Clin Chem Lab Med 2005;43(1):49–53  2005 by Walter de Gruyter • Berlin • New York. DOI 10.1515/CCLM.2005.007 Article in press - uncorrected proof Serum amyloid A protein levels as a possible aid in the diagnosis of acute appendicitis in children Lilia Lycopoulou 1 , Charalambos Mamoulakis 2 , Eugenia Hantzi 3 , Dimitrios Demetriadis 2 , Spyros Antypas 2 , Maria Giannaki 4 , Chryssa Bakoula 1 , George Chrousos 1 and Ioannis Papassotiriou 3, * 1 First Department of Pediatrics, Athens University, Athens, Greece 2 First Department of Pediatric Surgery, 3 Department of Clinical Biochemistry, 4 Department of Microbiology, ‘‘Aghia Sophia’’ Children’s Hospital, Athens, Greece Abstract Hematological and biochemical tests, including white blood cell count (WBC), C-reactive protein (CRP) and other acute-phase reactants, have been used in the diagnosis of acute appendicitis. However, there is controversy among physicians about the value of this practice in children. The objective of our study was to evaluateserumamyloidAprotein(SAA)levelsinchil- dren with confirmed acute appendicitis and to com- pare the sensitivity and specificity of this marker of inflammation with those for WBC and CRP. A pro- spective cohort study of 60 children admitted with abdominal pain to rule out appendicitis was used in the study. Of these, 42 underwent surgery, while 18 children who had spontaneous amelioration within 24 h of admission were not operated on and served as controls. WBC and serum SAA and CRP levels were obtained preoperatively. Serum concentrations of the analytes were determined with particle- enhanced immunonephelometric methods. Patients with acute appendicitis had WBC, SAA and CRP levels higher than those of the control group (p-0.001). There was no appendicitis patient with a normal SAA value, while 21.4% of the patients had CRP values within the normal range. The performance of each test was measured by receiver-operating characteris- tic curves. Area under the curve (AUC) values were 0.849 for WBC, 0.868 for CRP and 0.964 for SAA. The sensitivity and specificity of these methods were 76% and 75% for WBC)10.0=10 9 /L, 62% and 94% for CRP)10 mg/L and 86% and 83% for SAA )45.0 mg/L, respectively. Circulating SAA levels have better discriminatory value than WBC or CRP in the assess- ment of acute appendicitis in children. Thus, this test appears to be of higher value than the current stan- dards of care in the diagnosis of this condition. *Corresponding author: Ioannis Papassotiriou, PhD, Department of Clinical Biochemistry, ‘‘Aghia Sophia’’ Children’s Hospital, 115 27 Athens, Greece Phone: q30-210-7467931, Fax: q30-210-7467171, E-mail: biochem@paidon-agiasofia.gr, jpapasotiriou@ath.forthnet.gr Keywords: acute-phase reactant; appendicitis; C-reac- tive protein; serum amyloid A protein. Introduction Acute appendicitis is the most common surgical emergency in childhood, occurring in up to 8% of all children seen at pediatric emergency departments for abdominal pain (1). The younger the age of the child, the more likely is a delay in diagnosis and the chance of perforation and peritonitis (2). The incidence of complications, including peritoneal cavity and wound infections, female sterility and even death, has been positively correlated with perforation caused by a delay in treatment. Early accurate diagnosis of appen- dicitis should reduce the number of negative appen- dectomies, without increasing the rate of perforation. Today, with the help of clinical laboratory and imag- ing studies, the accuracy of diagnosis has improved, yet the rate of negative pediatric appendectomies still is 20–50% (3, 4) while the incidence of perforated appendicitis remains between 40% and 70% (5). These data suggest that there is room for improve- ment. For several decades the laboratory tests most wide- ly used in the diagnosis of appendicitis have been white blood cell count (WBC) and C-reactive protein (CRP) (6, 7). Recently, serum amyloid A protein (SAA) was introduced in clinical practice as a sensitive acute-phase reactant. Both SAA and CRP reflect endo- toxin levels, tissue injury molecules and cytokine- mediated hepatic production triggered by most forms of infection, tissue injury and inflammation. Inflam- matory cytokines, such as tumor necrosis factor-a (TNF-a), interleukin-1 (IL-1) and interleukin-6 (IL-6), are increased within 2–3 h after activation of immune and immune accessory cells. SAA and CRP secretions also start within hours of liver activation, reach a peak in 2–3 days (from 100- to over 1000-fold basal levels) and return to basal levels after 5–7 days (8). Healthy individualsmayhaveSAAlevelsofupto9.7mg/L(9). SAA consists of a family of apolipoproteins secret- ed during different inflammatory processes, such as those caused by infections, burns and allograft rejec- tion in transplantation (10–12). As soon as they enter the systemic circulation, SAA molecules are rapidly associated with bacterial lipopolysaccharides and are incorporated into high-density lipoprotein (HDL) par- ticles, neutralizing foreign toxic products and altering cholesterol metabolism. SAA may stimulate chemo- taxis and the adhesion of phagocytic cells and lym- phocytes in inflammatory sites. The aim of this prospective study was to evaluate the diagnostic value of SAA in children with acute Brought to you by | Karolinska Institute Authenticated Download Date | 5/28/15 2:47 PM