Management of fever in sickle cell disease
- Zora R Rogers, MD
Zora R Rogers, MD
- Professor of Pediatrics
- The University of Texas Southwestern Medical Center
- Section Editors
- Donald H Mahoney, Jr, MD
Donald H Mahoney, Jr, MD
- Section Editor — Pediatric Hematology
- Professor of Pediatrics
- Baylor College of Medicine
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
Fever is a common presenting symptom for many manifestations of sickle cell disease (SCD). In particular, fever is frequently the first indication of serious and life-threatening bacterial infections. While commonly discussed in pediatric care, this is a problem throughout the lifespan. Fever is also present in other serious SCD-associated conditions such as acute chest syndrome or vasoocclusive pain episodes. As a result, patients with SCD and fever should be evaluated and treated promptly to avoid significant morbidity and mortality.
Although patients with sickle cell anemia (hemoglobin SS; HbSS) and the closely related sickle cell-β0 thalassemia (HbS-β0 thalassemia) are at highest risk of bacteremia because of their predictable early loss of splenic function, many centers evaluate patients with the variant hemoglobinopathies such as sickle-hemoglobin C disease (HbSC) and sickle cell-β+ thalassemia (HbS-β+ thalassemia) in a similar fashion when a predetermined level of fever develops. Splenic dysfunction worsens with age in patients with all genotypes, and all adults with SCD and fever should be evaluated promptly according to similar guidelines.
The management of the patient with SCD and fever will be reviewed here. Overviews of the other clinical manifestations and their management in patients with SCD are presented separately. (See "Overview of the clinical manifestations of sickle cell disease" and "Overview of the management and prognosis of sickle cell disease".)
The prevention of infections is a major goal of the management of individuals with SCD, especially young children. This is discussed separately. (See "Overview of the management and prognosis of sickle cell disease", section on 'Infection prevention'.)
RATIONALE FOR MANAGEMENT APPROACH
Despite the widespread availability of pneumococcal and Haemophilus influenzae vaccines and the general use of penicillin prophylaxis, individuals with SCD and fever remain at risk for invasive infections from pneumococcus and other organisms. In children with SCD, the major cause of death historically has been infection [1,2]. Prior to the availability of H. influenzae type b and pneumococcal vaccines, young children (below five years of age) with SCD in the United States had a 13 percent risk of developing bacterial sepsis or meningitis with mortality rates of 30 and 10 percent in patients with sepsis and meningitis, respectively . Although mortality has significantly decreased since the introduction of vaccines, particularly since licensure of the conjugate pneumococcal vaccine (Prevnar) in 2000, approximately one-quarter of deaths between 1999 and 2002 in children with SCD in the first nine years of life continue to be due to infectious causes . Case series published since the introduction of the conjugate pneumococcal vaccine indicate that the prevalence of bacteremia in febrile patients with SCD remains significant at 0.8 to 4 percent [4,5]. (See "Overview of the management and prognosis of sickle cell disease", section on 'Introduction'.)
- Barrett-Connor E. Bacterial infection and sickle cell anemia. An analysis of 250 infections in 166 patients and a review of the literature. Medicine (Baltimore) 1971; 50:97.
- Overturf GD, Powars D, Baraff LJ. Bacterial meningitis and septicemia in sickle cell disease. Am J Dis Child 1977; 131:784.
- Yanni E, Grosse SD, Yang Q, Olney RS. Trends in pediatric sickle cell disease-related mortality in the United States, 1983-2002. J Pediatr 2009; 154:541.
- Patel A, Zuzo A, Imran H, Siddiqui AH. Prevalence of pneumococcal bacteremia in children with sickle cell disease. Pediatr Hematol Oncol 2013; 30:432.
- Baskin MN, Goh XL, Heeney MM, Harper MB. Bacteremia risk and outpatient management of febrile patients with sickle cell disease. Pediatrics 2013; 131:1035.
- Powars D, Overturf G, Turner E. Is there an increased risk of Haemophilus influenzae septicemia in children with sickle cell anemia? Pediatrics 1983; 71:927.
- Pearson HA, Gallagher D, Chilcote R, et al. Developmental pattern of splenic dysfunction in sickle cell disorders. Pediatrics 1985; 76:392.
