The surgical management of metastatic cutaneous Crohn’s Disease: A case series from a tertiary centre in the United Kingdom

The surgical management of metastatic cutaneous Crohn’s Disease: A case series from a tertiary centre in the United Kingdom | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The surgical management of metastatic cutaneous Crohn’s Disease: A case series from a tertiary centre in the United Kingdom Deepak Selvakumar, David Leiberman, Alex O'Connor, Calum Lyon, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8785435/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background and Aims Metastatic Crohn’s disease (MCD) is a rare extra-intestinal manifestation (EIM) of Crohn’s disease (CD), defined by granulomatous inflammation of skin non-contiguous to the gastrointestinal tract. This study describes the clinical features, surgical management and wound healing outcomes of the largest national surgical cohort of patients with severe MCD, a topic that remains poorly represented in the literature. Methods This retrospective single-centre case series included adults (>18 years) undergoing surgical management for MCD from 2019 to 2024. Diagnosis was confirmed by expert clinical and histopathological assessment. We describe pre-operative optimisation, individualised surgical approaches and post-operative management delivered by a multi-disciplinary team led by Consultant Colorectal and Plastic surgeons. Wound healing was assessed clinically in a specialist complex wounds clinic at 6 and 12 months and at final long-term follow-up. Results Eleven female patients (median age = 37 years) underwent surgical intervention. At 6 and 12 months, 45.5% achieved complete healing, improving to 81.8% by final follow-up (median = 36 months). Most underwent a combined medical and surgical approach with proctocolectomy and tailored perineal reconstruction. Persistent lesions and non-healing ulcers required additional adjuncts to treatment which included topical tacrolimus, hyperbaric oxygen therapy and surgical re-excision to improve healing outcomes. Conclusions MCD is a challenging condition requiring surgical treatment in refractory cases despite medical therapy. Our study highlights the need for multidisciplinary working alongside meticulous pre-operative optimisation and close post-operative follow-up to improve long-term wound healing outcomes for patients with this rare and complex disease. Figures Figure 1 Figure 2 Introduction Metastatic Crohn’s disease (MCD) is an uncommon but debilitating extra-intestinal manifestation (EIM) of Crohn’s Disease (CD) first described by Parks et al. 1965 [ 1 ]. It is characterised by non-caseating granulomatous inflammation of the skin at sites anatomically separate from the gastrointestinal tract. Importantly, MCD represents a distinct cutaneous manifestation of CD, which may occur alongside perianal Crohn’s Disease (pCD) or independently, rather than representing a direct extension or progression of perianal disease. Lesions most commonly affect intertriginous, perineal, and genital skin, but may occur at any cutaneous site. People can present with MCD symptoms before, concurrently or years after symptoms of luminal CD, compounding the diagnostic challenge [ 3 ]. Its heterogeneous clinical presentation often results in patients being assessed across multiple specialties, including primary care, gastroenterology, colorectal surgery, gynaecology, urology, and dermatology. In the absence of coordinated multidisciplinary care, delays in diagnosis and initiation of appropriate treatment are common. Despite increasing recognition, the underlying pathogenesis of MCD remains poorly understood [ 4 ]. There are currently no established diagnostic or treatment guidelines for MCD. Several treatment modalities have previously been reported, in case reports and series. Treatment options include topical and systemic therapies such as antibiotics, corticosteroids, thiopurines and biologic therapies. Surgery is an important treatment option for lesions refractory to medical therapy. However, data describing and assessing surgical management is limited, with only one previously reported case series which predated the biologic era [ 5 ]. This case series explores the clinical features, surgical management, and outcomes of patients with MCD, providing insight into preoperative optimization, surgical decision-making, and postoperative care for patients with this rare and complex disease. Methods Study design This is a retrospective single-centre consecutive case series of adult patients undergoing surgical intervention for the management of MCD between January 2019 and January 2024 at the Manchester University NHS Foundation Trust, a large tertiary academic institution in Manchester, United Kingdom. All research was conducted in accordance with the Declaration of Helsinki principles. This study (IRAS ID: 321786) was reviewed and approved by the Wales Research Ethics Committee (REC reference: 23/WA/0164). All identifiable patient information were removed, and all analyses were performed using anonymised data. Participants Adult patients (>18 years age) were identified through review of inflammatory bowel disease (IBD) multi-disciplinary meeting (MDT) lists, gastroenterology and colorectal surgery clinic lists. Those without a definitive clinical or histological diagnosis of CD were excluded. MCD was defined by combined expert clinical assessment and histological diagnosis on skin biopsy. Additional stains for acid-fast Bacilli were performed to exclude other causes of granulomatous inflammation such as tuberculosis. Hidradenitis suppurativa (HS) was excluded based on clinical and histopathological examination. Patients were also screened against guidelines for monogenic Crohn’s testing and excluded if they met criteria for genetic testing [6]. Patients underwent careful and thorough counselling with consultant colorectal and plastic surgeons prior to undergoing surgery. Pre-intervention patient optimisation Multi-modal pre-operative optimisation was an essential part of treatment. Expert assessment by specialist dietitians and if necessary, admission for enteral and parenteral nutritional support was a key intervention. All patients received broad-spectrum antibiotics pre-operatively to treat super-imposed infection of MCD lesions. Smokers were engaged in smoking cessation programmes and started nicotine replacement therapy. Steroid treatment was weaned, anaemia corrected with intravenous iron infusions and surgery timed between biologic doses. Pre-operative assessment by a consultant anaesthetist and an individualised plan for peri and post-operative analgesia was undertaken in each case. All patients were offered psychological support through a clinical psychologist. Interventions After optimisation, all patients underwent surgical procedures tailored to their specific clinical scenarios. Procedures are detailed in Table 2 and described in ‘Results’. Following surgery, patients received specialist post-operative wound care focused on intensive flap monitoring, infection control and nutritional optimisation. They were nursed to avoid pressure on the flap and supported with early mobilisation. Advanced medical therapies were determined on an individual basis by multi-disciplinary discussion. All patients were followed up regularly in a specialist complex wound clinic attended by consultant plastic and colorectal surgeons and specialist tissue viability nurses. Wound healing status, determined by clinical evaluation, is reported at 6 and 12 months. Minimum follow-up was 12 months with up to 5 years long-term follow-up. Statistics Descriptive statistics are used to summarise patient characteristics and phenotypic traits. Categorical data are presented as frequencies and percentages. Phenotypic trait co-occurrences were visualized using a heatmap, illustrating the number of patients who simultaneously exhibited specific pairs of traits. No inferential statistical tests were applied due to the descriptive nature of the analysis and the relatively small sample size. Results Between January 2019 and January 2024 fifteen patients were diagnosed with MCD. Three patients had complete healing of their skin lesions with medical treatment and did not require surgical intervention. One patient had severe MCD with extensive lesions refractory to medical therapy but was too frail for any surgical intervention. Eleven operated patients were included in this series. Eight (72.7%) patients had florid granulomatous inflammation of the skin on histological examination. Three (27.3%) patients had accumulation of multi-nucleate giant cells in the dermis, with an inflammatory lymphocytic infiltrate. Patient demographics All eleven patients were Caucasian females. Median age at the time of surgery was 37 years, ranging from 20 to 74 years. Median body mass index was 24.4, ranging from 20.4 to 40 ( Table 1 ). One patient was an active smoker with the remaining ten being non- or ex-smokers. One patient was an insulin-dependent diabetic. Smoking cessation and optimisation of glycaemic control were undertaken pre-operatively. Luminal CD Phenotype The median age of luminal CD diagnosis was 27 years, ranging from 16 to 73 years. Ten (90.9%) patients were diagnosed under the age of 40 years. Nine (81.8%) patients