Orofacial Granulomatosis associated with Crohn's Disease : a Multicentre Case Series

Orofacial granulomatosis (OFG) is a rare syndrome that may be associated with Crohn's disease (CD). We aimed to characterise this relationship and the management options in the biologic era.This multicentre case series was supported by the European Crohn's and Colitis Organisation (ECCO), and performed as part of the Collaborative Network of Exceptionally Rare case reports (CONFER) project. Clinical data were recorded in a standardised collection form.This report includes 28 patients with OFG associated with CD: 14 males (mean age of 32 years, ±12.4 SD) and 14 females (40.3 years, ±21.0 SD). Non-oral upper gastrointestinal tract involvement was seen in 6 cases and perianal disease in 11. The diagnosis of OFG was made prior to CD diagnosis in 2 patients, concurrently in 8 and after CD diagnosis in 18. The distribution of OFG involved the lips in 16 cases and buccal mucosa in 18. Pain was present in 25 cases, with impaired swallowing or speaking in 6. Remission was achieved in 23 patients, notably with the use of anti-TNFs in 9 patients, vedolizumab in 1, ustekinumab in 1 and thalidomide in 2. A further 5 cases were resistant to therapies including anti-TNFs.OFG associated with CD may occur before, concurrently or after the diagnosis of CD. Perianal and UGI disease are common associations and there is a significant symptom burden in many. Remission can be obtained with a variety of immunosuppressive treatments, including several CD approved biologicals

Pneumocystis jirovecii pneumonia in patients with inflammatory bowel disease - A case series

Pneumocystis jirovecii pneumonia (PJP) is a very rare, potentially life-threatening pulmonary fungal infection that occurs in immunocompromised individuals including patients with inflammatory bowel disease (IBD). Our aim was to describe immunosuppressive treatment exposure as well as the outcome in IBD patients with PJP. PJP cases were retrospectively collected through the COllaborative Network For Exceptionally Rare case reports of the European Crohn's and Colitis Organization. Clinical data were provided through a case report form. 18 PJP episodes were reported in 17 IBD patients (10 ulcerative colitis and 7 Crohn's disease). The median age on PJP diagnosis was 55 years (IQR, 40-68 years). Two PJP (11.1%) occurred in patients on triple immunosuppression, 10 patients (55.6%) had double immunosuppressive treatment, 4 patients (22.2%) had monotherapy and 2 PJP occurred in absence of immunosuppressive treatment (one in a human immunodeficiency virus patient and one in a patient with a history of autologous stem cell transplantation). Immunosuppressive therapies included steroids (n=12), thiopurines (n=10), infliximab (n=4), ciclosporin (n=2), methotrexate (n=1) and tacrolimus (n=1). None of the patients diagnosed with PJP had received prophylaxis. All patients were treated by trimethoprim/sulfamethoxazole or atovaquone and an ICU stay was required in 7 cases. Two patients (aged 71 and 32 years) died, and one patient had a recurrent episode 16 months after initial treatment. Evolution was favourable for the others. This case series reporting potentially fatal PJP highlights the need for adjusted prophylactic therapy in patients with IBD on immunosuppressive therapy

Genital Granulomatosis in Male and Female Patients With Crohn's Disease: Clinical Presentation and Treatment Outcomes.

BACKGROUND: Genital granulomatosis [GG] is a metastatic form of Crohn's disease [CD], characterised by granulomatous inflammation of the genital skin without contact with the gastrointestinal tract. Little is known about GG, as most publications are case reports or small series, and only sporadic in male cases. METHODS AND AIMS: Cases of GG were retrospectively collected through the Collaborative Network For Exceptionally Rare case reports project of the European Crohn's and Colitis Organisation. RESULTS: A total of 43 patients [9 males, 34 females] were diagnosed as having GG, mostly as oedema and/or ulcers. Histological confirmation of granulomas was obtained in 70% of the cases. CD location was colonic or ileocolonic in 97% and perianal disease was documented in 57%. There was no significant difference between males and females in CD phenotype or genital lesions. GG was the first manifestation of inflammatory bowel disease [IBD] in one-third of the patients; these patients were younger at the time of GG occurrence and they all were non-smokers. GG occurred in the absence of gastrointestinal disease activity in 30% of the cases. Ten out of 11 patients [91%] responded to systemic corticosteroid treatment, 5/9 patients responded to immunomodulators, and 9/11 patients responded to anti-tumour necrosis factor alpha [TNF-α] agents. CONCLUSIONS: GG is a rare extraintestinal manifestation of CD. It mainly occurs among women, in the setting of colonic involvement of CD, and perianal disease is often associated. Most cases are successfully managed with systemic corticosteroids or anti-TNF agents

Inflammatory cutaneous lesions in inflammatory bowel disease treated with Vedolizumab or Ustekinumab: an ECCO CONFER multicentre case series

This was a multicentre case series supported by the European Crohn's and Colitis Organisation (ECCO) and, performed as part of the Collaborative Network of Exceptionally Rare case reports (CONFER) project. The aim was to report on whether cutaneous lesions associated with inflammatory bowel disease (IBD) and refractory to standard medical therapy including anti-TNFs, would respond to the newer biologic agents Ustekinumab (UST) or Vedolizumab (VDZ). This report includes 28 patients with cutaneous lesions form 14 centres, all of whom had failed immunomodulator and anti-TNF therapy. Metastatic Crohn's disease (MCD) was diagnosed in 10 patients: UST led to remission in 5 cases and partial response in 4 cases, with a single report of VDZ inducing remission. All cases of MCD treated with UST responded after the first or second dose, whilst the median time for the 5 cases that attained remission was 5 months. Pyoderma gangrenosum (PG) was diagnosed in 4 cases: 3 of these attained remission with UST (median time to remission 4 months) whilst one case did not respond to VDZ. There were 7 cases of erythema nodosum (EN): UST led to remission in 4 cases and partial response in 1 case whilst VDZ had partial response in 2 cases and non-response in 2 cases. There were 7 single cases of other inflammatory lesions. In summary, UST appears to be useful for different cutaneous lesions including MCD, PG and EN, whilst VDZ does not appear to be useful for lesions that are independent of disease activity

