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Rheumatology Advance Access published online on April 17, 2008
Rheumatology, doi:10.1093/rheumatology/ken122
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Recent-onset childhood arthritis—association with Streptococcus pyogenes in a population-based study

Ø. R. Riise1,2, A. Lee2, M. Cvancarova3, K. S. Handeland1, K.-O. Wathne2, B. Nakstad4,5, P. Gaustad6,7 and B. Flatø1

1Department of Rheumatology, Rikshospitalet Medical Centre, 2Department of Paediatrics, Ullevål University Hospital, 3Department of Biostatistics, Rikshospitalet Medical Centre, Oslo, 4Department of Paediatrics, Akershus University Hospital, 5University of Oslo, Akershus Faculty Division, Nordbyhagen, 6Institute of Microbiology, Rikshospitalet Medical Centre and 7University of Oslo, Oslo, Norway.

Correspondence to: Ø. R. Riise, Department of Rheumatology, Rikshospitalet Medical Centre N-0027, Oslo, Norway. E-mail: oystein.riise{at}rikshospitalet.no


   Abstract
Top
 Abstract
Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Objectives. To assess the frequency of Streptococcus pyogenes in children with early arthritis, compare the characteristics in patients with post-streptococcal ReA (PSReA) with those in patients with other types of arthritis, and describe the occurrence of carditis in PSRA.

Patients. In a population-based Norwegian study, the physicians were asked to refer all children with suspected arthritis. The arthritis patients were followed up at 6 weeks, 6 months and 18 months. The presence of S. pyogenes was based on throat smear or antibodies. Echocardiography was performed in the patients with ARF or PSRA.

Results. Thirty-two (18%) of the 173 children with arthritis tested positive for S. pyogenes. The percentage of positive tests rose steadily with age and peaked at ages 8–11 (35%). Six weeks after admission arthritis was present in 33% of the PSRA patients, which was less frequent than in the juvenile idiopathic arthritis (JIA) patients (P < 0.001), but more frequent than in the transient arthritis patients (P = 0.012). Hip arthritis was more frequent and knee/ankle arthritis, ANA and HLA-B27 were less frequent in PSRA than in JIA (P < 0.001, P = 0.009 and P = 0.029, respectively). The PSRA patients were older than those with transient arthritis (P = 0.007). One child with ARF had carditis.

Conclusions. Streptococcus pyogenes was present in 18% of children with arthritis. The patient characteristics, clinical presentation and early disease course in PSRA was different from that of JIA and transient arthritis.

KEY WORDS: Post-streptococcal reactive arthritis, Streptococcal infection, Reactive arthritis, Child


   Introduction
Top
 Abstract
 Introduction
Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
An epidemiological association between Streptococcus pyogenes infection and the development of ARF has been established, and the cardiac sequelae are a significant cause of cardiovascular disease in children [1]. In 1982, Goldsmith and Long [2] described a post-streptococcal syndrome in children that was characterized by arthritis but was clinically different from ARF.

In 1997, Ayoub and Ahmed [3] proposed criteria for post-streptococcal ReA (PSReA): a usually non-migratory arthritis with evidence of recent streptococcal infection, and exclusion of ARF. Most authors have suggested that PSRA is a distinct clinical entity that must be distinguished from ARF, while others consider it to be part of the spectrum of ARF [2, 4–6]. An association between HLA-DRB*1 and PSRA patients was found in a study from the US, but was not confirmed in Italian children [7, 8]. A review of the literature concluded that the term PSRA has been used heterogeneously [9].

In children with PSRA, the arthritis can last up to 8 months [9]. A small number of children develop carditis, and it has therefore been suggested that children with PSRA should receive penicillin treatment and long-term penicillin prophylaxis [9–13].

PSRA in children has only been reported in the form of case reports and retrospective studies; thus the frequency of the disease and its potential cardiac complications may have been underestimated or overestimated. If PSRA patients have a more prolonged disease course than transient arthritis patients, and are at risk of carditis, testing for S. pyogenes may help the physician to identify patients who require special care.

