinary mediators
o clinical benefit with MC-therapy
o and/or increased intestinal MC density
SIBO Dx: lactulose breath test (LBT) with ≥20 ppm H2
rise within 90 min of baseline
Methane plateau Dx: high >10 ppm, low 3 – 9 ppm
Primary aim: LBT results in MCAS compared to
Secondary aims: effect of co-morbid syndromes and
medications on LBT. Effect of antibiotics on GI Sx.
MCAS could cause SIBO due to altered
motility caused by local release of MC
mediators next to nerves or muscles,
alterations of the GI immune system, or MC
damage to interstitial cells of Cajal as in
(Achalasia reference: Liu. Neurogast Mot. 2019)
139 MCAS subjects (116 F, 23 M, mean 47 yrs)
30 controls (19 F, 11 M, mean 44 yrs).
GI Sx prior to other MCAS Sx in 66% pts.
Abdominal pain (87%), bloating (74%),
constipation (66%), diarrhea (63%), nausea
(61%), heartburn (54%), and dysphagia (30%).
Rome IV criteria for IBS-mixed (40%), IBS-
constipation (22%), and IBS-diarrhea (19%).
SIBO in 31% vs. Controls 10% (p=0.023)
Higher methane levels were associated with
IBS-constipation compared to H2 positive
subjects: 43% vs. 9% (p=0.02)
Antibiotics prescribed in 74 subjects:
68% marked improvement in GI Sx
SIBO was not associated with postural
orthostatic tachycardia syndrome,
hypermobile Ehlers-Danlos syndrome, PPI
or statin Rx, or thyroid supplementation.
Abnormal lactulose breath tests are
common in MCAS patients.
SIBO pattern is statistically more common
than controls.
... Small intestinal bacterial overgrowth (SIBO) was shown to be common in MCAS in a recent study [51]. Bacterial overgrowth was present in 30.9% of 139 MCAS subjects vs. 10.0% of 30 controls. ...
... In a recent prospective study, 139 MCAS patients with refractory GI symptoms had comorbid POTS in 25.2% and EDS in 23.7%. Both syndromes were present in 15.1% (51%) [51]. In a retrospective chart review, patients with hypermobile EDS and/or POTS were evaluated for symptoms suggestive of MC activation [63]. ...
Full-text available
Mast cell activation syndrome is thought to be a common, yet under-recognized, chronic multi-system disorder caused by inappropriate mast cell activation. Gastrointestinal symptoms are frequently reported by these patients and are often mistaken by physicians as functional gastrointestinal disorders. This syndrome can be diagnosed by the medical history and measurable biomarkers. Gastroenterologists manage diseases associated with active inflammatory cells including neutrophils, lymphocytes, macrophages, and eosinophils. The mast cell has only recently been recognized as a major player in our specialty. Gastrointestinal disorders from mast cell mediators often present with apparent irritable bowel syndrome, dyspepsia, chronic or cyclical nausea, and heartburn. Individuals with mast cell activation syndrome experience significant delays in diagnosis. The gastrointestinal symptoms are often refractory to symptom-targeted prescription medications. Beyond avoiding triggers, the best therapy is directed at modulating mast cell activation and the effects of the mediators. Many of these therapies are simple over-the-counter medications. In this article, we review mast cell function and dysfunction and the gastrointestinal symptoms, comorbid conditions, diagnosis, and management of mast cell activation syndrome. Gastroenterologists who become aware of this syndrome can dramatically improve the quality of life for their patients who previously have been labeled with a functional gastrointestinal disorder.
... We thus propose that either the consensus-1 or consensus-2 proposal be accepted for diagnosing any given case of MCAS until criteria can be developed using the modern, robust methodologies now being employed to create classification criteria for similarly complex and heterogeneous conditions such as lupus [90]. It has been little more than a decade since the first case reports of MCAS were published; there have not yet been any large-scale studies of any aspects of the disease, though a few small-scale such studies are beginning to emerge [12,33,91]. As such, we fail to see why there must be a rush to pronounce only one approach as definitively diagnostic of a disease of such complexity/heterogeneity. ...
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The concept that disease rooted principally in chronic aberrant constitutive and reactive activation of mast cells (MCs), without the gross MC neoplasia in mastocytosis, first emerged in the 1980s, but only in the last decade has recognition of "mast cell activation syndrome" (MCAS) grown significantly. Two principal proposals for diagnostic criteria have emerged. One, originally published in 2012, is labeled by its authors as a "consensus" (re-termed here as "consensus-1"). Another sizable contingent of investigators and practitioners favor a different approach (originally published in 2011, newly termed here as "consensus-2"), resembling "consensus-1" in some respects but differing in others, leading to substantial differences between these proposals in the numbers of patients qualifying for diagnosis (and thus treatment). Overdiagnosis by "consensus-2" criteria has potential to be problematic, but underdiagnosis by "consensus-1" criteria seems the far larger problem given (1) increasing appreciation that MCAS is prevalent (up to 17% of the general population), and (2) most MCAS patients, regardless of illness duration prior to diagnosis, can eventually identify treatment yielding sustained improvement. We analyze these proposals (and others) and suggest that, until careful research provides more definitive answers, diagnosis by either proposal is valid, reasonable, and helpful.
Hypermobile Ehlers–Danlos syndrome (hEDS) is the most common type of EDS, yet has remained steadfastly inscrutable vis‐à‐vis efforts to identify its cellular, molecular, and pathophysiologic roots. Once thought to principally affect just connective tissues, hEDS is now appreciated to be a multisystem disease of great heterogeneity with many symptoms and findings difficult to attribute solely to disordered connective tissue development. In the last decade, there has been growth in the appreciation of the existence of a wide range of disorders of chronic inappropriate mast cell (MC) activation (a large heterogeneous pool of MC activation syndromes [MCAS]) distinguishable from other MC disorders such as rare neoplastic mastocytosis. Via chronic aberrant release of the MC's vast repertoire of potent mediators, MCAS can drive extraordinary arrays of pathologies, most commonly of inflammatory, allergic, and dystrophic natures. Although hEDS is seen in only a minority of MCAS cases, limited studies have identified an association between hEDS and MCAS, fueling speculation that certain variants of MCAS may drive hEDS. No laboratory studies probing cellular or molecular linkages between hEDS and MCAS have been conducted yet, and research efforts to identify the genetic roots of hEDS should also consider those of MCAS.
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