Differentiation of PSRA due to Group A and due to Nongroup A Streptococci in Patients with Early Arthritis and Elevated Antisteptolysin-O at Presentation
Open accessAbstract
A study was performed of consecutive patients presenting to a Dutch early arthritis clinic with a primary suggested diagnosis of reactive arthritis due to streptococci between April 1998 and January 2003, in a well-defined reference population consisting of 600 000 inhabitants. At 1 year after presentation out of 45 acute arthritis patients with initially an elevated antistreptolysin-O and without an alternative rheumatic diagnosis only 9 patients (20%) were not diagnosed as PSRA; 16 cases (36%) were due to NGAS, 20 cases (44%) due to GAS. The estimate of the annual incidence rate of PSRA in the Netherlands during the study was 1.26 per 100 000: 0.70 GAS-related. A diagnostic set of criteria was formulated based on the original Ayoub&Ahmed criteria by adding a serological criterium ASO/antiDNaseB ratio <1.4 and excluding a clinical criterium on chronicity/recurrency of arthritis: likelihood ratio for a positive test 7.9 [95% confidence interval (95%CI: 2.7–22.7)], for a negative test 0.06 [95%CI: 0.009–0.39].
AI snapshot
Written from the paper’s full text.
TL;DR
In a Dutch early arthritis cohort, 45 patients with acute arthritis and elevated antistreptolysin-O at presentation were followed; 20 were classified as group A streptococcal PSRA, 16 as nongroup A streptococcal PSRA, and 9 as non-PSRA. A modified diagnostic criteria set adding ASO/antiDNaseB ratio <1.4 and dropping the chronicity/recurrency criterion performed well for GAS-induced PSRA.
Key findings
- Of 45 acute arthritis patients with initially elevated ASO and no alternative rheumatic diagnosis, 20 (44%) were GAS-related PSRA, 16 (36%) NGAS-related PSRA, and 9 (20%) non-PSRA at 1 year.
- Estimated annual incidence of PSRA was 1.26 per 100,000: 0.70 per 100,000 for GAS-related and 0.56 per 100,000 for NGAS-related PSRA.
- The modified criteria set—Ayoub & Ahmed criteria plus ASO/antiDNaseB ratio <1.4 and excluding the chronicity/recurrency criterion—gave LR+ 7.9 (95% CI 2.7–22.7) and LR− 0.06 (95% CI 0.009–0.39).
- GAS-related cases had higher mean swollen joint count than NGAS-related cases: 5.2 (SD 1.3) versus 1.9 (SD 0.4).
Methods
- Consecutive patients presenting April 1998–January 2003 to a Dutch early arthritis clinic with acute arthritis and serological evidence of recent β-haemolytic streptococcal infection, from a reference population of 600,000.
- Patients were followed with routine clinical and serological assessment; PSRA was considered definite when no alternative diagnosis was made after at least 1 year, and cases were subdivided by ASO/antiDNaseB ratio (<1.40 GAS, >1.5 NGAS).
- Test characteristics (sensitivity, specificity, PPV, NPV, likelihood ratios) were calculated for combinations of Ayoub & Ahmed criteria and added serological criteria, using GAS-induced PSRA diagnosed at 1 year as the reference standard.
Limitations
- The paper states that some circularity in reasoning cannot be ruled out because many referred patients had already been diagnosed using serological criteria generally applied in the Netherlands.
- The paper states possible underdiagnosis because not all suspected patients will have been referred, and that epidemiological reasoning from these data cannot prove PSRA exists; prospective validation in other GAS-induced PSRA groups is needed.
- Evident from the text: single-center study with a small sample (45 patients, including 20 GAS-related cases) and no strict study protocol for PSRA patients.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
3 of 15 cited sources checked · 0 supported · 0 flagged · accuracy not yet measured
- Interpretationcitation
An additional serological criterion-elevated antiDNase-B or an ASO/antiDNaseB ratio <1.4-improves the criteria set in the presented population.
“An additional serological criterion, that is, either the elevated antideoxyribonuclease-B or the lower antistreptolysin-O/antideoxyribonuclease-B ratio (<1.4), as described previously [5], may be applied elegantly and leads to an improved criteria set in our presented population.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [5] source
The Results report higher anti-DNase-B titres and a lower mean ASO/anti-DNase-B ratio in group A than non-group A cases; the Discussion says the combined measurements may aid differentiation. The paper does not establish <1.4 as a cutoff. Improvement of the citing authors’ criteria set in their own population is their conclusion, not a finding attributed to this source. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Premisecitation
An ASO/antiDNaseB ratio <1.40 at 4-10 weeks after pharyngitis/tonsillitis suggests GAS-induced reactive arthritis.