The aim of this population-based study was to investigate the frequency of S. pyogenes in a cohort of children with recent-onset arthritis. We wanted to compare the characteristics and early disease course of PSRA patients with those of transient arthritis and juvenile idiopathic arthritis (JIA) and describe the role of patient characteristics, disease duration, auto-antibodies and HLA-B27 in the early identification of PSRA. We also wanted to report the occurrence of cardiac involvement during the first 18 months of disease duration in patients with ARF and PSRA.


   Materials and methods
Top
 Abstract
 Introduction
 Materials and methods
Results
 Discussion
 Acknowledgements
 References
 
We conducted a population-based multi-centre study in three counties (Oslo, Akershus and Buskerud) in South-Eastern Norway between 1 May 2004 and 30 June 2005. The total population was 1 252 835 and the number of children under the age of 16 was 255 303 on 1 January 2004 [14]. In Scandinavia, the majority of patients receive care within their county of residence, and the homogeneous health care and social security system, with its equality of access, facilitates recruitment to epidemiological studies [15].

Recruitment
The children were examined at one of the paediatric departments in the counties or at the regional department of rheumatology (i.e. at Akershus University Hospital, Buskerud Hospital, Ullevål University Hospital or Rikshospitalet Medical Centre). The patient series was an extension of an epidemiological study in which all primary care physicians were sent a letter every third month requesting them to refer children with possible or evident recent-onset arthritis to the appropriate hospital on the day the patient was first seen [16]. We also searched the hospitals’ computerized records for 181 relevant diagnoses based on the International Classification of Diseases, 10th edition (ICD 10) [17], at the end of the study in order to identify any arthritis patients who had not been included.

Inclusion criteria
The inclusion criteria were: (i) presence of arthritis; (ii) permanent residence in one of the three participating counties; (iii) age <16 yrs on admission; and (iv) test performed for S. pyogenes. Arthritis was defined by the presence of one of the following three signs: (i) swelling of a joint; (ii) restricted mobility of a joint with warmth and/or tenderness and/or pain; and (iii) arthritis demonstrated by ultrasound or MRI.

Exclusion criteria
Patients who had been diagnosed with JIA before 1 May 2004 or had inflamed synovia related to trauma, orthopaedic disease or malignant disease were excluded.

Classification procedure
All the follow-up data from the medical charts relevant to the final diagnosis were included up until March 2006 (range 10–22 months). In addition, the patients with PSRA received a further examination up until November 2006 (range 17–30 months). Two researchers recorded the clinical information independently on a standardized form. In the event of disagreement, the classification was established in consultation with specialists in paediatric infectious diseases and paediatric rheumatology.

Written informed consent was obtained from the parents of the children included in the study. The study was approved by the regional ethics committee for medical research and the Ombudsman for Privacy in Research at the Norwegian Social Science Data Services.

Classification criteria
ARF was classified according to the modified Jones criteria [18], PSRA according to the criteria proposed by Ayoub and Ahmed [3] and JIA according to the ILAR criteria, i.e. arthritis of unknown aetiology that has persisted for at least 6 weeks with onset before the age of 16 [19]. Arthritis with no established association with infection was classified as transient arthritis.

Clinical examination
A general clinical examination was performed on admission, at 6 weeks and at 6 months, and for the PSRA patients, also at 18 months. The number of swollen, tender and mobility-restricted joints was recorded [20], and a history of joint pain was obtained at each follow-up visit.

Active joint disease at the follow-up visits was defined as the presence of (i) persistent arthritis, (ii) use of DMARDs or corticosteroids for arthritis during the previous 6 weeks or (iii) CRP >20 mg/l and/or ESR >20 mm/h without a history of infection during the previous 2 weeks.

Cardiac investigation
A standard 12-lead electrocardiogram was performed in the PSRA patients at the 18-month follow-up visit. In addition, two-dimensional and Doppler echocardiography was performed by a single paediatric cardiologist. The patients with ARF were given a cardiac assessment during the first weeks after admission and after that received yearly routine follow-up by a paediatric cardiologist.

