Systemic adalimumab induces peripheral corneal infiltrates: a case report.

BACKGROUND: Tumor necrosis factor-alpha inhibitors are widely used agents in the treatment of immune disorders such as rheumatoid arthritis and inflammatory bowel disease. Despite their anti-inflammatory action, paradoxical drug-induced inflammatory events have been occasionally associated with the use of infliximab, etanercept, and in a lesser extent adalimumab. However, eye involvement is uncommon and anterior uveitis is the only reported ocular adverse manifestation. It can be induced by etanercept, but has also been described during adalimumab therapy. We present here the first report of recurrent peripheral corneal infiltrates following subcutaneous injections of adalimumab. CASE PRESENTATION: A 34 year-old Caucasian woman with Crohn's disease presented to the emergency department with bilateral red eyes and discomfort 36 hours after she received her bimonthly dose of subcutaneous adalimumab. Examination revealed bilateral peripheral corneal infiltrates with characteristic features of immune infiltrates. Symptoms and infiltrates regressed after topical corticosteroid therapy, but recurred after each adalimumab injection over the following weeks. CONCLUSION: Paradoxical immune reactions associated with tumor necrosis factor-alpha inhibitors may result either from hypersensitivity mechanisms, or from immune-complex deposition via anti-adalimumab antibodies. Both mechanisms could explain this newly described manifestation. Care should be taken to search for corneal infiltrates in the event of red eye symptoms during adalimumab therapy since they respond to topical corticosteroids and do not necessarily prompt the discontinuation of the immunosuppressive therapy

Misleading pustular plaques of the lower limbs during Crohn's disease: two case reports

<p>Abstract</p> <p>Background</p> <p>Extraintestinal manifestations of Crohn's disease may involve the skin, the eyes, the genital mucosa, and the joints. Dermatoses associated with Crohn's disease include neutrophilic dermatoses, erythema nodosum, granulomatous dermatitis, blistering dermatoses, and non-specific skin manifestations. Cutaneous Crohn's disease is characterized by skin non-caseating epithelioid granulomatas with giant cells, remote from the gastrointestinal tract. We report herein two new cases.</p> <p>Observations</p> <p>On both patients, differential diagnosis of neutrophilic dermatoses and infectious disease were evoked, and antimicrobial agents were introduced in one of them. Given the atypical presentation, the final diagnosis of cutaneous Crohn's disease could only be made with histological examination. In patient 1, the plaques decreased in size and infiltration by more than 75% after 3 weeks of treatment with bethametasone dipropionate 0.05% cream. In patient 2, the plaques decreased by more than 50% after 6 weeks of treatment with prednisolone (45 mg/day) and azathioprine (100 mg/day).</p> <p>Discussion</p> <p>Cutaneous Crohn's disease may present as dusky, erythematous, infiltrated, and ulcerated plaques and nodules. Female-to-male sex ratio is about 2, and the mean age at onset is 35. Recurrently, the hypothesis of a skin mycobacterial or fungal infection greatly delays proper treatment. Rarity of cutaneous Crohn's disease hampers therapeutic assessment in controlled trials. Thus, available literature is limited to case reports and sparse small series, with contradictory results. These reports are subject to publication bias, and no definite evidence-based recommendations can be made on the most adequate therapeutic strategy.</p

Factors affecting outcomes in Crohn's disease over 15 years

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Impact on Life Expectancy of Withdrawing Thiopurines in Patients with Crohn’s Disease in Sustained Clinical Remission: A Lifetime Risk-Benefit Analysis

Berenice Study GroupInternational audienceObjectiveLong-term treatment with thiopurines is associated with a decreased risk of Crohn’s disease (CD) flare but an increased risk of various cancers depending on gender, age, and presence of extensive colitis. We evaluated risks and benefits of withdrawing thiopurines in patients with CD in prolonged remission.MethodsWe developed a Markov model assessing risks and benefits of withdrawing thiopurines compared to continuing thiopurines in a lifetime horizon. The model was stratified by age (35 and 65 years old at thiopurine withdrawal), gender and presence of extensive colitis. Parameter estimates were taken from French cohorts and hospital databases, cancer and death national registries and published literature. Life expectancy, rates of relapse, serious adverse events, and causes-of-death were evaluated.ResultsIn patients without extensive colitis, continuing thiopurines increased life expectancy up to 0.03 years for 35 year-old men and women but decreased life expectancy down to 0.07 years for 65 year-old men and women. Withdrawal strategy became the preferred strategy at 40.6 years for men, and 45.7 years for women without extensive colitis. In patients with extensive colitis, continuation strategy was the preferred strategy regardless of age. Risk-benefit analysis was not modified by duration of CD activity.ConclusionsFactors determining life expectancy associated with withdrawal or continuation of thiopurines in patients with CD and in sustained clinical remission vary substantially according to gender, age and presence of extensive colitis. Individual decisions to continue or withdraw thiopurines in patients with CD in sustained remission should take into account these parameters

