Case Presentation: A 37-year-old previously healthy woman developed nausea, non-bloody vomiting and abdominal cramping a few hours after eating a beef chili followed by two episodes of self-limiting “chocolate” colored diarrhea. She presented three days later with persistent nausea, increasing fatigue and lethargy. Vital signs included a heart rate of 99/minute, blood pressure of 117/74 and temperature of 36.4C. Examination of the abdomen revealed normal bowel sounds and no tenderness. Neurological examination was remarkable for hypophonia, psychomotor slowing and occasional right upper extremity myoclonus. Laboratory data revealed a WBC count of 12,980 cells/mm3, hemoglobin of 9.4 gm/dL, platelet count of 50,000 cells/mm3, BUN of 82 mg/dL and creatinine of 8.2 mg/dL. A focused hematological work-up was notable for a haptoglobin of < 8 mg/dL, elevated LDH (1,134 U/L) and normal direct antiglobulin test. Coagulation profile revealed a normal PT, PTT and fibrinogen. Schistocytes on peripheral smear led to a diagnosis of thrombotic microangiopathy (TMA). Apheresis was begun on hospital day 1 supplemented by eculizumab on hospital day 2. In the ensuing hours on hospital day 2, the patient became comatose and developed bilateral upper extremity myoclonus associated with left gaze deviation and left facial droop. This was associated with persistent mastication and exaggerated deep tendon reflexes. Laboratory data was remarkable for a BUN of 103 mg/dL and creatinine of 10 mg/dL. EEG revealed a suppressed background with rare and to continuous and activity, consistent with severe encephalopathy. MRI brain was unremarkable. The encephalopathy demonstrated no improvement with lorazepam, levetiracetam and hemodialysis. Normal ADAMTS 13 activity (0.92 IU/ml) and stool PCR positivity for a Shiga toxin producing organism confirmed the diagnosis of hemolytic-uremic syndrome (HUS).

Discussion: HUS is a rare syndrome usually seen in pre-school children and characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. However, a recent outbreak in 2011 due to a new variant affected predominantly adults and women. Although most commonly seen after Shiga toxin producing O157:H7 and O104:H4 E. coli infection, other strains may also cause HUS, as in our case. Neurologic manifestations of HUS range from dysphasia, memory deficits and hyperreflexia to coma and seizures. Unlike renal injury that is caused by platelet-fibrin thrombi, Shiga toxin neurotoxicity is mediated by toxic/metabolic alteration of neurons through Gb3 receptor activation. Neurologic symptoms do not correlate with the severity of renal dysfunction or the extent of MRI findings. EEG findings range from normal ⍺ frequency to severe general slowing with 2-3/second waves in frontal derivations. Shiga toxin-associated HUS (ST-HUS) is treated with supportive measures, with eculizumab and apheresis typically reserved for compliment-mediated HUS and thrombotic thrombocytopenic purpura (TTP) respectively.

Conclusions: Due to the prevalence of new variants, the diagnosis of ST-HUS needs to be strongly considered in all adults with a recent diarrheal illness and thrombotic microangiopathy. Many ST-HUS patients present with severe neurologic complications due to more potent Shiga toxins, making differentiation from TTP difficult. Consequently, initial treatment often includes apheresis and eculizumab until a definite diagnosis is possible with return of stool PCR and ADAMTS13 levels.