An Unusual Cause for Recurrent Pneumatosis Intestinalis and Asymptomatic Pneumoperitoneum

Abstract

CASE REPORT: A 65 y.o. woman with h/o mixed connective tissue disease was admitted to the hospital with mild epigastric pain and persistent N/V. Apart from MCTD, she had h/o SBO s/p symphysiolysis x 2, HTN, rec. DVTs on anticoagulation, CRD, chronic functional diarrhea and GERD. Her home medications included: ibuprofen/acetaminophen prn, prednisone 10 mg po qd, metoprolol, lisinopril, PPI, amlodipine, rivaroxaban and tofacitinib (Xeljanz) 5 mg po bid. CT scan revealed extensive pneumatosis intestinalis (including the stomach) and pneumoperitoneum. Surgical and GI consultations were requested. Because of her benign clinical picture and multiple comorbidities, conservative management with bowel rest and IV antibiotics was recommended. EGD was negative for PUD. NSAID and steroids were considered the probable culprit and were stopped. Perforation was not mentioned as one of the possible adverse reactions of tofacitinib at the time. She was discharged home after 8 days. She presented again with similar symptoms one month later in clinic, and a repeat CT scan showed recurrence of diffuse PI and pneumoperitoneum. She was admitted and started on TPN and antibiotics with bowel rest for 4 weeks. In discussion with Rheumatology we decided to stop tofacitinib after we found case reports of perforation while on a JAK inhibitor. She had no recurrence. Currently there is a black box warning for the association of tofacitinib with gastrointestinal perforations. DISCUSSION: Pneumatosis intestinalis (PI) is idiopathic (15%) or secondary (85%) to a wide variety of illnesses including intraabdominal catastrophes (e.g. ischemia, infarction, typhlitis), mucosal disruption (e.g. PUD, IBD, ruptured diverticulum), infection (e.g. C. difficile, TB, Whipple's, HIV/AIDS), pulmonary disorders (e.g. CF, COPD, mechanical ventilation), endoscopic procedures, motility disorders (e.g. DM, scleroderma) and immunological disturbances (e.g. chemotherapy, steroids, HIV/AIDS, GvH disease, post transplant). The mechanism that tofacitinib/JAK inhibition causes PI and perforation is unknown. In the clinical trials, this was seen on patients with RA that were also taking NSAIDs. There was no discernable difference in frequency of GI perforation between the placebo and the tofacitinib arms in clinical trials of patients with UC, and many of them were receiving background steroids.Tofacitinib should be used with caution in patients who may be at risk perforation (e.g. history of diverticulitis).