Microbiological and immunological examinations
Microbiological, immunological and HLA-B27 tests were performed at each of the hospitals as part of the routine diagnostic procedure. Streptococcal throat swab, anti-streptolysin-O (ASO) and anti-deoxyribonuclease B (anti-DNase B) tests were performed on admission and in the PSRA patients also after 18 months. A positive test for S. pyogenes was defined as the presence of one of the following: (i) S. pyogenes or group A streptococci (GAS) in throat culture or by rapid antigen testing either on admission or during the previous 4 weeks by a primary care physician on the basis of clinical indications, (ii) ASO ≥600 IU/ml and/or anti-DNase B ≥800 IU/ml on admission. (iii) ARF and positive streptococcal serology within 6 weeks if streptococcal tests had not been performed on admission. The titre levels used as criteria for positive streptococcal antibodies were above what several other studies have estimated to be the upper limit of normal range in healthy children [21–24].

One ANA titre ≥40 or a ratio >1.4 was considered positive. In addition, anti-cyclic citrullinated peptide antibody (anti-CCP) ≥25 U or >5 IU/ml or IgM RF >24.0 was considered positive.

Statistical analysis
Data were described using percentages or median and range for continuous variables. Continuous variables were compared using the Mann–Whitney–Wilcoxon test, and crude associations between categorical variables were assessed by the chi-square and Fisher's exact tests when the number of patients was small. Additionally, two multiple logistic regression models were fitted in order to investigate whether hip arthritis and active disease at 6 weeks were independently associated with PSRA vs JIA, and whether age and active disease at 6 weeks were independent predictors of PSRA vs transient arthritis. The results were expressed in terms of odds ratios (ORs) and their 95% CIs. P-values of <0.05 were considered statistically significant. Sensitivity was defined in terms of the proportion of positives correctly identified by the test. Specificity was defined in terms of the proportion of negatives correctly identified by the test. Positive predictive value was defined in terms of the proportion of patients with positive test results who are correctly diagnosed. Negative predictive value was defined as the proportion of patients with negative test results who are correctly diagnosed. All analyses were performed using SPSS for MS Windows, version 13.


   Results
Top
 Abstract
 Introduction
 Materials and methods
 Results
Discussion
 Acknowledgements
 References
 
Two hundred and seventeen (45%) of the recruited 483 patients fulfilled the criteria for arthritis (Fig. 1). One hundred and seventy-three (80%) of these were tested for S. pyogenes, 72 (42%) of whom were girls. The median age of the 173 arthritis patients on admission was 4.9 yrs (range 0.3–15.7) and the median duration of arthritis symptoms was 3 days (range 0–1112).


Figure 1
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  		FIG. 1. Flowchart for enrolment of children with recent onset arthritis tested for S. pyogenes.

 
The 173 children who were included and the 44 arthritis patients who had not been tested for S. pyogenes were comparable with regard to age, sex and duration of arthritis symptoms (data not shown).

Thirty-two (18%) of the 173 patients tested positive by streptococcal smear (group A) and/or serology, 17 (53%) of whom were girls (Table 1). Seventeen (53%) of the 32 patients with a positive streptococcal test were admitted in winter or spring and the rest in summer or autumn. Seventeen (12%) of 139 patients tested, were positive for GAS from throat smear. Two of the 17 arthritis patients were also antibody positive on admission (ASO, n = 1; anti-DNAse B, n = 1). In addition, two patients who were throat swab positive and initially antibody negative were antibody positive after 6 weeks (ASO, n = 1; anti-DNAse B, n = 1). Five patients tested positive for other streptococci by throat smear: group B (n = 1), group C (n = 3) and group G (n = 1). Eleven (7%) of 157 patients tested positive for anti-DNase B and seven of 158 (4%) tested positive for ASO. Three patients (9%) had positive values in more than one test on admission. The median age was higher in the patients who tested positive for streptococci than for those who tested negative (6.3, range 1.7–15.6 vs 4.7, range 0.3–15.7, P = 0.003).


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  		TABLE 1. Streptococcus pyogenes in children with recent onset arthritis by diagnostic groups

 
The percentage of children who tested positive for streptococci increased steadily with age up to a peak of 35% at 8–11 yrs, after which it dropped to 21% in children aged 12–15 (Fig. 2). The percentage of patients with a positive throat swab peaked to 20% at 6–7 yrs of age and no positive throat swab was found in the patients aged 12–15 yrs. The percentage of patients who tested positive for anti-DNase B or ASO reached a peak (20 and 15%, respectively) at 8–11. However, no patient <6 yrs of age tested positive for ASO and no patient <2 yrs of age tested positive for anti-DNase B.


