Young adults with juvenile arthritis in remission attain normal peak bone mass at the lumbar spine and forearm.

OBJECTIVE: To assess the impact of disease activity on acquired peak bone mass and bone turnover in young adult patients with either persistent juvenile arthritis (JA) or a history of JA (JA in remission). METHODS: Two hundred twenty-nine patients with JA were studied after a mean +/- SD of 15.6 +/- 2.4 years in women and 14.9 +/- 2.1 years in men since disease onset. One hundred forty-five women and 84 men were over the age of 20 at the time of examination (mean +/- SD age 24.9 +/- 2.9 years for women and 25.2 +/- 3.1 years for men). Forty-one healthy women (mean +/- SD age 27.4 +/- 3.1 years) and 55 healthy men (mean +/- SD age 25.7 +/- 3.1 years) served as a reference group. Bone mineral density (BMD) was analyzed by dual x-ray absorptiometry. Serum osteocalcin concentrations and urinary concentrations of deoxypyridium (D-Pyd) were measured. Linear regression analyses were performed to evaluate the impact of disease on BMD. RESULTS: Patients with persistent disease had significantly lower BMD compared with healthy subjects (P < 0.001 for women at all measured sites and for men at the femoral neck and total body; P < 0.05 for men at the radius and lumbar spine). Of the patients with a history of JA, only women had significantly lower BMD at the femoral neck and total body (P < 0.05). Patients with persistent JA had significantly more osteopenia and osteoporosis than healthy subjects, while patients with a history of JA had more frequent osteopenia only in the total body. Weight, urinary concentration of D-Pyd, and belonging to the patient group significantly affected BMD at all measured sites in the entire study population, while analysis of all patients found that only the number of months taking corticosteroids significantly affected BMD at all measured sites. However, the impact of the variables differed from site to site. CONCLUSION: Our findings imply that most young adults with JA attain the same BMD as healthy subjects if the disease goes into remission, while young adults with active disease have increased risk for osteopenia and osteoporosis.

[Classification of idiopathic juvenile arthritis]. / Klassifisering av idiopatiske juvenile artritter.

We present a review of the criteria for the classification of juvenile arthritides. Historical aspects, the present situation and proposals for new criteria are outlined. The most commonly used classification criteria today are the European juvenile chronic arthritis criteria (JCA), the European League Against Rheumatism (EULAR) criteria, and the American juvenile rheumatoid arthritis (JRA), the American Rheumatoid Association (ARA) criteria. They differ in nomenclature and have different inclusion and exclusion demands. This has made it difficult to compare studies using different criteria. Neither of them can define homogeneous subgroups of disease. The most recent proposal for new classification criteria of juvenile arthritides is that of the International League Against Rheumatism, ILAR. They are primarily designed to define homogeneous subgroups of disease. The goal is also to obtain an international consensus. Advantages and disadvantages are discussed in this article. The criteria have not yet been validated, and should not be used by clinicians until they have been approved by the international scientific society. We also present guidelines recommended for the classification of juvenile arthritis in Norway today. We recommend using the term juvenile arthritis. Disease duration of arthritis must be at least six weeks. A diagnosis of arthritis should not be made on painful and restricted joint movement alone, as is the case in both the EULAR and ARA criteria today, but at least be based on definite swelling of joints verified by either clinical examination and/or by imaging techniques such as ultrasound, X-ray or EMR.

Measuring disability in early juvenile rheumatoid arthritis: evaluation of a Norwegian version of the childhood Health Assessment Questionnaire.