- Rogers ZR, Wang WC, Luo Z, et al. Biomarkers of splenic function in infants with sickle cell anemia: baseline data from the BABY HUG Trial. Blood 2011; 117:2614.
- Quinn CT, Rogers ZR, Buchanan GR. Survival of children with sickle cell disease. Blood 2004; 103:4023.
- Powars DR. Natural history of sickle cell disease--the first ten years. Semin Hematol 1975; 12:267.
- Quinn CT, Rogers ZR, McCavit TL, Buchanan GR. Improved survival of children and adolescents with sickle cell disease. Blood 2010; 115:3447.
- Halasa NB, Shankar SM, Talbot TR, et al. Incidence of invasive pneumococcal disease among individuals with sickle cell disease before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis 2007; 44:1428.
- Adamkiewicz TV, Silk BJ, Howgate J, et al. Effectiveness of the 7-valent pneumococcal conjugate vaccine in children with sickle cell disease in the first decade of life. Pediatrics 2008; 121:562.
- Narang S, Fernandez ID, Chin N, et al. Bacteremia in children with sickle hemoglobinopathies. J Pediatr Hematol Oncol 2012; 34:13.
- American Academy of Pediatrics. Pneumococcal infections. In: Red Book: 2012 Report of the Committee on Infectious Diseases, 29th Ed, Pickering LK, Baker CJ, Kimberlin DW, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2012. p.571.
- Zarkowsky HS, Gallagher D, Gill FM, et al. Bacteremia in sickle hemoglobinopathies. J Pediatr 1986; 109:579.
- Workman MR, Philpott-Howard JN, Casewell MW, Bellingham AJ. Salmonella bacteraemia in sickle cell disease at King's College Hospital: 1976-1991. J Hosp Infect 1994; 27:195.
- McCavit TL, Quinn CT, Techasaensiri C, Rogers ZR. Increase in invasive Streptococcus pneumoniae infections in children with sickle cell disease since pneumococcal conjugate vaccine licensure. J Pediatr 2011; 158:505.
- Yawn BP, Buchanan GR, Afenyi-Annan AN, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA 2014; 312:1033.
- Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014 http://www.nhlbi.nih.gov/health-pro/guidelines/sickle-cell-disease-guidelines/ (Accessed on January 25, 2016).
- Savage WJ, Buchanan GR, Yawn BP, et al. Evidence gaps in the management of sickle cell disease: A summary of needed research. Am J Hematol 2015; 90:273.
- Ellison AM, Thurm C, Alessandrini E, et al. Variation in pediatric emergency department care of sickle cell disease and fever. Acad Emerg Med 2015; 22:423.
- Mountain States Regional Genetic Services Network. Sickle Cell Disease in Children and Adolescents: Diagnosis, Guidelines for Comprehensive Care, and Protocols for Management of Acute and Chronic Complications. 2001.
- Section on Hematology/Oncology Committee on Genetics, American Academy of Pediatrics. Health supervision for children with sickle cell disease. Pediatrics 2002; 109:526.
- Rogers ZR, Morrison RA, Vedro DA, Buchanan GR. Outpatient management of febrile illness in infants and young children with sickle cell anemia. J Pediatr 1990; 117:736.
- Wang CJ, Kavanagh PL, Little AA, et al. Quality-of-care indicators for children with sickle cell disease. Pediatrics 2011; 128:484.
- Powars D, Overturf G, Weiss J, et al. Pneumococcal septicemia in children with sickle cell anemia. Changing trend of survival. JAMA 1981; 245:1839.
- Okuonghae HO, Nwankwo MU, Offor EC. Pattern of bacteraemia in febrile children with sickle cell anaemia. Ann Trop Paediatr 1993; 13:55.
- Kizito ME, Mworozi E, Ndugwa C, Serjeant GR. Bacteraemia in homozygous sickle cell disease in Africa: is pneumococcal prophylaxis justified? Arch Dis Child 2007; 92:21.
- Akinyanju O, Johnson AO. Acute illness in Nigerian children with sickle cell anaemia. Ann Trop Paediatr 1987; 7:181.
- Aken'ova YA, Bakare RA, Okunade MA. Septicaemia in sickle cell anaemia patients: the Ibadan experience. Cent Afr J Med 1998; 44:102.