Figure 2
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  		FIG. 2. Proportion of patients with positive tests for S. pyogenes in children with arthritis by age group (n = 173).

 
In addition to the 21 patients with PSRA and the two with ARF, a positive test for streptococcal infection was found in four (44%) of the nine patients with HSP, three (9%) of 33 JIA patients and two (11%) of 18 patients with other types of arthritis (Table 1).

Streptococcus pyogenes from throat swab and the various titres of ASO and anti-DNase B had a high specificity (≥86%) and a high negative predictive value (≥87%) for differentiating PSRA from JIA and transient arthritis patients (Table 2). Throat swab had a sensitivity of 61% and positive predictive value of 100%. The sensitivity of the serological tests was generally low (11–58%). With regard to the serological tests, a cut-off titre for ASO ≥600 and anti-DNase B ≥800 gave high positive predictive values (80 and 82%, respectively).


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  		TABLE 2. Streptococcus pyogenes tests for identifying PSRA patients (n = 21) vs those with JIA and transient arthritis (n = 123)

 
The characteristics of the PSRA patients were compared with those of the JIA and transient arthritis patients (Table 3). Of these 144 patients, 125 (87%) were re-examined after 6 weeks and 100 (69%) after 6 months. The patients who did not attend these planned follow-up visits reported (at their previous visit or by phone) that they no longer had symptoms of arthritis. The patients with JIA had a longer duration of arthritis symptoms before admission than those with PSRA at median 20 days vs 3 days (P = 0.002). The patients with transient arthritis had a history of respiratory tract infection during the 4 weeks before admission more frequently than the PSRA patients (84 vs 33%, P = 0.002). The PSRA patients were older than those with transient arthritis (median 6.6 vs 4.8 yrs, P = 0.007). Penicillin had been given for streptococcal infection within the previous 4 weeks or on admission in 33% of the PSRA patients vs 3% of the JIA patients and none of the transient arthritis patients (P < 0.001 vs P = 0.004, respectively). Hip arthritis was more frequent and knee or ankle arthritis less frequent in the patients with PSRA than in those with JIA (57 vs 6%, P < 0.001, and 43 vs 76%, P < 0.001). Affection of other joints was less common in the PSRA than in the JIA patients (P = 0.002). Six weeks after admission, active arthritis was still present in 33% of the PSRA patients, which was less frequent than in the JIA patients (91%, P < 0.001), but more frequent than in the transient arthritis patients (10%, P = 0.012). Two (14%) of the 14 PSRA patients vs 19 (58%) of 33 JIA patients reported joint pain at 6 weeks (P < 0.001). Use of NSAID in the first 6 weeks of follow-up was less frequent in the PSRA than in the JIA patients (43 vs 97%, P < 0.001).


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  		TABLE 3. Characteristics of patients with PSRA, JIA and transient arthritis

 
Six months after admission two of the 21 (10%) PSRA patients had arthritis vs 27 of the 33 (81%) JIA patients (P < 0.001). None of the PSRA patients and 33% of the JIA patients had one positive ANA test (P = 0.009). HLA-B27 was positive in one (5%) of 19 PSRA patients and 9 (35%) of 26 JIA patients (P = 0.029).

To identify the most important factors associated with PSRA we performed a multiple logistic regression analysis. PSRA vs JIA was the dependent variable, and hip arthritis and active disease at 6 weeks as explanatory variables. (We did not adjust for any other explanatory variable due to a small sample size). We found that the children with JIA had arthritis at 6 weeks more frequently than those with PSRA (OR = 9.2, 95% CI 1.8, 48). Hip arthritis was more common in the PSRA group than in those with JIA (OR = 7.9, 95% CI 1.2, 51.3).

In the second multiple logistic regression analysis, PSRA vs transient arthritis was the dependent variable and age and active disease at 6 weeks were explanatory variables. Active arthritis at 6 weeks was more frequent in the PSRA group than in those with transient arthritis (OR = 3.8, 95% CI 1.1, 13.5). Age on admission was higher in children with PSRA than in those with transient arthritis (OR = 1.2/yr, 95% CI 1.0, 1.3).

