Hemolytic uremic syndrome in children

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy defined by thrombocytopenia, non-immune microangiopathic hemolytic anemia and acute renal failure. HUS is typically classified into two primary types: 1) HUS due to infections, often associated with diarrhea (D+HUS, Shiga toxin-producing Escherichia Coli-HUS), with the rare exception of HUS due to a severe disseminated infection caused by Streptococcus; 2) HUS related to complement, such HUS is also known as "atypical HUS" and is not diarrhea associated (D-HUS, aHUS); but recent studies have shown other forms of HUS, that can occur in the course of systemic diseases or physiopathological conditions such as pregnancy, after transplantation or after drug assumption. Moreover, new studies have shown that the complement system is an important factor also in the typical HUS, in which the infection could highlight an underlying dysregulation of complement factors. Clinical signs and symptoms may overlap among the different forms of HUS. Shiga toxin-producing Escherichia Coli (STEC) infection cause a spectrum of clinical sings ranging from asymptomatic carriage to non-bloody diarrhea, hemorrhagic colitis, HUS and death. The average interval between ingestion of STEC and illness manifestation is approximately 3 days, although this can vary between 2 and 12 days. Patients with pneumococcal HUS usually have a severe clinical picture with microangiopathic hemolytic anemia, respiratory distress, neurological involvement. The atypical HUS, in contrast to STEC-HUS which tends to occur as a single event, is a chronic condition and involves a poorer prognosis. Early diagnosis and identification of underlying pathogenic mechanism allow instating specific support measures and therapies. Typical management of STEC-HUS patients relies on supportive care of electrolyte and water imbalance, anemia, hypertension and renal failure. For the aHUS the initial management is supportive and similar to the approach for STEC-HUS; currently we have moved from the historic plasma therapy to new therapeutic approaches, first of all eculizumab, a monoclonal antibody that blocks the C5 cascade. This drug has shown an improvement in platelet count, cessation of hemolysis, improvement of renal function within a few days after the treatment. In patients with end-stage renal disease (ESRD) renal transplantation from a non-related donor and prophylactic administration of eculizumab to prevent recurrent disease in the allograft could be considered.