had granulomas present on luminal biopsies (Figure 1). Distribution of luminal CD was colonic in nine (81.8%) cases and ileocolonic in the remaining two. None had luminal CD affecting the upper gastrointestinal tract or isolated ileal disease. Inflammatory disease behaviour was present in eight (72.7%) cases with the remaining three cases having a penetrating behavioural phenotype. Eight (72.7%) patients had perianal fistulae present on MRI. Heatmap visualising the co-occurrence of phenotypic traits among patients. Each row and column represent a specific phenotypic trait, and the values indicate the number of patients exhibiting both traits simultaneously. The colour bar on the right provides a reference for interpreting the co-occurrence counts. (CD = Crohn’s disease) Table 1 : Patient demographics and treatment history. Case Demographics (Age, sex, ethnicity) Montreal Classification Smoking status BMI Previous medical treatment Previous surgery 1 31 years, F, Caucasian A2 L2 B1p Non-smoker 20.4 Prednisolone, Azathioprine, Adalimumab, Ustekinumab, Vedolizumab, 0.1% prolonged courses of antibiotics Defunctioning ileostomy (2019) 2 37 years, F, Caucasian A2 L2 B1p Non-smoker 32.5 Prednisolone, Azathioprine, Mercaptopurine, Methotrexate, Infliximab, Adalimumab, Ustekinumab, Vedolizumab, 0.1%, prolonged courses of antibiotics Subtotal colectomy and end ileostomy (2009) 3 74 years, F, Caucasian A3 L2 B1 Ex-smoker 24.4 Prednisolone, Azathioprine, Infliximab, Ustekinumab, prolonged courses of antibiotics Defunctioning ileostomy (2019) 4 26 years, F, Caucasian A1 L2 B1p Non-smoker 22.8 Prednisolone, Azathioprine, Mercaptopurine, Adalimumab, prolonged courses of antibiotics Defunctioning ileostomy (2012) 5 56 years, F, Caucasian A2 L2 B1p Ex-smoker 24.3 Prednisolone, Azathioprine, Infliximab, Vedolizumab, prolonged courses of antibiotics Subtotal colectomy and end ileostomy (2014) 6 27 years, F, Caucasian A2 L3 B1p Non-smoker 20.8 Prednisolone, Azathioprine, Infliximab, Adalimumab, prolonged courses of antibiotics Ileocaectomy and ileocolostomy (2014) 7 50 years, F, Caucasian A2 L3 B3p Ex-smoker 24.2 Prednisolone, Azathioprine, Methotrexate, Infliximab, prolonged courses of antibiotics Ileocaecectomy and ileocolostomy (2013) 8 37 years, F, Caucasian A2 L2 B1p Non-smoker 36.4 Prednisolone, Azathioprine, Infliximab, Adalimumab, Ustekinumab, prolonged courses of antibiotics Defunctioning ileostomy (2019) 9 55 years, F, Caucasian A2 L2 B3 Ex-smoker 30.1 Prednisolone, Azathioprine, Infliximab, Adalimumab, prolonged courses of antibiotics Panproctocolectomy and end ileostomy (2006) 10 29 years, F, Caucasian A2 L2 B3p Non-smoker 28.9 Prednisolone, Azathioprine, Infliximab, Ustekinumab, prolonged courses of antibiotics Defunctioning colostomy (2018), Panproctocolectomy and end ileostomy (2019) 11 20 years, F, Caucasian A2 L2 B1 Smoker 40.0 Prednisolone, Azathioprine, Infliximab, prolonged courses of antibiotics Defunctioning ileostomy (2022) Table 2 : Surgical treatment and wound healing outcomes. Case Surgical treatment Perineal reconstruction technique 6-month healing outcome 12-month healing outcome Post-surgical medical treatment Further surgical treatment Total length of follow-up (months) Outcome at final follow-up 1 Laparoscopic panproctocolectomy V-Y advancement flap Healed Healed None None 13 Healed 2 Open completion proctocolectomy Lotus petal flap V-Y advancement flap Partial healing Partial healing Tacrolimus Excision of non-healing ulcer left mons pubis 32 Healed 3 Laparoscopic panproctocolectomy V-Y advancement flap Healed Healed None None 57 Healed 4 Laparoscopic panproctocolectomy N/A Partial healing Partial healing Tacrolimus Healed at last follow-up 62 Healed 5 Open completion proctocolectomy and excision of abdominal wall V-Y advancement flap Partial healing Partial healing Tacrolimus Ustekinumab Re-excision of abdominal wall lesion 48 Partial healing 6 Laparoscopic proctocolectomy Gluteal flap Partial healing Partial healing Tacrolimus HBOT Re-excision of natal cleft ulcer and V-Y advancement flap 51 Healed 7 Open completion proctocolectomy N/A Healed Healed None None 15 Healed 8 Open panproctocolectomy and perineal reconstruction (gluteal flap) Gluteal flap Healed Healed None None 37 Healed 9 Transperineal excision of perineal sinus and perineal reconstruction (gluteal flap) Gluteal flap Partial healing Partial healing Tacrolimus Adalimumab Re-excision of non-healing ulcer 36 Healed 10 Excision of retained mesorectum, perineal sinus and peritoneal inclusion cyst and perineal reconstruction (gluteal flap) Gluteal flap Partial healing Partial healing Tacrolimus HBOT Ustekinumab Upadacitinib None 19 Partial healing 11 Laparoscopic panproctocolectomy N/A Healed Healed Adalimumab None 12 Healed MCD lesions All patients had ulcerating MCD lesions affecting the perineum (the skin between the anus and external genitalia). The groins (54.6%) and external genitalia (45.5%) were the next most affected sites. In this series, lesions were classed as affecting the genitalia if ulceration involved the labia majora and/or labia minora. Distant lesions in the abdominal wall were present in three cases, specifically in intertriginous areas, and the axilla involved in two cases. Seven (63.6%) patients had multiple affected sites with five (45.5%) patients having three or more affected areas. Previous treatment Prior to definitive surgical treatment, all patients had received courses of oral corticosteroids, antibiotics, azathioprine and topical tacrolimus ointment – with persistent lesions. Anti-TNF therapies had been used in all cases, with seven (63.6%) having two or more biologics and three (27.3%) with three or more biologics. Ustekinumab was used in five (45.5%) patients and vedolizumab in three (27.3%) patients. At referral all patients had already undergone surgery to form a stoma, with four (36.4%) patients having already had a major colonic resection as part of their prior treatment. Two (18.2%) patients had undergone a proctectomy for CD, in their referring centre, and were referred having developed recurrent MCD lesions refractory to medical treatment. Operative management Surgical interventions were individualised to each patient’s specific clinical scenario, performed by consultant colorectal and plastic surgeons and described in ( Table 2 ). Nine (81.8%) patients underwent proctocolectomy or completion proctectomy at our centre. Proctectomy was performed with a total mesorectal excision and intersphincteric dissection, with a laparoscopic approach used in five (55.6%) patients. Six (66.7%) patients underwent perineal skin and subcutaneous tissue reconstruction at the time of their proctectomy/ proctocolectomy. Perineal reconstruction was undertaken using a V-Y advancement flap for three patients (case 1, 3 and 5). A gluteal flap was used in two patients (case 6 and 8) with one patient (case 2) requiring a combination of a lotus-petal and advancement flap to achieve adequate reconstruction (Figure 2). The remaining three patients had primary closure of their perineal defect by the plastic surgery team. All patients were managed in a high-dependency unit in the immediate post-operative period. Two (18.2%) patients (case 9 & 10) had already undergone a pan-proctocolectomy for their CD and subsequently referred with symptomatic, non-healing perineal ulcers clinically and histologically consistent with MCD after biopsy of the skin. MRI scans of the perineum were performed to define the anatomy of the post-proctectomy sinus. For case 10, the original proctectomy was performed with a close-rectal dissection, so an abdominal-pelvic approach was undertaken to excise the remaining mesorectum, along with the ulcerated perineal skin and the perineum reconstructed utilising a gluteal flap. Granulomatous inflammation of the skin was found on histology and histological examination of the remnant mesorectum found persistent granulomatous inflammation - a potential driver of cutaneous recurrence. Wound healing outcomes Following surgery and inpatient discharge, patients were reviewed monthly in a complex wound clinic and received specialist care from experienced tissue viability nurses. In addition to regular follow-up by colorectal surgery, specialist IBD gastroenterologists, dieticians, specialist pharmacists and IBD nurse specialists supported their recovery. Healing outcomes were assessed clinically at 6- and 12-months post-surgery. At 6 months, five (45.5%) patients achieved complete wound healing, while six (54.5%) had persistent unhealed wounds, although a lower overall wound burden. This remained the same at 12-months. However, at long-term follow-up (median = 36 months) nine (81.8%) patients had complete wound healing. Post-operative treatment The six patients with unhealed wounds at 6-months went on to receive additional treatment. This was given in an escalated manner, with topical 0.1% tacrolimus, oral antibiotics, escalation of advanced medical therapies and HBOT. Four patients went on to have surgical local re-excision of small non-healing areas after biopsies demonstrated persistent granulomatous inflammation, achieving complete wound healing in three (75%) cases. These findings highlight the recurrent and refractory nature of MCD in certain patients, necessitating ongoing combined surgical and medical