“ratio <1.40 a plea for GAS-induced reactive arthritis”
- Also stated in: § 2.3. Analysis of Criteria · hedged
“ratios <1.4 plea for GAS-induced reactive arthritis [5]”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [5] source
The Results (page not indicated) report a lower mean ASO/antiDNase-B ratio in GAS than NGAS reactive arthritis (0.89 versus 2.60), and the Discussion says the ratio may help distinguish the groups. The paper does not establish a <1.40 cutoff or specify a 4–10-week diagnostic window. (LLM, conf=0.87)
Experimental — accuracy not yet measured
- Also stated in: § 2.3. Analysis of Criteria · hedged
- Premisecitation
An ASO/antiDNaseB ratio >1.5 at 4-10 weeks after pharyngitis/tonsillitis suggests NGAS-induced PSRA.
“whereas ratio >1.5, a plea for NGAS-induced PSRA [5]”
- Also stated in: § 2.3. Analysis of Criteria · hedged
“ratios >1.5 plea for nongroup A streptococcal (NGAS) infection”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [5] source
The Discussion (page unavailable) says higher ASO/antiDNase-B ratios were suggestive of NGAS infection, and the Results report a higher mean ratio in NGAS than GAS patients. The paper does not establish a >1.5 cutoff or specify 4–10 weeks after throat infection as the window for that interpretation; the Serological Measurements section describes sampling at several time points. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Also stated in: § 2.3. Analysis of Criteria · hedged
- Findingown data
Among those 45 acute arthritis patients, 20 cases (44%) were due to GAS.
“20 cases (44%) due to GAS”
Quote in the paperSubstantial claim - Findingown data
The same diagnostic criteria set had a negative likelihood ratio of 0.06 (95% CI 0.009-0.39).
“for a negative test 0.06 [95%CI: 0.009–0.39]”
Quote in the paperSubstantial claim
- Findingown data
Half of the presented GAS-induced PSRA patients do not fulfil the previously proposed Ayoub and Ahmed criteria for PSRA.
“Half of the presented GAS-induced PSRA patients, however, do not fulfil the previously proposed criteria by Ayoub and Ahmed on PSRA.”
- Also stated in: § 4. Discussion · hedged
“as these appear to exclude half of our presumably GAS-induced PSRA patients [17].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] 1997, Current Problems in Pediatric
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Also stated in: § 4. Discussion · hedged
- Findingown data
The criterion of a protracted course of arthritis is met in only half of presumably GAS-induced PSRA patients.
“Particularly the criterion of a protracted course of arthritis is met in only half of presumably GAS-induced PSRA patients.”
Quote in the paperSubstantial claim - Findingown data
A protracted course was not present in any of the NGAS-induced patients diagnosed by serological data.
“Interestingly, a protracted course was not present in any of our NGAS-induced patients, diagnosed by serological data.”
Quote in the paperNot a substantial claim - Findingown data
The estimated annual incidence rate of GAS-related PSRA in the Netherlands during the study was 0.70 per 100 000.
“The estimate of the annual incidence rate of PSRA in the Netherlands during the study was 1.26 per 100 000: 0.70 GAS-related.”
Quote in the paperNot a substantial claim- Rests on an assumption: The early arthritis clinic's catchment population of 600 000 is representative of the Netherlands for estimating national PSRA incidence.
- Findingown data
Among 45 acute arthritis patients with initially elevated antistreptolysin-O and no alternative rheumatic diagnosis, at 1 year after presentation only 9 patients (20%) were not diagnosed as PSRA.
“At 1 year after presentation out of 45 acute arthritis patients with initially an elevated antistreptolysin-O and without an alternative rheumatic diagnosis only 9 patients (20%) were not diagnosed as PSRA”
Quote in the paperSubstantial claim - Findingown data
A diagnostic criteria set based on the original Ayoub&Ahmed criteria, adding ASO/antiDNaseB ratio <1.4 and excluding the clinical criterion on chronicity/recurrency of arthritis, had a positive likelihood ratio of 7.9 (95% CI 2.7-22.7).