OBJECTIVE: To assess the reliability, validity, and sensitivity to change of the Norwegian version of the childhood Health Assessment Questionnaire (CHAQ) and to examine the relationship between disability, disease severity, and psychosocial factors in patients with early juvenile rheumatoid arthritis (JRA). METHODS: Physical functioning was assessed by the CHAQ in 109 patients (median age 6.6 years, range 1.0-16.6) with JRA and a median of 4 months' (range 2-23) disease duration. Eighty-three patients were reassessed after a median of 6 months (range 3-21). Psychosocial functioning was assessed by the Child Behavior Checklist (n=39). RESULTS: The internal consistency of the CHAQ was good (Cronbach's alpha=0.83). The test-retest and parent-patient correlations were high [intraclass correlation coefficients 0.85 (n=18) and 0.75 (n=20), respectively, p < 0.001]. The CHAQ correlated moderately with number of tender, swollen and mobility restricted joints, morning stiffness, C-reactive protein, pain, and patients' and physicians' global assessments [correlation coefficients (r) ranging from 0.55 to 0.30, p < 0.01], but weakly with erythrocyte sedimentation rate (r=0.17, NS). The CHAQ also correlated with low levels of social competence (r=-0.49, p < 0.05) and high levels of internalizing behavior problems in the patients (r=0.43, p < 0.01) and low education levels of the mothers (r=-0.31, p < 0.01). Pain (beta 0.45, p < 0.001), number of swollen joints (beta 0.31, p < 0.001), and internalizing behavior problems (beta 0.45, p < 0.01) were predictors of disability. The median CHAQ changed from 0.25 to 0.00 (p < 0.05) in the 41 patients who improved, from 0.31 to 0.85 (p < 0.05) in the 18 patients whose condition was worse, and from 0.50 to 0.59 (NS) in the 24 patients whose condition was unchanged after 6 months. The effect size of the change was small (0.28) in those who improved and moderate (0.54) in those who became worse. CONCLUSION: The Norwegian version of the CHAQ is a reliable and valid instrument for measuring disability in children with early JRA. Pain, joint inflammation, and psychosocial factors are the most important correlates of disability and the CHAQ is sensitive to clinical change.

Outcome and predictive factors in juvenile rheumatoid arthritis and juvenile spondyloarthropathy.

OBJECTIVE: To describe outcome and determine predictive factors in juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthopathy (JSpA). METHODS: Seventy-two children with chronic arthritis were studied on first admission to the pediatric rheumatology clinic and after a mean of 9.7 +/- 1.8 yrs of disease duration. RESULTS: At followup, 53 patients had JRA and 19 had JSpA. Eleven (21%) of the patients with JRA did not meet the criteria for JRA on first admission, and 12 (22%) of 54 children diagnosed as having JRA on first admission were later reclassified as having another disease. Remission occurred in 43 (60%) of the 72 patients with JRA and JSpA. Forty-four patients (60%) reported no disability by the childhood or adult Health Assessment Questionnaire and 18 patients (25%) had developed joint erosions. Disease modifying antirheumatic drugs (DMARD) were given to 49 patients (68%) after a median of 0.8 yrs (range 0.2-10.8) disease duration. The patients who developed erosions and disability tended to have started treatment later than those who did not (NS). Active disease 5 years after onset was a predictor of disability in JRA and JSpA (OR 4.5, 95% CI 1.6-12.5). Predictors of joint erosions were long duration of elevated erythrocyte sedimentation rate (ESR) (OR 3.7/yr of elevated ESR, 95% CI 1.9-7.2), long disease duration before first admission (OR 1.5/yr of duration, 95% CI 1.1-2.1), long disease duration before treatment with DMARD (OR 1.8, 95% CI 1.0-3.3), and IgM rheumatoid factor (OR 12 x 10(4), 95% CI 0-1.2 x 10[52]). CONCLUSION: The longterm outcome in JRA and JSpA was more favorable than previously reported. This may be explained by less selection in favor of severely diseased patients and by the use of early aggressive treatment regimes.

Toxicity of antirheumatic and anti-inflammatory drugs in children.

