Value of combined measurement of C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase and serum ferritin in etiological diagnosis of fever of unknown origin in children
XIE Ting, PAN Jia-Hua, ZHANG Xue
Department of Pediatrics, Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, China
Abstract Objective To study the clinical value of combined measurement of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), and serum ferritin (SF) in the etiological diagnosis of fever of unknown origin (FUO) in children.Methods The clinical data of 154 hospitalized children who had FUO for at least two weeks were retrospectively analyzed, and they were classified into infection (n=54), rheumatism (n=67), and tumor (n=33) groups according to the diagnosis at discharge. The levels of CRP, ESR, LDH, and SF were compared between the three groups, and the diagnostic values of the four indices alone or together were analyzed using the receiver operating characteristic (ROC) curve.Results Serum CRP and ESR levels were elevated in all the three groups, and increased most significantly in the rheumatism group. Serum LDH level was increased most significantly in the tumor group. SF level was significantly increased in the rheumatism and tumor groups. The area under the ROC curve (AUC) of LDH for diagnosing rheumatism and the AUC of ESR and CRP for diagnosing tumors were lower than 0.7 (P>0.05). The AUC of CRP for diagnosing infection and rheumatism was 0.861 and 0.782, respectively. The AUC of ESR for diagnosing infection and rheumatism was 0.770 and 0.743, respectively. LDH had relatively low AUC, sensitivity, specificity, and Youden's index in diagnosing infection and tumors. SF had the highest AUC, sensitivity, and Youden's index in diagnosing infection, but had the lowest specificity. SF had relatively high AUC, sensitivity, specificity, and Youden's index in diagnosing rheumatism, but had relatively low AUC in diagnosing tumor. The four indices had higher AUC, sensitivity, and specificity in diagnosing rheumatism and tumors when measured together than when measured alone.Conclusions In the etiological diagnosis of FUO in children, CRP, ESR, LDH, and SF have certain clinical significance in the preliminary diagnosis of rheumatic diseases, but have limited value in the diagnosis and differentiation of infectious diseases and malignant tumors. Combined measurement of the four indices is superior to the determination of each one for the etiological diagnosis of FUO in children.
XIE Ting,PAN Jia-Hua,ZHANG Xue. Value of combined measurement of C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase and serum ferritin in etiological diagnosis of fever of unknown origin in children[J]. CJCP, 2015, 17(9): 950-955.
XIE Ting,PAN Jia-Hua,ZHANG Xue. Value of combined measurement of C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase and serum ferritin in etiological diagnosis of fever of unknown origin in children[J]. CJCP, 2015, 17(9): 950-955.
Standage SW, Wong HR. Biomarkers for pediatric sepsis and septic shock[J]. Expert Rev Anti Infect Ther, 2011, 9(1):71-79.
[4]
Sanders S, Barnett A, Correa-Velez I, et al. Systematic review of the diagnostic accuracy of C-reactive protein to detect bacterial infection in nonhospitalized infants and children with fever[J]. J Pediatr, 2008, 153(4):570-574.
[5]
Keshet R, Boursi B, Maoz R, et al. Diagnostic and prognostic significance of serum C-reactive protein levels in patients admitted to the department of medicine[J]. Am J Med Sci, 2009, 337(4):248-255.
[6]
Wu JJ, Rowan CG, Bebchuk JD, et al. Association between tumor necrosis factor inhibitor (TNFi) therapy and changes in C-reactive protein (CRP), blood pressure, and alanine aminotransferase (ALT) among patients with psoriasis, psoriatic arthritis, orrheumatoid arthritis[J]. J Am Acad Dermatol, 2015, 72(5):917-919.
[7]
Zeft A, Yaish H, Prince J, et al. A 6-year-old child with fever of unknown origin, anemia, and abdominal pain[J]. J Pediatr, 2008, 153(2):283-286.
[8]
Flood RG, Badik J, Aronoff SC. The utility of serum C-reactive protein in differentiating bacterial from nonbacterial pneumonia in children:a meta-analysis of 1230 children[J]. Pediatr Infect Dis J, 2008, 27(2):95-99.
[9]
Sklavou R, Karavanaki K, Critselis E, et al. Variation of serum C-reactive protein (CRP) over time in pediatric cancer patients with febrile illness and its relevance to identified pathogen[J]. Clin Biochem, 2012, 45(15):1178-1182.
[10]
Ramsay ES, Lerman MA. How to use the erythrocyte sedimentation rate in paediatrics[J]. Arch Dis Child Educ Pract Ed, 2015, 100(1):30-36.
[11]
Abbag FI, Al Qahtani JM. Extreme elevation of the erythrocyte sedimentation rate in children[J]. Ann Saudi Med, 2007, 27(3):175-178.
[12]
Song XY, Huang JY, Hong Q, et al. Platelet count and erythrocyte sedimentation rate are good predictors of Kawasaki disease:ROC analysis[J]. J Clin Lab Anal, 2010, 24(6):385-388.
[13]
Pelegrín L, Casaroli-Marano R, Antón J, et al. Predictive value of selected biomarkers, polymorphisms, and clinical features for oligoarticular juvenile idiopathic arthritis-associated uveitis[J]. Ocul Immunol Inflamm, 2014, 22(3):208-212.
[14]
Bień E, Balcerska A. Serum soluble interleukin-2 receptor, beta2-microglobulin, lactate dehydrogenase and erythrocyte sedimentation rate in children with Hodgkin's lymphoma[J]. Scand J Immunol, 2009, 70(5):490-500.
[15]
Bień E, Balcerska A.Clinical significance of erythrocyte sedimentation rate, C-reactive protein and serum lactate dehydrogenase levels in the diagnosis, prognosis and treatment monitoring of children suffering from cancer[J]. Med Wieku Rozwoj, 2004, 8(4 Pt 2):1081-1089.
Tamashiro MS1, Aikawa NE, Campos LM, et al. Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset[J]. Clinics (Sao Paulo), 2011, 66(10):1665-1669.
[19]
VanWagner LB, Green RM. Elevated serum ferritin[J]. JAMA, 2014, 312(7):743-744.
[20]
Moore C Jr, Ormseth M, Fuchs H. Causes and significance of markedly elevated serum ferritin levels in an academic medical center[J]. J Clin Rheumatol, 2013, 19(6):324-328.
Bebeshko VG, Bruslova KM, Cvjetkova NM, et al. Effect of RBC concentrate transfusions on serum ferritin content in children with acute leukaemia[J]. Probl Radiac Med Radiobiol, 2013, 8(18):173-179.
[24]
Zhang XZ, Su AL, Hu MQ, et al. Elevated serum ferritin levels in patients with hematologic malignancies[J]. Asian Pac J Cancer Prev, 2014, 15(15):6099-6101.
[25]
Meany HJ, London WB, Ambros PF, et al. Significance of clinical and biologic features in Stage 3 neuroblastoma:a report from the International Neuroblastoma Risk Group project[J]. Pediatr Blood Cancer, 2014, 61(11):1932-1939.
[26]
Yamazaki E, Tomita N, Koyama S, et al. Serum ferritin level is prognostic of patient outcome in extranodal NK/T cell lymphoma, nasal type[J]. Med Oncol, 2014, 31(9):149.
[27]
Hara S, Kawada J, Kawano Y, et al. Hyperferritinemia in neonatal and infantile human parechovirus-3 infection in comparison with other infectious diseases[J]. J Infect Chemother, 2014, 20(1):15-19.