At the 18-month follow-up of 19 of the 21 PSRA patients, none of the patients had arthritis or a history of joint swelling or morning stiffness during the previous 6 months. The parents of the two PSRA patients who were not examined after 18 months reported by phone that the children were healthy and had no joint symptoms. All 19 PSRA patients were tested by throat swab. Eighteen of these were also tested by ASO and anti-DNAse B. Seven (37%) of 19 PSRA patients tested positive for streptococcal infection at 18 months. Six children (33%) had anti-DNase B ≥ 800 IU/ml. GAS from throat smear was positive in one patient, and ASO was ≥600 IU/ml in another patient. Two of the PSRA patients reported that they received penicillin for throat GAS after admission and both patients underwent tonsillectomy between the 6-month and 18-month follow-up visit (one was anti-DNAse B positive at 18 months). In addition, one PSRA patient received penicillin prophylaxis (also anti-DNAse B positive at 18 months). Auscultation revealed a systolic physiological heart murmur in three children. Echocardiography revealed no structural anomaly in any of the PSRA patients. With the Doppler technique we detected physiological pulmonary regurgitation in four patients and physiological tricuspid regurgitation in three patients. There was no sign of either mitral or aortic valve regurgitation. Electrocardiograms were normal.

One of the two children with ARF had a cardiac murmur and mitral valve disease at 6 weeks. In addition to carditis, this patient (Sri Lankan origin) also had subcutaneous nodules as the major manifestation and two minor manifestations (arthralgia and elevated acute-phase reactants). The ARF patients received penicillin treatment and penicillin prophylaxis, and their cardiac involvement had not progressed during the first 18 months after admission.

Two of the three JIA patients and two of the four HSP patients who tested positive for S. pyogenes were given penicillin treatment, and had a normal echocardiography at 6 weeks.


   Discussion
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
Acknowledgements
 References
 
In this study, the percentage of positive streptococcal tests correlated with the age of the child and was found in 35% of the arthritis patients aged 8–11 yrs. Patients with PSRA were older and had a longer disease duration than those with transient arthritis. Hip involvement, inactive disease at 6 weeks and 6 months and negative ANA and HLA-B27 were more frequent in PSRA than in the JIA patients. One-third of the patients with PSRA still had signs of streptococcal infection after 18 months. Carditis was only found in one child, who had ARF.

We based our study on three tests for recent streptococcal infection: throat smear, ASO and anti-DNase B. This was done to increase the probability of identifying all patients with possible carditis. In most studies on PSRA, only one test has been used for evidence of streptococcal infection, primarily ASO [4, 10, 12, 25], although some authors have also used anti-DNase B [8, 11]. Streptococcus pyogenes by throat smear was found in 12% of all our arthritis patients and in 61% of our PSRA patients at inclusion. A positive throat smear can be due to a chronic pharyngeal carrier state. In this case, the prolonged presence of S. pyogenes in the pharynx without evidence of infection is shown by the absence of an active immune or inflammatory response [26]. However, the fact that only one patient in our PSRA group was throat S. pyogenes-positive at 18 months suggests that the high frequency of S. pyogenes at inclusion was not due to chronic carriers. One of our ARF patients was throat S. pyogenes-positive but had normal streptococcal antibody titres, which indicates that throat testing for S. pyogenes could be a valuable aid in identifying children with arthritis who need special care.

We considered that titres of ASO ≥600 IU/ml and/or anti-DNAseB ≥800 IU/ml were elevated in our population. The normal titre levels in our population are not known. In the literature, the upper normal limit for ASO and anti-DNase B in healthy children is reported to be 120–480 IU/ml and 100–400 IU/ml, respectively [21–24]. In other studies of PSRA, the cut-off titres for ASO and anti-DNase B have been reported to be from ≥200 to 1025 IU/ml and from 680 to 865 IU/ml, respectively [4, 8, 11, 12, 25].

One-third of our PSRA patients still had signs of streptococcal infection after 18 months, as indicated by elevated anti-DNase B titres. In the absence of re-infection, ASO titres normally return to pre-infection levels after 6–12 months, whereas anti-DNase B titres may remain elevated for longer periods [27]. Our results suggest that the period of elevated anti-DNase B titres is longer than previously described; however, subclinical re-infection in our patients cannot be excluded. Anti-DNase B may also be elevated after skin infections [28]. However, none of our patients had a history of impetigo during the 2 months prior to admission.

The arthritis patients in the age group 8–11 had the highest percentage of positive streptococcal tests (35%). A positive throat swab or an elevated titre of ASO or anti-DNase B are more frequent in school-age children than in very young children or adults, presumably owing to a more frequent exposure to streptococcal infections [21–23, 29]. Furthermore, the age-related incidence of ARF follows that of GAS pharyngitis and peaks between the ages of 6 and 15 yrs [30, 31]. Our PSRA patients had a median age of 6.6 yrs, which is slightly younger than in most other studies [12, 32, 33].

We found that 7 of the 21 PSRA patients had active disease at 6 weeks. Even when we adjusted for age, the percentage of patients with active disease was higher in those with PSRA than in those with transient arthritis. This is likely to be due to the fact that transient arthritis normally lasts for <1 week [34, 35]. Our result is in accordance with a previous study demonstrating a mean duration of arthritis of 66 days in PSRA patients [7]. In our patients, active disease at 6 weeks and 6 months was more frequent in JIA than in PSRA, and no patient with PSRA had active disease at 18 months. Most of our JIA patients had active disease the first 6 months after admission, which is in accordance with a study by Selvaag et al. [36]. Due to multiple testing, a P-value >0.01 should be interpreted cautiously.

In accordance with other studies, we found PSRA to be mostly non-migratory [7, 8]. All our PSRA patients had monoarthritis and 57% had hip arthritis. Monoarthritis and hip arthritis are reported to be less frequent in other studies [9]. This could be due to geographical or ethnic differences or to the fact that we intended to test all our arthritis patients for S. pyogenes, which means that children with suspected transient synovitis of the hip were included.

In our study, a history of recent respiratory tract infection was found more frequently in the transient arthritis patients (84%) than in the PSRA patients (33%). A high percentage of nasopharyngitis (48%) has been reported in one study of children with transient synovitis of the hip [37]. A history of sore throat within the last 4 weeks before admission was reported by 19% of the PSRA patients, and this percentage was not statistically significant compared with the percentage of patients with transient arthritis and JIA. In other studies of PSRA in children, 44–100% have had a history of sore throat [7, 11, 25], and the low percentage of patients with a history of sore throat in our study may indicate the presence of sub-clinical throat infections in our unselected cohort of arthritis patients or false-positive test results for recent streptococcal infections.

Carditis was found in one patient with ARF, but not in any of our patients with PSRA. Only one of our PSRA patients received penicillin prophylaxis. A review of recent studies has shown that 4 of 88 children with PSRA develop carditis [9]. Although our sample is small, our data do not support that all Norwegian children with arthritis who test positive for S. pyogenes should be followed up by a cardiologist. However, this may not apply to PSRA patients in other geographical areas, especially those where ARF and carditis are common.

Up to 35% of children with recent-onset arthritis tested positive for S. pyogenes. Our PSRA patients were older, had a recent history of respiratory tract infection less frequently and active joint disease after 6 weeks more frequently than the transient arthritis patients. We found that the duration of symptoms before admission was shorter, hip arthritis was more frequent, and knee/ankle or other joint involvement, positive ANA and HLA-B27, and persistent arthritis were less frequent in the PSRA than in the JIA patients. Although the patients with PSRA in our study had different characteristics from those with transient arthritis or JIA, they did not have carditis. PSRA may be a specific disease entity or it may be a heterogeneous group of diseases in which some patients ought to be classified with JIA or transient arthritis. Since carditis has been reported in patients with PSRA, further research is needed to identify arthritis patients who need cardiological follow-up and treatment.

Formula


   Acknowledgements
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
References
 
We are indebted to the patients, parents, guardians and primary care physicians who made this work possible. We also thank the staff of the Departments of Clinical Chemistry, Microbiology, Immunology and Radiology at Akershus University Hospital, Sykehuset Buskerud, Ulleval University Hospital and Rikshospitalet Medical Centre.

