ABSTRACT
Checkpoint inhibitor-induced side effects such as diarrhea and colitis occur in up to 30% of patients. We present a case of recurrent episodes of checkpoint inhibitor-induced colitis and subsequent Fournier gangrene that resolved after ileostomy formation. Once the Fournier gangrene and colitis had resolved, the ileostomy was reversed. However, within only 4 days, another serious flare-up of colitis occurred, necessitating emergent re-formation of the ileostomy. Expertise in the management of side effects of immune checkpoint inhibitor therapy is currently limited. Although most side effects are mild to moderate and transient, a minority of patients suffer from life-threatening complications, such as colitis. The creation of an ileostomy might be a valid treatment option in severe or recurrent colitis due to immune checkpoint inhibitor therapy. Intestinal diversion surgery may be useful if conservative treatment has failed, similar to other forms of immune-mediated intestinal inflammation.
Subject(s)
Colitis/etiology , Colitis/surgery , Ileostomy , Immune Checkpoint Inhibitors/adverse effects , Colitis/diagnosis , Colitis/rehabilitation , Colonoscopes , Disease Management , Disease Susceptibility , Humans , Ileostomy/adverse effects , Ileostomy/methods , Immune Checkpoint Inhibitors/therapeutic use , Male , Middle Aged , Nivolumab/adverse effects , Nivolumab/therapeutic use , Perioperative Care , Postoperative Complications , Treatment OutcomeSubject(s)
Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism , CARD Signaling Adaptor Proteins/physiology , Colitis/rehabilitation , Gastrointestinal Microbiome , Adult , Animals , CARD Signaling Adaptor Proteins/genetics , Colitis/genetics , Colitis/microbiology , Cytokines/metabolism , Disease Susceptibility/microbiology , Humans , Inflammation/genetics , Inflammation/metabolism , Inflammation/microbiology , Ligands , Mice , Mice, Inbred C57BL , Mice, Knockout , Young AdultABSTRACT
Increased levels of chemokines and prostaglandins have been reported in patients with inflammatory bowel disease, although their changes during disease development are less understood. The aim of this study was to investigate the local production of nine selected chemokines and prostaglandin E(2) (PGE(2)) to elucidate their role in colitis progression in BALB/c and C57BL/6 mice exposed to dextran sulphate sodium. The acute inflammation in both strains was accompanied by a significant up-regulation of CXCL1, CXCL2/3, CXCL10, CCL2, CCL4 and CCL22 and a downregulation of PGE(2). In the recovery phase in BALB/c, one-week post-DSS, PGE(2) levels were significantly increased with a concomitant downregulation of CXCL1, CXCL2/3, CXCL10, CCL2, and CCL4. In contrast, in C57BL/6 mice CXCL1, CXCL2/3, CXCL10, CCL2, CCL3 and CCL4 production remained high during the chronic phase, without any up-regulation of PGE(2). In addition, CCL5 was significantly increased at d26 and 33 compared to d5. Interestingly, the number of macrophages was significantly increased during the acute phase, whereas T cells were significantly increased in both the acute and chronic phase in C57BL/6 mice. Thus, our results show that chemokines are produced in a dynamic manner during colitis progression.
Subject(s)
Chemokines/biosynthesis , Colitis/metabolism , Dinoprostone/biosynthesis , Acute Disease , Animals , Anticoagulants/toxicity , Chemokines/immunology , Chronic Disease , Colitis/chemically induced , Colitis/immunology , Colitis/pathology , Colitis/rehabilitation , Dextran Sulfate/toxicity , Dinoprostone/immunology , Down-Regulation/drug effects , Down-Regulation/immunology , Humans , Inflammation/chemically induced , Inflammation/immunology , Inflammation/metabolism , Inflammation/rehabilitation , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/pathology , Mice , Mice, Inbred BALB C , Up-Regulation/drug effects , Up-Regulation/immunologyABSTRACT
GOALS: Unemployment and disability rates in Crohn's disease patients from the ACCENT I trial were assessed. Factors associated with employment and disability status were explored. BACKGROUND: Limited data regarding unemployment and disability status in patients with active Crohn's disease are available. STUDY: Baseline data were used to assess unemployment and disability rates. Logistic regression analysis examined factors that were associated with employment and disability status. Analysis of variance was used to compare quality of life. RESULTS: The baseline full-and part-time employment rates were 48% and 13%, respectively, with 39% of patients unemployed and 25% receiving disability compensation. Only 14% of 225 unemployed patients felt well enough to work if a job were available. Younger age, female gender, shorter disease duration, and prior bowel resection predicted a higher likelihood of unemployment. Younger age and female gender also predicted a higher likelihood of not being employed full-time. Prior bowel resection predicted a higher likelihood of receiving disability compensation. Quality of life (Inflammatory Bowel Disease Questionnaire, Short Form-36) scores were significantly higher in employed patients. CONCLUSIONS: Patients with moderately to severely active Crohn's disease had low employment and high disability rates. Given their economic importance, assessment of these outcomes should be integrated into future evaluations of therapy, including clinical trials.
