Development of new extra-glandular manifestations or associated auto-immune diseases after establishing the diagnosis of primary Sjögren's syndrome : A long-term study of the Antonius Nieuwegein Sjögren (ANS) cohort.

To investigate in a long-term study, the development of new extra-glandular manifestations (EGM) or associated auto-immune diseases (AID) from 1 year after establishing the diagnosis of primary Sjögren's syndrome (pSS). The primary goal was to examine the frequency and type of these manifestations and to find out which demographic, clinical and serological profile was most at risk. All outpatients diagnosed with primary Sjögren's syndrome were included in a retrospective study, with at least one check-up per year, from June 1991 until August 2015. Patients also fulfilling the criteria for concomitant connective tissue disorders were excluded. Data were collected with respect to the cumulative prevalence of a new EGM or associated AID. 140 patients were included in the final analysis. After 10 years of follow-up, the cumulative incidence of a new EGM or associated AID was 30.7%. The most frequent events were polyneuropathy, interstitial lung disease, (poly)arthritis, discoid lupus erythematosus (LE)/subacute cutaneous LE and Hashimoto's disease. Non-Hodgkin lymphoma was not diagnosed during the follow-up. Patients without chronic benign pain syndrome (CBP) (HR 2.13; 95% CI [0.94-4.76]; p = 0.061), but in particular those with cryoglobulins (HR 2.87; 95% CI [1.20-6.86]; p = 0.013), developed more events. Age at diagnosis, gender, the presence of ANA, anti-Ro/SSA, anti-La/SSB, IgM-RF, decreased levels of C3 or C4, or hypergammaglobulinaemia did not show any statistically significant differences. The burden of disease in pSS is higher than expected due to the development of EGM or associated AID. Therefore, we recommend long-term follow-up of all pSS patients, particularly those with cryoglobulinaemia.

Polyarthritis in primary Sjögren's syndrome represents a distinct subset with less pronounced B cell proliferation a Dutch cohort with long-term follow-up.

The primary goal was to investigate the differences in patients with and without polyarthritis (PA) in primary Sjögren's syndrome (pSS) in a clinical-based (real-life) setting, with respect to demographic characteristics, cumulative prevalence of other extra-glandular manifestations (EGM), hypergammaglobulinaemia and serological profile. The secondary goal was to describe the characteristics of polyarthritis in our pSS cohort. Patients diagnosed with pSS and polyarthritis but without rheumatoid arthritis (RA)-like changes on X-rays were followed up prospectively from June 1991 until August 2014, with at least one check-up each year. Patients fulfilling the criteria for concomitant connective tissue disorders were excluded. Data were collected with respect to the prevalence of systemic auto-antibodies (anti-nuclear antibodies (ANA), anti-Sjögren's syndrome-related antigen A (anti-SSA), anti-Sjögren's syndrome type B (anti-SSB) and immunoglobulin M-rheumatoid factor (IgM-RF)) and other EGM related to pSS. A total of 134 patients were included for the final analysis. The median follow-up was 86 months (range 0-368 months). Twenty-two patients (16.4 %) had polyarthritis. The prevalence of systemic auto-antibodies including rheumatoid factor did not differ between the two groups. Anti-cyclic citrullinated peptide (CCP) occurred much more frequently in the polyarthritis-positive (PA+) patients (13.7 vs 0.9 %; p = 0.015). Hypergammaglobulinaemia (p = 0.002) and increased levels of IgG (p = 0.013) occurred much less frequently in the PA+ group compared to the polyarthritis-negative (PA-) group. The mean total number of EGM or of any specific EGM did not differ between the two groups. Most patients had a mild, symmetrical PA predominantly involving the finger joints (proximal interphalangeal joints/metacarpophalangeal joints (PIP/MCP)) and/or wrists and/or metatarsophalangeal (MTP) joints. Significant morning stiffness lasting ≥1 h was found infrequently (32 %). All patients were treated with a classic (c) disease-modifying antirheumatic drug (DMARD), but in two cases, treatment was necessary with a tumour necrosis factor (TNF) inhibitor. PA+ pSS patients are more frequently anti-CCP positive and have a less pronounced B cell proliferation than PA- patients. PSS patients with PA seem to have a relatively mild articular expression with a favourable course.

