Nivolumab-Induced Colitis in a Patient With Esophageal Adenocarcinoma: A Case Report.

Nivolumab is an immune checkpoint inhibitor used in the treatment of several types of cancer. Among the adverse effects of this drug, immune-mediated colitis (IMC) has been described. However, in contrast to other checkpoint inhibitors, such as ipilimumab, drug-induced colitis due to nivolumab is not commonly reported. We report the case of a 59-year-old male who had undergone surgical resection for gastroesophageal junction adenocarcinoma, had been on nivolumab during the past five months, and presented with worsening diarrhea. Colonoscopy demonstrated local edema and mild colitis in a region of the colonic mucosa located 30 cm distal to the ileocecal valve. Biopsies revealed acute moderate colitis. The patient responded well to loperamide and dietary modifications. Although nivolumab rarely causes IMC, this occurrence requires proper management in order to avoid further complications.

Acute ischemic colitis associated with oral decongestant use: a systematic review.

Background and Aim: Acute ischemic colitis (IC) has been linked with the use of oral decongestants. However, clinical evidence on this association remains limited. We aim to evaluate the occurrence and clinical outcomes of acute IC following over-the-counter (OTC) use of pseudoephedrine and phenylephrine. Methods: We conducted a systematic review of the MEDLINE, Google Scholar, Scopus, and Embase databases between inception and July 20, 2022. Specific search terms were used. The inclusion criteria consisted of English-language articles describing acute IC secondary to pseudoephedrine or phenylephrine. Results: A total of 18 case reports (level of clinical evidence: IV) fulfilled our inclusion criteria. The mean age of patients was 51.6 ± 15.3 years, with 14 (77.8%) cases reported in women. The clinical presentation was mainly related to abdominal pain 16 (88.9%), hematochezia 15 (83.3%), and/or abdominal tenderness 10 (55.6%). The medical background showed that 5 (27.8%) patients were previously healthy. In the 13 (72.2%) patients with comorbidities, hypertension 6 (46.2%), a history of tobacco use 5 (38.5%), and psychiatric illnesses 4 (30.8%) were commonly reported. Leukocytosis was encountered in 13 (72.2%) patients. Diagnostic investigations included a combination of computed tomography scan and colonoscopy in 10 (55.6%), colonoscopy alone in 6 (33.3%), and flexible sigmoidoscopy in 1 (5.6%) patient. Colonoscopic biopsy was the mainstay of diagnosis in 15 (83.3%) patients. Treatment was based on supportive care in 18 (100%), concurrent antibiotic use in 2 (11.1%), and surgical intervention in 1 (5.6%) patient. Recurrent episodes of IC occurred in 4 (22.2%) patients. Conclusions: Acute IC secondary to oral decongestants remains a rare but important clinical phenomenon. Clinical suspicion and imaging findings are important for the early diagnosis. Relevance to Patients: In unexplained cases of IC, clinicians should specifically inquire about oral decongestants since they are OTC and patients commonly fail to reveal their usage. These drugs should be avoided for transient cold symptoms, especially in women.

The Perfect Storm: An Unusual Cause of Intestinal Perforation in a Solid Organ Transplant Patient.

Immunosuppressants are used to prevent rejection in transplant patients. Many of these medications commonly cause gastrointestinal (GI) symptoms. We present a 38-year-old kidney and pancreas transplant recipient who had severe ulceration throughout his GI tract leading to perforations of his stomach and cecum, despite early discontinuation of mycophenolate mofetil-the most likely culprit medication. The ongoing injury observed despite holding mycophenolate suggests a possible compounding effect of tacrolimus and everolimus. Both these agents are underrepresented causes of GI injury. This perfect storm of agents may have accounted for the severity and extensive presentation observed in our patient.

Two cases of ulcerative colitis that developed while using abatacept.

