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.

Spontaneous ankylosis in erosive osteoarthritis of the finger joints: a case series of eight postmenopausal women.

Osteoarthritis of the hands is very common, particularly in elderly people. Little is known though, is the subset of erosive osteoarthritis (EOA), which predicts a poorer prognosis and causes much more discomfort. Even less known is the fact that this subset can evolve into spontaneous ankylosis. We describe eight women (average age 62.6, range 54-74 years) with EOA and spontaneous ankylosis of the proximal interphalangeal (PIP) and/or distal interphalangeal (DIP) joints. In total, 21 PIP joints (0-7 per patient) were found with EOA and nine PIP joints (0-3 per patient) with ankylosis. In one patient, ankylosis of the PIP was already seen at the first presentation. In the other cases, it took an average of 77.4 months (range 34-119) for EOA to develop into ankylosis of the PIP. For DIP joints, the numbers were 17 joints (1-4 per patient) with EOA and three joints (0-1 per patient) with ankylosis, respectively. In one patient, ankylosis of the DIP was already seen at the first presentation. Ankylosis was found significantly more often on the left hand (n = 10) compared to the right hand (n = 2; p < 0.0005), while all the patients were right handed. No difference in handedness was found for the occurrence of EOA. Although rare, PIP or DIP joint with EOA can-over the course of several painful years-develop into a spontaneous pain-free ankylosis. Ankylosis was more commonly found in the left hand than in the right hand, probably due right handedness.

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.

An index for breathlessness and leg fatigue.

The features of perceived symptoms causing discontinuation of strenuous exercise have been scarcely studied. The aim was to characterize the two main symptoms causing the discontinuation of heavy work in healthy persons as well as describe the growth of symptoms during exercise. Breathlessness (b) and leg fatigue (l) were assessed using the Borg CR10 Scale and the Borg CR100 (centiMax) Scale, during a standardized exercise test in 38 healthy subjects (24-71 years). The b/l-relationships were calculated for terminal perceptions (ERI(b/l)), and the growth of symptoms determined by power functions for the whole test, as well as by growth response indexes (GRI). This latter index was constructed as a ratio between power levels corresponding to a very strong and a moderate perception. In the majority (71%) of the test subjects, leg fatigue was the dominant symptom at the conclusion of exercise (P<0.001) and the b/l ratio was 0.77 (CR10) and 0.75 (CR100), respectively. The GRI for breathlessness and leg fatigue was similar, with good correlations between GRI and the power function exponent (P<0.005). In healthy subjects, leg fatigue is the most common cause for discontinuing an incremental exercise test. The growth functions for breathlessness and leg fatigue during work are, however, almost parallel.

Candidate gene association study for noise-induced hearing loss in two independent noise-exposed populations.

Millions of people are daily exposed to high levels of noise. Consequently, noise-induced hearing loss (NIHL) is one of the most important occupational health hazards worldwide. In this study, we performed an association study for NIHL based on a candidate gene approach. 644 Single Nucleotide Polymorphisms (SNPs) in 53 candidate genes were analyzed in two independent NIHL sample sets, a Swedish set and part of a Polish set. Eight SNPs with promising results were selected and analysed in the remaining part of the Polish samples. One SNP in PCDH15 (rs7095441), resulted in significant associations in both sample sets while two SNPs in MYH14 (rs667907 and rs588035), resulted in significant associations in the Polish sample set and significant interactions with noise exposure level in the Swedish sample set. Calculation of odds ratios revealed a significant association of rs588035 with NIHL in the Swedish high noise exposure level group. Our studies suggest that PCDH15 and MYH14 may be NIHL susceptibility genes, but further replication in independent sample sets is mandatory.

Rituximab in life threatening antisynthetase syndrome.

This case study reports a patient with severe interstitial pneumonitis, mild polyarthritis and polymyositis, accompanied by the presence of anti-Jo-1 antibodies diagnosed as antisynthetase syndrome. The concurrence of anti-Jo-1 with anti-Ro/SSA antibodies leads to a more severe form of interstitial lung disease. This patient was referred to our hospital because of life threatening respiratory failure. He was refractory to glucocorticoids and cyclophosphamide, but was successfully treated with two sequential infusions of rituximab. Clinical condition improved very rapidly. Response to treatment was well correlated with a fall of levels of serum soluble IL2-receptor. A decrease in pulmonary disease activity was visualized on PET-scans before and after two sequential rituximab infusions.

