Dexamethasone/prednisolone/tocilizumab

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

In a case series, 3 men aged 57−65 years were described; they developed gastrointestinal perforation during treatment with prednisolone, dexamethasone or off-label tocilizumab for COVID-19 pneumonia [routes and times to reaction onsets not stated].

Case 1: A 65-year-old man was admitted to the ICU with COVID-19 pneumonia. On day 5, he was intubated for respiratory failure. Since day 16, he had recurring fevers despite multiple antibiotics. On day 22, he started receiving prednisolone 120 mg/day for 5 days, which was tapered over 19 days. On day 28, rectal bleeding was noticed. On day 34, lower rectum perforation with perirectal abscess was diagnosed. He underwent diverting colostomy. On day 49, he was discharged. His ICU course was complicated by ischaemic stroke, which hampered his recovery. On day 90, he was discharged to a rehabilitation facility. During follow-up conducted on day 370, he had returned home; however, he had not recovered completely. Imaging and endoscopy revealed that the defect had fully healed. At the time of this report, the restoration of intestinal continuity was under consideration. The lower rectum perforation was attributed to prednisolone.

Case 2: A 58-year-old man was transferred to the ICU with COVID-19 pneumonia. He was intubated and started receiving dexamethasone 6 mg/day, which was continued for 19 days. He also received off-label tocilizumab 8 mg/kg on the day of intubation. Due to increasing abdominal distension and failure to pass stool, he was administered neostigmine on day 13, with rapid results. On day 14, CT scan of the chest and abdomen revealed marked intraperitoneal air without free fluid or signs of focal inflammation, and a distended caecum. Peritoneal lavage was performed; however, the results were negative. After 36h, he developed signs of sepsis. A repeat CT scan revealed increased free air and focal inflammation of the caecal region. Exploratory laparotomy revealed perforation of focal necrosis/ischaemia of the caecum. He underwent iliocaecectomy, and end-ileostomy was created. On post-operative day 10, he was extubated. On day 14, a perisplenic abscess was drained percutaneously. On post-operative day 19, he was discharged from the ICU. Histology showed circumscript ulceration with transmural abscess formation and necrosis. Perforation of the caecum was attributed to dexamethasone and off-label tocilizumab.

Case 3: A 57-year-old man was admitted with COVID-19 pneumonia. He started receiving dexamethasone 6 mg/day, which was continued for 17 days. On day 2, he developed respiratory failure and was shifted to the ICU. On day 3, he was intubated and received off-label tocilizumab 8 mg/kg. On day 10, CT scan was performed due to increasing abdominal distension and failure to pass stool. CT scan revealed distended colon and distal small intestine, a small amount of ascites and no free air. He was administered neostigmine, with rapid results. On day 14, there was progression of abdominal distension, and an abdominal CT scan showed moderately distended caecum and massive intraperitoneal air. Exploratory laparotomy revealed a distended proximal colon fixed to the ventral abdominal wall with perforation of the distal transverse colon. An extended right hemicolectomy was performed, and an end-ileostomy was created. On postoperative day 2, he was extubated. On postoperative day 4, he was discharged from the ICU. On postoperative day 19, he was discharged to a rehabilitation facility. Histology of the colon revealed abrupt transitions from normal tissue to non-specific ischaemic necrotic changes with a regenerative response. After 189 days of initial admission, elective stoma reversal was performed. Perforation of the distal transverse colon was attributed to dexamethasone and off-label tocilizumab.