Original article
Hemolytic Uremic Syndrome Associated with Invasive Pneumococcal Disease: The United Kingdom Experience

https://doi.org/10.1016/j.jpeds.2007.03.055Get rights and content

Objective

To describe the presentation, management, and outcome of 43 cases of pneumococcal-associated hemolytic uremic syndrome (P-HUS). An increased incidence of P-HUS has been noted in the United Kingdom between January 1998 and May 2005.

Study design

Cases with microangiopathic hemolytic anemia (Hb <10 g/dL with fragmented RBCs), thrombocytopenia (platelet count < 130 × 109/L), acute renal impairment with oliguria and elevated plasma creatinine for age, confirmed or suspected pneumococcal infection and/or T-activation were included.

Results

The median age at presentation was 13 months (range, 5-39 months). Pneumococcus was identified in 34 of 43 cases; T-activation was identified in 36 of 37 cases. Twelve strains were serotyped: serotypes 3 (n = 2), 6A (n = 2), 12F (n = 1), 14 (n = 1), 19A (n = 6). Empyema was present in 23 of 35 pneumonia cases; 13 cases had confirmed (9) or suspected (4) pneumococcal meningitis; 36 cases required dialysis (median, 10 days; range, 2-240 days). The mortality rate was 11%, comprising 3 cases of meningitis, 1 case of sepsis and 1 case of pulmonary embolism at 8 months follow up while on dialysis. Follow-up data were available for 35 of 38 patients who survived (median follow-up period, 9 months; range, 1-63 months); of these, 10 patients had renal dysfunction, 1 patient was dialysis-dependent, 5 patients had hypertension and 8 patients had at least 1+ proteinuria on urinalysis.

Conclusion

P-HUS has increased compared with historic surveys (0/288 in 1985-1988; 8/413 in 1997-2001, 43/315 in 1998-May 2005). Early mortality remains high (8-fold that of VTEC-induced HUS). Ten of 12 strains identified would not be covered by the PCV7 vaccine.

Section snippets

Methods

Cases were defined as those presenting with microangiopathic hemolytic anemia (Hb <10 g/dL with fragmented RBCs), thrombocytopenia (platelet count < 130 × 109/L), and acute renal impairment with oliguria and elevated plasma creatinine for age associated with confirmed or suspected pneumococcal infection and/or T-activation. In two centers (Great Ormond Street Hospital, London and Guy’s Hospital, London), cases were identified between January 1998 and May 2005. Further cases were identified from

Clinical Presentation

Forty-three children fulfilled our criteria for inclusion in the study. The median age at presentation was 13 months (range, 5-39 months). There were 25 boys and 18 girls (male:female, 1.4). Pneumonia was a presenting feature in 35 of 43 cases (81%), with empyema complicating 23 of 35 cases (66%; Table I). Pleural drainage was undertaken in 16 of 23 cases (70%), and only 7 of these 16 cases (44%) had a positive yield for S pneumoniae by culture (n = 3) or 16S rRNA sequencing (n = 4). Of those

Discussion

In the past 3 decades, the number of reported cases of pneumococcal HUS has increased, with >100 cases reported to date.11, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 46, 47, 48 Also, in recent years, certain centers have reported an increased prevalence of pneumococcal HUS.30, 34 Between 1985 and 1988, national epidemiological surveys of childhood HUS in the United Kingdom reported atypical HUS in only 15 of 288 cases (5.2%),

References (54)

  • K. Fischer et al.

    [Severe pneumonia with hemolysis caused by neuraminidase. Detection of cryptantigens by indirect immunofluorescent technic]

    Monatsschr Kinderheilkd

    (1971)
  • R.A. Seges et al.

    Pediatric surgical patients with severe anaerobic infection: report of 16 T-antigen positive cases and possible hazards of blood transfusion

    J Pediatr Surg

    (1981)
  • J. Ramasethu et al.

    T activation

    Br J Haematol

    (2001)
  • A.F. Eder et al.

    Does red-cell T activation matter?

    Br J Haematol

    (2001)
  • C. Gasser et al.

    [Hemolytic-uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia]

    Schweiz Med Wochenschr

    (1955)
  • R. Seger et al.

    [Neuraminidase-producing pneumococci in the pathogenesis of hemolytic-uremic syndrome]

    Schweiz Med Wochenschr

    (1980)
  • J. Yahav et al.

    Hemolytic uremic syndrome due to pneumococcal sepsis

    Int J Pediatr Nephrol

    (1980)
  • C. Loirat et al.

    Secondary hemolytic uremic syndromes (HUS) in children

    Eur J Pediatr

    (1983)
  • R.W. Novak et al.

    Hemolytic-uremic syndrome and T-cryptantigen exposure by neuraminidase-producing pneumococci: an emerging problem?

    Pediatr Pathol

    (1983)
  • U. Alon et al.

    Hemolytic-uremic syndrome associated with Streptococcus pneumoniaeReport of a case and review of the literature

    Am J Dis Child

    (1984)
  • L.G. Feld et al.

    Pneumococcal pneumonia and hemolytic uremic syndrome

    Pediatr Infect Dis J

    (1987)
  • A. Martinot et al.

    Haemolytic-uraemic syndrome associated with Streptococcus pneumoniae meningitis

    Eur J Pediatr

    (1989)
  • M.E. McGraw et al.

    Haemolytic uraemic syndrome and the Thomsen Friedenreich antigen

    Pediatr Nephrol

    (1989)
  • R. Begue et al.

    Hemolytic uremic syndrome associated with Streptococcus pneumoniae

    N Engl J Med

    (1991)
  • S.W. Eber et al.

    [Hemolytic-uremic syndrome in pneumococcal meningitis and infection. Importance of T-transformation]

    Monatsschr Kinderheilkd

    (1993)
  • L.C. Erickson et al.

    Streptococcus pneumoniae-induced hemolytic uremic syndrome: a case for early diagnosis

    Pediatr Nephrol

    (1994)
  • C.G. Pan et al.

    Hepatocellular injury in Streptococcus pneumoniae-associated hemolytic uremic syndrome in children

    Pediatr Nephrol

    (1995)

    • Cited by (0)

    Supported by the Nicholas Head and Steven Langrish Funds, Trust Fund of Great Ormond Street Hospital contribution to the European Pediatric Research Group for HUS.

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