Lower prevalence of extra-glandular manifestations and anti-SSB antibodies in patients with primary Sjögren's syndrome and widespread pain: evidence for a relatively benign subset.

OBJECTIVES: To investigate in primary Sjögren's syndrome, the differences between patients with and without widespread pain (WSP) with respect to the cumulative prevalence of extra-glandular manifestations (EGMs) and systemic auto-antibodies. METHODS: All outpatients diagnosed with primary Sjögren's syndrome (2) were included in a prospective follow-up, with at least one check up each year, from June 1991 until November 2011. Patients who also fulfilled criteria for concomitant connective tissue disorders were excluded. Widespread pain was defined as the presence of long-lasting (>one year) diffuse pain in all four body quadrants. Data were collected with respect to the cumulative prevalence of systemic auto-antibodies (anti-nuclear antibodies [ANA], anti-Sjögren syndrome A antigen [anti-SSA], anti-Sjögren syndrome B antigen [anti-SSB] and immunoglobulin M-Rheumatoid factor [IgM-RF]) and EGMs related to primary Sjögren's syndrome. RESULTS: Eighty-three patients were included in the final analysis. Thirty-nine (34.9%) patients had widespread pain. Anti-SSB was found less frequently (p<0.05) in patients with WSP than in patients without WSP. The WSP-positive patients were more frequently negative for all four tested autoantibodies (p<0.05). The patients with WSP had fewer EGMs than the patients without WSP (p<0.01); more specifically, polyneuropathy occurred less frequently (p<0.05) in the patients with WSP. Cytopenia, uveitis, pericarditis, pleuritis, interstitial lung disease, vasculitis, monoclonal gammapathy of unknown significance and non-Hodgkin lymphoma only occurred in the patients without WSP. CONCLUSIONS: Primary Sjögren's patients with WSP form a benign subgroup, with a lower prevalence of anti-SSB and EGMs (in particular polyneuropathy). We suggest a shorter period of follow-up for this subset than for the WSP-negative patients.

Monoarthritis of the elbow due to metastatic colon carcinoma: diagnosis based on the presence of adenocarcinoma cells in synovial fluid.

There are many diseases that can cause monoarthritis, malignancy being one of the more rare causes. We present such a case and discuss the relationship between malignancy and arthritis. Typically a large joint is involved, most frequently the knee and very rarely the elbow. The value of cytological examination of synovial fluid is stressed. Synovial fluid in malignant joint disease is usually sanguineous and not consistent with an inflammatory process. Synovial fluid analysis can avoid a biopsy of bone or synovium and lead to an early diagnosis and palliative treatment.

Relationship between histological subtypes and clinical characteristics at presentation and outcome in biopsy-proven temporal arteritis. Identification of a relatively benign subgroup.

Temporal arteritis (TA) may offer major complications, whilst high dosage of prednisone may result in serious side effects. We tried to identify a subgroup of TA, which can be treated with a lower dosage of prednisone. Retrospectively, clinical and laboratory data were studied at presentation, as well as the outcome in 44 consecutive patients with biopsy-proven temporal arteritis. These data were related to three particular histological subgroups, (a) classical giant cell arteritis, (b) atypical arteritis, and (c) 'healed arteritis', defined according to Allsop and Gallagher (The American Journal of Surgical Pathology 5:317-332, 1981). At presentation in subgroup c, erythrocyte sedimentation rate was lower and the level of haemoglobin was higher than in the other two subgroups. During follow-up in the healed arteritis group, reactivation, recurrence, or early death were not observed, whilst prednisone dosage after 2 and 3 years was lower compared to subgroup b. Major complications (permanent blindness and cerebrovascular accident) were only observed in subgroups a and b. We believe that the healed arteritis subgroup represents a relatively benign subgroup with a mild clinical presentation and a good prognosis. Therefore, a much lower initial prednisone dosage (15 mg/day) is suggested for patients in subgroup c than in the other two subgroups (40-60 mg/day).