interventions. Discussion This study highlights the complexities of managing MCD, a rare and challenging extra-intestinal manifestation of Crohn’s disease. Our findings emphasise the critical role of a combined medical and surgical multidisciplinary approach, and the need for individualised surgical treatment strategies to improve outcomes for patients with this debilitating condition. Specifically, we showed that rigorous phenotyping and tailored surgical intervention combined with medical therapy, thorough pre-operative optimisation, close MDT follow-up and wound care resulted in long-term improvements in wound healing outcomes; 45.5% of patients achieved complete healing by six months with the healing rate increased to 81.8%, at the final follow-up (median = 36 months). We stress the importance of pre-operative optimisation to address modifiable risk factors such as active steroid use, anaemia, malnutrition (weight loss >10%), smoking and poorly controlled diabetes in achieving these results. This study emphasises the recurrent and refractory nature of MCD. All patients had a severe disease phenotype requiring multiple treatment modalities, with symptoms persisting despite the use of multiple biologic agents and faecal diversion. Nine (81.8%) patients had granulomas evident on luminal biopsy histopathology, another marker of an aggressive disease phenotype [7]. An important observation from our cohort is the distinction between MCD and pCD. Although these phenotypes frequently coexist, our findings support the concept that MCD represents a separate cutaneous manifestation of CD rather than an advancement of refractory perianal disease. Of the 11 patients undergoing surgery for MCD, eight had perianal fistulae at the time of operation, three patients had no fistulising pCD and all 11 patients had histological evidence of non-caseating granulomatous inflammation within the skin. This supports the hypothesis that MCD can occur alongside or independently of fistulising pCD and should not be regarded solely as a complication or progression of it and warrants separate diagnostic and therapeutic consideration. Currently there are no accepted guidelines for the management of MCD. Biologics targeting TNF-alpha, IL-12/23 and IL-17 inflammatory pathways have a well-established role in treating immune-mediated inflammatory skin diseases such as psoriasis and hidradenitis suppurativa [8], [9]. However, their efficacy and use for cutaneous manifestations of CD is poorly understood. A ‘top-down’ treatment approach for luminal CD, with early initiation of biologics, has been shown to be highly effective, safe and result in sustained steroid and surgery-free remission in the recent PROFILE trial [10]. Emerging evidence suggests a potential role for Janus Kinase (JAK) Inhibitors in the management of refractory MCD. A recent report in JAMA Dermatology described successful treatment of metastatic Crohn’s disease with JAK inhibition, highlighting its efficacy in inflammation resistant to conventional therapies [11]. In addition, experience from the UK has demonstrated benefit of JAK inhibitors in the treatment of chronic post-proctectomy perineal sinus in CD [12]. Although data remain limited, these observations support further exploration of JAK inhibition as a therapeutic option in selected patients with refractory disease. Very little has previously been published on the role of surgery in the management of MCD. The largest series to date was in 1993 in which Williams et al reported surgical debridement of post proctectomy skin lesions in 5 patients [5]. The paucity of evidence to guide the surgical approach in those requiring proctectomy for CD is an area of unmet clinical need with unhealed perineal wounds and persistent perineal symptoms seen in up to 45% of patients [13], [14], [15]. The role of total mesorectal excision (TME) at time of proctectomy is debated, but the concept of the mesentery being an immunological driver of disease recurrence in CD is gaining traction [16], [17], [18], [19]. TME is the approach undertaken for patients undergoing proctectomy in our institution as close-rectal dissection (CRD) has previously been identified as a risk factor for perineal wound complications [19]. This is cautiously supported by our finding of persistent granulomatous inflammation in the retained mesorectum of one patient who had previously had proctectomy with CRD and developed MCD in the perineal wound. Primary skin closure may be suitable for small, superficial ulcers, but is often not an option in severe cases due to the poor quality of inflamed tissue, poor wound healing, significant soft tissue destruction and high risk of breakdown [20]. Excision of the cutaneous ulceration with subcutaneous flap-based reconstruction after inter-sphincteric proctectomy is needed when soft tissue destruction compromises function, particularly in anovaginal ulceration, posterior vaginal wall defects, and perineal body loss, commonly seen in these cases. The authors favour excision of the cutaneous ulceration if possible, to reduce the wound burden and improve quality of life, although the lack of quality-of-life data is a limitation of this study. Ulceration of the external genitalia is not excised to preserve tissue and reduce functional complications and scaring. Common reconstructive techniques include the V-Y advancement flap which allows local tissue preservation while mobilising healthy skin and subcutaneous tissue to cover perianal defects. Gluteal flaps are better suited for larger perineal cutaneous wounds requiring bulk tissue replacement [21]. The lotus petal flap, a perforator-based fasciocutaneous flap harvested from the gluteal region, provides well-vascularised, sensate soft tissue, making it an excellent option for perineal and vaginal wall reconstruction. The choice of reconstructive flap must be tailored to each patient, with the aim of achieving structural support, functional restoration, and good cosmetic outcomes with minimal donor site morbidity [22]. In our series, re-excision of residual lesions or sinus tracts was necessary in some cases, reflecting the complex and aggressive disease course. Clinicians should continue medical therapy as risk of recurrence is high. Combined medical and surgical management along with adjuncts to wound management such as topical 0.9% tacrolimus, HBOT and re-excision should all be considered in the management of recurrent lesions. We report use of HBOT in two of our patients, resulting in a complete clinical response in one patient. There is some evidence supporting the use of HBOT in the treatment of severe post-proctectomy wound complications and recurrent perineal sinus [23], [24], [25], [26]. This study is limited by the retrospective nature of its design and lack of a comparator group of CD proctectomy without MCD involvement. However, given the rarity of this condition, and lack of previously published data on outcomes in those requiring surgery for MCD, this study represents the largest national cohort of patients undergoing surgical management for MCD and provides an early assessment of the clinical features, surgical management and wound healing outcomes for this aggressive disease. Declarations Author Contribution D.S and D.L wrote the main manuscript text. D.S, A.O. and L.H. prepared figures 1 and 2. J.M., R.W, S.C and L.H. designed the study and conception of the work. D.S, D.L, C.L., A.B., R.W. and L.H. acquired the data and provided interpretation and analysis. 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Davis, ‘Healing of severe perineal and cutaneous Crohn’s disease with hyperbaric oxygen’, Gastroenterology , vol. 97, no. 3, pp. 756–760, 1989. C. A. Lansdorp, C. J. Buskens, K. B. Gecse, G. R. D’Haens, and R. A. Van Hulst, ‘Wound healing of metastatic perineal Crohn’s disease using hyperbaric oxygen therapy: A case series’, United Eur. Gastroenterol. J. , vol. 8, no. 7, pp. 820–827, 2020. P. Dulai, M. Gleeson, D. Taylor, J. Buckey Jr, and S. Corey, ‘Hyperbaric oxygen therapy for the treatment of inflammatory bowel disease: A systematic review’, Inflamm. Bowel Dis. , vol. 19, 2013, [Online]. Available: https://academic.oup.com/ibdjournal/article/19/suppl_1/S77-S78/4605118 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 12 Feb, 2026 Reviewers agreed at journal 12 Feb, 2026 Reviews received at journal 11 Feb, 2026 Reviews received at journal 09 Feb, 2026 Reviewers agreed at journal 09 Feb, 2026 Reviewers agreed at journal 07 Feb, 2026 Reviewers agreed at journal 06 Feb, 2026 Reviewers invited by journal 06 Feb, 2026 Editor assigned by journal 05 Feb, 2026 Submission checks completed at journal 05 Feb, 2026 First submitted to journal 04 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8785435","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":588595094,"identity":"f7305a6a-78dc-4655-9ce6-8b57a1c2fbde","order_by":0,"name":"Deepak Selvakumar","email":"","orcid":"","institution":"University of Manchester","correspondingAuthor":false,"prefix":"","firstName":"Deepak","middleName":"","lastName":"Selvakumar","suffix":""},{"id":588595095,"identity":"67cd8bad-413a-424e-a93f-843b8c0585f1","order_by":1,"name":"David Leiberman","email":"data:image/png;base64,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","orcid":"","institution":"University