The aim of the study was to describe the long-term toxicity of antirheumatic and anti-inflammatory drugs in a paediatric rheumatology clinic population. One hundred and seventeen children were studied on first admission to a paediatric rheumatology clinic and after a mean of 8.6 +/- 0.4 years of follow-up. Medical records from the intermediate period were reviewed. The patients had 155 exposures to non-steroidal anti-inflammatory drugs (NSAIDs), 88 exposures to disease-modifying antirheumatic drugs (DMARDs) and 12 exposures of prednisolone during a total of 682 patient years. Drug toxicity was measured in terms of the number of toxic events, number of drug discontinuations due to toxicity, number of side-effects per patient year of drug exposure and as a toxicity index. Side-effects were seen in 69 (27%) of the drug exposures, corresponding to 0.10 toxic events per patient year of exposure. Abdominal pain was the most common side-effect, and was reported in 21 (14%) of the exposures to NSAIDs. Five severely toxic events, all leading to hospitalisation, occurred. The toxicity of NSAIDs was not significantly different from that of DMARDs with regard to the number of toxic events (21% and 31%, respectively, NS) and drug discontinuations due to toxicity (17% and 14%, respectively, NS). Piroxicam tended to be more toxic than ibuprofen (46% versus 18% toxic events, p <0.05; 36% versus 16% discontinuations due to toxicity, NS; 0.33 versus 0.05 side-effects per patient year and a toxicity index of 1.45 versus 0.20 units per patient year). Gold tended to be more toxic than antimalarials (41% versus 15% toxic events, p<0.05; 24% versus 12% discontinuations, NS; 0.37 versus 0.08 side-effects per patient year and a toxicity index of 1.56 versus 0.23 units per patient year). It was concluded that antirheumatic and anti-inflammatory drugs led to side-effects in 27% of the exposed children during 9 years of follow-up. There was an overlap of the toxicity of certain NSAIDs and the most commonly employed DMARDs.

Quantitative and qualitative assessments of pain in children with juvenile chronic arthritis based on the Norwegian version of the Pediatric Pain Questionnaire.

Quantitative and qualitative aspects of pain were studied using a standardized questionnaire (the Varni/Thompson Pediatric Pain Questionnaire--PPQ). Fifty-seven of 64 consecutive in- and out-patients (6-18 yrs) with juvenile chronic arthritis (pauciart. n = 27, polyart. n = 30) and 52 parents participated. The patients were examined by the same rheumatologist and randomly interviewed by either a disabled or a non-disabled person. Present pain, worst pain intensity and disease severity were scored (on visual analogue scales [10 cm. VAS]) by patients, parents and rheumatologist. Eighty-two percent of the children reported pain lasting from 30 min up to 24 h daily (mean 4.3 h). No significant differences were found between median pain scores of children, parents and the physician, but the correlations found between children's and parent's assessment of pain and assessment of disease severity were low, indicating that the two sets of raters did not agree to an acceptable level. Two-thirds of the adolescents reported that they would become more physically active if pain disappeared. Should the pain suddenly vanish, a positive change in family relationships was anticipated by one out of four patients. Forty-two percent of the patients thought it valuable to be interviewed by a disabled physician. The Norwegian Varni/Thompson PPQ is easy to administer to children down to six years and makes it possible to compare results internationally. Lack of agreement on the assessment of pain by a child and his/her parent indicates the need to interview both parties.

Evidence for monoclonal expansion of synovial T cells bearing V alpha 2.1/V beta 5.5 gene segments and recognizing a synthetic peptide that shares homology with a number of putative autoantigens.

A peptide of 15 amino acids derived from the cereal glycine-rich cell wall protein (GRP), sharing a significant homology with Epstein-Barr virus nuclear antigen-1 (EBNA-1), fibrillar and procollagen, stimulated synovial fluid (SF) T cells from juvenile (JRA) and adult (RA) rheumatoid arthritis patients. An overexpression of the V alpha 2 gene family was found in the SF from patients who responded significantly to the peptide. To investigate in more detail the SF T-cell responses to the GRP peptide, we established peptide-specific T-cell lines and clones from a DR8+ positive JRA patient with pauciarticular form. The T-cell clones were phenotyped as T-cell receptor (TCR)alpha beta+/CD4+ and their clonality was investigated by polymerase chain reaction (PCR) and flow cytometric analysis. TCR sequences from different clones demonstrated that the clones were identical and used the V alpha 2.1/J alpha 6 combined with V beta 5.5/J beta 2.7 gene segments. Interestingly, direct sequencing of the V alpha 2 family PCR product obtained from cDNA prepared from freshly isolated SF mononuclear cells identified the same TCR sequence as that used by the clones, suggesting the monoclonality of SF CD4+ T cells bearing V alpha 2.1/J alpha 6 gene products. The present data suggest a recruitment and expansion of a SF T-cell subpopulation, and also support the hypothesis that autoimmune diseases can be triggered by protein epitopes with crucial amino acids homologous to self-proteins.