Optic neuritis and TNF antagonists in IBD

BACKGROUND AND AIMS: Acute optic neuritis [ON] is an inflammatory condition affecting the optic nerve. Clinicians should suspect optic neuritis in cases of painful and rapidly progressive loss of central visual field. This condition may be associated with a multitude of diseases, and mostly with multiple sclerosis [MS] where it may present as an initial symptom. The literature reports that optic neuritis and MS occur in patients with inflammatory bowel disease [IBD] before and after the era of anti-tumour necrosis factor-α [TNFα] drugs. At the present moment, there is little consensus for managing this complication, currently treated with corticosteroids and discontinuation of the causative agents. METHODS: We collected cases through a retrospective multicentre European Crohn's and Colitis Organisation CONFER [COllaborative Network For Exceptionally Rare case reports] project. We also performed a comprehensive retrospective search of the available literature on this topic. RESULTS: We report herein 12 new cases of ON, including 10 under anti-TNF therapy, collected through the CONFER project. We also compare characteristics of ON associated or not with anti-TNFα agents. CONCLUSIONS: The exceptional and current observation of distant family history of MS in 17% of our patients who developed ON, despite the small number and the lack of a control arm, might be an important signal that should be taken into account in our therapeutic strategies in the future

Cogan's syndrome in patients with inflammatory bowel disease--a case series

BACKGROUND: Cogan's syndrome (CSy) is a very rare autoimmune disorder, mainly affecting the inner ear and the eye, and is associated with inflammatory bowel disease (IBD). METHODS: This was a European Crohn's and Colitis Organisation (ECCO) retrospective observational study, performed as part of the CONFER project. A call to all ECCO members was made to report concomitant CSy and inflammatory bowel disease (IBD) cases. Clinical data were recorded in a standardized questionnaire. RESULTS: This international case series reports on 22 concomitant CSy-IBD cases from 14 large medical centres. Mean duration of IBD until diagnosis of CSy was 8.7 years (range 0.0-38.0) and mean age at CSy diagnosis was 44.6 years (range 9.0-67.0). Six patients had underlying ulcerative colitis (UC) and 16 had Crohn's disease. Eleven patients (50%) had active disease at CSy diagnosis. Sixteen patients were under IBD treatment at the time of CSy diagnosis, of whom 6 (37.5%) were on anti-tumour necrosis factor (TNF). Seven out of 10 patients, who were treated for CSy with immunomodulators (mostly with corticosteroids), demonstrated at least partial response. CONCLUSION: This is the largest CSy-IBD case series so far. Although CSy is considered to be an autoimmune disease and is associated with IBD, immunomodulatory IBD maintenance treatment and even anti-TNF therapy do not seem to prevent disease onset. Moreover, IBD disease activity does not seem to trigger CSy. However, vigilance may prompt early diagnosis and directed intervention with corticosteroids at inception may potentially hinder audiovestibular deterioration. Finally, vigilance and awareness may also offer a better setting to study the pathophysiological mechanisms of this rare but debilitating phenomenon

Diagnosis and outcome of oesophageal Crohn's disease

Abstract BACKGROUND AND AIMS: Crohn's disease (CD) can involve any part of the gastrointestinal tract. We aimed to characterize clinical, endoscopic, histologic features and treatment outcomes of CD patients with oesophageal involvement. METHODS: We collected cases through a retrospective multicentre European Crohn's and Colitis Organisation CONFER [COllaborative Network For Exceptionally Rare case reports] project. Clinical data were recorded in a standardized case report form. RESULTS: A total of 40 patients were reported [22 males, mean (\ub1SD, range) age at oesophageal CD diagnosis: 25 (\ub113.3, 10-71) years and mean time of follow-up: 67 (\ub168.1, 3-240) months]. Oesophageal involvement was established at CD diagnosis in 26 patients (65%) and during follow-up in 14. CD was exclusively located in the oesophagus in 2 patients. Thirteen patients (32.2%) were asymptomatic at oesophageal disease diagnosis. Oesophageal strictures were present in 5 patients and fistulizing oesophageal disease in one. Eight patients exhibited granulomas on biopsies. Proton-pump inhibitors (PPIs) were administered in 37 patients (92.5%). Three patients underwent endoscopic dilation for symptomatic strictures and none oesophageal-related surgery. Diagnosis in pre-established CD resulted in treatment modifications in 9/14 patients. Clinical remission of oesophageal disease was seen in 33/40 patients (82.5%) after a mean time of 7 (\ub15.6, 1-18) months. Follow-up endoscopy was performed in 29/40 patients and 26/29 (89.7%) achieved mucosal healing. CONCLUSION: In this case series the endoscopic and histologic characteristics of isolated oesophageal CD were similar to those reported in other sites of involvement. Treatment was primarily conservative, with PPIs administered in the majority of patients and modifications in pre-existing IBD-related therapy occurring in two thirds of them. Clinical and endoscopic remission was achieved in more than 80% of the patients