INTRODUCTION: Approximately 500,000 Clostridioides difficile infections (CDIs) occur annually in the USA. Recurrent CDI occurs in 20 to 30% patients with increasing rates of recurrence with each subsequent episode. Initial recurrences are treated with additional antibiotic regimens. Current treatment guidelines recommend fecal microbiota transplant (FMT) therapy after a 2nd recurrence treatment failure. Intravenous Immunoglobulin (IVIG) has been shown to be effective as a treatment adjunct in patients with CDI and hypogammaglobulinemia as well as in cases of severe and refractory CDI. Herein, we present a case of a patient with refractory CDI for two and a half years whose symptoms resolved after the addition of therapy with IVIG. CASE DESCRIPTION/METHODS: A 47 year old woman with refractory CDI for 2.5 years was admitted to our facility. She typically had 20 to 40 episodes of non-bloody diarrhea per day. Prior treatment courses included 4 fecal microbiota transplants, 13 oral vancomycin tapers, courses of metronidazole, 1 course of fidaxomicin, and colonic lavage with vancomycin installation, none of which provided relief for more than 1 week. Previously she had undergone EGD and colonoscopy with gastric, duodenal, colonic and terminal ileum biopsies which were unrevealing. Testing for celiac disease, TSH, ESR, CRP, gastrin level, Chromogranin A, vasoactive intestinal peptide 5-HIAA levels and stool osmolar gap were unremarkable. The patient had normal vital signs and had no major laboratory abnormalities. Total IgG was only slightly low at 667 mg/dL, normal range per hospital lab is 700-1600 mg/dL. Stool studies revealed persistent CDI. CT abdomen and pelvis w/o contrast showed no acute findings. She was started on Vancomycin 500 mg PO qid and diarrhea persisted. Colonoscopy with random biopsies revealed normal colonic mucosa and biopsies were negative. IVIG was added to enhance her immune response to refractory CDI. IVIG 20 g was administered daily for 2 days resulting in a dramatic decrease in diarrhea and the patient was discharged in good condition on hospital day 10. DISCUSSION: For our patient adjunctive treatment with IVIG led to resolution of infection and the avoidance of a total colectomy. We suggest consideration for incorporating IVIG therapy in difficult to manage CDI regardless of immunoglobulin status. A need remains for randomized control trials to better establish the optimal timing and dosing of IVIG in the treatment of CDI.

INTRODUCTION: Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that blocks the function of programmed cell death (PD-1) activity by binding to the PD-1 receptor. This prevents suppression of T-cell activity, which can lead to T-cells targeting cancer cells. Unfortunately, these medications induce various types of immune related adverse events including colitis, pneumonitis, endocrinopathies and hepatitis. We report rare case of of nivolumab-induced hepatitis. CASE DESCRIPTION/METHODS: An 86-year-old female with history of metastatic melanoma and was started on nivolumab 3 mg/kg every 3 weeks. Patient noted to have abnormal liver chemistries, nausea and yellowing of skin after 6 months of nivolumab. On presentation she was found to have a total bilirubin of 7.79 mg/dL, INR 1.3, AST 885 IU/L and ALT 999 IU/L. Physical examination was significant for mild scleral icterus only. An ultrasound of liver was notable prominent left lobe of liver but no focal hepatic masses and s/p cholecystectomy with no bile duct dilation. Infectious etiologies were unrevealing for viral hepatitis and acute EBV. Her autoimmune serologies were negative for anti-smooth muscle antibody and anti-mitochondrial antibody. Work up was negative for herbal supplements, illicit substance or other medications. The most likely culprit for her hepatitis was due to nivolumab. Patient was started on prednisone at 1 mg/kg daily for a total of 100 mg prednisone daily and her nivolumab dose was held. On discharge her total bilirubin was 2.45, INR 1.2, AST 62, ALT 249 and Alk Phos 252. Patient continued prednisone taper over 30-day period and by end of the month her liver chemistries had normalized and patient was asymptomatic. DISCUSSION: Nivolumab-induced hepatoxicity is rare and accounts for 3-6% of all immune-related adverse effects. The median time of onset was 3.3 months (range: 6 days to 9 months). In addition to systemic corticosteroid, alternative immunosuppressive therapies may be employed if symptoms continue after 3-5 days. Etiologies of liver dysfunction such as viral infection, obstruction and other forms of autoimmune hepatitis must be excluded. In such an event, oral mycophenolate mofetil 500 mg every 12 hours can be used for treatment. Our patient showed rapid improvement in liver chemistries and had minimal physical side effects. Healthcare provides managing patients with liver injury should be able to recognize and treat prior to development of fulminant hepatitis.