of Manchester","correspondingAuthor":true,"prefix":"","firstName":"David","middleName":"","lastName":"Leiberman","suffix":""},{"id":588595097,"identity":"b4e3fca7-fe5a-4a52-bc26-2f5a282a42e8","order_by":2,"name":"Alex O'Connor","email":"","orcid":"","institution":"Manchester University NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Alex","middleName":"","lastName":"O'Connor","suffix":""},{"id":588595099,"identity":"53dcba35-80d9-4d23-a85f-1fe5687908cd","order_by":3,"name":"Calum Lyon","email":"","orcid":"","institution":"Salford Royal Hospital","correspondingAuthor":false,"prefix":"","firstName":"Calum","middleName":"","lastName":"Lyon","suffix":""},{"id":588595100,"identity":"8ba88d72-40b8-4736-ae15-a3bfff5bfa87","order_by":4,"name":"Andrew Brass","email":"","orcid":"","institution":"University of Manchester","correspondingAuthor":false,"prefix":"","firstName":"Andrew","middleName":"","lastName":"Brass","suffix":""},{"id":588595101,"identity":"c9153958-281f-4bbb-9ea0-667aefab1c02","order_by":5,"name":"John McLaughlin","email":"","orcid":"","institution":"University of Manchester","correspondingAuthor":false,"prefix":"","firstName":"John","middleName":"","lastName":"McLaughlin","suffix":""},{"id":588595104,"identity":"7bfb9f16-1b9d-47a9-a9cf-09e8f78899c4","order_by":6,"name":"Robert Winterton","email":"","orcid":"","institution":"Manchester University NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"","lastName":"Winterton","suffix":""},{"id":588595106,"identity":"f14ca85f-31fa-40d5-9c47-e24ddeecdc1a","order_by":7,"name":"Sheena Cruickshank","email":"","orcid":"","institution":"University of Manchester","correspondingAuthor":false,"prefix":"","firstName":"Sheena","middleName":"","lastName":"Cruickshank","suffix":""},{"id":588595109,"identity":"2bd4f036-3e73-4a99-8963-77f825451475","order_by":8,"name":"Laura Hancock","email":"","orcid":"","institution":"Manchester University NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Laura","middleName":"","lastName":"Hancock","suffix":""}],"badges":[],"createdAt":"2026-02-04 10:58:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8785435/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8785435/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102440142,"identity":"684cd193-ba7d-4871-87bd-777936144e67","added_by":"auto","created_at":"2026-02-11 16:46:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":63801,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePhenotypic co-occurrence in patients with MCD.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHeatmap visualising the co-occurrence of phenotypic traits among patients. Each row and column represent a specific phenotypic trait, and the values indicate the number of patients exhibiting both traits simultaneously. The colour bar on the right provides a reference for interpreting the co-occurrence counts. (CD = Crohn’s disease)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8785435/v1/6919454d91bd278f82a90f13.png"},{"id":102440143,"identity":"f2a626c9-9363-4597-9da1-3f653aca1c7a","added_by":"auto","created_at":"2026-02-11 16:46:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":653824,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePre-operative and post-operative clinical images of patients undergoing surgical management of MCD.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Case 11 - pre-operative left lateral view and (B) post-operative lithotomy and (C) left lateral view. (D) Case 2 - pre-operative lithotomy view and (E) post-operative lithotomy view. (F) Case 3 – pre-operative lithotomy view and (G) post-operative lithotomy and (H) left lateral view.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8785435/v1/b3892966ed1e8c9487a8f5ae.png"},{"id":102440145,"identity":"fd1f72fd-d0ce-4e03-b77e-2e9982cfa2ce","added_by":"auto","created_at":"2026-02-11 16:46:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1656533,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8785435/v1/0cf9d8e0-fa92-4e54-b545-18828625355f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The surgical management of metastatic cutaneous Crohn’s Disease: A case series from a tertiary centre in the United Kingdom","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMetastatic Crohn\u0026rsquo;s disease (MCD) is an uncommon but debilitating extra-intestinal manifestation (EIM) of Crohn\u0026rsquo;s Disease (CD) first described by Parks et al. 1965 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It is characterised by non-caseating granulomatous inflammation of the skin at sites anatomically separate from the gastrointestinal tract. Importantly, MCD represents a distinct cutaneous manifestation of CD, which may occur alongside perianal Crohn\u0026rsquo;s Disease (pCD) or independently, rather than representing a direct extension or progression of perianal disease. Lesions most commonly affect intertriginous, perineal, and genital skin, but may occur at any cutaneous site. People can present with MCD symptoms before, concurrently or years after symptoms of luminal CD, compounding the diagnostic challenge [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Its heterogeneous clinical presentation often results in patients being assessed across multiple specialties, including primary care, gastroenterology, colorectal surgery, gynaecology, urology, and dermatology. In the absence of coordinated multidisciplinary care, delays in diagnosis and initiation of appropriate treatment are common. Despite increasing recognition, the underlying pathogenesis of MCD remains poorly understood [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e There are currently no established diagnostic or treatment guidelines for MCD. Several treatment modalities have previously been reported, in case reports and series. Treatment options include topical and systemic therapies such as antibiotics, corticosteroids, thiopurines and biologic therapies. Surgery is an important treatment option for lesions refractory to medical therapy. However, data describing and assessing surgical management is limited, with only one previously reported case series which predated the biologic era [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This case series explores the clinical features, surgical management, and outcomes of patients with MCD, providing insight into preoperative optimization, surgical decision-making, and postoperative care for patients with this rare and complex disease.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch2\u003eStudy design\u003c/h2\u003e\n\u003cp\u003eThis is a retrospective single-centre consecutive case series of adult patients undergoing surgical intervention for the management of MCD between January 2019 and January 2024 at the Manchester University NHS Foundation Trust, a large tertiary academic institution in Manchester, United Kingdom.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll research was conducted in accordance with the Declaration of Helsinki principles. This study (IRAS ID: 321786) was reviewed and approved by the Wales Research Ethics Committee (REC reference: 23/WA/0164). All identifiable patient information were removed, and all analyses were performed using anonymised data.\u003c/p\u003e\n\u003ch2\u003eParticipants\u003c/h2\u003e\n\u003cp\u003eAdult patients (\u0026gt;18 years age) were identified through review of inflammatory bowel disease (IBD) multi-disciplinary meeting (MDT) lists, gastroenterology and colorectal surgery clinic lists. Those without a definitive clinical or histological diagnosis of CD were excluded.\u003c/p\u003e\n\u003cp\u003eMCD was defined by combined expert clinical assessment and histological diagnosis on skin biopsy. Additional stains for acid-fast \u003cem\u003eBacilli\u003c/em\u003e were performed to exclude other causes of granulomatous inflammation such as tuberculosis. Hidradenitis suppurativa (HS) was excluded based on clinical and histopathological examination. Patients were also screened against guidelines for monogenic Crohn’s testing and excluded if they met criteria for genetic testing\u0026nbsp;[6]. Patients underwent careful and thorough counselling with consultant colorectal and plastic surgeons prior to undergoing surgery.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003ePre-intervention patient optimisation\u003c/h2\u003e\n\u003cp\u003eMulti-modal pre-operative optimisation was an essential part of treatment. Expert assessment by specialist dietitians and if necessary, admission for enteral and parenteral nutritional support was a key intervention. All patients received broad-spectrum antibiotics pre-operatively to treat super-imposed infection of MCD lesions. Smokers were engaged in smoking cessation programmes and started nicotine replacement therapy. Steroid treatment was weaned, anaemia corrected with intravenous iron infusions and surgery timed between biologic doses. Pre-operative assessment by a consultant anaesthetist and an individualised plan for peri and post-operative analgesia was undertaken in each case. All patients were offered psychological support through a clinical psychologist.