Joint surgery in the Utrecht Rheumatoid Arthritis Cohort: the effect of treatment strategy.

OBJECTIVE: To investigate the prevalence and prognostic factors of joint surgery in a large cohort of patients with rheumatoid arthritis, whose treatment, clinical and radiographic data have been assessed at predefined points in time since disease onset. METHODS: Data on surgical interventions were retrospectively obtained from 482 patients with rheumatoid arthritis whose follow-up data for at least 2 years were available, including treatment and response to treatment during the first 2 years. Survival time until the first surgical intervention and until the first major surgical intervention was determined for the total study population by Kaplan-Meier survival curves. Three separate Cox regression analyses were carried out to determine which variables measured at baseline, during the first year and during the first 2 years were predictors for joint surgery. RESULTS: 27% of the patients underwent surgical interventions. Mean survival time until the first surgical intervention was 10.4 years. The percentage of patients with a surgical intervention was 10% lower in the group with response to treatment when compared with the non-response group. Next to a delayed start with disease-modifying antirheumatic drugs, fast radiographic progression during the first year and first 2 years was a predictor of joint surgery in the multivariate regression analyses. CONCLUSION: Treatment with disease-modifying antirheumatic drugs immediately after diagnosis results in less joint surgery when compared with a delayed start. Furthermore, joint surgery is carried out more often in patients who do not respond to treatment.

[Diagnostic image (71). A woman with obesity, diabetes mellitus and use of corticosteroids. Mediastinal lipomatosis]. / Diagnose in beeld (71). Een vrouw met adipositas, diabetes mellitus en corticosteroïdgebruik. Mediastinale lipomatose.

In a 69-year-old obese woman on prednisone treatment for temporal arteritis a widened mediastinum on chest X-ray proved to be mediastinal lipomatosis on CT-scan.

High frequency of hysterectomies and appendectomies in fibromyalgia compared with rheumatoid arthritis: a pilot study.

We investigated, in retrospect, if there were differences in the frequency and types of abdominal surgery between newly diagnosed female fibromyalgia (n = 80) and rheumatoid arthritis (n = 47) patients performed before the formal diagnosis. There was no difference in the total number of abdominal operations between both groups. In the rheumatoid arthritis group more cholecystectomies (p = 0.01) were performed, probably due to the older age of these patients (58.5 vs 48.5 years). However, in the fibromyalgia group there were more hysterectomies (p = 0.04) and appendectomies (p = 0.05) than in the rheumatoid arthritis group.

Ileal pouch arthritis: a case report.

A patient is described with arthritis of both wrists and tendinitis of one achilles tendon in the presence of severe pouchitis. The rapid disappearance of arthritis and tendinitis after removal of the pouch strongly suggests their relationship. The pathogenesis of arthritis in pouchitis has not been elucidated but may be the same as in ulcerative colitis. Rheumatologists should be aware of the occurrence of arthritis in patients with ulcerative colitis after the construction of an ileo-anal anastomosis with a so-called pouch.

Milwaukee shoulder associated with primary hyperparathyroidism.

We describe a 69-year-old woman with a Milwaukee shoulder syndrome in the presence of primary hyperparathyroidism. After removal of a parathyroid adenoma, effusion of the shoulder did not recur. We believe that primary hyperparathyroidism and Milwaukee shoulder can be causally related.

Plasma concentration of IL-6 in systemic lupus erythematosus; an indicator of disease activity?