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.

Nocardiosis: a case series and a mini review of clinical and microbiological features.

Infections caused by Nocardia species are uncommon and have a wide variety of clinical manifestations in immunocompetent and immunocompromised patients. The diagnosis of nocardiosis can easily be missed because there are no characteristic symptoms. We present one case of a Nocardia infection in detail and give a brief description of eight other cases, including a relatively unique type of Nocardia veterana, diagnosed in our hospital during a five-year period. The diversity of clinical manifestations, microbiological identification and general principles of treatment of nocardiosis are reviewed.

Extremely high serum ferritin levels as diagnostic tool in adult-onset Still's disease.

The diagnosis of adult-onset Still's disease (ASD) is difficult to establish due to the nonspecific clinical and laboratory findings. A markedly raised serum ferritin level is a typical finding, although it is not well understood why ferritin levels are extremely high in ASD. We discuss several possible explanations leading to the extremely high levels of ferritin.

Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial).

BACKGROUND: To investigate whether intensive treatment with methotrexate (MTX) according to a strict protocol and a computerised decision program is more beneficial compared to conventional treatment with MTX in early rheumatoid arthritis. METHODS: In a two-year multicentre open label strategy trial, 299 patients with early rheumatoid arthritis were randomly assigned to the intensive strategy group or the conventional strategy group. Patients in both groups received MTX, the aim of treatment being remission. Patients in the intensive treatment group came to the outpatient clinic once every month; adjustment of the MTX dosage was tailored to the individual patient on the basis of predefined response criteria, using a computerised decision program. Patients of the conventional strategy group came to the outpatient clinic once every three months; they were treated according to common practice. Cyclosporine was added if patients had an inadequate response to maximal tolerated MTX doses. RESULTS: Seventy six (50%) patients in the intensive strategy group achieved at least one period of remission during the two year trial, versus 55 patients (37%) in the conventional strategy group (p = 0.03). Areas under the curve for nearly all clinical variables were significantly lower-that is, there was a better clinical effect for the intensive treatment group compared with the conventional treatment group. CONCLUSION: The results of this study show that it is possible to substantially enhance the clinical efficacy early in the course of the disease by intensifying treatment with MTX, aiming for remission, tailored to the individual patient. Furthermore, participating rheumatologists indicated that the computerised decision program could be a helpful tool in their daily clinical practice.

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.

A comparison between three rating scales for perceived exertion and two different work tests.

In the present article, three scales developed by Borg are compared on bicycle ergometer work. In the first study, comparing the Borg Ratings of Perceived Exertion (RPE) and Category scales with Ratio properties (CR10) scales, 40 healthy subjects (12 men and eight women for each scale) with a mean age of about 30 years (SD approximately 6) participated. A work-test protocol with step-wise increase of work loads every minute was used (20 W increase for men and 15 W for women). Ratings and heart rates (HRs) were recorded every minute and blood lactates every third minute. Data obtained with the RPE scale were described with linear regressions, with individual correlations of about 0.98. Data obtained with the CR10 scale could also be described by linear regressions, but when described by power functions gave exponents of about 1.2 (SD approximately 0.4) (with one additional constant included in the power function). This was significantly lower than the exponent of between 1.5 and 1.9 that has previously been observed. Mean individual correlations were 0.98. Blood lactate concentration grew with monotonously increasing functions that could be described by power functions with a mean exponent of about 2.6 (SD approximately 0.6) (with two additional constants included in the power functions). In the second study, where also the more recently developed Borg CR100 scale (centiMax) was included, 24 healthy subjects (12 men and 12 women) with a mean age of about 29 years (SD approximately 3) participated in a work test with a step-wise increase of work loads (25 W) every third minute. Ratings and HRs were recorded. RPE values were described by linear regressions with individual correlations of about 0.97. Data from the two CR scales were described by power functions with mean exponents of about 1.4 (SD approximately 0.5) (with a-values in the power functions). Mean individual correlations were about 0.98. In both studies, a tendency for a deviation from linearity between RPE values and HRs was observed. The obtained deviations from what has previously been obtained for work of longer duration (4-6 min) points to a need for standardization of work-test protocols and to the advantage of using CR scales.

[A patient with sclerosing autoimmune pancreaticocholangitis as the cause of recurrent cholangitis following a pylorus-sparing pancreaticoduodenectomy]. / Een patient met scleroserende auto-immune pancreaticocholangitis als oorzaak van recidiverende cholangitis na pylorussparende pancreaticoduodenectomie.

