Hemolytic Uremic Syndrome Associated With Escherichia coli O157 Infection in an Allogenic Stem Cell Transplant Recipient

A 67-year-old woman presented to a local emergency department with abdominal pain and hematochezia that developed after she attended an agricultural state fair where she ate local products. Her medical history was notable for well-controlled type 2 diabetes and hypertension, and over 1 year previously, she had undergone matched unrelated donor allogenic peripheral blood stem cell transplant for the treatment of high-risk acute myeloid leukemia. The posttransplant course was complicated by the development of biopsy-proven grade 2 lower gastrointestinal graft-vs-host disease (GvHD) on day 39 that was successfully treated with tacrolimus and corticosteroids. At the time of current presentation, she was taking tacrolimus, 0.5 mg daily, and prednisone, 5 mg daily.

Two days before this presentation, she started experiencing loose bowel movements associated with abdominal pain that rapidly progressed to frequent episodes of bloody diarrhea, severe abdominal pain, nausea, and vomiting on the day of presentation. She was admitted to a local hospital for further management. At the time of admission, she reported no fever, chills, night sweats, or respiratory or urinary symptoms. She had eaten crepes and nutty bars at the fair 3 days before admission as well as drinking from a water fountain. She denied any sick contacts and had no relevant travel history. After admission, she underwent a diagnostic colonoscopy with random biopsies. Pathological examination revealed extensive hemorrhage within the lamina propria, extensive surface erosions, prominent crypt dropout, and foci of hyalinization within the lamina propria, suggesting severe mucosal inflammation.

She was transferred to our institution the next day for further management. On arrival, she continued to report considerable abdominal pain, nausea, and diarrhea.

Computed tomography of the abdomen and pelvis demonstrated markedly thickened and edematous colon, extending from the cecum to the splenic flexure. Findings were consistent with severe colitis (Figure 1).

Initial laboratory evaluation revealed leukocytosis, new-onset thrombocytopenia, and an elevated creatinine level. Hemoglobin on admission was within normal limits. Stool studies demonstrated positivity to Shiga toxin–producing Escherichia coli O157 serotype. At the time of transfer, she was receiving metronidazole, doxycycline, and cephalexin (initiated for a presumed diagnosis of infectious colitis), which were discontinued because of potential increased risk for transformation to hemolytic uremic syndrome (HUS). Prophylactic acyclovir and posaconazole were continued.

Supportive management with intravenous fluids was initiated. Neurological evaluation was performed every 4 hours. Hemolysis parameters were monitored with daily peripheral blood smear and haptoglobin, lactate dehydrogenase (LDH), and reticulocyte measurements. Three days after admission, mild confusion was reported overnight, and examination revealed a somnolent patient who was disoriented to time and place. The patient continued to experience diarrhea. In addition, schistocytes were identified on peripheral smear for the first time that morning (Figure 2). Laboratory values over the course of a few days continued to show deterioration with new-onset anemia, worsening thrombocytopenia, increasing creatinine levels, LDH elevation, and haptoglobin decrease. Total complement, factor B and H complement assay, and complement C3 and C4 were within normal limits, SC5b-9 complement was elevated (348 ng/mL [<251 ng/mL]), and ADAMTS13 activity was normal at 71%, consistent with the development of microangiopathy and HUS. Because of the concern for drug-induced microangiopathy, tacrolimus was withheld at the time of admission. Because of the patient’s continued decline in renal function, the multidisciplinary team decided to administer eculizumab (Soliris). Eculizumab is a monoclonal antibody against complement C5 and therefore is associated with increased risk of meningococcal infection. It is therefore recommended that patients receive meningococcal vaccination at least 2 weeks before eculizumab therapy. However, there is concern that administration of meningococcal vaccine at that time may increase complement activity and potentially worsen HUS. As a result, the decision was made to initiate azithromycin beginning 12 hours after eculizumab infusion at a dose of 500 mg intravenously daily for meningococcal prophylaxis. The decision to use azithromycin was made after considering the risks and benefits including the possibility that introducing an antibiotic could increase the risk of toxin production and worsen HUS.

During the 3 days following the eculizumab infusion, the patient’s neurological status continued to worsen, with reports of visual hallucinations and agitation. Microangiopathic parameters continued to worsen, with hemoglobin decreasing to 7.8 g/dL, platelet count decreasing to 12 × 10⁹/L, LDH increasing to 804 U/L, and creatinine increasing to 2.6 mg/dL (Table). Interestingly, the patient’s hematochezia improved and her diarrhea resolved.

Six days after the eculizumab infusion, the patient’s neurological status improved. She was alert and oriented on examination. She continued to have borderline renal function. Diuretics were administered because of evidence of hypervolemia.

A second dose of eculizumab was administered 7 days after the initial dose. Creatinine continued to rise, and there was ongoing evidence of hemolysis, requiring a total of 5 units of packed red blood cell transfusions over a period of 15 days (transfusion threshold of <7 g/dL). Platelets remained at less than 20 × 10⁹/L, with subsequent increase to 78 × 10⁹/L 15 days after the second infusion. No platelet transfusion was required.

The patient's serum creatinine level peaked at 5.5 mg/dL at 20 days after admission. She experienced volume overload and hyperkalemia, managed only with diuretics. Dialysis was never required during the disease course; interestingly, persistent polychromasia, moderate schistocytes, and helmet cells remained present (Figure 3).

She was discharged from the hospital 23 days after admission with close outpatient follow-up. She continued to experience borderline renal function and required monitoring of her hemoglobin with periodic red blood cell transfusions. Two weeks after hospitalization, she received immunizations with the Menomune meningococcal polysaccharide vaccine, BEXSERO meningococcal group B vaccine, pneumococcal vaccine series, and Haemophilus influenzae vaccination.

Seven months after her initial presentation to the emergency department with hematochezia, the patient’s renal function remained stable, no signs of GvHD were identified, her energy level improved significantly, and dialysis has not been required.