Abatacept (ABT) is a recombinant fusion protein consisting of the Fc domain fragment of human IgG1 and the extracellular domain of human cytotoxic T lymphocyte antigen-4 (CTLA-4). The function of ABT is similar to that of CTLA-4, which selectively regulates T-cell activation by inhibiting the co-stimulation of CD80/CD86 on antigen-presenting cells and CD28 on T lymphocytes. ABT is used for the treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis. We report two cases of ulcerative colitis (UC) that developed while using ABT. Case 1 is of a 58-year-old man who developed diarrhea and hematochezia 2 months after starting ABT therapy for RA. Case 2 is of a 66-year-old man who experienced hematochezia 15 months after starting ABT therapy for RA. In both cases, no obvious gastrointestinal symptoms were observed before ABT therapy was initiated. Colonoscopy after disease onset showed UC findings in both cases. The patients' condition improved following ABT withdrawal and treatment for UC. Several cases of UC development during ABT therapy have been reported. The complication of UC should be considered when diarrhea and hematochezia are observed in patients with RA being treated with CTLA-4Ig agents.

Intestinal Haemorrhage and Colitis Induced by Treatment With Osimertinib for Non-Small-Cell Lung Carcinoma: A Case Report.

Background: Osimertinib is recommended either as the first-line therapy for sensitizing EGFR-mutations (FLAURA trial) or at progression to first-/second-generation EGFR inhibitors in the presence of resistance mutation T790M (AURA 3 study). It can effectively improve the prognosis of patients with NSCLC with manageable adverse reactions. Among adverse events, intestinal haemorrhage is rare and requires extensive study on its potential lethality. Case presentation: A 59-year-old female, diagnosed with relapsed stage IV (cT4N2M1c) NSCLC with T790M mutation of the EGFR gene, received osimertinib treatment. Eight months after osimertinib treatment, she complained of lower abdominal pain and haematochezia without haemorrhoids. Potential causes of intestinal haemorrhage other than osimertinib toxicity were ruled out. Colonoscopy examination showed severe colitis with grade 3 CTCAE. Osimertinib was discontinued, and prednisone 0.5 mg/kg was administered. Follow-up endoscopy showed no pathological findings. A novel third-generation EGFR-TKI, aumolertinib, was administrated. Five months after aumolertinib initiation, CT evaluation showed stable disease (SD), and this patient was free of colitis recurrence. Conclusion: To our knowledge, this is the first case report of severe colitis as an adverse event associated with osimertinib. Although osimertinib is the standard treatment for NSCLC in patients with T790M mutation and has fewer side effects, colitis may occur after months of treatment. Aumolertinib, a novel third-generation EGFR-TKI, might be an effective alternative for the treatment of patients with NSCLC experiencing colitis from osimertinib.

Hematochezia Due to Panitumumab-induced Colitis with Vitamin K Deficiency.

Panitumumab, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody, has been shown to be useful in treating either advanced or recurrent KRAS/NRAS/BRAF wild-type colorectal cancer. We herein report the case of a 60-year-old man with short bowel syndrome who developed hematochezia due to panitumumab-induced colitis with vitamin K deficiency during third-line chemotherapy. The cause of vitamin K deficiency was the lack of intravenous vitamin K supplementation following a change from central venous nutrition to peripheral venous nutrition. We advise clinicians to carefully check for colitis and manage the infusions of chemotherapy patients with short bowel syndrome.

Ipilimumab and Nivolumab-Induced Colitis in a Patient With Recurrent Metastatic Melanoma.

Ipilimumab and nivolumab are immune checkpoint inhibitors that have recently been used in the treatment of metastatic melanoma and other cancers. Immune-mediated colitis is one of their adverse events that need to be differentiated from low-grade diarrhea as one of the most common side effects. A 51-year-old woman with relapsed metastatic melanoma presented with intractable diarrhea, nausea, vomiting, and generalized abdominal pain. The patient had been treated with ipilimumab and nivolumab in the past two months. The infectious workup was inconclusive. Colonoscopy demonstrated severe colitis, and biopsies were consistent with colitis. Combination chemotherapy was stopped. The patient was treated with intravenous and oral steroids, and her symptoms improved. A combination of ipilimumab and nivolumab increases the chance of immune-mediated colitis, and steroids should be started promptly to avoid complications such as bowel perforation and toxic megacolon.

Histopathology of Non-IBD Colitis. A practical approach from the Italian Group for the study of the gastrointestinal tract (GIPAD).

Non-IBD colitides (NIBDC) are intestinal diseases clinically and endoscopically overlapping with Inflammatory Bowel Diseases (IBD), sometimes with a similar histological picture. NIBDC include entities such as infectious colitis, ischemic colitis, pseudomembranous colitis, eosinophilic colitis, autoimmune enterocolitis, segmental colitis associated with diverticulosis, drug-induced colitis, radiation-induced colitis, diversion colitis, and microscopic colitis, this last including two entities: collagenous and lymphocytic colitis. The knowledge of the most useful histological features and the main clinical data for each entity is mandatory in daily clinical practice, for correct pathological diagnosis and clinical management.

Mycophenolate-induced Colitis: A Case Report with Focused Review of Literature.

Mycophenolate mofetil (MMF) is an immunosuppressive medication used for the management of various autoimmune diseases, and patients with bone marrow and solid organ transplants. Gastrointestinal side effects are seen 45% of the time and they include nausea (29%), vomiting (23%), constipation (38%), diarrhea (50%-92%), and colitis (9%). In 98% of cases, resolution of diarrhea occurs within 20 days upon discontinuation of the MMF. Data is scarce regarding approach in the treatment of MMF-induced colitis. We report a case of MMF-induced colitis diagnosed by colonoscopy and histopathology. This case illustrates the challenges encountered while managing MMF-induced colitis.

Phenotype of histologically suspected drug-induced colitis; results of a comparative, retrospective cohort study.

Background/aims: Drug-induced colitis (DiC) is a rarely reported form of colonopathy and data about the clinical and endoscopic characteristics are scarce. The aim was to investigate the phenotype of DiC. Methods: Patients in a retrospective case control study were assigned to either DiC or one of two age- and gender-matched control groups (non-inflammatory controls and inflammatory colitis from other causes) based on histopathological findings. Patients' basic characteristics, symptoms, biochemical results and endoscopic appearance were collected. Statistical analysis included ANOVA, the chi-squared test and two-tailed t-test. Results: A total of 211 patients with DiC were included (97 males, age 62.1 ± 16.1 years, BMI 25.9 ± 6.1 kg m-2). In comparison to both control groups, DiC patients presented higher ASA and ECOG-scores and more particularly atherosclerotic comorbidities. The most abundant symptoms were abdominal pain (51.8%), diarrhoea (50.7%) and haematochezia (24.3%). The red blood cell count demarcated anaemia (12.7 ± 2.3 mg/dl) and C-reactive protein was slightly elevated (2.7 ± 5.2 mg/dl). The endoscopic features included erythema (46.9%), oedema (29.9%), erosions (29.9%) and ulcers (14.7%). The inflammation affected the rectum rarely (2.4%) but affected the rest of the colon without predilection in a segmental manner (p<.05). The severity of DiC was mostly mild (85.7%). Conclusions: The phenotype of DiC differs slightly from that of colitis from other causes. Taking the clinical features into account might help to confirm drug-induced aetiology once the pathologist has raised the suspicion.

Triggers of histologically suspected drug-induced colitis.

BACKGROUND: Drug toxicity is a common and even serious problem in the gastrointestinal tract that is thought to be caused by a broad spectrum of agents. Although withdrawal of the causative agent would cure the disease knowledge is scarce and mostly derives from case reports and series. AIM: To investigate potential triggers of drug-induced colitis (DiC). METHODS: We conducted a retrospective, observational case control study. Patients were assigned to DiC or one of two age- and gender-matched control groups (non-inflammatory controls and inflammatory colitis of another cause) based on histopathological findings. Histopathology was reassessed in a subset of patients (28 DiC with atherosclerosis, DiC without atherosclerosis and ischaemic colitis each) for validation purposes. Medical history was collected from the electronic database and patient records. Statistical analysis included chi-squared test, t-test, logistic and multivariate regression models. RESULTS: Drug-induced colitis was detected in 211 endoscopically sampled biopsy specimens of the colon mucosa (7% of all screened colonoscopic biopsy samples); a total of 633 patients were included equally matched throughout the three groups (291 males, mean age: 62.1 ± 16.1 years). In the univariate analysis, DiC was associated with diuretics, dihydropyridines, glycosides, ASS, platelet aggregation inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), statins and fibrates, and with atherosclerosis, particularly coronary heart disease, and hyperlipoproteinaemia. Echocardiographic parameters did not show substantial differences. In the multivariate analysis only fibrates [odds ratio (OR) = 9.1], NSAIDs (OR = 6.7) and atherosclerosis (OR = 2.1) proved to be associated with DiC. Both DiC reassessment groups presented milder inflammation than ischaemic colitis. The DiC patients with atherosclerosis exhibited histological features from both DiC without atherosclerosis and ischaemic colitis. CONCLUSION: Several drugs indicated for the treatment of cardiovascular and related diseases are associated with DiC. Atherosclerosis and microcirculatory disturbances seem to play an important pathogenetic role.

