Hemolytic uremic syndrome associated with group A beta-hemolytic streptococcus
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- Shepherd, A.B., Palmer, A.L., Bigler, S.A. et al. Pediatr Nephrol (2003) 18: 949. doi:10.1007/s00467-003-1191-4
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Group A beta-hemolytic streptococcal (GABS) hemorrhagic colitis due to Streptococcus pyogenes is extremely rare and its association with hemolytic uremic syndrome (HUS) in children has not been described. We report a 9-year-old white male who developed biopsy-proven HUS while continuing to have GABS-positive bloody diarrhea. Renal function deteriorated rapidly requiring intermittent hemodialysis. Three months following discharge, his renal function is normal for age except for significant proteinuria.
KeywordsHemolytic uremic syndromeGroup A beta-hemolytic streptococcusHemorrhagic colitisDialysis
Hemolytic uremic syndrome (HUS) is a common cause of acute renal failure (ARF) in children . Typically, the syndrome occurs about a week following an episode of bloody diarrhea secondary to Escherichia coli O157:H7 even though other etiologies have been described [1, 2]. Streptococcus pyogenes, a Group A beta-hemolytic streptococcus (GABS), as a cause of bloody diarrhea, is extremely rare [3, 4]. To our knowledge the association between HUS and GABS in children has not been described. We report a child who developed sudden onset of ARF while having bloody diarrhea due to GABS and whose renal biopsy showed findings consistent with HUS.
The biopsy findings included 26 glomeruli, eight of which were necrotic. Seven of the glomeruli were engorged with red blood cells, and many of the glomeruli displayed double contouring of the capillary basement membranes when viewed with the periodic acid methenamine silver (PAMS) stain. One afferent arteriole contained a fibrin thrombus, while other vessels were unremarkable. The tubules were lined by flattened, regenerative epithelium. Immunofluorescence studies were essentially negative in the glomeruli, except that fibrin/fibrinogen was identified within the glomerular capillary walls and lumen. By electron microscopy, the glomeruli demonstrated prominent lucent widening of the subendothelial portion of the capillary basement membranes, with complete effacement of podocyte foot processes, fragmentation of erythrocytes, and a moth-eaten appearance of the mesangium.
Hemorrhagic colitis as a presenting symptom of GABS disease is extremely rare [3, 4]. Its occurrence should normally suggest enteric pathogens such as Shigella sp., Campylobacter sp., and E. coli O157:H7, the clinical presentation of which would be similar to our case. We believe that the bloody diarrhea in our patient was due to GABS as pure growth was isolated from the stool cultures on two occasions. Moreover, the stool was negative for Shiga toxin and the serum antibody titers to 0157 LPS by ELISA were non-significant. The source of GABS in our patient is not known. Presence of systemic GABS infection does at times result in diarrhea, but this was not the case in our patient. Positive cultures for GABS have been found in the stool and rectum of patients with streptococcal pharyngitis . Our patient did not have any preceding sore throat or perianal disease.
The sudden onset of microangiopathic hemolytic anemia, thrombocytopenia, and ARF in our patient along with the renal biopsy picture certainly fits with the diagnosis of HUS. The unusual features were the age of onset and the initial normal laboratory findings followed by the sudden onset of ARF and microangiopathic hemolytic anemia while continuing to have bloody diarrhea. These findings prompted an early renal biopsy. Despite a period of anuria and marked deterioration of renal function requiring intermittent hemodialysis, his renal function is currently normal for age and he is off all antihypertensives although he continues to have 2+ proteinuria.
Low serum levels of C3 have been described in the acute phase of the illness both in typical and atypical HUS [6, 7]. The C3, however, returned to normal levels with the remission of the disease. Remuzzi et al.  have recently shown that the serum C3 levels in cases of familial HUS were consistently decreased as compared to the controls even during remission of the disease. They believe that the reduced C3 serum levels may indicate increased C3 consumption secondary to a genetically determined factor H deficiency, thus predisposing to microvascular thrombosis in familial HUS. Our patient had no family history of HUS and the C3 levels promptly returned to normal with the remission of the disease.
The association of GABS with HUS is not well known. GABS, however, has several virulence factors that may predispose to microangiopathy. Burns et al.  have described activation of an endothelial cell matrix metalloprotease by GABS extracellular cysteine protease in human umbilical vein endothelial cells. Activation of this metalloprotease resulted in endothelial cell damage. Pandiripally et al.  demonstrated that GABS M1 and Fba proteins bind Factor H. Decreased circulating Factor H levels may result in complement mediated endothelial cell damage secondary to decreased clearance of C3b and uncontrolled formation of the C3bBb complex .
To our knowledge, this is the first case report of HUS associated with GABS hemorrhagic colitis with or without bacteremia in a child. We do emphasize that GABS-associated bloody diarrhea, although extremely rare, does occur in children. Physicians taking care of such children should follow them closely for the development of HUS.