Crohn's-like disease in a patient exposed to anti-Interleukin-17 blockade (Ixekizumab) for the treatment of chronic plaque psoriasis: a case report.

BACKGROUND: Plaque psoriasis and inflammatory bowel disease (IBD) are both chronic immune-mediated inflammatory diseases with an overlapping genetic profile and have been linked in epidemiological studies. Psoriasis and IBD share similar components in their inflammatory pathways and animal and human studies have suggested a potential role for targeting interleukin (IL)-17 with novel antibody therapies in the treatment of these diseases. These studies, while promising for psoriasis, have been associated with deterioration in patients with IBD. Post-hoc analyses of clinical trials involving Ixekizumab revealed adverse outcomes in a small cluster of patients with IBD, prompting recommendations to monitor this population with the use of this drug. CASE PRESENTATION: Forty-two year old Caucasian male with treatment-refractory chronic plaque psoriasis who developed new onset diarrheal illness and rectal bleeding following a 12 week induction period with Ixekizumab (anti-IL-17 neutralizing antibody). Colonoscopy revealed severe ulceration throughout the ascending and transcending colon. Histopathology, combined with endoscopic findings, led to a diagnosis of Crohn's-like colitis. The patient's anti-IL-17 medication was discontinued and endoscopic remission was induced with the use of corticosteroids, escalated anti-TNF therapy and eventually anti IL-12/23 neutralizing antibody (ustekinumab). CONCLUSION: Murine studies implicate IL-17 and the downstream effects of its inhibition, in the breakdown of the gut epithelial layer, the disruption of normal host immune responses and the propagation of intestinal inflammation. The increasing use of IL-17 inhibitors has led to reports of exacerbation and potential development of inflammatory bowel disease. While clinical trials have revealed clusters of new inflammatory bowel disease cases amongst psoriasis patients using an IL-17 inhibitor, there remains a lack of evidence to suggest a causal relationship. This is the first case report of de-novo severe Crohn's-like IBD in association with the use of Ixekizumab requiring rescue with escalated dosing of anti-TNF therapy and highlights the importance of close monitoring in patients being treated with IL-17 inhibitors, especially in those patients with known risk factors for inflammatory bowel disease.

Association between childhood physical abuse, unprotected receptive anal intercourse and HIV infection among young men who have sex with men in Vancouver, Canada.

INTRODUCTION: The association between childhood sexual abuse and HIV risk among men who have sex with men (MSM) is well established. However, no studies have examined the potential impact of other forms of childhood maltreatment on HIV incidence in this population. METHODS: We explored the impact of child physical abuse (CPA) on HIV seroconversion in a cohort of gay/bisexual men aged 15 to 30 in Vancouver, Canada. Cox proportional hazard models were used, controlling for confounders. RESULTS: Among 287 participants, 211 (73.5%) reported experiencing CPA before the age of 17, and 42 (14.6%) reporting URAI in the past year. After a median of 6.6 years follow-up, 16 (5.8%) participants HIV-seroconverted. In multivariate analysis, CPA was significantly associated with HIV seroconversion (adjusted hazard ratio [AHR] = 4.89, 95% confidence interval (CI): 1.65-14.48), after controlling for potential confounders. CONCLUSION: Our study uncovered a link between childhood physical violence and HIV incidence. Results highlight an urgent need for screening of young gay and bisexual men for histories of violence, and social and structural supports to prevent HIV transmission in this population.