INTRODUCTION: Over the past decade immune-checkpoint inhibitors have been playing an increasing role in cancer treatment. One of the targets of these therapies is the Programmed Death (PD-1) protein; a protein that prevents T cells from recognizing and attacking inflamed tissues and cancer cells. Our reports describes a case in which a patient treated with nivolumab, a PD-1 inhibitor, presented with endoscopic findings characteristic of ulcerative colitis (UC). CASE DESCRIPTION/METHODS: Our case involves a 69-year-old male with past medical history of metastatic melanoma who presented with complaints of diarrhea rectal bleeding. Patient was on nivolumab 3 mg/kg every 2 weeks which was started 5 months ago. He reported lower abdominal cramping, bright rectal bleeding and diarrhea ongoing for 4 days. Physical examination was significant for moderate tenderness to palpation in lower abdomen. Initial abnormal laboratory results including hemoglobin of 11.2 g/dL otherwise unremarkable comprehensive metabolic panel. On computed tomography (CT) of abdomen and pelvis he was noted to have marked colitis involving the ascending, transverse and descending colon. All the following stool testing was negative for clostridium difficile, stool cultures camplyobacter, salmonella, shigella, ova and parasite. Patient was noted to have pancolitis on colonoscopy and pathology showed acute and chronic inflammation with superficial ulceration. Nivolumab was stopped and he was started on IV methylprednisolone 80 mg TID. Patient had little improvement over the next three days and hemoglobin decreased to 8.0 g/dL. Therefore he was given a dose of infliximab 5 mg/kg. His symptoms improved and he was in complete clinical remission soon after discharge. Patient was continued on oral prednisone 100 mg daily and instructed to taper slowly over the coming months. DISCUSSION: The PD-1 pathway will continue to be manipulated in future cancer treatments. Inhibition of PD-1 pathway in mice has resulted in various autoimmune diseases. In a safety profile study with 576 patients on nivolumab dosing of 3 mg/kg the most common adverse effect was noted to be a fatigue in 25% of patients. The incidence of grade 3 or 4 colitis was noted to be present in 0.7% of patients or 4 in total. Although the incidence of severe colitis may be low, infectious etiology must be ruled out prior to initiating immunosuppressive therapy. Patients with corticosteroid resistant colitis should have prompt initiation of infliximab therapy.

INTRODUCTION: Anabolic-androgenic steroid abuse has been steadily increasing in the general population. According to a 2014 study, approximately 1 in 50 students in the 12th grade reported using anabolic steroids. Trenbelone acetate is a synthetic anabolic androgen which is an agonist of the androgen receptor and most often used in cattle. CASE DESCRIPTION/METHODS: A 23 year old male with no significant past medical history presented with complaints of jaundice and generalized weakness which began 10 days prior to presentation. Patient endorsed weekly IM trenbelone 1000 mg weekly over the last 8 weeks. Physical examination was remarkable for icterus and appropriate mentation. Initial investigations reflected a total bilirubin of 13.44 mg/dL, AST 159 IU/L, ALT 425 IU/L, PT 11.0, INR 1.0, and Alk Phos of 142. Serologies were negative for viral hepatitis, anti-mitochondrial antibody, anti-smooth muscle antibody and ANA of 1:40. A liver ultrasound reported normal liver size without biliary obstruction. Patient's liver chemistries improved over the next three days and he was discharged with total bilirubin of 12.54 mg/dL, AST 135 IU/L, ALT 320 IU/L, PT 11.0, INR 1.0 and Alk Phos of 121. Patient advised to abstain from any future use of trenbelone. On repeat labs in 10 days, his total bilirubin of 29.50 mg/dL, AST 78, ALT 123, PT 20.1, INR 1.85 and Alk Phos 242. Physical examination noted worsening jaundice overall along with icterus but mentation remained appropriate. Patient denied any new medications and no further use of trenbelone since discharge. Patient's liver chemistries remained stable and he underwent MRI abdomen which was unremarkable. Patient was discharged home on ursodiol 300 mg BID. Patient's liver chemistry improved in one week and returned to baseline in one month. DISCUSSION: Anabolic steroids have been linked to four different forms of liver injury including an acute cholestatic syndrome such as in our patient, elevation in serum enzymes, chronic vascular injury and hepatic tumors including adenomas and hepatocellular carcinoma. Mechanism of cholestatic syndrome is not well defined in this type of injury. Urosdiol has been used in the past for treatment however efficacy has not been shown in a study. Healthcare provides managing patients with elevated liver chemistries should able to recognize anabolic induced liver injury given increasing use and ease of availability of such performance enhancing drugs.