To investigate the possible role of IL-6 in the activation of the autoimmune process in systemic lupus erythematosus (SLE), we serially measured concentrations of IL-6, IgG, and anti-dsDNA antibodies before and during exacerbations in patients with SLE. In addition, we serially related the IL-6 response to the generation of the acute phase reactant C-reactive protein (CRP). Sixteen consecutive patients who developed an exacerbation were analysed in this study. Blood samples were drawn in EDTA monthly. At the time of maximal disease activity during exacerbation, IL-6 plasma concentrations were increased (greater than or equal to 6 pg/ml) in 12 out of the 16 cases. Concentrations of IL-6 correlated with the concentrations of CRP (P less than 0.01) and the score of the disease activity index (P less than 0.05). No correlation was found between IL-6 concentrations and concentrations of anti-dsDNA or IgG. The course of changes in IL-6 concentrations before the exacerbation was variable. Five out of the 16 exacerbations studied were characterized by a prominent rise of IL-6 at the time of maximum disease activity. In this subgroup serositis as well as elevated concentrations of CRP were observed more frequently (P less than 0.02). Seven exacerbations were not accompanied or preceded by changes in IL-6 concentrations and showed generally low IL-6 concentrations. In this latter subgroup cerebral involvement was seen more frequently (P less than 0.02). Our data do not suggest a pathogenic role for IL-6 in the generation of IgG and/or anti-dsDNA antibodies before exacerbations. Rises of IL-6 concentrations before exacerbations in SLE seem only to occur in a subgroup of patients with SLE characterized by the presence of serositis and elevated concentrations of CRP during exacerbation.

Changes in levels of antibodies against the 70 kDa and a polypeptides of the U1RNP complex in relation to exacerbations of systemic lupus erythematosus.

In order to investigate whether disease exacerbations of systemic lupus erythematosus (SLE) are accompanied or preceded by changes in antibody levels against the U1RNA associated 70 kDa and A polypeptides, we prospectively collected plasma specimens from 71 patients with SLE. We compared changes in anti-70 kDa/anti-A levels, measured by ELISA using cloned antigens, with changes in levels of anti-dsDNA and total IgG. Measurable levels of anti-70 kDa (n = 10) and/or anti-A antibodies (n = 6) were detected during 10 exacerbations. Four of the 10 exacerbations with a measurable level of anti-70 kDa antibodies were preceded by a significant rise in anti-70 kDa levels, 2 by a significant fall, while levels of anti-70 kDa did not change in the remaining 4 cases. Only one of the 6 exacerbations with detectable anti-A antibody levels was preceded by a significant rise in anti-A antibodies, while levels did not change before exacerbation in the other 5 cases. Six of the 10 exacerbations were preceded by a significant rise in anti-dsDNA; in 4 cases levels of anti-dsDNA did not change before exacerbation. In contrast to anti-dsDNA, no relation was found between changes in levels of anti-70 kDa/anti-A and changes in disease activity. Significant changes in levels of anti-70 kDa/anti-A, occurring in 6 cases, were accompanied by parallel changes in total IgG in 5 of these 6. We conclude that, in contrast to anti-dsDNA, serial measurement of levels of anti-70 kDa/anti-A is not useful for monitoring disease activity or predicting disease exacerbations in SLE.(ABSTRACT TRUNCATED AT 250 WORDS)

Shifts of anti-Sm-specific antibodies in patients with systemic lupus erythematosus: analysis by counter-immunoelectrophoresis, immunoblotting and RNA-immunoprecipitation.

We investigated serial changes in anti-Sm-specific antibodies by counter-immunoelectrophoresis (CIE), immunoblotting (IB) and RNA-immunoprecipitation (RNA-IP) in three patients with SLE. To assess the immuno-regulatory processes underlying anti-Sm antibody production, we compared changes in anti-Sm-specific antibodies with changes in titres of antinuclear and anti-ds DNA antibodies. IB and RNA-IP detected anti-Sm antibodies earlier than did CIE. The induction of the immune responses against the Sm-specific BB' and D polypeptides occurred separately in two of the three patients. Anti-Sm developed in all three cases after a flare-up of disease, whereas anti-ds DNA antibody levels fluctuated in parallel with disease activity. Thus, anti-Sm and anti-ds DNA antibody production seems to be independently regulated.

Tubular dysfunction in proliferative lupus nephritis.

