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Gastrointestinal Involvement in the Ehlers-Danlos Syndromes

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Gastrointestinal Involvement in the Ehlers-Danlos Syndromes American Journal of Medical Genetics Part C (Seminars in Medical Genetics) 175C:181–187 (2017) ARTICLE Gastrointestinal Involvement in the Ehlers–Danlos Syndromes ASMA FIKREE, GISELA CHELIMSKY, HEIDI COLLINS, KATCHA KOVACIC, AND QASIM AZIZ* Current evidence suggests that an association exists between non-inflammatory hereditary disorders of connective tissue such as the Ehlers–Danlos syndromes (EDS) and gastrointestinal (GI) symptoms. Patients with EDS can present with both structural problems such as hiatus hernias, visceroptosis, rectoceles, and rectal prolapse as well as functional problems such as disordered gut motility. It has recently been demonstrated that patients with hypermobile EDS (hEDS) present with GI symptoms related to the fore and hind-gut and these patients frequently meet the criteria for functional gastrointestinal disorders such as functional dyspepsia and irritable bowel syndrome. Presence of GI symptoms in EDS patients influences their quality of life. Specific evidence based management guidelines for the management of GI symptoms in EDS patients do not exist and these patients are often treated symptomatically. There is, however, recognition that certain precautions need to be taken for those patients undergoing surgical treatment. Future studies are required to identify the mechanisms that lead to GI symptoms in patients with EDS and more specific treatment guidelines are required. © 2017 Wiley Periodicals, Inc. KEY WORDS: Ehlers–Danlos syndrome; gut motility; abdominal pain; constipation; diarrhea How to cite this article: Fikree A, Chelimsky G, Collins H, Kovacic K, Aziz Q. 2017. Gastrointestinal involvement in the Ehlers–Danlos syndromes. Am J Med Genet Part C Semin Med Genet 175C:181–187. INTRODUCTION and each member should provide a list of and care guidelines for the management references relevant to specific areas. of EDS-related GI symptoms. GI The current information on the gastroin- The search terms used were “Ehlers– symptoms are normally managed on testinal manifestations of Ehlers–Danlos Danlos and gastrointestinal,”“Ehlers– empirical grounds using best practice syndrome (EDS) are summarized in this Danlos and GI,”“Joint-hypermobility models and evidence. review. Information about management and joint hypermobility syndrome (JHS) There are anecdotal reports of global principles based on current evidence is and gastrointestinal,”“Ehlers–Danlos hy- improvement of hypermobile type of provided together with suggestions for permobility (EDS-HT),”“Ehlers–Danlos Ehlers–Danlos syndrome (hEDS) related future research in the field. and perforation,”“Ehlers–Danlos vascu- symptoms following patient-led “trial lar,”“Ehlers–Danlos type IV and and error” diet-based interventions, as METHODS gastrointestinal.” well as through the use of enteral The gastrointestinal (GI) group had a nutrition via nasogastric feeding, percu- number of telephone conferences to taneous endoscopic gastrostomy/jeju- Management and Care Guidelines discuss the content of the literature nostomy feeding, and total parenteral review. It was agreed that a comprehen- There are currently no well validated nutrition. In 2005, a novel and theoreti- sive literature search should be conducted national or international management cal approach to symptom management in Dr. Asma Fikree is a consultant gastroenterologist at the Royal London Hospital, London, UK. Her Ph.D. was on gut manifestations of hypermobile EDS. Dr. Gisela Chelimsky is a pediatric gastroenterologist in Milwaukee, Wisconsin, and is affiliated to Children's Hospital of Wisconsin and the Medical College of Wisconsin. Dr. Heidi Collins is a physical medicine and rehabilitation specialist. She is chair of the EDNF Professional Advisory Network and works at Beacon Medical Group, Memorial Hospital, South Bend, IN. Dr. Kovacic is assistant professor and a Pediatric Gastroenterologist. She is part of the nationally recognized GI motility program at the Children's Hospital of Wisconsin, Center for Pediatric Neurogastroenterology, Motility and Autonomic Disorders. Prof. Qasim Aziz is a professor of neurogastroenterology at Barts and The London School of Medicine and Dentistry, and specialists in disorders of gut function. *Correspondence to: Professor Qasim Aziz, The Wingate Institute of Neurogastroenterology, 26 Ashfield Street, London E1 2AJ. E-mail: [email protected] DOI 10.1002/ajmg.c.31546 Article first published online 10 February 2017 in Wiley Online Library (wileyonlinelibrary.com). ß 2017 Wiley Periodicals, Inc. 182 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS) ARTICLE EDS was described by Mantle et al. GI complications such as bleeding or poorer pain-related