Funding: The study was supported by a grant from the Norwegian Foundation for Health and Rehabilitation via the Norwegian Rheumatism Association.

Disclosure statement: The authors have declared no conflicts of interest.


   References
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 

  1. WHO. Rheumatic fever and rheumatic heart disease. In: Report of a WHO expert consultation. Geneva. 29 October–1 November 2001. WHO Technical Report Series. 2004;923:1.
  2. Goldsmith DP, Long SS. Streptococcal disease of childhood–a changing syndrome. Arthritis Rheum (1982) 25(suppl 4):S18.
  3. Ayoub EM, Ahmed S. Update on complications of group A streptococcal infections. Curr Probl Pediatr (1997) 27:90–101.[Medline]
  4. Tutar E, Atalay S, Yilmaz E, Ucar T, Kocak G, Imamoglu A. Poststreptococcal reactive arthritis in children: is it really a different entity from rheumatic fever? Rheumatol Int (2002) 22:80–3.[CrossRef][Web of Science][Medline]
  5. Moon RY, Greene MG, Rehe GT, Katona IM. Poststreptococcal reactive arthritis in children: a potential predecessor of rheumatic heart disease. J Rheumatol (1995) 22:529–32.[Web of Science][Medline]
  6. Ayoub EM, Majeed HA. Poststreptococcal reactive arthritis. Curr Opin Rheumatol (2000) 12:306–10.[CrossRef][Web of Science][Medline]
  7. Ahmed S, Ayoub EM, Scornik JC, Wang CY, She JX. Poststreptococcal reactive arthritis: clinical characteristics and association with HLA-DR alleles. Arthritis Rheum (1998) 41:1096–102.[CrossRef][Web of Science][Medline]
  8. Simonini G, Porfirio B, Cimaz R, Calabri GB, Giani T, Falcini F. Lack of association between the HLA-DRB1 locus and post-streptococcal reactive arthritis and acute rheumatic fever in Italian children. Semin Arthritis Rheum (2004) 34:553–8.[CrossRef][Web of Science][Medline]
  9. Mackie SL, Keat A. Poststreptococcal reactive arthritis: what is it and how do we know? Rheumatology (2004) 43:949–54.[Abstract/Free Full Text]
  10. Schaffer FM. Poststreptococcal reactive arthritis and silent carditis: a case report and review of the literature. Pediatrics (1994) 93:837–9.[Abstract/Free Full Text]
  11. De Cunto CL, Giannini EH, Fink CW, Brewer EJ, Person DA. Prognosis of children with poststreptococcal reactive arthritis. Pediatr Infect Dis J (1988) 7:683–6.[Web of Science][Medline]
  12. Kocak G, Imamoglu A, Tutar HE, Atalay S, Turkay S. Poststreptococcal reactive arthritis: clinical course and outcome in 15 patients. Turk J Pediatr (2000) 42:101–4.[Web of Science][Medline]
  13. Ayoub EM. Acute rheumatic fever and poststreptococcal reactive arthritis. In: Textbook of pediatric rheumatology—Cassidy JT, Petty RE, eds. (2001) Geneva: W.B Saunders Company. 690–705.
  14. Statistics Norway. (1 March 2005, date last accessed). Oslo: Statistisk sentralbyrå. http://www.ssb.no.2005.
  15. Gare BA, Fasth A. Epidemiology of juvenile chronic arthritis in southwestern Sweden: a 5-year prospective population study. Pediatrics (1992) 90:950–8.[Abstract/Free Full Text]
  16. Riise OR, Handeland KS, Cvancarova M, et al. Incidence and characteristics of arthritis in Norwegian children. A population based study. Pediatrics (2008) 121:e299–306.[Abstract/Free Full Text]
  17. WHO. The International Statistical Classification of Diseases and Related Health Problems (ICD-10). (2003) Pennsylvania: WHO.
  18. Guidelines for the diagnosis of rheumatic fever. Jones Criteria, 1992 update. Special Writing Group of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association. J Am Med Assoc (1992) 268:2069–73.[Abstract/Free Full Text]