“A diagnostic set of criteria was formulated based on the original Ayoub&Ahmed criteria by adding a serological criterium ASO/antiDNaseB ratio <1.4 and excluding a clinical criterium on chronicity/recurrency of arthritis: likelihood ratio for a positive test 7.9 [95% confidence interval (95%CI: 2.7–22.7)]”
Quote in the paperSubstantial claim - Findingown data
Among those 45 acute arthritis patients, 16 cases (36%) were due to NGAS.
“16 cases (36%) were due to NGAS”
Quote in the paperSubstantial claim - Premisecitation
Some of the Ayoub and Ahmed criteria for PSRA cannot be applied at the patient's presentation, which limits their diagnostic applicability.
“However, some of these cannot be applied at the patient's presentation, which thwarts diagnostic applicability.”
- Also stated in: § 4. Discussion · hedged
“Ayoub and Ahmed have originally proposed criteria that are applicable only in full-blown clinical situations, not specifically for diagnostic purposes from the onset; as these appear to exclude half of our presumably GAS-induced PSRA patients [17].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] 1997, Current Problems in Pediatric
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Also stated in: § 4. Discussion · hedged
- Interpretationreasoning
It is doubtful whether genetics are responsible for an individual's susceptibility to developing a particular type of post-streptococcal syndrome.
“It is therefore doubtful whether genetics are responsible for an individual's genetic susceptibility for developing the type of post-streptococcal syndrome.”
Quote in the paperNot a substantial claim - Premisenone given
The presence of antibodies to type 5 streptococcal M protein cross-reacting with tissue has not been convincingly demonstrated in PSRA.
“However, the presence of antibodies to an antigen in the membrane of the organism, the type 5 streptococcal M protein cross-reacting with tissue, has not been convincingly demonstrated in PSRA.”
Quote in the paperSubstantial claim - Interpretationreasoning
The causal role of streptococcal infection in PSRA remains to be demonstrated pathogenetically.
“The assumed causal role of streptococcal infection therefore remains to be demonstrated pathogenetically.”
Quote in the paperSubstantial claim - Interpretationreasoning
A protracted course of arthritis cannot be used for diagnosis at presentation because meeting the criterion requires a delay in time.
“On the other hand, one cannot apply this feature for diagnosing purposes at presentation as clearly a certain delay in time is needed to meet this criterion.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 12
- May combine two claims. 5
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataThe estimated annual incidence rate of PSRA in the Netherlands during the study was 1.26 per 100 000.
“The estimate of the annual incidence rate of PSRA in the Netherlands during the study was 1.26 per 100 000: 0.70 GAS-related.”
Quote in the paperNot a substantial claim- Rests on an assumption: The early arthritis clinic's catchment population of 600 000 is representative of the Netherlands for estimating national PSRA incidence.
Classified as probably not a substantial claim.
Interpretationnone givenCriterion B (protracted or recurrent arthritis) is difficult to score prospectively from onset in an individual patient.
“Criterion (B) is however difficult to score prospectively in a diagnostic phase from the onset in an individual patient.”
- Also stated in: § 1. Introduction · plain
“particularly criterion (B) is unclear from the onset”
Quote in the paperSubstantial claim- Also stated in: § 1. Introduction · plain
Classified as probably not a substantial claim.
Study design and conductnone givenBefore inclusion, other causes of arthritis were excluded.
“Before inclusion, other causes of arthritis were excluded: septic arthritis, rheumatoid arthritis, connective tissue disease, crystal deposition disease, reactive arthritis attributable to parvovirus B19/salmonella/shigella/campylobacter/chlamydia/gonococ-ci/spirochetes, and arthritis secondary to inflammatory bowel disease.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationThe association of ARF with HLA DRB1*16 and PSRA with HLA DRB1*01 could not be confirmed by Simonini et al.
“This could not be confirmed by Simonini et al. [23].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [23] source
Classified as probably not a substantial claim. May combine two claims.
PremisecitationThe literature describes a heterogeneous spectrum of PSRA without proven prognostic implications.
“so far literature describes a heterogeneous spectrum of PSRA without proven prognostic implications [18]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] source
Classified as probably not a substantial claim.
Study design and conductreasoningThe presented data cannot be used in epidemiological reasoning to prove that PSRA really exists.
“Epidemiological reasoning to prove that PSRA really exists cannot be done by using the presented data.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationIn GAS-induced PSRA, M-serotypes 9, 11, and 28 have been found, and these M-serotypes are not known from acute rheumatic fever.
