Potential use of procalcitonin concentrations as a diagnostic marker of the PFAPA syndrome

Abstract

PFAPA syndrome is a clinical entity of unknown etiology characterized by periodic episodes of high fever accompanied by aphthous stomatitis, pharyngitis/tonsillitis, and cervical adenitis [3,5]. Since specific laboratory abnormalities for the PFAPA syndrome are inexistent, it is usually diagnosed clinically after excluding other probable causes of the fever, such as infection [1]. In PFAPA patients, discriminating between a fever attack due to bacterial infection and a fever attack due to noninfectious inflammation constitutes a major difficulty. Because procalcitonin, a propeptide of calcitonin, is reported to be a sensitive marker of systemic bacterial infection [2, 4], we followed peripheral leukocyte counts, CRP values and procalcitonin concentrations during the fever attacks associated with PFAPA syndrome in the hope of defining reliable criteria for its diagnosis. We determined serum procalcitonin concentrations in six PFAPA syndrome patients (two males and four females) with a median age of 7.5 (range 3-10) years and in 32 controls (bacterial, n=10 and non-bacterial, n=22). Sampling was performed on the third to fifth day of fever. In the PFAPA syndrome patients, febrile episodes started at the median age of 2.5 (range 1-7) years with each episode lasting 5-7 days and recurring every 3-4 weeks. The ethical committees of our institutes approved the study protocol and the guardians of all the patients gave their informed consent. Serum procalcitonin concentrations were measured by using the fully automated enzyme immunoluminescent assay (Wako Pure Chemical Industries, Ltd.), which employs katacalcin monoclonal antibody and calcitonin polyclonal antibody labeled with peroxidase for SphereLight 180 (Olympus Corporation). The detection limit was 0.1 ng/ml and the normal reference was set at <0.5 ng/ml. In PFAPA patients, the correlations between procalcitonin, CRP values and leukocyte counts were examined over 13 febrile episodes. Serum procalcitonin values ranged from 0.20 to 11.36 (median value 1.05) ng/ml in positive control subjects (Table 1), while all the negative controls had undetectable levels.During febrile episodes in PFAPA patients, which were confirmed not to be due to adenoviral or group A streptococcal infections, leukocyte counts and serum concentrations of CRP were invariably and significantly Eur J Pediatr (2007) 166:621-622

Current Diagnosis and Treatment Models of Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Lymphadenitis Syndrome

“…Serum immunoglobulin (Ig) levels are normal, IgD is normal or slightly elevated (20,23). All inflammatory parameters return to normal between the attacks (22).…”

“…C-reactive protein (CRP) is high at the beginning of the attack, sedimentation may (20). Procalcitonin does not increase like other acute phase reactants (22). Serum immunoglobulin (Ig) levels are normal, IgD is normal or slightly elevated (20,23).…”

Procalcitonin Levels in PFAPA Syndrome

“…Yoshihara et al found that levels of CRP were moderately elevated while PCT was normal during febrile attacks in children with PFAPA (10) . In our study, while PCT values were found to be within normal limits during the fever attacks in the study group, they were significantly increased in the control group.…”

“…Lastly, CXCL10 was shown to be elevated during febrile episodes of PFAPA but not during other periodic fever syndromes or infectious conditions (6) . CRP and PCT proved to be promising in the diagnosis of PFAPA in some studies (7)(8)(9)(10) . A limited number of studies exist where CRP and PCT have been evaluated together to diagnose this syndrome.…”

Marshall syndrome – a challenge in medical practice

“…During febrile attacks, patients present elevation of white blood cells, with preponderance of neutrophils and of acute phase reactants. Procalcitonin has normal values during fl ares and this fi nding can exclude bacterial infection (9,10). Between attacks, all infl ammatory parameters are normal.…”