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eInterventions\u003c/h2\u003e\n\u003cp\u003eAfter optimisation, all patients underwent surgical procedures tailored to their specific clinical scenarios. Procedures are detailed in Table 2 and described in ‘Results’. \u0026nbsp;Following surgery, patients received specialist post-operative wound care focused on intensive flap monitoring, infection control and nutritional optimisation. They were nursed to avoid pressure on the flap and supported with early mobilisation. Advanced medical therapies were determined on an individual basis by multi-disciplinary discussion.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll patients were followed up regularly in a specialist complex wound clinic attended by consultant plastic and colorectal surgeons and specialist tissue viability nurses. Wound healing status, determined by clinical evaluation, is reported at 6 and 12 months. Minimum follow-up was 12 months with up to 5 years long-term follow-up. \u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eStatistics\u003c/h2\u003e\n\u003cp\u003eDescriptive statistics are used to summarise patient characteristics and phenotypic traits. Categorical data are presented as frequencies and percentages. Phenotypic trait co-occurrences were visualized using a heatmap, illustrating the number of patients who simultaneously exhibited specific pairs of traits. No inferential statistical tests were applied due to the descriptive nature of the analysis and the relatively small sample size.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eBetween January 2019 and January 2024 fifteen patients were diagnosed with MCD. Three patients had complete healing of their skin lesions with medical treatment and did not require surgical intervention. One patient had severe MCD with extensive lesions refractory to medical therapy but was too frail for any surgical intervention. Eleven operated patients were included in this series. Eight (72.7%) patients had florid granulomatous inflammation of the skin on histological examination. Three (27.3%) patients had accumulation of multi-nucleate giant cells in the dermis, with an inflammatory lymphocytic infiltrate.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003ePatient demographics\u003c/h2\u003e\n\u003cp\u003eAll eleven patients were Caucasian females. Median age at the time of surgery was 37 years, ranging from 20 to 74 years. Median body mass index was 24.4, ranging from 20.4 to 40 (\u003cstrong\u003eTable 1\u003c/strong\u003e). One patient was an active smoker with the remaining ten being non- or ex-smokers. One patient was an insulin-dependent diabetic. Smoking cessation and optimisation of glycaemic control were undertaken pre-operatively.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eLuminal CD Phenotype\u003c/h2\u003e\n\u003cp\u003eThe median age of luminal CD diagnosis was 27 years, ranging from 16 to 73 years. Ten (90.9%) patients were diagnosed under the age of 40 years. Nine (81.8%) patients had granulomas present on luminal biopsies (Figure 1). Distribution of luminal CD was colonic in nine (81.8%) cases and ileocolonic in the remaining two. None had luminal CD affecting the upper gastrointestinal tract or isolated ileal disease. Inflammatory disease behaviour was present in eight (72.7%) cases with the remaining three cases having a penetrating behavioural phenotype. Eight (72.7%) patients had perianal fistulae present on MRI.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHeatmap visualising the co-occurrence of phenotypic traits among patients. Each row and column represent a specific phenotypic trait, and the values indicate the number of patients exhibiting both traits simultaneously. The colour bar on the right provides a reference for interpreting the co-occurrence counts. (CD = Crohn\u0026rsquo;s disease)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e: Patient demographics and treatment history.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"126%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003eCase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003eDemographics\u003c/p\u003e\n \u003cp\u003e(Age, sex, ethnicity)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eMontreal Classification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eSmoking status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003ePrevious medical treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003ePrevious surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e31 years, F, Caucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eA2 L2 B1p\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eNon-smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e20.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003ePrednisolone, Azathioprine, Adalimumab, Ustekinumab, Vedolizumab, 0.1% prolonged courses of antibiotics\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003eDefunctioning ileostomy (2019)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e37 years, F, Caucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eA2 L2 B1p\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eNon-smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e32.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003ePrednisolone, Azathioprine, Mercaptopurine, Methotrexate, Infliximab, Adalimumab, Ustekinumab, Vedolizumab, 0.1%, prolonged courses of antibiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003eSubtotal colectomy and end ileostomy (2009)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e74 years, F, Caucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eA3 L2 B1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eEx-smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e24.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003ePrednisolone, Azathioprine, Infliximab, Ustekinumab, prolonged courses of antibiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003eDefunctioning ileostomy (2019)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e26 years, F, Caucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eA1 L2 B1p\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eNon-smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e22.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003ePrednisolone, Azathioprine, Mercaptopurine, Adalimumab, prolonged courses of antibiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003eDefunctioning ileostomy (2012)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e56 years, F, Caucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eA2 L2 B1p\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eEx-smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e24.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003ePrednisolone, Azathioprine, Infliximab, Vedolizumab, prolonged courses of antibiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003eSubtotal colectomy and end ileostomy (2014)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e27 years, F, Caucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eA2 L3 B1p\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eNon-smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e20.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003ePrednisolone, Azathioprine, Infliximab, Adalimumab, prolonged courses of antibiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003eIleocaectomy and ileocolostomy (2014)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e50 years, F, Caucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eA2 L3 B3p\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eEx-smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e24.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003ePrednisolone, Azathioprine, Methotrexate, Infliximab, prolonged courses of antibiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003eIleocaecectomy and ileocolostomy (2013)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e37 years, F, Caucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eA2 L2 B1p\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eNon-smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e36.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003ePrednisolone, Azathioprine, Infliximab, Adalimumab, Ustekinumab, prolonged courses of antibiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003eDefunctioning ileostomy (2019)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e55 years, F, Caucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eA2 L2 B3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eEx-smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e30.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003ePrednisolone, Azathioprine, Infliximab, Adalimumab, prolonged courses of antibiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003ePanproctocolectomy and end ileostomy (2006)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e29 years, F, Caucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eA2 L2 B3p\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eNon-smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e28.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003ePrednisolone, Azathioprine, Infliximab, Ustekinumab, prolonged courses of antibiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003eDefunctioning colostomy (2018), Panproctocolectomy and end ileostomy (2019)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e20 years, F, Caucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eA2 L2 B1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eSmoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e40.