Association to HLA-DRB1*08, HLA-DPB1*0301 and homozygosity for an HLA-linked proteasome gene in juvenile ankylosing spondylitis.

To assess the role of HLA genes other than those encoding B27 in predisposing to JAS and AAS, we analyzed the distribution of B*4001, as well as the DRB1, DPB1, and LMP2 alleles, using PCR-based techniques in 63 JAS and 44 AAS patients (all B27 positive). The NBMDR (N = 4724) provided a source of controls matched with the patients for B27 (or other markers when necessary). We found an increase of the B*4001, DRB1*08, and DPB1*0301 alleles, as well as the LMP2 b/b genotype (the latter was most pronounced among patients with acute iridocyclitis), in JAS compared to B27-positive controls. The increase of DRB1*08 and DPB1*0301 was due to an increase of DRB1*08 and DPB1*0301 in combination, whereas the association with B*4001 could be due to linkage disequilibrium with LMP2b. None of these associations were detected in AAS. We conclude that in JAS, in addition to the association to B27, there are also weaker but distinct associations to the DRB1*08, DPB1*0301 alleles and homozygosity for LMP2b.

Methotrexate in juvenile rheumatoid arthritis. Evidence of age dependent pharmacokinetics.

Children with juvenile rheumatoid arthritis (JRA) have been reported to require higher doses (per kg body weight) of methotrexate (MTX) than adults with rheumatoid arthritis to control their disease. The purpose of the present study was to characterise the plasma pharmacokinetics of MTX and its major metabolite, 7-hydroxymethotrexate (7-OHMTX) in children, and to compare the results with those previously obtained in adults. Thirteen patients (age 5-16 y) with JRA (median disease duration 5.5 y) were studied after once weekly oral administration of MTX (median 0.21 mg.kg-1). The analytical method was sufficiently sensitive to permit determination of plasma and urinary concentrations of MTX and 7-OHMTX during the entire dose interval in most of the patients. The dose normalized area under the plasma concentration versus time-curve (AUC) of MTX increased with the age of the children and was lower than previously found in adults. The dose normalized AUC of 7-OHMTX was not dependent on age. No correlation was found between the AUCs of MTX and 7-OHMTX. The results suggest that the age-dependence of the pharmacokinetics of MTX might explain the observation that at least some children require higher doses of MTX than adults to obtain a sufficient therapeutic effect.

Polymorphism of human major histocompatibility complex-encoded transporter associated with antigen processing (TAP) genes and susceptibility to juvenile rheumatoid arthritis.

The TAP1 and TAP2 genes encode a peptide transporter supplying peptides for binding to HLA class I molecules. Both genes are located in the class II region of the HLA complex and are polymorphic. Here we report the distribution of TAP alleles in a group of 285 JRA patients (including various subsets), 165 random controls, and 82 DR8-positive controls. We found a pronounced increase of TAP1B and TAP2C/D in patients, compared with controls. The difference was, however, mainly secondary to a strong linkage disequilibrium between these TAP alleles and DR8, which is significantly increased in JRA. When we compared patients and controls after stratification for DR8 the differences decreased, although an increase of TAP1B in DR8-negative patients remained significant. We conclude that a primary association of JRA with given TAP allels cannot explain the HLA class II associations in JRA. However, we cannot exclude the possibility that TAP1B acts as an additive susceptibility factor in JRA.

Ketoprofen controlled release (CR) in the treatment of osteoarthrosis; a double blind, randomized multicentre study of single morning versus evening dose. Norwegian Study Group of General Practitioners.