- Akuse RM. Variation in the pattern of bacterial infection in patients with sickle cell disease requiring admission. J Trop Pediatr 1996; 42:318.
- Williams TN, Uyoga S, Macharia A, et al. Bacteraemia in Kenyan children with sickle-cell anaemia: a retrospective cohort and case-control study. Lancet 2009; 374:1364.
- Viner Y, Hashkes PJ, Yakubova R, et al. Severe hemolysis induced by ceftriaxone in a child with sickle-cell anemia. Pediatr Infect Dis J 2000; 19:83.
- Bernini JC, Mustafa MM, Sutor LJ, Buchanan GR. Fatal hemolysis induced by ceftriaxone in a child with sickle cell anemia. J Pediatr 1995; 126:813.
- Smith-Whitley K, Zhao H, Hodinka RL, et al. Epidemiology of human parvovirus B19 in children with sickle cell disease. Blood 2004; 103:422.
- Kellermayer R, Faden H, Grossi M. Clinical presentation of parvovirus B19 infection in children with aplastic crisis. Pediatr Infect Dis J 2003; 22:1100.
- Magnus SA, Hambleton IR, Moosdeen F, Serjeant GR. Recurrent infections in homozygous sickle cell disease. Arch Dis Child 1999; 80:537.
- Hongeng S, Wilimas JA, Harris S, et al. Recurrent Streptococcus pneumoniae sepsis in children with sickle cell disease. J Pediatr 1997; 130:814.
- Knight-Madden J, Serjeant GR. Invasive pneumococcal disease in homozygous sickle cell disease: Jamaican experience 1973-1997. J Pediatr 2001; 138:65.
- Wilimas JA, Flynn PM, Harris S, et al. A randomized study of outpatient treatment with ceftriaxone for selected febrile children with sickle cell disease. N Engl J Med 1993; 329:472.
- McIntosh S, Rooks Y, Ritchey AK, Pearson HA. Fever in young children with sickle cell disease. J Pediatr 1980; 96:199.
- Lobel JS, Bove KE. Clinicopathologic characteristics of septicemia in sickle cell disease. Am J Dis Child 1982; 136:543.
- Cole TB, Smith SJ, Buchanan GR. Hematologic alterations during acute infection in children with sickle cell disease. Pediatr Infect Dis J 1987; 6:454.
- West DC, Andrada E, Azari R, et al. Predictors of bacteremia in febrile children with sickle cell disease. J Pediatr Hematol Oncol 2002; 24:279.
- Norris CF, Smith-Whitley K, McGowan KL. Positive blood cultures in sickle cell disease: time to positivity and clinical outcome. J Pediatr Hematol Oncol 2003; 25:390.
- Poncz M, Kane E, Gill FM. Acute chest syndrome in sickle cell disease: etiology and clinical correlates. J Pediatr 1985; 107:861.
- Buchanan GR, Smith SJ, Holtkamp CA, Fuseler JP. Bacterial infection and splenic reticuloendothelial function in children with hemoglobin SC disease. Pediatrics 1983; 72:93.
- Rogers ZR, Buchanan GR. Bacteremia in children with sickle hemoglobin C disease and sickle beta(+)-thalassemia: is prophylactic penicillin necessary? J Pediatr 1995; 127:348.
- Lane PA, O'Connell JL, Lear JL, et al. Functional asplenia in hemoglobin SC disease. Blood 1995; 85:2238.
- Lane PA, Rogers ZR, Woods GM, et al. Fatal pneumococcal septicemia in hemoglobin SC disease. J Pediatr 1994; 124:859.
- Schultz CL, Tchume-Johnson T, Schapira MM, et al. Adherence to prompt fever evaluation in children with sickle cell disease and the health belief model. Pediatr Blood Cancer 2015; 62:1968.
- RATIONALE FOR MANAGEMENT APPROACH
- ACUTE MANAGEMENT
- Empiric antibiotic therapy
- Evaluation for associated conditions
- Inpatient versus outpatient management
- - Decision about admission
- - Inpatient management
- - Outpatient management
- Specific infections
- MANAGEMENT IN VARIANT SICKLE CELL SYNDROMES
- Hemoglobin SS
- Hemoglobin SC
- Sickle cell-beta thalassemia
- DISCHARGE INSTRUCTIONS
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS