Hyperbaric oxygen therapy for refractory pyoderma gangrenosum: a salvage treatment.

Case report Hyperbaric oxygen therapy for refractory pyoderma gangrenosum: a salvage treatment Rui de Sousa Magalhães,1,2,3 Maria João Moreira,1,2,3 Bruno Rosa,1,2,3 José Cotter1,2,3 1 Gastroenterology Department, Hospital Senhora da Oliveira, Guimarães, Portugal 2 Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal 3 ICVS/3B’s, PT Government Associate Laboratory, Guimarães/Braga, Portugal Correspondence to Dr Rui de Sousa Magalhães; Accepted 2 February 2021 SUMMARY A 42-year-old woman with left-side ulcerative colitis (E2 – rectum to splenic flexure) was diagnosed with pyoderma gangrenosum (PG) on a persistent ulcerated wound with peripheral erythema, in the left leg’s gemelar surface, associated with tenderness and pain. Due to incomplete response to wound care and oral prednisolone, treatment with infliximab was initiated. As PG remained unresponsive after 12 weeks, the patient was switched to adalimumab with concomitant oral prednisolone. Before the second induction dosage of adalimumab, the refractory PG complicated with a superinfection by Pseudomonas aeruginosa. A course of wide spectrum antibiotic therapy, daily wound care including negative pressure bandages and a physiotherapy rehabilitation programme controlled the infection, but the pyoderma persisted non-healed, with visible deep muscle layers and tendons. We proposed hyperbaric oxygen therapy in addition to weekly adalimumab, achieving full remission of the PG and recovering of the left foot’s function. therapy, including topical corticosteroids and tacrolimus or systemic therapy, for instance corticosteroids, ciclosporin and anti- tumournecrosis factor-alpha (anti-TNF-α) agents.2 PG is challenging to diagnose and to manage. There are few quality studies to help the guidance of this condition and the guidelines provide only vague information. Thus, PG management will ultimately rely on tailored case by case decisions. We herewith provide insight over a salvage therapy, the hyperbaric oxygen therapy, and its potential benefits in treating refractory PG. CASE PRESENTATION We present the case of a 42-year-old woman, with history of long-term left-side ulcerative colitis (E2 – rectum to splenic flexure), diagnosed in 2010, clinically and endoscopically quiescent, controlled with daily 3 g oral mesalazine as maintenance treatment and presenting occasional mild flares managed with topical mesalazine and increased oral dosing to 4.5 g. In the end of July 2018 BACKGROUND © BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ. To cite: de Sousa Magalhães R, Moreira MJ, Rosa B, et al. BMJ Case Rep 2021;14:e238638. doi:10.1136/bcr-2020238638 Pyoderma gangrenosum (PG) is a rare skin disease often arising as an extra-intestinal manifestation in inflammatory bowel disease (IBD). Nearly 30% of the patients with PG have IBD with a cumulative prevalence of 0.75% over 5 years.1 2 In a recent systematic review, Agarwal A reported a higher rate of PG during active disease,3 although some studies have described PG during periods of quiescent colitis.4 PG should be a diagnosis of exclusion, mainly based on clinical features, rendering biopsy of the lesion unnecessary, although it may assist with differential diagnosis.2 The condition primarily affects the lower extremities, and skin ulcers may appear isolated or multiple.1 Powell FC et al described four subtypes, the most common being ulcerative, followed by bullous, pustular and vegetative.5 PG is usually described as a painful nodule with rapid progression to an expansive ulcer with a raised irregular undermined erythematous border. The induction of an exuberant inflammatory process after minimal skin trauma is called pathergy and is commonly present in PG. Binus AM et al reported that almost one-third of PG cases are triggered by this phenomenon.6 The therapeutic goal should be rapid healing,2 reducing inflammation, limiting pain and preventing infection. The overall management relies on wound care, analgesia and immunosuppression. Regarding the latter, the recommendations are based on topical The patient presented with a violaceous painful, nodule, that evolved into a persistent ulcerated wound with surrounding peripheral erythema and undermined borders, in the left leg’s gemelar surface, associated with tenderness, pain and discomfort. The wound was steadily increasing in size over the last month and not responding to daily wound care. The patient denied recalling any triggering cause, rejecting local trauma. No other signs or symptoms to report regarding ulcerative colitis activity, namely sanguinolent or mucinous diarrhoea or abdominal pain. The absence of fever and purulent wound exudate precluded a wound- related infection. To avoid pathergy, a condition intrinsically related to PG, we postponed wound biopsy and by acknowledging the typical physical examination signs and clinical course, PG was diagnosed. The patient was started with daily wound care, analgesia on demand and oral prednisolone 60 mg (0.75 mg/kg/day). Time since initial presentation: 2 months The PG displayed an incomplete response to prednisolone, with wound persistence and concomitant symptoms. At this point we initiated the patient on infliximab (induction phase: 10 mg/kg week 0; 2 and 6), followed by maintenance therapy every 6 weeks (10 mg/kg). Time since initial presentation: 6 months After the infliximab induction plan and two maintenance dosages, PG’s response was unsatisfactory, de Sousa Magalhães R, et al. BMJ Case Rep 2021;14:e238638. doi:10.1136/bcr-2020-238638 1 Case report Figure 1 The several phases of the pyoderma gangrenosum (PG). (A) Initial violaceous painful, nodule, suspicious of PG. (B) PG unresponsive to infliximab, exhibiting a wound with deep invasion of the soft tissue and visualisation of the inner muscle layer and tendons. (C) Unresponsive superinfected PG, showing a deep invaded wound and mucopurulent exudate. (D) PG’s healing with complete wound closure, achieved after 60 sessions of hyperbaric oxygen therapy. the wound was progressively worsening and starting to exhibit deep invasion of soft tissue (figure 1A). Infliximab was suspended and adalimumab initiated (induction phase: 80 mg week 0 and 2; maintenance phase: 40 mg every 2 weeks) with concomitant oral prednisolone (0.75 mg/kg/day). Time since initial presentation: 9 months Before the second induction dosage of adalimumab, the patient was hospitalised with a refractory PG overlapping with a superinfection. The wound showed mucopurulent exudate and concomitant deep invasion of the soft tissue with visualisation of the inner muscle layer and tendons, and impairment of movement of the left foot (figure 1B). The blood workup had no major alterations and the wound exudate was positive for Pseudomonas aeruginosa, susceptible to meropenem. After 11 days of treatment with meropenem (500 mg, intrav (...truncated)