Severe Shiga-toxin induced haemolytic uraemic syndrome with widespread lytic bone lesions requiring Eculizumab.

Abstract

Shiga-toxin producing Escherichia coli induced haemolytic uraemic syndrome (STEC-HUS) is a thrombotic microangiopathy that manifests with macroangiopathic haemolytic anaemia, thrombocytopaenia, and end organ damage caused by micro-thrombi. It is typically observed in the paediatric population. When presenting in adults is typically seen in those aged over 50. Presentations in younger adults are rare. We present the case of a previously well 31-year-old female presenting with bloody diarrhoea and acute kidney injury. The patient was clinically hypovolaemic and managed with intravenous fluids and empirical antibiotics out of concern for abdominal sepsis. Imaging of the abdomen revealed severe uncomplicated colitis but noted widespread lytic lesions. Further imaging revealed lytic lesions extending from the patient’s skull to bilateral femurs, multiple vertebral bodies, ribs, scapula, and pelvis. During the first two days of admission the patient continued to deteriorate, developing rapidly progressive anaemia and thrombocytopaenia, with anuric renal failure and pulmonary oedema. Concern was for thrombotic microangiopathy, with the lytic lesions confounding diagnostic workup. The patient was transferred to the Intensive Care Unit and commenced on high dose dexamethasone, plasma exchange (PLEX), and haemofiltration. Thrombotic Thrombocytopenic Purpura was excluded on ADAMST13 testing. Lytic lesion biopsy was non-diagnostic. Blood film revealed red cell fragmentation consistent with evidence of haemolysis. Flow cytometry and bone marrow aspirate did not reveal evidence of malignancy or cause of the lytic lesions. A diagnosis of STEC-HUS was made after faecal specimen returned positive identification of STX-2 toxin. Dexamethasone was subsequently ceased. PLEX was also ceased after recurrent anaphylactoid reactions, thought to be secondary to blood products. Off these therapies we observed the patient’s haemolysis to accelerate with D-dimer peaking >20 (reference <0.50) and lactate dehydrogenase >2800 (reference 120-250). The patient deteriorated with worsening encephalopathy and tonic-clonic seizures requiring intubation. Persistent haemolysis and ongoing renal and neurological end organ dysfunction prompted the decision to commence Eculizumab. Following two doses of the complement protein C5 inhibitor we observed dramatic improvement, with the patient’s haemolysis resolving without further transfusion requirement. After several weeks of intermittent haemodialysis, her renal recovery was adequate to wean from dialysis. Upon discharge the patient returned home with her family to their property where they grow organic produce. No other family members or contacts developed symptoms of STEC-HUS, and the patient never consumed unpasteurised milk or had other epidemiological exposures. No contact to STEC was confirmed. This represents a severe manifestation of a disease that is rare in the patient’s demographic and reminds clinicians to consider the diagnosis in the workup of patients presenting with diarrhoea who develop acute kidney injury, anaemia, and thrombocytopaenia. The aetiology of the patients’ widespread lytic lesions remains unclear due to patient preference to delay further investigation but provided added complexity to the diagnostic workup in this case.