Cumulative incidence of, risk factors for, and outcome of dermatological complications of anti-TNF therapy in inflammatory bowel disease: a 14-year experience.

OBJECTIVES: The broader and prolonged use of anti-tumor necrosis factor (TNF) agents in inflammatory bowel disease (IBD) could expose patients to an increased risk of adverse reactions, including dermatological complications. We assessed the cumulative incidence of anti-TNF-induced cutaneous adverse reactions in IBD patients, their risk factors, their dermatological management, and their outcome in a large cohort of IBD patients. METHODS: In a single-center observational retrospective study, including all consecutive adult IBD patients treated with an anti-TNF agent between 2001 and 2014, all patients with dermatological complications under anti-TNF therapy were identified in a well-defined cohort of IBD patients. We conducted a survival analysis to determine the cumulative incidence of dermatological complications and risk factors for developing any dermatological complications, cutaneous infections, and psoriasiform lesions. Survival curves were estimated by the Kaplan-Meier method, and we used a Cox proportional hazards model to test the association between parameters and time to each event: any dermatological complication, cutaneous infections, and psoriasis lesions. RESULTS: Among 583 IBD patients, 176 dermatological complications occurred, involving 20.5% of patients. Median duration of follow-up was 38.2 months (range: 1-179). Psoriasiform lesions (10.1%; 59/583) and cutaneous infections (11.6%, 68/583) were the most frequently observed, with a cumulative incidence of, respectively, 28.9% and 17.6% at 10 years. They led to anti-TNF discontinuation, respectively, in 18.6% and 2.9% of patients. In case of switching to another anti-TNF agent for psoriasiform lesions, recurrence occurred in 57% of patients. Ulcerative colitis was associated with a lower risk of developing cutaneous infections than Crohn's disease (hazard ratio (HR)=0.25; 95% confidence interval (CI)=0.09-0.68; P=0.007). Higher dosing of anti-TNF agent was associated with a higher risk of developing cutaneous infections (HR=1.99; 95% CI=1.09-3.64; P=0.025). A younger age at time of anti-TNF initiation was associated with a higher risk of dermatological complications (HR=2.25; 95% CI=1.39-3.62; P<0.001). CONCLUSIONS: Dermatological complications involve one of five patients treated with anti-TNF therapy after a 14-year follow-up. Association of cutaneous infections with higher anti-TNF dosing suggests a dose-dependent effect. Discontinuation of anti-TNF therapy due to dermatological complications is required in one out of five patients with psoriasiform lesions, but specific dermatological treatment allows to continue anti-TNF therapy in half of them.

IgE antibodies and skin tests in immediate hypersensitivity reactions to infliximab in inflammatory bowel disease: impact on infliximab retreatment.

BACKGROUND: Infliximab (IFX) is used for the treatment of inflammatory bowel diseases (IBD). Immediate hypersensitivity reactions (HR) to IFX are frequently reported. OBJECTIVES: We investigated immunoglobulin E (IgE)-mediated mechanisms underlying immediate HR to IFX. We also evaluated the clinical utility of allergological tests as well as the tolerability of IFX retreatment in these patients. METHODS: This was a prospective single-center study including IBD patients with previous immediate HR to IFX. Skin tests to IFX, including prick tests and intradermal tests, and measurement of anti-IFX IgE antibodies were performed at least 4 weeks after HR. In case of negative skin tests and absence of IgE antibodies, readministration of IFX was performed with a twice-reduced infusion rate. In case of positive tests or recurrence of HR during readministration of IFX, a 12-step desensitization or induction of tolerance protocol was proposed. RESULTS: A total of 24 IBD patients were included (Crohn's disease: n=20). Prick tests to IFX were all negative. Intradermal test was positive in one patient. Anti-IFX IgE antibodies were not detected in 21 patients and were detected in three patients (significant level in one patient and intermediate level in two patients). No relationship was observed between positive skin tests and the presence of anti-IFX IgE antibodies. Switch to adalimumab was well tolerated in 10/11 patients. The readministration of IFX was well tolerated in 4/11 patients. Desensitization to IFX was successful in three out of four patients. CONCLUSION: The vast majority of immediate HR to IFX is not IgE-mediated. Allergological tests are of poor clinical utility. Desensitization or induction of tolerance protocol may allow continuation of IFX therapy in IBD patients with a history of immediate HR.

Dietary beliefs and behavior among inflammatory bowel disease patients.

BACKGROUND: We investigated dietary beliefs and behavior in a large population of adult inflammatory bowel disease (IBD) patients and evaluated their impact on patients' social life. METHODS: A questionnaire of 14 items was administered to all consecutive IBD patients followed at the Nancy University Hospital Department of Gastroenterology from February to July 2011. RESULTS: A total of 244 patients participated in the survey; 15.6% (n = 38) of patients believed that diet could initiate the disease, while 57.8% (n = 141) believed that food can play a role in causing a relapse. Forty percent (107/244) of patients identified food as a risk factor for relapse. Seventy-three percent of respondents reported having already received nutritional advice. The majority of respondents (47.5%, n = 116) reported that the disease had changed the pleasure of eating. Only one-quarter of patients had a normal diet in case of relapse. Almost two out of three patients (66.8%, n = 163) reported not eating certain foods they usually like to eat in order to prevent a relapse. Dietary beliefs and behavior had an impact on their social life for one-fifth of patients. Excluding food was associated with refusing outdoor dining for fear of causing relapse (P = 0.006) and not sharing the same menu as the other members of the family living under the same roof (P = 0.002). CONCLUSIONS: The majority of IBD patients are avoiding certain foods. Dietary beliefs and behavior have a strong impact on their social life.

Ocular symptoms are not predictive of ophthalmologic inflammation in inflammatory bowel disease.

BACKGROUND: Ocular manifestations are frequent in patients with inflammatory bowel disease. AIM: To evaluate for the first time the value of ocular symptoms in predicting ophthalmologic inflammation in inflammatory bowel disease. METHODS: All consecutive inflammatory bowel disease patients seen in the Department of Gastroenterology (Nancy, University Hospital, France) between April 2009 and July 2011 were interviewed for this cross-sectional study using a pre-established questionnaire. If the patient had at least one ocular symptom, he systematically underwent an ophthalmologic examination (visual acuity, Break-Up Time test, Schirmer Test, slit-lamp exam with fundus examination). RESULTS: This cross-sectional survey was completed by 305 patients: 169 were women (55.2%), 228 had Crohn's disease (74.5%). Ninety-eight patients (32%) reported at least one ocular symptom: ocular irritation (56.8%), red eye (40.5%), blurred vision (37.8%), progressive visual loss (34.4%), ocular pain (31.1%), myodesopsia (23.3%), eyelid secretion (12.2%), dry eye (9.5%), watering (6.8%), diplopia (5.4%), metamorphopsia (4%), and sudden visual loss (4%). Following ophthalmologic examination (n=74), 41.9% patients had evidence of dry eye (n=31), 14.9% blepharitis (n=11) and 1.4% scleritis (n=1). No uveitis was reported. CONCLUSION: Ocular symptoms are frequent in inflammatory bowel disease, but are non-specific and rarely associated with ocular inflammation. Systematic ocular symptoms assessment is of poor value for diagnosing ocular inflammation in inflammatory bowel disease.