Fever

Background
People with SCA have an increased risk of severe bacterial infection, resulting primarily from reduced or absent splenic function. By 2 or 3 months of age, as their fetal hemoglobin declines, infants with SCA begin to develop splenic impairment. The result is an extremely high risk of septicemia and meningitis, primarily due to Streptococcus pneumoniae. Although the incidence of invasive pneumococcal infection has declined as a result of prophylactic penicillin and pneumococcal vaccination, febrile illnesses in people with SCD are still considered an emergency due to the possibility of penicillin-resistant organisms and incomplete vaccination status. The risk of such infections continues throughout childhood and to a lesser extent in adults. Serious infections can also affect persons with other forms of SCD (e.g., HbSC and HbSp+-thalassemia).

As a presenting symptom, fever heralds many acute and sometimes life-threatening conditions, such as ACS and osteomyelitis. In many cases, the cause of fever is unclear, but because individuals with SCA have a highly increased risk of overwhelming bacterial infection, it is critical that fever alone is taken seriously in these individuals and considered a potential emergency situation. Fever associated with pain should not be considered a VOC until infection is ruled out.

People with SCD who develop fever may have ACS due to diverse organisms (including Mycoplasma) and are also at risk of gram-negative enteric infections involving the urinary tract, hepatobiliary system, or bones. Acute osteomyelitis, another complication associated with fever, may be unifocal or multifocal and may be caused by Staphylococcus aureus, salmonella, or other enteric pathogens. Persons with SCD have normal T cell and B cell function, so the risk of acute infection is generally limited to those micro-organisms mentioned above. Opportunistic infections are infrequent.

Summary of the Evidence
An adequate systematic review of the literature with fair sensitivity and specificity for all studies indexed by SCD terms and the symptom of fever was not feasible. A large and nonspecific return of studies with significant heterogeneity, high miss rate, and low-quality evidence (lack of comparative studies) was anticipated. No systematic review was conducted, and the panel used a consensus process to develop a proposed strategy for triaging and promptly managing fever.

Recommendations
In people with SCD and a temperature 101.3°F(38.5°C), immediately evaluate with history and physical examination,complete blood count (CBC) with differential, reticulocyte count, blood culture,and urine culture when urinary tract infection is suspected. (Consensus-Panel Expertise)

In children with SCD and a temperature 101.3 °F (38.5 °C), promptly administer ongoing empiric parenteral antibiotics that provide coverage against Streptococcus pneumoniae and gram-negative enteric organisms. Subsequent outpatient management using an oral antibiotic is feasible in people who do not appear ill. (Consensus-Panel Expertise)

Hospitalize people with SCD and a temperature 103.1°F (39.5 °C) and who appear ill for close observation and intravenous antibiotic therapy. (Consensus-Panel Expertise)

In people with SCD whose febrile illness is accompanied by shortness of breath, tachypnea, cough, and/or rales, manage according to the preceding recommendations and obtain an immediate chest x ray to investigate for ACS. (Consensus-Panel Expertise)

Recommendations
In febrile people withSCD who have localized or multifocal bone tenderness, especially when accompanied by erythema and swelling, include bacterial osteomyelitis in the differential diagnosis and manage accordingly. (Consensus-Panel Expertise)