quality of life com- [2005]. The authors suggested that perforation has been described in the pared to those without the overlap. attention to nutrient intake, by use of literature. These approaches range from Thus, it is likely that management of supplements, may impact on symptom refrain from intervention with conser- FGID patients with and without EDS severity in EDS. Tinkle [2009] has also vative non-surgical management of overlap may differ. For instance, those reported his experience with similar intestinal perforation [Casey et al., with overlap may require earlier identi- selected nutraceuticals in hEDS. In a 2014] to more conventional surgical fication and holistic multidisciplinary 2015 review of gastrointestinal and management with resections of appro- management involving for instance nutritional issues in hEDS, Castori priate segments of the gut. It has been rheumatologists, autonomic neurolo- et al. [2015] suggested that there is a suggested that during surgery, all organs gists, and pain specialists. theoretical basis which suggests that must be treated gently due to tissue Chronic musculoskeletal and vis- lifestyle and nutrients may be beneficial fragility [Omori et al., 2011]. A system- ceral pain is common in patients with in hEDS. Consequently, it is reasonable atic review of GI surgery and related EDS. It is, therefore, likely that opioids to postulate that these features may be complications in EDS [Burcharth and will be considered in the management of managed or improved by nutritional Rosenberg, 2012] suggests that surgery these patients, which can significantly supplementation and lifestyle modifica- in patients with EDS is associated with a influence GI function and lead to tions. In the author’s own clinical high risk of complications, which is why deterioration in symptoms. Hence, practice, low FODMAP (Fructose, Oli- preoperative indications should be care- avoidance of opioids should be a con- gosaccharides, Disaccharides, Mono- fully considered. Furthermore, optimal sideration in those with GI involvement. amines, and Polyols) diet is frequently therapy for these patients includes the used to good effect for abdominal awareness that EDS is a systemic disease bloating, pain, and diarrhea, these fea- involving fragility, bleeding, and spon- tures often overlap with irritable bowel taneous perforations from almost all Chronic musculoskeletal and syndrome (IBS) where the efficacy of this organ systems. The authors suggested diet is now well established. Given that that a nonsurgical approach can be the visceral pain is common in approximately 37% of patients with a best choice for these patients, depending patients with EDS. It is, diagnosis of IBS meet the criteria of on the condition. hEDS [Fikree et al., 2015], it is not Desmopressin has been used in a therefore, likely that opioids surprising that efficacyof this diet is being preliminary study of hEDS associated will be considered in the seen. However, further controlled studies bleeding symptoms such as easy bruis- management of these patients, are required to determine efficacy of the ing, epistaxis, menorrhagia, and gum diet based interventions in patients with bleeding [Mast et al., 2009]. In these which can significantly GI symptoms associated with hEDS. patients, desmopressin was given intra- influence GI function and lead nasally or intravenously and led to significantly reduced bleeding time. In to deterioration in symptoms. In the author’s own clinical the same study, desmopressin was also Hence, avoidance of opioids given to patient’s pre-surgery (non-GI practice, low FODMAP surgery) and none of these patients should be a consideration in (Fructose, Oligosaccharides, suffered from any post-surgical bleeding those with GI involvement. complications, in contrast, 30% of the Disaccharides, Monoamines, patients who did not receive desmo- and Polyols) diet is frequently pressin developed post-operative bleed- Recognition that anatomical ab- used to good effect for ing complications. This suggests that normalities such as diverticulosis, rec- desmopressin may have a role in the toceles, and prolapse can occur in abdominal bloating, pain, and management of GI peri-surgical bleed- patients with EDS may help to plan diarrhea, these features often ing complications in EDS patients but investigation and treatment in patients further studies are required to test this with GI symptoms. For instance, con- overlap with irritable bowel hypothesis. stipation is common in patients with syndrome (IBS) where the Recently, Fikree et al. [2015] have hEDS [Fikree et al., 2014], and recog- demonstrated that a significant propor- nition that symptoms may at least partly efficacy of this diet is now tion of patients with Functional Gastro- be due to rectal evacuatory dysfunction well established. intestinal Disorders (FGID)
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