What is the management of markedly elevated C-Reactive Protein (CRP) in pediatric patients?

From the Guidelines

Management of markedly elevated C-Reactive Protein (CRP) in pediatric patients requires prompt identification and treatment of the underlying cause, with consideration of immunomodulatory therapy such as anakinra or glucocorticoids for patients with COVID-19 and hyperinflammation, as recommended by the American College of Rheumatology 1.

Initial Approach

The initial approach should include a thorough clinical assessment, complete blood count, blood cultures, and appropriate imaging based on symptoms.

• For bacterial infections causing elevated CRP, empiric antibiotic therapy should be initiated promptly, typically with broad-spectrum antibiotics.
• Non-infectious causes of high CRP such as autoimmune disorders may require anti-inflammatory medications or immunomodulators.

Immunomodulatory Therapy

For patients with COVID-19 and hyperinflammation, anakinra should be considered as first-line immunomodulatory treatment, with a dose of >4 mg/kg/day IV or SC, as it appears safe in severe infections and in children with hyperinflammatory syndromes 1.

• Glucocorticoids may also be considered for use as immunomodulatory therapy in patients with COVID-19 and hyperinflammation.
• Tocilizumab may be effective in reducing mortality and ICU admission in patients with severe COVID-19 pneumonia and signs of hyperinflammation, but patients treated with tocilizumab may be at higher risk for bacterial and fungal infections 1.

Monitoring and Supportive Care

Serial CRP measurements should be obtained to monitor treatment response, with values typically decreasing within 48-72 hours of effective therapy.

• Supportive care including adequate hydration, antipyretics (acetaminophen 10-15 mg/kg/dose or ibuprofen 5-10 mg/kg/dose for fever), and close monitoring of vital signs is essential.
• CRP levels above 100 mg/L often suggest serious bacterial infection, while extremely high levels (>200 mg/L) may indicate sepsis, osteomyelitis, or severe inflammatory conditions requiring hospitalization and specialist consultation.

From the Research

Management of Markedly Elevated C-Reactive Protein (CRP) in Pediatric Patients

• The management of markedly elevated CRP in pediatric patients involves distinguishing between bacterial and non-bacterial causes of infection, as the use of a single CRP value for this purpose is limited 2.
• Estimated CRP velocity (eCRPv) has been shown to be a useful predictor of bacterial infection in pediatric patients with very elevated CRP levels, particularly in those presenting 72 hours or more after symptom onset 2.
• A CRP value of 40 mg/L has been suggested as a useful cutoff for differentiating between viral and bacterial infections in children, with higher values indicating a higher likelihood of bacterial infection 3.
• Extremely elevated CRP levels (≥ 30 mg/dL) have been associated with unfavorable outcomes, including death, in pediatric patients, particularly those with infectious diseases such as pneumonia 4.
• The combination of CRP and ferritin levels has been shown to be useful in identifying pediatric sepsis patients at high risk of mortality, with very high levels of both markers indicating a poor prognosis 5.

Diagnostic Considerations

• CRP levels should be interpreted in conjunction with other clinical and laboratory findings, as low CRP values do not rule out bacterial infection and high CRP values do not necessarily indicate bacterial infection 3.
• The trajectory of CRP and ferritin levels over time may provide additional information on the severity of infection and the risk of mortality 5.
• Other markers, such as soluble interleukin 2 receptor (sIL-2R) levels, may also be useful in the diagnosis and prognosis of pediatric patients with markedly elevated CRP levels 6.

Treatment Implications

• Pediatric patients with markedly elevated CRP levels and suspected bacterial infection should be considered for antibiotic treatment, particularly if they present with severe symptoms or have underlying conditions that increase their risk of complications 2, 3.
• The use of anti-inflammatory therapies may be considered in pediatric patients with hyperinflammatory sepsis, although further research is needed to determine the optimal approach to treatment 5.