A pylorus-sparing pancreaticoduodenectomy was performed in a 67-year-old man because of indications for a carcinoma of the distal common bile duct. Histology of the postoperative specimen, however, revealed a sclerosing inflammation of the distal common bile duct and the surrounding pancreatic parenchyma. Initial postoperative recovery was followed by recurrent cholangitis. Stenosis of the choledocho-jejunostomy could not be demonstrated. Instead, repeated endoscopic retrograde cholangiopancreaticography revealed extensive sclerosis of the intrahepatic bile ducts, which suggested a sclerosing cholangitis associated with an autoimmune pancreatitis: sclerosing autoimmune pancreaticocholangitis. This disorder was recently described; it is characterised by a disorder in the pancreas that is indistinguishable from malignancy by imaging techniques and that is followed by a sclerosing inflammation of the bile ducts. The disease responds well to steroids. The patient described demonstrated a complete clinical and biochemical recovery after initiation ofprednisone therapy.

[Favourable effect of lacrimal plugs after 3 and 9 months in 20 patients with severe sicca syndrome]. / Gunstig effect van traanbuispluggen bij 20 patiënten met ernstig siccasyndroom na 3 en na 9 maanden.

OBJECTIVE: To describe the results of the insertion of lacrimal plugs in patients with severe symptoms of dry eyes. DESIGN: Prospective descriptive study. METHOD: 20 patients who had severe symptoms of dry eyes despite topical therapy were included. The diagnoses were: 'primary Sjögren's syndrome' (n = 10), 'probably a primary Sjögren's syndrome' (n = 5) and 'secondary Sjögren's syndrome' (n = 5). Following a favourable subjective reaction to resorbable plugs, a non-resorbable silicone plus was inserted bilaterally into the openings of the inferior lacrimal ducts. During follow-up, the effect of treatment was assessed by means of various measurements of function of the lacrimal glands. RESULTS: After 3 and 9 months there was a measurable favourable effect with regard to tear production (Schirmer-test), tear film stability ('tear film break-up time'), the damage to the cornea (Bengal-red-test) and the subjective symptoms of dry eye on a visual analogue scale (VAS). The difference in comparison with the initial values was significant except for the Bengal-red-test after 9 months. There were no complications. In the 5 patients with a basal Schirmer test value of o mm after 5 min, there was no improvement.

Long-term effects of integrated rehabilitation in patients with advanced angina pectoris: a nonrandomized comparative study.

OBJECTIVES: An evaluation of Integrative Rehabilitation (IR) of patients with angina pectoris with respect to death rate, the need for invasive treatment, and cost effectiveness. DESIGN: A report from a clinical database. Death rates were compared to those of the general Danish population matched for age, gender, and observation period, as well as with data from the literature concerning medical and invasive treatments. SETTING: The treatment was carried out as an ambulatory treatment in a private clinic. SUBJECTS: One hundred and sixty-eight (168) patients with angina pectoris, of whom 103 were candidates for invasive treatment and 65 for whom this had been rejected. INTERVENTIONS: Integrated rehabilitation consists of acupuncture, a self-care program including acupressure, Chinese health philosophy, stress management techniques, and lifestyle adjustments. OUTCOME MEASURES: Death rate from any cause, the need for invasive treatment, and health care expenses. RESULTS: The 3-year accumulated risk of death was 2.0% (95% confidence limits: 0.0%-4.7%) for the 103 candidates for invasive treatment, 6.4% for the general Danish population, 5.4% (4.7%-6.1%), and 8.4% (7.7%-9.1%) for patients who underwent percutaneous transluminal balloon angioplasty and coronary artery bypass grafting, respectively, in New York. For the 65 inoperable patients the risk of death due to heart disease was 7.7% (3.9%-11.5%), compared to 16% (10%-34%) and 25% (18%-36%) for American patients, who were treated with laser revascularization or medication, respectively. Of the 103 candidates for invasive treatment, only 19 (18%) still required surgery. Cost savings over 3 years were US 36,000 dollars and US 22,000 dollars for surgical and nonsurgical patients, respectively. These were mainly achieved by the reduction in the use of invasive treatment and a 95% reduction in in-hospital days. CONCLUSIONS: Integrated rehabilitation was found to be cost effective, and added years to the lives of patients with severe angina pectoris. The results invite further testing in a randomized trial.