Sickle Cell Disease is a terrible disease and can be associated with many complications that cause patients to present to the emergency department.  We have previously touched on several clinical issues related to sickle cell disease. We have covered Acute Chest Syndrome and the need to always look for splenomegaly in patients presenting with complaints related to sickle cell disease. We have also discussed causes of abdominal pain and bone pain.  Certainly, pain is also a common complaint and we have even considered potential novel therapies for sickle cell pain. One presentation that deserves specific attention, though, is Fever in the patient with sickle cell disease.

Sickle Cell and Fever: The Background

• The overall mortality rate of sickle cell disease has decreased substantially since 1983.
  • Likely due to combination of improved vaccinations and prophylactic penicillin use. [Yanni, 2009]
  • Advances in vaccinations have helped to reduce the risk:
    • Haemophilus influenza vaccination
    • Pneumococcal polysaccharide vaccination (23-valent)
    • Pneumococcal conjugate vaccinations (7-valent; 13-valent)

• Unfortunately, sepsis remains the most common cause of mortality in sickle cell disease. [Yanni, 2009]
  • Sickle cell disease associated with a functional asplenia and reduced immune system response (ex, defects in complement pathways, low nitric oxide bioavailability).
  • Increased risk for infections with encapsulated organisms.
  • Fever may be the only symptom on presentation!

Sickle Cell and Fever: The Concerns

• As with any child with fever, the most common cause is a viral illness, but because of the functional asplenia, more ominous infections must be considered first.
• Overall, the incidence of serious bacterial infections was found to be 16% in one study. [Bansil, 2013]
  • Bacteremia
    • In the US, incidence typically reported to be ~1% in febrile patients with sickle cell disease. [Narang, 2012; Rogovik, 2009]
    • Incidence of S. pneumonia bacteremia has been found to be low since
  • • Salmonella, Alpha-hemolytic strep, Acinetobacter jejuni have been cultured.  [Narang, 2012]
  • Pneumonia
    • Essentially, this is concerning for Acute Chest Syndrome! Be alert!
    • Was most common cause of serious bacterial infections in one study (13.8%). [Bansil, 2013]
    • May still be due to S. pneumoniae serotypes not covered by vaccinations.
  • Urinary Tract Infection
    • Incidence vary greatly (1% – 21%). [Bansil, 2013; Asinobi, 2003]
    • E. Coli and Klebsiella species are common causes.
  • Osteomyelitis
    • Much more rare.
    • May present with similar findings as a vaso-occlusive crisis (pain, swelling, redness).
    • Salmonella osteomyelitis needs to be considered.
  • Meningitis
    • Rarely encountered.
    • Presents similar to meningitis in patients without sickle cell disease.

Sickle Cell and Fever: The Evaluation

• Due to the significant risk of morbidity and mortality, there are recommended Guidelines published by National Heart, Lung and Blood Institute for the evaluation of fever in patients with sickle cell disease.
• If a patient with sickle cell disease presents with a fever of 38.5 C (101.3 F), then:
  • Obtain history and perform rapid clinical exam
  • Obtain:
    • CBC  with Differential
    • Reticulocyte count
    • Blood Culture
    • Urine Culture (if UTI is suspected)
  • Obtain Chest X-ray, if short of breath, tachypneic, coughing, or with abnormal auscultation.

Sickle Cell and Fever: The Management

• While risk for Serious Bacterial Infection is lower than it once was, it is still prominent enough to justify empiric antibiotic covered after obtaining cultures.
• Administer antibiotics that cover S. pneumoniae and gram-negative enteric organisms.
• Often a dose of ceftriaxone is given. Add vancomycin if concern for meningitis.

• Disposition?
  • Often the biggest question is whether the child will benefit for hospitalization.
  • Since the incidence of bacteremia has improved, many now advocate for considering outpatient management. [Sokol, 2016; Bansil, 2013]
  •  There are reported “Low Risk Criteria” – See CHOP Clinical Pathway
    • > 12 months of age
    • Well appearing with good vital signs
    • No recent doses of ceftriaxone in preceding 8 weeks
    • No history of “badness” – sepsis, bacteremia, splenic sequestration
    • Up to date with all vaccinations
    • Compliant with prophylactic antibiotics (if appropriate)
    • Has normal CXR (if obtained)
    • Reassuring labs:
      • Hgb > 5
      • Reticulocyte > 1% (unless Hgb > 10)
      • No reduction in Hgb > 2 grams
      • WBC > 5,000 and < 30,000
      • Normal U/A (if obtained)
    • Has good access to healthcare and good social situation / support.
    • From what I have seen, the Low Risk Criteria are based on consensus statements and, therefore, may vary between individual institutions.
    • It is imperative that you discuss disposition (home vs hospitalize) with the patients hematologist!
      • They will know the patient’s history of complications as well as compliance.
      • They will also know how best to get the patient to access care for follow-up.
      • Some will prefer the child be discharged with oral antibiotics as well.

References