OBJECTIVE: To compare the morning and evening dose of 200 mg ketoprofen controlled release formulation with regard to both efficacy and GI tolerability. DESIGN: Double-blind, randomized multicentre prospective trial with cross-over design combined with a parallel design. PARTICIPANTS: One hundred and eight female and 55 male patients with osteoarthrosis in hip(s) or knee(s) necessitating treatment with nonsteroidal antiinflammatory drugs. MAIN OUTCOME MEASURE: The degrees of pain and stiffness and joint movement ability in joints with osteoarthrosis. RESULTS: Both the morning and the evening dose demonstrated a significant effect (p < 0.01) on all efficacy variables. The reduction in degree of pain in the afternoon and in the evening was significantly higher (p < 0.01) for the morning dose. The total frequency and degree of gastrointestinal discomfort increased significantly (p < 0.01) during both treatment periods. The increases were mainly caused by increased gastric pain and constipation. No significant differences were found between the two regimes regarding tolerability. CONCLUSION: Ketoprofen controlled release given once daily in the morning compared to the evening to patients with osteoarthrosis may increase the efficacy without reducing the tolerability of the drug.

HLA class II alleles and heterogeneity of juvenile rheumatoid arthritis. DRB1*0101 may define a novel subset of the disease.

OBJECTIVE: To examine the distribution of HLA class II alleles in clinically distinct juvenile rheumatoid arthritis (JRA) subsets. METHODS: We typed 298 patients and 181 controls for HLA-DRB1, DQA1, DQB1, and DPB1 alleles using polymerase chain reaction and oligonucleotide probe techniques. RESULTS: Each JRA subset was characterized by a distinct distribution of HLA class II alleles. For the persistently pauciarticular and rheumatoid factor-negative polyarticular JRA subsets, certain combinations of DRB1 and DPB1 alleles were characteristic. In patients without antinuclear antibodies and chronic iridocyclitis, there was an increase of DRB1*0101/02 and DQA1*0101. CONCLUSION: Findings of HLA typing support clinical subdivisions of the disease and suggest the existence of a novel DRB1*0101/02 and DQA1*0101 associated disease subset.

A high proportion of the V delta 1+ synovial fluid gamma delta T cells in juvenile rheumatoid arthritis patients express the very early activation marker CD69, but carry the high molecular weight isoform of the leucocyte common antigen (CD45RA).

We have previously shown that gamma delta T cells in the synovial compartment of patients with juvenile rheumatoid arthritis (JRA) express activation antigens (CD69 and HLA-DR) and that they are predominantly of the V delta 1 subset. In this study we have analysed the expression of activation antigens (CD69 and HLA-DR) and different isoforms of the leucocyte common antigen (CD45RO and CD45RA) on the V delta 1 and the V delta 2 subsets of gamma delta T cells in paired samples of synovial fluid and peripheral blood of nine patients with JRA, and in the peripheral blood of five children with idiopathic scoliosis. In the synovial fluid of children with JRA, there were significantly more V delta 1+CD69+ and V delta 2+CD69+ cells compared with the peripheral blood of the same patients. In contrast, however, in the synovial fluid the V delta 1 and the V delta 2 subsets differed with respect to the expression of the two isoforms of the leucocyte common antigen. The majority of the V delta 1+ cells expressed the high molecular weight isoform (CD45RA+) while most of the V delta 2+ cells carried the low molecular weight variant (CD45RO+) of this molecule.

Limited heterogeneity of T cell receptor variable region gene usage in juvenile rheumatoid arthritis synovial T cells.

The aim of this study was to determine whether synovial fluid (SF) T cells in patients with juvenile rheumatoid arthritis (JRA) are restricted in their T cell receptor (TcR) gene repertoire. The quantitative polymerase chain reaction (QPCR) was used to compare the transcription of V beta and V alpha gene families in freshly isolated SF T cells, in interleukin-2 receptor-positive (IL-2R+) T cells and in peripheral blood (PB) T cells from 18 patients. Significantly less V beta families are detected in SF when compared with PB (p greater than 0.0003). The TcR V beta gene usage by IL-2R+ T cells was even less heterogeneous when compared with freshly isolated SF T cells (p greater than 0.0002). Freshly isolated SF T cells from the left and the right knees of four patients transcribed the same V beta families. Furthermore, we demonstrate that in SF the distribution of certain TcR V beta gene segments in CD4+ and CD8+ T cells differed from that in PB of the same patient. The TcR V alpha usage was studied in IL-2R+ T cells from six patients who had shown restriction in their SF TcR V beta gene usage. Only two to five TcR alpha transcripts were detected in three of these patients while a broad TcR V alpha usage was seen in the other three patients. Sequence analysis of the SF V beta 20 cDNA clones generated from the IL-2R+ T cells of two patients demonstrated an oligoclonal expansion. Taken together, our data could indicate an antigen- and/or superantigen-driven expansion of selected T cells in the synovial compartment.

T gamma delta cells in juvenile rheumatoid arthritis and rheumatoid arthritis. In the juvenile rheumatoid arthritis synovium the T gamma delta cells express activation antigens and are predominantly V delta 1+, and a significant proportion of these patients have elevated percentages of T gamma delta cells.

Using the anti-TcR gamma/delta-1 monoclonal antibody and flow cytometry, we examined the number of T gamma delta cells in paired samples of peripheral blood and synovial fluid or tissue from 24 children with juvenile rheumatoid arthritis (JRA), five adult patients with JRA, and 14 patients with rheumatoid arthritis (RA). No significant difference was found in the synovial compartment T gamma delta values compared with the blood in JRA, adult JRA, or RA patients. Nor was any significant difference found in the peripheral blood or synovial compartment T gamma delta values in any of the three patient groups compared with the peripheral blood of normal controls. However, seven of the children with JRA had very high T gamma delta values in the synovial compartment while none of the normal children had high T gamma delta values in the blood (P = 0.02, Fisher's exact test). This may indicate a possible separate JRA patient group with high T gamma delta levels in the synovial compartment. In six JRA patients further analysed for T gamma delta subpopulations, a significant predominance of V delta 1+ cells was found in the synovial compartment compared with the corresponding peripheral blood samples (P less than 0.05, Wilcoxon's signed test) and with peripheral blood of child controls (P less than 0.05, Mann-Whitney U test). In these six patients, the T gamma delta-cell expression of the very early activation antigen CD69 were significantly higher (P less than 0.05, Wilcoxon's signed test) in the synovial compartment compared with the peripheral blood. Synovial T gamma delta cells expressing HLA-DR and interleukin 2 receptors could also be detected, in contrast to the peripheral blood in which no T gamma delta cells expressing these antigens could be found. These data suggest that the synovial T gamma delta cells had been activated in vivo.

[Pathologic urine findings related to medication]. / Patologiske urinfunn relatert til medikamentbruk.

We examined urine specimens from 144 consecutive patients attending a rheumatological department. Transient abnormal findings were frequent, but most urine samples normalized spontaneously. We found no association with use of non-steroidal anti-inflammatory drugs, but there was an association between pathological urine findings and the combined use of such drugs and systemic steroids.

IgA and rheumatoid factor in ankylosing spondylitis.

The elevated serum IgA in seronegative arthritis and psoriasis is not well understood. We examined 112 patients with ankylosing spondylitis for IgA RF, IgG RF and IgM RF by an ELISA method. Two, two and ten patients were RF positive in each Ig class, respectively. Presence of RF was not correlated with Ig concentrations, with presence of HLA-B27, nor with clinical disease signs. It was concluded that RF may be seen in ankylosing spondylitis, but the increased IgA concentrations in such patients are not IgA RF.

Radiography of the spine and sacro-iliac joints in ankylosing spondylitis and psoriasis.

A grading system involving six stages of arthritis from grade 0 = normal joints to grade V = extensive bony ankylosis in the sacro-iliac joints and a scheme applicable for quantitative registration of the radiographic findings of the spine in ankylosing spondylitis (AS) are detailed. These radiographic grading systems were used in a study comprising 48 patients with psoriasis (group A), 19 patients with AS and psoriasis (group B), 103 patients with AS (group C) and 231 first-degree relatives of the patients belonging to groups B and C (group D). Radiographic abnormalities of the spine were found totally in 80 per cent of the patients belonging to groups B and C. In these groups sclerotic anterior borders of vertebrae (SABS) and/or straightened anterior surfaces of vertebrae were seen totally in 66 per cent. SABS were earlier findings than syndesmophyte formation which was found in 60 per cent of the patients belonging to groups B and C. Except for ankylosis of the apophyseal joints and ossified interspinous ligament most frequently found in the lower lumbar region in patients with duration of disease more than 20 years, all abnormalities of the spine were most frequent in the dorsolumbar junction. Grade V sacro-iliitis was associated with ankylosis of two or more segments of the spine. Such spinal changes were infrequently seen in patients with grade IV sacro-iliitis. This finding supports the previous notion that among patients fulfilling the criteria for AS, there is a group with a non-ankylosing disease. Thus two different subgroups of AS could be identified. Except for frequent unilateral sacro-iliitis and slight changes of the spine in group A no radiographic differences were found between the groups A, B and C. Sacro-iliitis was found in 22 (9%) in group D, and 11 of those with sacro-iliitis had abnormalities of the spine compatible with AS.

Bechterew's syndrome (ankylosing spondylitis). A syndrome with distinct subgroups.

The results of tests for associations among radiographic findings of the dorsolumbar spine, peripheral joints, tendon insertions and the pubic symphysis are presented. Ankylosis of sacro-iliac joints, ankylosis of apophyseal joints, bridging syndesmophytes, ossified interspinous ligament, block vertebrae, arthritis of the pubic symphysis and new bone formation of the ischium were strongly mutually associated. They probably belong to the same subgroup of disease. Such findings were negatively associated with distal peripheral joint arthritis. Mixed osteophytes, parasyndesmophytes or shining corners (anterior spondylitis) showed associations suggesting that the etiology may be mixed. A late stage of sacro-iliitis, regressive changes, characterized by narrow joint spaces without extensive ankylosis and with minimal sclerosis (grade IV sacro-iliitis) was associated with distal peripheral joints arthritis, but negatively associated with signs of ankylosing processes of the dorsolumbar spine. On the basis of the radiographic findings, distinct subgroups of AS could be identified. These results confirm our previous results of an association pattern between clinical findings. We would also recommend that the grading system of sacro-iliitis put forward by Dale be adopted, since it turned out that this grading system often distinguished between distinct subgroups of this heterogeneous condition(s).

Radiographic evaluation of patients with Bechterew's syndrome (ankylosing spondylitis). Findings in peripheral joints, tendon insertions and the pubic symphysis and relations to non-radiographic findings.

One hundred and twenty-two consecutive hospitalized patients aged 35 years or more, and with definite radiographic bilateral sacro-iliitis were re-examined. All but 3 met established criteria for definite ankylosing spondylitis (AS). All peripheral joints from 114 of these patients were radiographed, and definite arthritis in one or several joints was demonstrated in 47 (41%) of them. The distribution pattern of arthritis was generally symmetric or slightly asymmetric. Articular new bone formation was a common finding in arthritic joints. The frequency of patients with hip arthritis was low (24% including patients with hip joint replacements); possible explanations include the selection of patients examined and difficulties in distinguishing between a primary osteoarthritis and osteoarthritis secondary to arthritis in a single radiographic examination in such patients. Although the hip joints were often severely affected, with extensive new bone formation, the erosions were generally small and protrusion of the acetabulum was not seen. Arthritis of the shoulder or of the hip was associated with an early onset of AS. Arthritis in the finger joints was associated with clinical psoriasis but was also a frequent finding in HLA B27-positive patients free from this condition (23%). Arthritic changes of small joints with extensive new bone formation ('egg in shell', 'pencil in cup' or 'gull wing' appearance) were seen in patients without clinical psoriasis. New bone formation of the ischium was frequent in HLA B27-positive patients (36%), but was not seen in HLA B27-negative patients. No differences concerning the frequency or severity of different radiographic pathologic changes recorded were observed between the sexes.