Case Presentation:
60yo F with PMHx of Hepatitis C presented with shortness of breath for 2 days, associated with chest tightness and lightheadedness. Further questioning revealed she had 2 days of bloody stools, hematuria, and minor nose bleeds. Physical examination was remarkable for dried blood in the nares, pale conjunctiva, and a flow murmur. Rectal exam showed brown stool. Admission labs revealed acute on chronic kidney disease, new normocytic anemia, and mild thrombocytopenia (Creat 4.75g/dL, baseline 1.55, Hgb 7.8g/dL, baseline 11.9, Plt count 130K/uL, baseline 237, all 1 month prior). Stool sample was occult positive. Urinalysis was yellow, with large blood (>182 RBCs). Anemia work up showed schistocytes on peripheral smear, lactate dehydrogenase (LDH) 999, haptoglobin 16, and normal bilirubins. C3 was elevated (250mg/dL) and C4 was low (3mg/dL). The patient underwent emergent plasmapheresis and hemodialysis, with marked improvement in clinical status and laboratory abnormalities (Hgb 10.8, LDH 498, Plt 206, Creat 2.98). Stool cultures were negative and ADAMTS13 activity was normal, ruling out toxin‐mediated hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, respectively. Renal biopsy findings were consistent with HUS and a final diagnosis of atypical HUS (aHUS) was made. She was discharged with a plan to continue hemodialysis and begin outpatient ecluzimab therapy.
Discussion:
HUS is characterized by the triad of hemolytic anemia, severe thrombocytopenia, and renal impairment. Commonly this is secondary to Shiga toxin‐producing enteric infections and presents as bloody diarrhea. In contrast, aHUS is both toxin and diarrhea negative, and is secondary to dysregulation of the alternate complement pathway. Our case of aHUS was unique because it presented with bloody diarrhea, only mild thrombocytopenia, and elevated rather than decreased C3 levels. These atypical presentations can result in delayed diagnosis and worsened outcomes.
Plasmapheresis is the first‐line therapy for aHUS and early initiation leads to better outcomes. Response is monitored by normalization of platelets, hemoglobin and LDH. Recently, a better understanding of the pathophysiology behind aHUS has led to the emergence of ecluzimab, a humanized anti‐C5 monoclonal antibody. This drug inhibits the critical steps in the alternative complement pathway and is currently being evaluated in clinical trials. This new treatment option is changing the therapeutic approach to aHUS.
Conclusions:
One should recognize that aHUS can present with or without bloody diarrhea and the hallmark laboratory data may not always follow the classic pattern. This is important as early intervention with plasmapheresis and more cutting edge therapy such as ecluzimab may be critical to improved outcomes.
