Plesiomonas shigelloides gastroenteritis in a patient with chronic lymphocytic leukemia

Chronic diarrhea, defined as symptoms ongoing for two or more weeks, in patients with chronic lymphocytic leukemia (CLL), has various causes, including medications, infections, autoimmunity, and gastrointestinal involvement by CLL. Awareness of the pathogenic roles of infectious agents in this particular group of immunocompromised patients has been growing over the last decade. For enteropathogens, this largely was due to growing use of multiplex molecular panels for the diagnosis of gastrointestinal infection. We present a case of Plesiomonas shigelloides gastroenteritis in a patient with CLL. A 75-year-old male with CLL was admitted to the hospital with a history of diarrhea for four weeks prior to presentation. The patient had been having 6–8 loose bowel movements per day. He was also having low-grade fevers and lost significant weight. Upon presentation, the patient was dehydrated and had progressive fatigue for the past few weeks. No blood was noted in the stool. The patient was initially diagnosed with CLL in 2010. White blood cell (WBC) count was 25,000. Fluorescence in situ hybridization (FISH) showed trisomy 12 and deletion 13q and flow cytometry was positive ZAP-70. He was initially managed with observation until his disease progressed in January 2013. He was enrolled on a clinical trial evaluating lenalidomide combination with rituximab. He achieved a partial remission on treatment; however, the disease progressed and was taken off treatment in February 2016. He was then started on ibrutinib, but he developed atrial fibrillation, ibrutinib was dosereduced, and the disease eventually progressed with intraabdominal disease in April 2017. The patient then was started on venetoclax, but developed a skin rash that precluded further venetoclax use, and he subsequently started idelalisib in July 2018. In November 2018, idelalisib was placed on hold due to drug–drug interactions, the patient has not developed signs of CLL relapse and has been managed with observation since that time. In November 2018, the patient developed diarrhea, and a colonoscopy revealed multiple ulcers in the rectum, sigmoid, descending, transverse, and ascending colon with involvement of the terminal ileum. A biopsy demonstrated signs of viral cytopathic changes consistent with viral enterocolitis. Immunohistochemical stains for CMV were strongly positive. The patient was started on intravenous ganciclovir (GCV) at dose of 5mg/kg q12hrs. Despite initiation of the antiviral therapy he continued to have persistent diarrhea, and viral resistance to GCV was a consideration. A CMV genotype was not obtainable due to low-level viremia. GCV was discontinued and the patient was started on intravenous foscarnet (FCN) at dose of 60mg/kg q8hrs with marked improvement of the diarrhea. After 12 days on FCN, the patient was discharged on oral valganciclovir at dose of 900mg q12hrs for one week, then 900mg once daily for 4 weeks. After completing therapy for CMV colitis, he was switched to CLL antiherpetic prophylaxis with oral valacyclovir. In April 2019, the patient presented back to the clinic with another episode of diarrhea over the past four weeks, and given the concern for CMV enterocolitis, the patient was admitted for diarrhea work up and further management. During his admission, the patient CMV PCR was undetectable in blood and stool. Surprisingly, however, the GI multiplex molecular panel came back positive for Plesiomonas shigelloides. Upon further inquiry about the patient’s dietary habits, he reported that he has been eating raw oysters on the half-shell every other week for many years. The patient was started on oral ciprofloxacin 500mg twice a day for 5 days, with improvement in his symptoms by day 4 and complete resolution of diarrhea by day 6 of admission. A repeat multiplex PCR panel in stool after 5 days of treatment was negative for Plesiomonas shigelloides. During this time, the patient also had C. diff PCR DNA positive; however, the toxin enzyme immunoassay (EIA) was negative. In this patient with CLL, previous episodes of diarrhea were found to be associated to infections with CMV and Clostridioides difficile. Other potential causes of diarrhea in this patient could have been related to medications such as venetoclax, ibrutinib, and idelalisib, in addition to progressive CLL. Nonetheless, on the GI multiplex molecular panel, Plesiomonas shigelloides was the pathogen identified in this patient, supported by history of raw seafood consumption, chronic diarrhea, and response to directed treatment with oral ciprofloxacin.