“in GAS-induced PSRA so far, the M-serotypes 9, 11, and 28 have been found, and these are M-serotypes not known from acute rheumatic fever [25].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [25] 2003, Netherlands Journal of Medicine
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe Ayoub and Ahmed criteria were intended for classification, not for diagnostic use.
“Though these criteria were meant for classification and not meant for diagnostic use”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] 1997, Current Problems in Pediatric
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe diagnostic procedure for PSRA was checked by an experienced clinician before study entrance.
“This procedure was checked by an experienced clinician before entrance into this study.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA high frequency of in vitro elevated D8/17 binding to B lymphocytes has been found as a susceptibility marker for developing ARF more than PSRA.
“A high frequency of in vitro elevated D8/17 binding to B lymphocytes has been found as a susceptibility marker for developing ARF more than PSRA [7, 8, 24].”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAyoub and Ahmed proposed a set of clinical and serological criteria for the diagnosis of PSRA.
“In 1997, Ayoub and Ahmed have proposed a set of clinical and serological criteria for the diagnosis of PSRA [17]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] 1997, Current Problems in Pediatric
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Classified as probably not a substantial claim.
PremisecitationAyoub and Ahmed proposed a set of criteria for PSRA in 1997.
“Already in 1997 Ayoub and Ahmed proposed a set of criteria for PSRA [17].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] 1997, Current Problems in Pediatric
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisereasoningThe classic paradigm for molecular mimicry in GAS-induced PSRA is similar to that in acute rheumatic fever after GAS infection, which underscores the existence of PSRA.
“Immunologically, the classic paradigm for molecular mimicry in GAS-induced PSRA is similar as in acute rheumatic fever after infection with GAS, underscoring the existence of PSRA.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationA weak genetic difference between ARF and PSRA has been demonstrated, with ARF possibly associated with HLA DRB1*16 and PSRA with HLA DRB1*01.
“Only a weak genetic difference between patients with ARF and PSRA has been demonstrated: ARF being possibly associated with HLA DRB1*16, and PSRA with HLA DRB1*01 [6].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [6] source
The paper relies on this without support.
The early arthritis clinic's catchment population of 600 000 is representative of the Netherlands for estimating national PSRA incidence.
“in a well-defined reference population consisting of 600 000 inhabitants”
“The estimate of the annual incidence rate of PSRA in the Netherlands during the study was 1.26 per 100 000”
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BackgroundPoststreptococcal reactive arthritis: what is it and how do we know?
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“Clinically, rheumatologists need to homogenize groups of PSRA patients as so far literature describes a heterogeneous spectrum of PSRA without proven prognostic implications [18].”
BackgroundInfluentialRheumatic fever‐associated B cell alloantigens as identified by monoclonal antibodies
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BackgroundUpdate on complications of group A streptococcal infections
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BackgroundAcute Rheumatic Fever in Adults
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InfluentialPresence of D8/17 B-cell marker in patients with poststreptococcal reactive arthritis
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Self-citation
Flagged first, then by citations
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Cited by
Sorted by citations
Kohannim, O., Rubin, Z., & Taylor, M. B. (2011) · Journal of clinical rheumatology · doi:10.1097/rhu.0b013e31820edb9d · Cited by 4
- Authors
- Jansen, T. L. T. A.
- Affiliations
- Medisch Centrum Leeuwarden (NL)
- Corresponding author
- Jansen, T. L. Th. A.
- ORCID
- Jansen, T. L. Th. A.
- Venue
- International Journal of Rheumatology
- Publisher
- Wiley
- Published
- 2009
- Volume
- 2009
- Pages
- 1-7
- ISSN
- 1687-9260 (ISSN-L)
- 1687-9279
- PMC
- PMC2809358
- OpenAlex
- W2049427989
- Semantic Scholar
- 8146a160a9f98570cdc14afa8ef1e9ccec75ebab
- Cited by
- 0
- References
- 27
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- International Journal of Rheumatology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Health and Medical Research Council (384330)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Streptococcal Infections and Treatments
- Health Sciences › Medicine › Rheumatology › Spondyloarthritis Studies and Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
- Keywords
- post-streptococcal reactive arthritis, Streptococcus pyogenes, antistreptolysin O, early arthritis, serological diagnosis, anti-DNase B, incidence, diagnostic criteria, likelihood ratios
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-18.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-18.
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