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003ePrednisolone, Azathioprine, Infliximab, prolonged courses of antibiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003eDefunctioning ileostomy (2022)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e: Surgical treatment and wound healing outcomes.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"715\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eCase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eSurgical treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003ePerineal reconstruction technique\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e6-month healing outcome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e12-month healing outcome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003ePost-surgical medical treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eFurther surgical treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eTotal length of follow-up (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eOutcome at final follow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eLaparoscopic panproctocolectomy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eV-Y advancement flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eOpen completion proctocolectomy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eLotus petal flap\u003c/p\u003e\n \u003cp\u003eV-Y advancement flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePartial healing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePartial healing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eTacrolimus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eExcision of non-healing ulcer left mons pubis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eLaparoscopic panproctocolectomy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eV-Y advancement flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eLaparoscopic panproctocolectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePartial healing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePartial healing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eTacrolimus\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eHealed at last follow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eOpen completion proctocolectomy and excision of abdominal wall\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eV-Y advancement flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePartial healing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePartial healing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eTacrolimus\u003c/p\u003e\n \u003cp\u003eUstekinumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eRe-excision of abdominal wall lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003ePartial healing\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eLaparoscopic proctocolectomy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eGluteal flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePartial healing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePartial healing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eTacrolimus\u003c/p\u003e\n \u003cp\u003eHBOT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eRe-excision of natal cleft ulcer and\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eV-Y advancement flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eOpen completion proctocolectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eOpen panproctocolectomy and perineal reconstruction (gluteal flap)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eGluteal flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eTransperineal excision of perineal sinus and perineal reconstruction (gluteal flap)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eGluteal flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePartial healing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePartial healing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eTacrolimus\u003c/p\u003e\n \u003cp\u003eAdalimumab\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eRe-excision of non-healing ulcer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eExcision of retained mesorectum, perineal sinus and peritoneal inclusion cyst and perineal reconstruction (gluteal flap)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eGluteal flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePartial healing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePartial healing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eTacrolimus\u003c/p\u003e\n \u003cp\u003eHBOT\u003c/p\u003e\n \u003cp\u003eUstekinumab\u003c/p\u003e\n \u003cp\u003eUpadacitinib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003ePartial healing\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eLaparoscopic panproctocolectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eAdalimumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eHealed\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch2\u003eMCD lesions\u003c/h2\u003e\n\u003cp\u003eAll patients had ulcerating MCD lesions affecting the perineum (the skin between the anus and external genitalia). The groins (54.6%) and external genitalia (45.5%) were the next most affected sites. In this series, lesions were classed as affecting the genitalia if ulceration involved the labia majora and/or labia minora. Distant lesions in the abdominal wall were present in three cases, specifically in intertriginous areas, and the axilla involved in two cases. Seven (63.6%) patients had multiple affected sites with five (45.5%) patients having three or more affected areas.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003ePrevious treatment\u003c/h2\u003e\n\u003cp\u003ePrior to definitive surgical treatment, all patients had received courses of oral corticosteroids, antibiotics, azathioprine and topical tacrolimus ointment \u0026ndash; with persistent lesions. Anti-TNF therapies had been used in all cases, with seven (63.6%) having two or more biologics and three (27.3%) with three or more biologics. Ustekinumab was used in five (45.5%) patients and vedolizumab in three (27.3%) patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt referral all patients had already undergone surgery to form a stoma, with four (36.4%) patients having already had a major colonic resection as part of their prior treatment. Two (18.2%) patients had undergone a proctectomy for CD, in their referring centre, and were referred having developed recurrent MCD lesions refractory to medical treatment.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eOperative management\u003c/h2\u003e\n\u003cp\u003eSurgical interventions were individualised to each patient\u0026rsquo;s specific clinical scenario, performed by consultant colorectal and plastic surgeons and described in (\u003cstrong\u003eTable \u003cem\u003e2\u003c/em\u003e\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNine (81.8%) patients underwent proctocolectomy or completion proctectomy at our centre. Proctectomy was performed with a total mesorectal excision and intersphincteric dissection, with a laparoscopic approach used in five (55.6%) patients. Six (66.7%) patients underwent perineal skin and subcutaneous tissue reconstruction at the time of their proctectomy/ proctocolectomy. Perineal reconstruction was undertaken using a V-Y advancement flap for three patients (case 1, 3 and 5). A gluteal flap was used in two patients (case 6 and 8) with one patient (case 2) requiring a combination of a lotus-petal and advancement flap to achieve adequate reconstruction (Figure 2). The remaining three patients had primary closure of their perineal defect by the plastic surgery team. All patients were managed in a high-dependency unit in the immediate post-operative period.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTwo (18.2%) patients (case 9 \u0026amp; 10) had already undergone a pan-proctocolectomy for their CD and subsequently referred with symptomatic, non-healing perineal ulcers clinically and histologically consistent with MCD after biopsy of the skin. MRI scans of the perineum were performed to define the anatomy of the post-proctectomy sinus. For case 10, the original proctectomy was performed with a close-rectal dissection, so an abdominal-pelvic approach was undertaken to excise the remaining mesorectum, along with the ulcerated perineal skin and the perineum reconstructed utilising a gluteal flap. Granulomatous inflammation of the skin was found on histology and histological examination of the remnant mesorectum found persistent granulomatous inflammation - a potential driver of cutaneous recurrence.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eWound healing outcomes\u003c/h2\u003e\n\u003cp\u003eFollowing surgery and inpatient discharge, patients were reviewed monthly in a complex wound clinic and received specialist care from experienced tissue viability nurses. In addition to regular follow-up by colorectal surgery, specialist IBD gastroenterologists, dieticians, specialist pharmacists and IBD nurse specialists supported their recovery. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHealing outcomes were assessed clinically at 6- and 12-months post-surgery. At 6 months, five (45.5%) patients achieved complete wound healing, while six (54.5%) had persistent unhealed wounds, although a lower overall wound burden. This remained the same at 12-months. However, at long-term follow-up (median = 36 months) nine (81.8%) patients had complete wound healing.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003ePost-operative treatment\u003c/h2\u003e\n\u003cp\u003eThe six patients with unhealed wounds at 6-months went on to receive additional treatment. This was given in an escalated manner, with topical 0.1% tacrolimus, oral antibiotics, escalation of advanced medical therapies and HBOT. Four patients went on to have surgical local re-excision of small non-healing areas after biopsies demonstrated persistent granulomatous inflammation, achieving complete wound healing in three (75%) cases. These findings highlight the recurrent and refractory nature of MCD in certain patients, necessitating ongoing combined surgical and medical interventions.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study\u0026nbsp;highlights the complexities of managing MCD, a rare and challenging extra-intestinal manifestation of Crohn’s disease. Our findings emphasise the critical role of a combined medical and surgical multidisciplinary approach, \u0026nbsp;and the need for individualised surgical treatment strategies to improve outcomes for patients with this debilitating condition.\u003c/p\u003e\n\u003cp\u003eSpecifically, we showed that rigorous phenotyping and tailored surgical intervention combined with medical therapy, thorough pre-operative optimisation, close MDT follow-up and wound care resulted in long-term improvements in wound healing outcomes; 45.5% of patients achieved complete healing by six months with the healing rate increased to 81.8%, at the final follow-up (median = 36 months). We stress the importance of pre-operative optimisation to address modifiable risk factors such as active steroid use, anaemia, malnutrition (weight loss \u0026gt;10%), smoking and poorly controlled diabetes in achieving these results.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study emphasises the recurrent and refractory nature of MCD. All patients\u0026nbsp;had a severe disease phenotype requiring multiple treatment modalities, with symptoms persisting despite the use of multiple biologic agents and faecal diversion. Nine (81.8%) patients had granulomas evident on luminal biopsy histopathology, another marker of an aggressive disease phenotype\u0026nbsp;[7].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAn important observation from our cohort is the distinction between MCD and pCD. Although these phenotypes frequently coexist, our findings support the concept that MCD represents a separate cutaneous manifestation of CD rather than an advancement of refractory perianal disease. Of the 11 patients undergoing surgery for MCD, eight had perianal fistulae at the time of operation, three patients had no fistulising pCD and all 11 patients had histological evidence of non-caseating granulomatous inflammation within the skin. This supports the hypothesis that MCD can occur alongside or independently of fistulising pCD and should not be regarded solely as a complication or progression of it and warrants separate diagnostic and therapeutic consideration.\u003c/p\u003e\n\u003cp\u003eCurrently there are no accepted guidelines for the management of MCD. Biologics targeting TNF-alpha, IL-12/23 and IL-17 inflammatory pathways have a well-established role in treating immune-mediated inflammatory skin diseases such as psoriasis and hidradenitis suppurativa\u0026nbsp;[8], [9]. However, their efficacy and use for cutaneous manifestations of CD is poorly understood. A ‘top-down’ treatment approach for luminal CD, with early initiation of biologics, has been shown to be highly effective, safe and result in sustained steroid and surgery-free remission in the recent PROFILE trial\u0026nbsp;[10]. Emerging evidence suggests a potential role for Janus Kinase (JAK) Inhibitors in the management of refractory MCD. A recent report in \u003cem\u003eJAMA Dermatology\u003c/em\u003e described successful treatment of metastatic Crohn’s disease with JAK inhibition, highlighting its efficacy in inflammation resistant to conventional therapies\u0026nbsp;[11]. In addition, experience from the UK has demonstrated benefit of JAK inhibitors in the treatment of chronic post-proctectomy perineal sinus in CD\u0026nbsp;[12]. Although data remain limited, these observations support further exploration of JAK inhibition as a therapeutic option in selected patients with refractory disease.\u003c/p\u003e\n\u003cp\u003eVery little has previously been published on the role of surgery in the management of MCD. The largest series to date was in 1993 in which Williams et al reported surgical debridement of post proctectomy skin lesions in 5 patients\u0026nbsp;[5]. The paucity of evidence to guide the surgical approach in those requiring proctectomy for CD is an area of unmet clinical need with unhealed perineal wounds and persistent perineal symptoms seen in up to 45% of patients\u0026nbsp;[13], [14], [15]. The role of total mesorectal excision (TME) at time of proctectomy is debated, but the concept of the mesentery being an immunological driver of disease recurrence in CD is gaining traction\u0026nbsp;[16], [17], [18], [19]. TME is the approach undertaken for patients undergoing proctectomy in our institution as close-rectal dissection (CRD) has previously been identified as a risk factor for perineal wound complications\u0026nbsp;[19]. This is cautiously supported by our finding of persistent granulomatous inflammation in the retained mesorectum of one patient who had previously had proctectomy with CRD and developed MCD in the perineal wound.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrimary skin closure may be suitable for small, superficial ulcers, but is often not an option in severe cases due to the poor quality of inflamed tissue, poor wound healing, significant soft tissue destruction and high risk of breakdown\u0026nbsp;[20]. Excision of the cutaneous ulceration with subcutaneous flap-based reconstruction after inter-sphincteric proctectomy is needed when soft tissue destruction compromises function, particularly in anovaginal ulceration, posterior vaginal wall defects, and perineal body loss, commonly seen in these cases. The authors favour excision of the cutaneous ulceration if possible, to reduce the wound burden and improve quality of life, although the lack of quality-of-life data is a limitation of this study. Ulceration of the external genitalia is not excised to preserve tissue and reduce functional complications and scaring.\u003c/p\u003e\n\u003cp\u003eCommon reconstructive techniques include the V-Y advancement flap which allows local tissue preservation while mobilising healthy skin and subcutaneous tissue to cover perianal defects. Gluteal flaps are better suited for larger perineal cutaneous wounds requiring bulk tissue replacement\u0026nbsp;[21]. The lotus petal flap, a perforator-based fasciocutaneous flap harvested from the gluteal region, provides well-vascularised, sensate soft tissue, making it an excellent option for perineal and vaginal wall reconstruction. The choice of reconstructive flap must be tailored to each patient, with the aim of achieving structural support, functional restoration, and good cosmetic outcomes with minimal donor site morbidity\u0026nbsp;[22].\u003c/p\u003e\n\u003cp\u003eIn our series, re-excision of residual lesions or sinus tracts was necessary in some cases, reflecting the complex and aggressive disease course. Clinicians should continue medical therapy as risk of recurrence is high. Combined medical and surgical management along with adjuncts to wound management such as topical 0.9% tacrolimus, HBOT and re-excision should all be considered in the management of recurrent lesions. We report use of HBOT in two of our patients, resulting in a complete clinical response in one patient. There is some evidence supporting the use of HBOT in the treatment of severe post-proctectomy wound complications and recurrent perineal sinus\u0026nbsp;[23], [24], [25], [26].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study is limited by the retrospective nature of its design and lack of a comparator group of CD proctectomy without MCD involvement. However, given the rarity of this condition, and lack of previously published data on outcomes in those requiring surgery for MCD,\u0026nbsp;this study represents the largest national cohort of patients undergoing surgical management for MCD and provides an early assessment of\u0026nbsp;the clinical features, surgical management and wound healing outcomes for this aggressive disease.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eD.S and D.L wrote the main manuscript text. D.S, A.O. and L.H. prepared figures 1 and 2. J.M., R.W, S.C and L.H. designed the study and conception of the work. D.S, D.L, C.L., A.B., R.W. and L.H. acquired the data and provided interpretation and analysis. All authors were involved in the critical appraisal and revision of the manuscript. All authors approved the version to be published.