We prospectively studied renal tubular function during 11 consecutive exacerbations of proliferative glomerulonephritis in 8 patients with systemic lupus erythematosus (SLE). We found a rise in the fractional excretion of beta 2-microglobulin (p less than or equal to 0.05) and dimercaptosuccinic acid (DMSA; p less than or equal to 0.02) during the exacerbations. These changes coincided with a fall in the glomerular filtration rate (p less than or equal to 0.02). Since fractional excretion of beta 2-microglobulin and DMSA can be considered as markers for tubular function, their rise during exacerbation and their fall (p less than or equal to 0.01) to control values during remission indicate that tubular dysfunction frequently occurs during active proliferative glomerulonephritis in SLE and can be influenced by immunosuppressive treatment. As no correlation was found between the different tubular function studies and the activity index of tubulointerstitial abnormalities in the renal biopsy, it is suggested that tubular function studies are probably a more sensitive indicator of tubulointerstitial disease than this activity index.

Clinical associations of antiribonucleoprotein antibodies in patients with systemic lupus erythematosus.

The authors undertook a cross-sectional study to investigate the clinical associations of antiribonucleoprotein (anti-RNP) antibodies in 49 patients with systemic lupus erythematosus (SLE) without other concomitant connective tissue disorders. The traditional counterimmunoelectrophoresis (CIE) and the immunoblotting (IB) technique were compared. Clinically, special attention was given to the identification of sclerodermalike features. All patients completed a detailed questionnaire, physical examination, and additional investigations including pulmonary function tests, chest roentgenogram, radionuclide transit studies of the esophagus, and nailfold capillary microscopy. Pulmonary function testing and radionuclide transit studies of the esophagus were very sensitive for the detection of (subclinical) pulmonary and esophageal involvement, respectively. Within the relatively homogeneous SLE population, a subset was recognized that was characterized clinically by the presence of sclerodermalike features such as Raynaud's phenomenon, sclerodactyly, interstitial changes on chest roentgenogram, and decreased numbers of nailfold capillary loops, and serologically by the presence of anti-RNP antibodies. IB was somewhat more sensitive than CIE for the detection of anti-RNP (anti-Sm/anti-nRNP) antibodies but did not identify other clinical associations. Thus, anti-RNP antibodies in SLE are associated with scleroderma-associated features. For clinical practice, CIE is the technique recommended for their detection.

Detection of autoantibodies to ribonucleoproteins by counter-immunoelectropheresis, immunoblotting and RNA-immunoprecipitation: comparison of results.

Counterimmunoelectropheresis (CIE), immunoblotting (IB) and RNA-immunoprecipitation (RNA-IP) were compared for their potential to detect antibodies to U1RNP, Sm and SS-B in sera from 50 patients with SLE and 18 with MCTD. Anti-SS-B were detected in 6 SLE-sera (12%) and one MCTD-serum (6%) by all three techniques. Anti-Sm were present in 7 SLE-sera (14%) by RNA-IP and IB; 3 of these sera showed identity with a-Sm and 4 with a-U1RNP by CIE. Antibodies precipitating U1RNA were present in 8 SLE sera (16%); 4 of these sera were positive for anti-U1RNP by CIE (8%) and 4 sera recognized one or more of the U1RNA-associated proteins by IB (8%). All MCTD-sera were positive for anti-U1RNP by RNA-IP including one serum negative by IB and CIE. RNA-IP allowed the detection of antibodies precipitating U1-U2RNA in 4 sera; in IB, the U2RNA specific protein B" was recognized by 3 sera. RNA-IP appears to be a sensitive method for detecting anti-URNP's.

Sequential development of antibodies to specific Sm polypeptides in a patient with systemic lupus erythematosus: evidence for independent regulation of anti-double-stranded DNA and anti-Sm antibody production.

We describe a patient with systemic lupus erythematosus who, after a disease flare, sequentially produced antibodies to specific Sm polypeptides (demonstrated by counterimmunoelectrophoresis, immunoblotting, and RNA immunoprecipitation) concomitantly with the disappearance of anti-double-stranded DNA antibodies. Immunoblotting studies revealed that antibodies to the D polypeptide appeared first, followed by antibodies to BB' and E polypeptides, respectively. Our findings suggest that antibodies to the Sm-specific polypeptides do not occur simultaneously and that the regulation of their production is independent of that of antibodies to double-stranded DNA.