Hyperbaric Oxygen Therapy for the Treatment of Perianal Fistulas in 20 Patients With Crohn's Disease

Corine A. Lansdorp; Krisztina B. Gecse; Christianne J. Buskens; Mark Löwenberg; Jaap Stoker; Willem A. Bemelman; Geert R.A.M. D'Haens; Rob A. van Hulst


Aliment Pharmacol Ther. 2021;53(5):587-597. 

In This Article

Abstract and Introduction


Background: Positive effects of hyperbaric oxygen on perianal fistulas in Crohn's disease have been reported.

Aim: To assess efficacy, safety and feasibility of hyperbaric oxygen in Crohn's disease patients with therapy-refractory perianal fistulas.

Methods: Twenty consecutive patients were recruited at the out-patient fistula clinic of the Amsterdam UMC. Crohn's disease patients with high perianal fistula(s) failing conventional treatment for over 6 months were included. Exclusion criteria were presence of a stoma, rectovaginal fistula(s) and recent changes in treatment regimens. Patients received treatment with 40 hyperbaric oxygen sessions and outcome parameters were assessed at Week 16.

Results: Seven women and 13 men were included (median age 34 years). At Week 16, median scores of perianal disease activity index and modified van Assche index (co-primary outcome parameters) decreased from 7.5 (95% CI 6–9) to 4 (95% CI 3–6, P < 0.001), and from 9.2 (95% CI 7.3–11.2) to 7.3 (95% CI 6.9–9.7, P = 0.004) respectively. Perianal disease activity index scores ≤4 (representing inactive perianal disease) were observed in 13/20 patients (65%). Twelve patients showed a clinical response (60%) and four (20%) clinical remission, assessed with fistula drainage assessment. Median C-reactive protein and faecal calprotectin levels decreased from 4.2 mg/mL (95% CI 1.6–8) to 2.2 (95% CI 0.9–4.3, P = 0.003) and from 399 μg/g (95% CI 52–922) to 31 (95% CI 16–245, P = 0.001), respectively.

Conclusions: We found significant clinical, radiological and biochemical improvement in Crohn's disease patients with therapy-refractory perianal fistulas after treatment with hyperbaric oxygen.

Clinical trial registration: www.trialregister.nl/trial/6489.


Perianal fistulas are common complications in Crohn's disease, with every third patient developing at least one fistulising episode during their disease course.[1] Clinical manifestations range from painless fistula discharge to abscess formation accompanied by pelvic sepsis.[2] Spontaneous fistula closure is rare, and most patients require medical and/or surgical intervention.

Medical treatment usually consists of anti-tumour necrosis factor therapy (anti-TNF, mostly infliximab and adalimumab) with success rates up to approximately 40%.[3,4] Surgical treatment generally includes placement of a loose seton as a first therapeutic approach in order to prevent retention in the fistula tract and abscess formation. Subsequent surgical interventions aimed at closure include mucosal advancement flaps and ligation of the intersphincteric fistula tract, depending on the anatomy of the fistula tracts. Success percentages have been described in up to 60% of patients.[5,6] Unfortunately, in up to 50% of patients, the fistula does recur in due time (follow-up of 48 months).[5,6]

The use of mesenchymal stem cells is a new treatment modality in selected cases with complex fistulas; A recent study showed that closure of the internal opening with injection of stem cells around the fistula tract can achieve combined clinical and radiological (assessed by magnetic resonance imaging [MRI]) remission in 50% of patients at Week 24, compared to 34% in the placebo group.[7]

Overall, even after multidisciplinary approach, long-term success rates remain disappointing. In a large epidemiological study, only one third of patients with complex perianal fistulas achieved clinical remission at the end of follow-up (median 10 years).[8] Furthermore, a substantial part (63.8%) of these patients underwent a defunctioning ostomy. Along with a significant impact on quality of life and inflammatory bowel disease (IBD)-related work disability, perianal fistulas represent one of the biggest unmet needs in the treatment of Crohn's disease.[9,10]

Hyperbaric oxygen therapy has been suggested as a potential adjunctive treatment for patients suffering from IBD.[11] Hyperbaric oxygen therapy consists of breathing 100% oxygen under higher than normal atmospheric pressure: usually 202–253 kilopascal (equivalent to 2.0–2.5 atmosphere absolute). The hyper oxygenation and oxidative stress associated with hyperbaric oxygen therapy has been shown to result in anti-inflammatory effects, stem cell mobilisation and upregulation of growth factors.[11–13] Treatment for chronic problems (eg wound healing) usually consists of daily sessions for 6 to 8 consecutive weeks. The 'Undersea and Hyperbaric Medical Society', a nonprofit organisation that plays an important role in providing scientific and medical information on hyperbaric medicine, currently lists 14 indications for hyperbaric oxygen therapy.[14] These include late radiation tissue injuries, diabetic foot ulcers and carbon monoxide poisoning. The therapy is considered safe with few complications. Barotrauma of the ears or sinuses are among the most frequently reported side effects.[15]

Positive outcomes with hyperbaric oxygen therapy for treating perineal Crohn's disease have been reported in small case series.[11,16,17] However, patient characteristics and outcome parameters were not well defined in these studies, leading to a significant risk of bias. The objective of this prospective interventional study was to assess efficacy, safety and feasibility of hyperbaric oxygen therapy in Crohn's disease patients with therapy-refractory perianal fistulas.