High ASO (Antistreptolysin O) levels in children and its relation with rheumatological diseases

HIGH ASO (ANTISTREPTOLYSIN-O) LEVELS IN CHILDREN AND ITS RELATION WITH RHEUMATOLOGICAL DISEASES Introduction: Extremity pain is the third common complaint after headache and abdominal pain in children. Seven to eight percent of children complain of joint pain while only 1% have chronic arthritis. Laboratory results are usually nondiagnostic for children who present with arthritis symptoms. Complete Blood Count (CBC), erythrocyte sedimentation rate (ESR), leukocyte formula, Anti Streptolysin-O (ASO), C-Reactive Protein (CRP) and rheumatoid factor (RF) are helpful markers for diagnosis. Streptococcal throat infections are the most common bacterial infection in children. The most commonly but the wrongly used test to show streptococcal infections is ASO. ASO titers can be affected by age, geographical area or the frequency of streptococcal infections. Eighty percent of patients in the early phase of acute rheumatic fever (ARF) and also 20 % of normal population have high levels of ASO. A high level of ASO was observed at the time of arthritis attack in 75 % of Familial Mediterranean Fever (FMF) patients. The fact that patients with post streptococcal reactive arthritis (PSRA) have especially have high levels of ASO warrants the need to associate high levels of ASO in patients with or without arthritis. Objective: We aimed to examine the relation between high levels of ASO , acute phase reactants and tests used in differential diagnosis of diseases like juvenile idiopatic arthritis (JIA), ARF, FMF, PSRA, connective tissue diseases (CTD). Cases and Methods: We retrospectively analysed 37 ARF patients followed by Pediatric Cardiology out-patient clinics, and 45 FMF, 29 CTD , 36 JIA and 34 PSRA patients followed by pediatric immunology out-patient clinics in Ege University Faculty of Medicine/ Department of Pediatrics. Forty-four patients with high levels of ASO that were were consulted within Ambulatory Pediatric clinics between May 2011 and May 2015 were followed up, prospectively. Another set of 44 patients who were throat culture positive for S.Pyogenes from Microbiology Laboratory data were also retrospectively analyzed. Seven patient groups were established within 249 patients. Average age of total patients was 9.3 ± 3.58 ,50.2 % of them (n:125) being females and 49.8 % (n:124) males. Patients' demographic data, symptoms, findings of physical examination , acute phase reactants like ESR, CRP, SAA beside CBC, complement levels, immunoglobulins, MRI findings in arthritis cases and MEFV gene analysis results were noted. All of these parameters were filled in patients' report forms for each patient. Informed consents were taken from all patients or their parents. The study was approved by the Ethical Committee of Ege University Hospital. Results: Family history with rheumatological diseases was found in %42,9 (n:19/45) of patients and the highest rate was in FMF group. Patients who have had upper respiratory infection two weeks before the symptoms started, were 85,3 %(n:29/34) in PSRA group , and 62,2 % (n:23/37) in ARA group. Arthritis presentation was as acute monoarthritis in PSRA, acute oligoarthritis in ARF; chronic, oligoarthritis and polyarthritis in JİA , within patients with arthritis complaints . JİA group had the highest level of IgG (p:0,016). In FMF group the most common symptom was abdominal pain and fever being, 68.9 % and 45.5 %, respectively. CTD and JIA groups had the lowest levels of ASO while the highest levels were in ARF group and those who had positive throat cultures. Positive ANA levels (>1/100 titre) were higher in CTD (%48,3) while the lowest levels were in ARF and FMF groups . Twenty five out of 45 FMF patients had M694V mutation. Seventeen of them had heterozygous and 4 of them had homozygous mutations and these were related to arthritis. The highest SAA level (p:0,002) was in FMF group. Statistically significant relationship was found between high ASO levels, leukocytosis (WBC>10000/mm3, p:0,001), high CRP levels (>0,5 mg/dl, p:0,003) and high SAA levels (>5 mg/L, p:0,021) . Forty-four patients with isolated high levels of ASO were followed prospectively for 3 years (2,44±1,26 years) and 2 of them were diagnosed as ARF, while 3 PSRA, 1 CTD, 3 FMF and 2 JİA diagnoses were recorded. These patients were included into relevant groups in this study. Most of (84.4 %) of the patients who had high levels of ASO not diagnosed having rheumatological diseases all had a negative CRP level (<0,5 mg/dl). It was observed that different measures of ASO showed gradually decreasing tendency as follow-up times increased. Patients with high level of ASO (ASO:>350 IU/ml) were younger (p:0,000). Eighty-one percent of ARF patients compared to 71.4% of patients with positive throat cultures had high ASO levels (>350 IU/ml). Conclusion: In this study, association of high ASO levels with rheumatologic diseases was investigated in juvenile patients. To the authors' knowledge, there was no study comparing ASO levels in diverse patient groups in academic literature. It was found that, rheumatologic diseases such as JIA, FMF, BDH and especially ARA and PSRA should also be considered for differential diagnosis in patients with joint complaints and elevated ASO. In case of high ASO levels with arthritis first ARA and PSRA should be considered; with accompanying ANA positivity, CTD; JIA for accompanying hypergammaglobulinemia or FMF for associated abdominal pain and fever. ASO tends to increase in patients with streptococcal infections and in ARF and PSRA in case of arthritis, decreasing gradually in 3 months' time. ASO levels were similar to healthy subjects' in JIA and CTD.CRP and ESR were also found to be high with high ASO in ARF. Twenty-five percent of subjects with isolated high ASO levels are diagnosed with rheumatologic disease during follow-up. ASO levels do not tend to decrease in these subjects. FMF and ASO association is still not verified. Opposed to common practice in developing countries, this study found no evidence towards using ASO levels as a marker for juvenile rheumatical diseases.