Letter: Is Enteric Neuropathy Absent in Hypermobility Spectrum Disorders/Hypermobile Ehler–Danlos Syndrome? Authors' Reply

We appreciate the interest and comments of Dr. Green and colleagues on our article about antroduodenal motility in patients with hypermobility spectrum disorders/hypermobile Ehlers–Danlos syndrome (HSD/hEDS) [1, 2].

They commented on the high frequency of food intolerance in the HSD/hEDS population resulting in a high prevalence of enteral and parenteral feeding, and the possible role of enteric dysmotility regarding this problem. Enteric dysmotility is often thought to be the underlying cause of food intolerance. However, in our study, enteric dysmotility was present less often (but not entirely absent) in the HSD/hEDS group with gastrointestinal symptoms compared to the control group despite the greater need for enteral/parenteral nutrition in the HSD/hEDS group.

Regarding the duration of antroduodenal manometry (ADM) protocols, we also see the added value of 24-h recordings. However, given the invasive nature and feasibility of 24-h measurements, we also see major challenges. Furthermore, two recent studies showed that shorter ADM studies of 4 or 7.5 h are reliable for evaluation of enteric motility [3, 4].

Our findings suggest that enteric dysmotility is not the main cause for gastrointestinal complaints in the HSD/hEDS population. A broader view on the pathophysiological mechanism underlying gastrointestinal symptoms in HSD/hEDS patients is necessary. Visceral hypersensitivity should be explored further in this context: it is well described in relation to disorders of gut-brain interaction and contributes significantly to symptom generation in response to normal physiological stimuli, such as food [5]. This phenomenon can be translated to patients with HSD/hEDS, who can exhibit characteristics of central sensitisation and enhanced pain perception, possibly linked to autonomic dysfunction [6]. Additionally, dietary habits and psychological comorbidities including disordered eating must be included in this broader framework because psychiatric problems such as eating disorders are not uncommon within the HSD/hEDS population [7, 8].

In conclusion, we agree that further research is warranted to elucidate the gastrointestinal manifestations of HSD/hEDS, with particular emphasis on food intolerances. However, we advocate for a more comprehensive approach that addresses gastric and enteric dysmotility but also encompasses factors such as visceral hypersensitivity, autonomic dysfunction, dietary habits and psychological factors.

Kim W. E. Sweerts: writing – original draft. Zlatan Mujagic: writing – review and editing. Daniel Keszthelyi: writing – review and editing. José M. Conchillo: writing – review and editing.

This article is linked to Sweerts et al. paper. To view this article, visit, https://doi.org/10.1111/apt.18471 and https://doi.org/10.1111/apt.70142.