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

A prospective evaluation of the predictive value of faecal calprotectin in quiescent Crohn’s disease

Background: The faecal calprotectin (FC) test is a non-invasive marker for gastrointestinal inflammation. Aim: To determine whether higher FC levels in individuals with quiescent Crohn’s disease are associated with clinical relapse over the ensuing 12 months.&lt;p&gt;&lt;/p&gt; Methods: A single centre prospective study was undertaken in Crohn's disease patients in clinical remission attending for routine review. The receiver operating characteristic (ROC) curve for the primary endpoint of clinical relapse by 12 months, based on FC at baseline, was calculated. Kaplan-Meier curves of time to relapse were based on the resulting optimal FC cutoff for predicting relapse.&lt;p&gt;&lt;/p&gt; Results: Of 97 patients recruited, 92 were either followed up for 12 months without relapsing, or reached the primary endpoint within that period. Of these, 10 (11%) had relapsed by 12 months. The median FC was lower for non-relapsers, 96µg/g (IQR 39-237), than for relapsers, 414µg/g (IQR 259-590), (p=0.005). The area under the ROC curve to predict relapse using FC was 77.4%. An optimal cutoff FC value of 240µg/g to predict relapse of quiescent Crohn’s had sensitivity of 80.0% and specificity of 74.4%. Negative predictive value was 96.8% and positive predictive value was 27.6%. FC≥240μg/g was associated with likelihood of relapse 5.7 (95% CI 1.9-17.3) times higher within 2.3 years than lower values (p=0.002).&lt;p&gt;&lt;/p&gt; Conclusions: In this prospective dataset, FC appears to be a useful, non-invasive tool to help identify quiescent Crohn’s disease patients at a low risk of relapse over the ensuing 12 months. FC of 240µg/g was the optimal cutoff in this cohort.&lt;p&gt;&lt;/p&gt

Interaction Between NOD2 and Smoking in the Pathogenesis of Crohn's Disease.

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Low prevalence of colonoscopic surveillance of inflammatory bowel disease patients with longstanding extensive colitis: a clinical practice survey nested in the CESAME cohort

International audienceBackground: Surveillance colonoscopy is recommended for inflammatory bowel disease (IBD) patients with longstanding extensive colitis (LEC). Aims: To assess modalities and results of colonoscopic surveillance in a subset of CESAME cohort patients at high risk of colorectal cancer (CRC) and followed in university French hospitals. Methods: Among 910 eligible patients with more than a 7-year history of extensive colitis at CESAME enrolment, 685 patients completed a questionnaire on surveillance colonoscopy and 102 were excluded because of prior proctocolectomy. Finally, 583 patients provided information spanning a median period of 41 months (IQR 38-43) between cohort enrolment and the end of follow-up. Details of the colonoscopic procedures and histological findings were obtained for 440 colonoscopies in 270 patients. Results: Only 53.5% (n=312) of the patients with LEC had at least one surveillance colonoscopy during the study period, with marked variations across the 9 participating centres (27.3% to 70.0%, p= < 0.0001). Surveillance rate was significantly lower in Crohn's colitis than in ulcerative colitis (UC) (47.6% vs 68.5%, p=< 0.0001). Independent predictors of colonoscopic surveillance were male sex, UC IBD subtype, longer disease duration, previous history of CRC, and disease management in a centre with large IBD population. Random biopsies, targeted biopsies and chromoendoscopy were performed during respectively 70.7%, 26.6 and 30.0% of surveillance colonoscopies. Two cases of high-grade dysplasia were detected in patients undergoing colonoscopic surveillance. Two advanced-stage CRC were diagnosed in patients who did not have colonosocopic surveillance. Conclusions: Colonoscopic surveillance rate is low in IBD patients with longstanding extensive colitis

Fungal microbiota dysbiosis in IBD.

International audienceThe bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD. Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation. We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis