Hans-Jacob Haga

Current concepts on diagnosis, autoantibodies and therapy in Sjögren's syndrome.

Sjögrens syndrome is a chronic autoimmune and rheumatic disorder. Most patients have mild to moderate complaints and this may explain the great discrepancy in prevalence found in population studies compared to studies performed in the clinic. However, there is no straightforward and simple diagnostic test for Sjögrens syndrome, although several classification criteria have been designed. Initiatives have been taken to propose a new set of classification criteria in a joint effort by research groups in Europe and USA. A large number of autoantibodies have been reported in Sjögrens syndrome where, in some cases, the antibodies are correlated with the extent and severity of disease. The finding of serum autoantibodies directed against the muscarinic M3 receptor is an important advance in understanding the pathogenesis of not only the impaired glandular function but also associated features of autonomic dysfunction in some patients. The treatment of primary Sjögrens syndrome is still mainly symptomatic.Sjögrens syndrome is a chronic autoimmune and rheumatic disorder. Most patients have mild to moderate complaints and this may explain the great discrepancy in prevalence found in population studies compared to studies performed in the clinic. However, there is no straightforward and simple diagnostic test for Sjögrens syndrome, although several classification criteria have been designed. Initiatives have been taken to propose a new set of classification criteria in a joint effort by research groups in Europe and USA. A large number of autoantibodies have been reported in Sjögrens syndrome where, in some cases, the antibodies are correlated with the extent and severity of disease. The finding of serum autoantibodies directed against the muscarinic M3 receptor is an important advance in understanding the pathogenesis of not only the impaired glandular function but also associated features of autonomic dysfunction in some patients. The treatment of primary Sjögrens syndrome is still mainly symptomatic.

Estimation of the prevalence of primary Sjogren's syndrome in two age-different community-based populations using two sets of classification criteria: the Hordaland Health Study

Objective: To estimate the point prevalence of primary Sjögrens syndrome (pSS) in two populations, aged 40–44 and 71–74 years, using two sets of classification criteria. Methods: The participating individuals were recruited from the Hordaland Health Study (HUSK) conducted during 1997–99. A total of 18 592 individuals born 1953–57 and 3346 individuals born 1925–27 were sent a questionnaire covering various health‐related questions, including four questions about sicca symptoms. Among those answering positive to at least one of the four questions, 99 and 90 individuals born 1953–57 and 1925–27, respectively, were examined further. For diagnosis of pSS two classifications were used, the preliminary European criteria from 1993, and the revised European criteria from 1996. Results: By using the two classification criteria from 1993 and 1996, the point prevalences were 0.44% [95% confidence interval (CI) 0.34–0.57] and 0.22% (95% CI 0.15–0.32), respectively, for the population group born 1953–57. The corresponding estimates were 3.39% (95% CI 2.77–4.14) and 1.40% (95% CI 1.02–1.92) for the population born 1925–27. Conclusion: The point prevalence of pSS was approximately seven times higher in the elderly population aged 71–74 years compared to individuals aged 40–44 years, regardless of the classification criteria used.

The influence of age on disease manifestations and serological characteristics in primary Sjögren's syndrome.

We have studied the influences of age on clinical manifestations and serological abnormalities in primary Sjögrens syndrome (pSS). The 67 patients included were diagnosed according to the preliminary European classification criteria for pSS, and disease manifestations were assessed according to a newly developed quantitative and qualitative classification model. We found that the age at diagnosis correlated to the presence of autoantibodies anti-SSA/SSB (r=-0.31, <0.02), rheumatoid factor (RF) (r=-0.33, p<0.01) and serum levels of IgG (r=-0.27, p<0.05). Young patients diagnosed before 45 years of age had the highest positivity of the autoantibodies anti-SSA/SSB (62.5%), RF (62.5%) and high levels of s-IgG (68.8%), while the corresponding values for old patients diagnosed after 60 years of age were anti-SSA/SSB: 20.8%, RF: 20.8%, and high s-IgG: 29.2%. None of these parameters correlated to age at onset nor disease duration. By applying a model for evaluating disease manifestations, no correlation between the global index nor the indices for subgroups of disease manifestations was found to age at onset, age at diagnosis, nor disease duration. We conclude that there is a significant influence of age on serological abnormalities in pSS, but not on disease manifestations.

Leukocyte protein calprotectin and outcome in rheumatoid arthritis: A longitudinal study

Objective: To determine if calprotectin is predictive for outcome in patients with rheumatoid arthritis (RA). Methods: Fifty six RA in-patients with variable disease duration were prospectively followed for five years. Clinical and laboratory data were collected to assess disease activity. Health Assessment Questionnaire (HAQ) and radiographic scores (of hands and wrists) as described by Larsen were used as outcome measures. Plasma calprotectin levels were determined with ELISA technique. Results: Significant correlations (r) were found cross-sectionally at follow-up between calprotectin concentration and other known parameters of disease activity and severity: CRP (r= 0.67), investigators global assessment of disease activity (r= 0.57), Waaler titre (r= 0.50), HAQ score (r= 0.48) and number of swollen joints (r= 0.48). Calprotectin at baseline was not identified as an independent predictor for HAQ or radiographic progression in the multivariate analysis. Conclusion: The results confirm calprotectin as a good measure of disease activity and joint inflammation in RA. However, the level of calprotectin at baseline was not predictive for radiographic damage or functional impairment five years later.

Severe deficiency of 25-hydroxyvitamin D3 (25-OH-D3) is associated with high disease activity of rheumatoid arthritis

This study aims to measure the serum level of 25-hydroxyvitamin D3 (25-OH-D3) in 302 patients with rheumatoid arthritis (RA), studying the association to disease activity. Three hundred two RA patients underwent clinical examination and serological analysis. 25-Hydroxyvitamin D3 was determined by high-performance liquid chromatography–tandem mass spectrometry. Vitamin D3 deficiency defined as serum levels of 25-hydroxyvitamin D3 below 50xa0nmol/l was detected in 101 RA patients (33.4xa0%). There was no significant correlation between the serum level of 25-hydroxyvitamin D3 and Disease Activity Score 28 (DAS28) (3w) score. In a subpopulation of RA patients with very low serum level of 25-OH-D3 (≤15xa0nmol/l) (nu2009=u200915), there were significant differences compared to patients with normal 25-OH-D3 (nu2009=u2009200): higher percentage of patients with positive rheumatoid factor (100.0 versus 77.5xa0%; pu2009=u20090.05), higher CRP (28.7 versus 14.8xa0mg/l; pu2009=u20090.001), higher number of patients treated with at least three disease-modifying antirheumatic drugs (DMARDs) (40.0 versus 14.5xa0%; pu2009=u20090.02), higher number of patients with high disease activity DAS28 score of ≥5.1 (20.0 versus 4.5xa0%; pu2009=u20090.01), lower age (54.5 versus 64.0xa0years; pu2009=u20090.003) and shorter disease duration (5.1 versus 10.3xa0years; pu2009=u20090.06). Deficiency of 25-hydroxyvitamin D3 was detected in 33.4xa0% of the RA patients. A subpopulation of patients with severe deficiency of vitamin D3 serum level of ≤15xa0nmol/l was characterised by all being positive for rheumatoid factor, high percentage of patients with very high disease activity and high percentage of patients treated with at least three DMARDs.

A study of the prevalence of sicca symptoms and secondary Sjögren's syndrome in patients with rheumatoid arthritis, and its association to disease activity and treatment profile

To examine the prevalence of sicca symptoms and secondary Sjögrens syndrome (sSS) in rheumatoid arthritis (RA) patients, and the impact of sSS on disease activity and treatment profile in RA patients.

IgA rheumatoid factor in primary Sjögren's syndrome

Objective: To assess the serum level of immunoglobulin A rheumatoid factor (IgA‐RF) in patients with primary Sjögrens syndrome (pSS) and study the association with immunological and clinical factors. Methods: Sera from 97 pSS patients diagnosed according to the preliminary European criteria and 100 controls were analysed for IgA‐RF in a cross‐sectional study design. Results: IgA‐RF was detected in serum of 25.8% of the pSS patients and in 1% of the controls. In patients with positive vs. negative IgA‐RF, the focus scores in biopsy of the minor salivary glands were 4.41 and 1.43 (p<0.0001), respectively. There was a correlation between positive IgA‐RF and positive antinuclear antibodies (ANA) (r = 0.263, p<0.009), IgM‐RF (r = 0.70, p<0.0001), anti‐SSA/SSB (r = 0.73, p<0.0001), and a high serum level of IgG (r = 0.59, p<0.0001). The presence of renal disease was higher in IgA‐RF‐positive vs. negative pSS patients (20.0% vs. 5.6%, p = 0.047). The serum level of the hormone prolactin (PRL) correlated to the serum level of IgA‐RF (r = 0.31, p = 0.026). Conclusions: The presence of IgA‐RF in patients with pSS is closely associated with the presence of autoantibodies, and with focus scoring in biopsies of the salivary glands. IgA‐RF is associated with renal disease in pSS but we found no correlation to other extraglandular manifestations.

Incidence of thromboembolic events in patients with primary Sjogren's syndrome

Primary Sjögrens syndrome (pSS) is a connective tissue disease with symptoms and serological findings often overlapping with systemic lupus erythematosus (SLE) 1. Thromboembolic events are common in SLE but not in pSS 23. However, case reports have described pSS patients who developed fulminant multiorgan disease due to thrombotic diathesis 4, and we have presented a case with acute catastrophic anti‐phospholipid syndrome (APS) in a pSS patient 5. In this study we wanted to examine the incidence of thromboembolic episodes and relate these to the presence of autoantibodies and coagulation abnormalities in 90 pSS patients during a 4.6‐year follow‐up.

Clinical utility of diagnostic tests for rheumatoid factor

Objective: To investigate and compare the accuracy and usefulness of diagnostic tests for rheumatoid factor (RF). Methods: In a cross-sectional study sera derived from patients admitted to the Section of Rheumatology were tested for presence of RF using either nephelometry or the Waaler test. Diagnostic sensitivity and predictive values of the tests were calculated and compared. The accuracy of the tests was compared using receiver-operating characteristics (ROC) methodology. Results: Good agreement was found between the tests (κ≈0.7). At cut-off 19 IU/mL nephelometry showed the highest sensitivity (82.4%) and specificity (95.9%) for rheumatoid arthritis (RA). In comparison, the Waaler test had a sensitivity of 60.3% and specificity of 95.9% at cut-off titer 128. The tests showed nearly equal performance characteristics when predicting SS. Conclusion: Although both tests exhibit good performance characteristics, nephelometry has a higher accuracy when predicting RA and SS. The common practice of using both tests for detection of RF is not recommended.OBJECTIVEnTo investigate and compare the accuracy and usefulness of diagnostic tests for rheumatoid factor (RF).nnnMETHODSnIn a cross-sectional study sera derived from patients admitted to the Section of Rheumatology were tested for presence of RF using either nephelometry or the Waaler test. Diagnostic sensitivity and predictive values of the tests were calculated and compared. The accuracy of the tests was compared using receiver-operating characteristics (ROC) methodology.nnnRESULTSnGood agreement was found between the tests (kappa approximately 0.7). At cut-off 19 IU/mL nephelometry showed the highest sensitivity (82.4%) and specificity (95.9%) for rheumatoid arthritis (RA). In comparison, the Waaler test had a sensitivity of 60.3% and specificity of 95.9% at cut-off titer 128. The tests showed nearly equal performance characteristics when predicting SS.nnnCONCLUSIONnAlthough both tests exhibit good performance characteristics, nephelometry has a higher accuracy when predicting RA and SS. The common practice of using both tests for detection of RF is not recommended.

Anti-cardiolipin autoantibodies and pulmonary embolism: A case for a common cause

A patient with primary SjöA patient with primary Sjögrens syndrome developed pulmonary embolism following infection with influenza A virus. IgM anti-cardiolipin autoantibodies (aCL) evolved two weeks after hospitalisation, synchronously with antibodies against influenza A. IgG aCL developed three weeks after hospitalization, peaked during the recovery period, and gradually declined to undetectable levels 12 months after admission. Antibodies against beta2 glycoprotein I were not detected. Our results assign a high likelihood to the hypothesis that influenza A virus caused the patients thromboembolic disease as well as development of aCL. aCL may have contributed to tissue pathology by forming immune-complexes with cardiolipin and rheumatoid factor.