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eA. G. Parks, B. C. Morson, and J. S. Pegum, \u0026lsquo;Crohn\u0026rsquo;s Disease with Cutaneous Involvement\u0026rsquo;, \u003cem\u003eJ. R. Soc. Med.\u003c/em\u003e, vol. 58, no. 4, pp. 241\u0026ndash;242, 1965, doi: 10.1177/003591576505800419.\u003c/li\u003e\n \u003cli\u003eJ. C. Mountain, \u0026lsquo;Cutaneous ulceration in Crohn\u0026rsquo;s disease\u0026rsquo;, \u003cem\u003eGut\u003c/em\u003e, vol. 11, no. 1, pp. 18\u0026ndash;26, 1970.\u003c/li\u003e\n \u003cli\u003eF. Ickrath, J. Stoevesandt, L. Schulmeyer, C. Glatzel, M. Goebeler, and A. Kerstan, \u0026lsquo;Metastatic Crohn\u0026rsquo;s disease: an underestimated entity\u0026rsquo;, \u003cem\u003eJ. Dtsch.\u0026nbsp;\u003c/em\u003e\u003cem\u003eDermatol. Ges. J. Ger. Soc. Dermatol. JDDG\u003c/em\u003e, vol. 19, no. 7, pp. 973\u0026ndash;982, 2021.\u003c/li\u003e\n \u003cli\u003eI. Palamaras \u003cem\u003eet al.\u003c/em\u003e, \u0026lsquo;Metastatic Crohn\u0026rsquo;s disease: a review\u0026rsquo;, \u003cem\u003eJ. Eur. Acad. Dermatol. Venereol.\u0026nbsp;\u003c/em\u003e\u003cem\u003eJEADV\u003c/em\u003e, vol. 22, no. 9, pp. 1033\u0026ndash;1043, 2008.\u003c/li\u003e\n \u003cli\u003eN. Williams, N. A. Scott, J. S. Watson, and M. H. Irving, \u0026lsquo;Surgical management of perineal and metastatic cutaneous Crohn\u0026rsquo;s disease\u0026rsquo;, \u003cem\u003eBr. J. Surg.\u003c/em\u003e, vol. 80, no. 12, pp. 1596\u0026ndash;1598, 1993.\u003c/li\u003e\n \u003cli\u003eJ. Kammermeier \u003cem\u003eet al.\u003c/em\u003e, \u0026lsquo;Genomic diagnosis and care co-ordination for monogenic inflammatory bowel disease in children and adults: consensus guideline on behalf of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition\u0026rsquo;, \u003cem\u003eLancet Gastroenterol. Hepatol.\u003c/em\u003e, vol. 8, no. 3, pp. 271\u0026ndash;286, Mar. 2023, doi: 10.1016/S2468-1253(22)00337-5.\u003c/li\u003e\n \u003cli\u003eS. W. Hong \u003cem\u003eet al.\u003c/em\u003e, \u0026lsquo;Clinical significance of granulomas in Crohn\u0026rsquo;s disease: A systematic review and meta-analysis\u0026rsquo;, \u003cem\u003eJ. Gastroenterol. Hepatol.\u003c/em\u003e, vol. 35, no. 3, pp. 364\u0026ndash;373, 2020, doi: 10.1111/jgh.14849.\u003c/li\u003e\n \u003cli\u003eT. 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Hanauer, \u0026lsquo;Persistent perineal sinus following proctocolectomy in the inflammatory bowel disease patient\u0026rsquo;, \u003cem\u003eJGH Open\u003c/em\u003e, vol. 7, no. 11, pp. 740\u0026ndash;747, 2023, doi: 10.1002/jgh3.12983.\u003c/li\u003e\n \u003cli\u003eM. Duan, J. C. Coffey, and Y. Li, \u0026lsquo;Mesenteric-based surgery for Crohn\u0026rsquo;s disease: evidence and perspectives\u0026rsquo;, \u003cem\u003eSurgery\u003c/em\u003e, vol. 176, no. 1, pp. 51\u0026ndash;59, Jul. 2024, doi: 10.1016/j.surg.2024.02.025.\u003c/li\u003e\n \u003cli\u003eC. J. Coffey \u003cem\u003eet al.\u003c/em\u003e, \u0026lsquo;Inclusion of the Mesentery in Ileocolic Resection for Crohn\u0026rsquo;s Disease is Associated With Reduced Surgical Recurrence\u0026rsquo;, \u003cem\u003eJ. Crohns Colitis\u003c/em\u003e, vol. 12, no. 10, pp. 1139\u0026ndash;1150, Nov. 2018, doi: 10.1093/ecco-jcc/jjx187.\u003c/li\u003e\n \u003cli\u003eJ. C. Coffey and D. P. 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Bosa \u003cem\u003eet al.\u003c/em\u003e, \u0026lsquo;Hyperbaric oxygen therapy is an effective adjunctive treatment for severe perianal Crohn\u0026rsquo;s disease\u0026rsquo;, \u003cem\u003eDig. Liver Dis.\u003c/em\u003e, vol. 49, no. 4, 2017, [Online]. Available: https://go.openathens.net/redirector/nhs?url=https%3A%2F%2Fwww.clinicalkey.com%2Fcontent%2FplayBy%2Fdoi%2F%3Fv%3D10.1016%2Fj.dld.2017.09.051\u003c/li\u003e\n \u003cli\u003eC. E. Brady, B. J. Cooley, and J. C. Davis, \u0026lsquo;Healing of severe perineal and cutaneous Crohn\u0026rsquo;s disease with hyperbaric oxygen\u0026rsquo;, \u003cem\u003eGastroenterology\u003c/em\u003e, vol. 97, no. 3, pp. 756\u0026ndash;760, 1989.\u003c/li\u003e\n \u003cli\u003eC. A. Lansdorp, C. J. Buskens, K. B. Gecse, G. R. D\u0026rsquo;Haens, and R. A. Van Hulst, \u0026lsquo;Wound healing of metastatic perineal Crohn\u0026rsquo;s disease using hyperbaric oxygen therapy: A case series\u0026rsquo;, \u003cem\u003eUnited Eur. Gastroenterol. J.\u003c/em\u003e, vol. 8, no. 7, pp. 820\u0026ndash;827, 2020.\u003c/li\u003e\n \u003cli\u003eP. Dulai, M. Gleeson, D. Taylor, J. Buckey Jr, and S. Corey, \u0026lsquo;Hyperbaric oxygen therapy for the treatment of inflammatory bowel disease: A systematic review\u0026rsquo;, \u003cem\u003eInflamm. Bowel Dis.\u003c/em\u003e, vol. 19, 2013, [Online]. Available: https://academic.oup.com/ibdjournal/article/19/suppl_1/S77-S78/4605118\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"techniques-in-coloproctology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"tcol","sideBox":"Learn more about [Techniques in Coloproctology](http://link.springer.com/journal/10151)","snPcode":"10151","submissionUrl":"https://submission.nature.com/new-submission/10151/3","title":"Techniques in Coloproctology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8785435/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8785435/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground and Aims\u003c/p\u003e\n\u003cp\u003eMetastatic Crohn’s disease (MCD) is a rare extra-intestinal manifestation (EIM) of Crohn’s disease (CD), defined by granulomatous inflammation of skin non-contiguous to the gastrointestinal tract. This study describes the clinical features, surgical management and wound healing outcomes of the largest national surgical cohort of patients with severe MCD, a topic that remains poorly represented in the literature.\u003c/p\u003e\n\u003cp\u003eMethods\u003c/p\u003e\n\u003cp\u003eThis retrospective single-centre case series included adults (\u0026gt;18 years) undergoing surgical management for MCD from 2019 to 2024. Diagnosis was confirmed by expert clinical and histopathological assessment. We describe pre-operative optimisation, individualised surgical approaches and post-operative management delivered by a multi-disciplinary team led by Consultant Colorectal and Plastic surgeons. Wound healing was assessed clinically in a specialist complex wounds clinic at 6 and 12 months and at final long-term follow-up.\u003c/p\u003e\n\u003cp\u003eResults\u003c/p\u003e\n\u003cp\u003eEleven female patients (median age = 37 years) underwent surgical intervention. At 6 and 12 months, 45.5% achieved complete healing, improving to 81.8% by final follow-up (median = 36 months). Most underwent a combined medical and surgical approach with proctocolectomy and tailored perineal reconstruction. Persistent lesions and non-healing ulcers required additional adjuncts to treatment which included topical tacrolimus, hyperbaric oxygen therapy and surgical re-excision to improve healing outcomes.\u003c/p\u003e\n\u003cp\u003eConclusions\u003c/p\u003e\n\u003cp\u003eMCD is a challenging condition requiring surgical treatment in refractory cases despite medical therapy. Our study highlights the need for multidisciplinary working alongside meticulous pre-operative optimisation and close post-operative follow-up to improve long-term wound healing outcomes for patients with this rare and complex disease.\u003c/p\u003e","manuscriptTitle":"The surgical management of metastatic cutaneous Crohn’s Disease: A case series from a tertiary centre in the United Kingdom","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-11 16:46:01","doi":"10.21203/rs.3.rs-8785435/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-12T14:20:27+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"91835183515720415170888767391415911483","date":"2026-02-12T10:26:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-11T23:29:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-09T23:24:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"197670094938304063895178260431796876279","date":"2026-02-09T22:13:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"274085575271611378857925910568257356715","date":"2026-02-07T12:45:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"204275107876288176792817472129002983465","date":"2026-02-06T13:38:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-06T13:22:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-06T02:46:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-05T08:03:05+00:00","index":"","fulltext":""},{"type":"submitted","content":"Techniques in Coloproctology","date":"2026-02-04T10:20:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"techniques-in-coloproctology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"tcol","sideBox":"Learn more about [Techniques in Coloproctology](http://link.springer.com/journal/10151)","snPcode":"10151","submissionUrl":"https://submission.nature.com/new-submission/10151/3","title":"Techniques in Coloproctology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8d874168-eb63-47fd-9201-2d076231ca08","owner":[],"postedDate":"February 11th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-09T19:53:48+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-11 16:46:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8785435","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8785435","identity":"rs-8785435","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}