A 30 yo female without significant medical history presented to hospital complaining of facial swelling and dyspnea on exertion of 3 days duration. She described increasing fatigue, nausea and throat discomfort but denied diarrhea, cough, sputum production, fever, chills, rigors, sweats or abdominal pain. The patient had attributed her symptoms to contact with small children who had recently become ill. She denied a change in urine output. Family history included a sister recently diagnosed with atypical hemolytic-uremic syndrome.
Physical examination revealed a well developed and well-nourished female, with initial vital signs significant only for blood pressure of 193/101. She exhibited mild bilateral facial edema in addition to mild non-pitting edema of the upper and lower extremities. Her cardiac, pulmonary, and abdominal examination was unremarkable.
Initial serum chemistry revealed a BUN 49 and serum creatitine of 4.16 mg/dl. Complete blood count revealed mild anemia with a serum hemoglobin 10.0 mg/dl, but normal white blood cell and platelet counts. Urine analysis showed 10 RBCs and >500 protein.
A broad work up for initiated for causes of acute renal failure with a focus on atypical hemolytic uremic syndrome given the patient’s family history. The patient was evaluated by Hematology and Nephrology services. Serum haptoglobin was found to be <20 mg/dl, and LDH of 564. A renal biopsy was performed revealing presence of thrombotic microangiopathy. ADAMTS13 levels were normal.
Amlodipine, hydralazine and labetalol were used to manage hypertension. Her serum creatitine remained unchanged but her symptoms and peripheral edema decreased. The patient was discharged and initiated eculizumab therapy within one week. 3 months later, the patient’s creatinine had improved to 1.5 mg/dl and her symptoms completely resolved.
Discussion:
Atypical hemolytic uremic syndrome (aHUS) is an increasingly recognized entity involving a disordered completement cascade resulting in acute renal failure, hemolytic anemia and thrombocytopenia. In contrast, “typical” hemolytic-uremic syndrome (HUS), prevalent in children, is considered to be an acquired disorder typically resulting from Shiga-toxin exposure in E. coli-related gastrointestinal illness. The pathophysiology of aHUS involves a genetic defect resulting in dysfunction of the completement cascade. Another diagnostic consideration with a similar clinical presentation is thrombotic thrombocytopenic purpura (TTP), arising as an acquired deficiency of ADAMTS13, an enzyme involved in von Willebrand factor metabolism. The diagnosis of aHUS should be suspected in the presence of hemolysis, thrombocytopenia and renal failure arising from thrombotic microangiopathy. Genetic testing may be initiated for several of the genetic mutations known to be associated with aHUS. Treatment includes control of hypertension, management of proteinuria and eculizumab, a humanized monoclonal antibody against complement which acts as an inhibitor of the complement cascade. The patient, and her sister, in our case both had excellent clinical response to eculizumab and were found to have an identical gene mutation associated with aHUS.
Conclusions:
aHUS is increasingly recognized disorder and hospitalist physicians should be familiar with the workup and management. Rapid recognition, exclusion of similar disorders and involvement of appropriate consultants is essential to avoiding negative patient outcomes in aHUS.