  19. Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol (2004) 31:390–2.[Free Full Text]
  20. Brewer EJ. Standard methodology for Segment I, II, and III Pediatric Rheumatology Collaborative Study Group studies. I. Design. J Rheumatol (1982) 9:109–13.[Web of Science][Medline]
  21. Klein GC, Baker CN, Jones WL. "Upper limits of normal" antistreptolysin O and antideoxyribonuclease B titers. Appl Microbiol (1971) 21:999–1001.[Web of Science][Medline]
  22. Renneberg J, Soderstrom M, Prellner K, Forsgren A, Christensen P. Age-related variations in anti-streptococcal antibody levels. Eur J Clin Microbiol Infect Dis (1989) 8:792–5.[CrossRef][Web of Science][Medline]
  23. Kim S, Lee NY. Asymptomatic infection by Streptococcus pyogenes in schoolchildren and diagnostic usefulness of antideoxyribonuclease B. J Korean Med Sci (2005) 20:938–40.[Web of Science][Medline]
  24. Danchin MH, Carlin JB, Devenish W, Nolan TM, Carapetis JR. New normal ranges of antistreptolysin O and antideoxyribonuclease B titres for Australian children. J Paediatr Child Health (2005) 41:583–6.[CrossRef][Web of Science][Medline]
  25. Harel L, Mukamel M, Zeharia A, et al. Presence of D8/17 B-cell marker in patients with poststreptococcal reactive arthritis. Rheumatol Int (2007) 27:695–8.[CrossRef][Web of Science][Medline]
  26. Kaplan EL. The group A streptococcal upper respiratory tract carrier state: an enigma1. J Pediatr (1980) 97:337–45.[CrossRef][Web of Science][Medline]
  27. Stollerman GH, Lewis AJ, Schultz I, Taranta A. Relationship of immune response to group A streptococci to the course of acute, chronic and recurrent rheumatic fever. Am J Med (1956) 20:163–9.[CrossRef][Medline]
  28. Kaplan EL, Anthony BF, Chapman SS, Ayoub EM, Wannamaker LW. The influence of the site of infection on the immune response to group A streptococci. J Clin Invest (1970) 49:1405–14.[Web of Science][Medline]
  29. Begovac J, Bobinac E, Benic B, et al. Asymptomatic pharyngeal carriage of beta-haemolytic streptococci and streptococcal pharyngitis among patients at an urban hospital in Croatia. Eur J Epidemiol (1993) 9:405–10.[CrossRef][Web of Science][Medline]
  30. Kaplan EL. Recent epidemiology of group A streptococcal infections in North America and abroad: an overview. Pediatrics (1996) 97:945–8.[Abstract/Free Full Text]
  31. Bland EF, Duckett JT. Rheumatic fever and rheumatic heart disease; a twenty year report on 1000 patients followed since childhood. Circulation (1951) 4:836–43.[Web of Science][Medline]
  32. Bont L, Brus F, Dijkman-Neerincx RH, Jansen TL, Meyer JW, Janssen M. The clinical spectrum of post-streptococcal syndromes with arthritis in children. Clin Exp Rheumatol (1998) 16:750–2.[Web of Science][Medline]
  33. Ahmed S, Ayoub EM. Poststreptococcal reactive arthritis. Pediatr Infect Dis J (2001) 20:1081–2.[CrossRef][Web of Science][Medline]
  34. Wingstrand H. Transient synovitis of the hip in the child. Acta Orthop Scand (1986) 57(Suppl 219):1–61.[Web of Science][Medline]
  35. Hardinge K. The etiology of transient synovitis of the hip in childhood. J Bone Joint Surg Br (1970) 52:100–7.[Medline]
  36. Selvaag AM, Lien G, Sorskaar D, Vinje O, Forre O, Flato B. Early disease course and predictors of disability in juvenile rheumatoid arthritis and juvenile spondyloarthropathy: a 3 year prospective study. J Rheumatol (2005) 32:1122–30.[Abstract/Free Full Text]
  37. Spock A. Transient synovitis of the hip joint in children. Pediatrics (1959) 24:1042–9.[Abstract/Free Full Text]
Submitted 17 December 2007; revised version accepted 19 February 2008.
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