The Differential Diagnosis of Acute Colitis: Clues to a Specific Diagnosis.

This review describes a systematic approach to the interpretation of colonic biopsy specimens of patients with acute colitis. Five main histologic patterns are discussed: acute colitis, focal active colitis, pseudomembranous colitis, hemorrhagic colitis, and ischemic colitis. For each pattern, the most common etiologic associations and their differential diagnoses are presented. Strategies based on histologic analysis and clinical considerations to differentiate acute from chronic colitides are discussed.

Idelalisib-induced colitis and skin eruption mimicking graft-versus-host disease.

INTRODUCTION: Idelalisib is a selective inhibitor of the delta isoform of phosphatidylinositol 3-kinase which was approved by the United States Federal Drug Administration in 2014 for the treatment of relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Drug-induced injury of the gastrointestinal tract is a relatively frequent but usually under-recognized disease entity. CASE PRESENTATION: We report the case of a 56-year-old male with a history of relapsed follicular lymphoma status post allogenic bone marrow transplant who developed severe diarrhea with a skin eruption mimicking graft-versus-host disease (GVHD) 6 months after starting idelalisib. He underwent a colonoscopy demonstrating a grossly normal-appearing colon and terminal ileum. Biopsies taken during the procedure revealed mild active ileitis, colitis, and proctitis with frequent epithelial apoptosis, and focal intra-epithelial lymphocytosis. Skin biopsies revealed sub-acute spongiotic dermatitis suggestive of either contact dermatitis or an eczematous drug reaction. Symptoms were attributed to idelalisib given their resolution with withdrawal of the drug in conjunction with the skin and colonic biopsies. CONCLUSION: High clinical suspicion and awareness of the histological features of idelalisib-associated colitis is important to distinguish it from potential mimickers such as GVHD and infectious colitis.

Colitis during new direct-acting antiviral agents (DAAs) therapy with sofosbuvir, simeprevir and ribavirin for genotype 1b hepatitis C.

Since 2014 several direct-acting antivirals (DAAs) have been made available, allowing interferon-free antiviral treatments with high sustained virological response rates. Side effects are, however, a real challenge during treatment. Sarkar et al. recently published a case of colitis following initiation of sofosbuvir and simeprevir for genotype 1 hepatitis C. We report the case of a patient with no prior history of inflammatory bowel disease, who developed significant bloody diarrhea within 3 weeks of sofosbuvir/simeprevir/ribavirin initiation. Colonoscopy and biopsy suggested a drug-induced colitis.

Severe apoptotic enteropathy caused by methotrexate treatment for rheumatoid arthritis.

The folic acid antagonist methotrexate is a cornerstone treatment of rheumatoid arthritis. Its use is limited chiefly by gastrointestinal toxicity, which is among the main reasons for methotrexate discontinuation. Here, we report the case of a 40-year-old man on chronic methotrexate therapy in whom life-threatening apoptotic enteropathy with watery diarrhea and hypovolemic shock developed after he was switched from the oral to the intramuscular route, with no change in dosage. Colonic biopsies suggested drug-induced colitis, showing a nonspecific, mildly inflammatory infiltrate of lymphocytes and plasma cells, dilated damaged crypts, and a marked increase in basal crypt apoptosis (>20 apoptotic bodies/100 crypts). Clinicians should be aware that methotrexate can cause life-threatening apoptotic enteropathy. Increased basal crypt apoptosis in colonic biopsies with more than 5 apoptotic bodies/100 crypts should routinely suggest drug-induced enteropathy.