Serum C-reactive protein concentrations closely follow the course of the acute-phase response to inflammation or tissue necrosis and theoretically provide a barometer for many disease processes. This polysaccharide fraction precipitated from Streptococcus pneumoniae is present in acutely ill patients and disappears as the patients recover. C-reactive protein has been detected in bacterial, viral and other infections, as well as in noninfectious diseases such as acute myocardial infarction, rheumatic disorders and malignancies. Synthesis of acute-phase proteins occurs in hepatocytes modulated by cytokines. In vitro studies suggest that C-reactive protein activates neutrophils, inhibits platelet aggregation, potentially facilitates cell-mediated cytotoxic reactions against cells infected with microbes and stimulates monocyte-macrophage tumoricidal activity. Jaye and Waites conducted a study to determine the clinical utility of C-reactive protein measurements in children, especially compared with erythrocyte sedimentation rate determination.
The erythrocyte sedimentation rate, an indirect measurement of fibrinogen levels that influence erythrocyte aggregation, is commonly used to measure the acute-phase response. The erythrocyte sedimentation rate has several disadvantages: it cannot be determined from a stored specimen; it rises slowly and may not return to normal for weeks despite clinical improvement in the patient; it may give false reactions because of red cell concentrations and morphology; and it is difficult to standardize because of age and gender variations.
Healthy persons generally have C-reactive protein levels no higher than 10 mg per L. In patients with invasive acute bacterial infections, the C-reactive protein level tends to range from 150 to 350 mg per L. In patients with viral infections, the C-reactive protein value is usually much lower, less than 20 to 40 mg per L. However, this distinction is not absolute. C-reactive protein values greater than 100 mg per L can occur in uncomplicated infections caused by adenovirus, cytomegalovirus, and the viruses that cause influenza, measles and mumps. C-reactive protein determination cannot be used to classify the precise microbial etiology of an infection, but it is useful in conjunction with other tests in distinguishing between viral and bacterial infection.
Early detection of neonatal sepsis is hampered by vague, nonspecific or nonexistent clinical manifestation. A panel of tests including cultures, white blood cell count and differential, erythrocyte sedimentation rate, C-reactive protein value, platelet count, blood glucose and chest radiographs is used to augment the physical examination in the recognition of the disease. Cerebrospinal fluid/C-reactive protein concentrations are probably not as useful in diagnosing meningitis because C-reactive protein metabolizes in the central nervous system, yielding lower levels. Bacteremia should be considered in the febrile child with elevated C-reactive protein values and no evidence of focal infection. The use of C-reactive protein determinations in the identification of bacterial otitis media have not demonstrated clear value. The utility of C-reactive protein determinations in diagnosing gastrointestinal and respiratory infections is still being evaluated. Serial C-reactive protein determinations have been shown to be useful in monitoring resolution of acute hematogenous osteomyelitis. C-reactive protein values do not appear to be useful in identifying children with acute appendicitis or perforation. Studies of C-reactive protein values in autoimmune and rheumatologic diseases demonstrate better correlation than erythrocyte sedimentation rate with severity of clinical disease activity.
The authors conclude that serial C-reactive protein measurements appear to be most useful in monitoring patient response to therapy after the primary diagnosis of invasive, infectious or inflammatory disease, and in monitoring patients after major surgical procedures and patients with serious burns. A secondary rise in C-reactive protein value during therapy or after surgery may indicate an inflammatory or infectious complication. Although several advantages are apparent in using C-reactive protein values rather than the erythrocyte sedimentation rate to monitor therapy, insufficient information currently supports using C-reactive protein values alone to make management decisions or to distinguish between bacterial and viral infections.