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).

A good response to early DMARD treatment of patients with rheumatoid arthritis in the first year predicts remission during follow up.

OBJECTIVE: To describe the frequency and duration of remission in the Utrecht rheumatoid arthritis cohort of patients followed since diagnosis, and the clinical and treatment characteristics of patients with remission v those without. METHODS: In 1990 the Utrecht rheumatoid arthritis cohort study group started a clinical trial in which patients with recent onset of rheumatoid arthritis (<1 year) were randomised into four treatment groups: hydroxychloroquine (n = 169); intramuscular gold (n = 163); methotrexate (n = 166); and pyramid (n = 64). After two years, rheumatologists were allowed to prescribe any disease modifying antirheumatic drug. Remission was defined as: duration of morning stiffness < or =15 min, mean VAS pain < or =10 mm, Thompson joint score < or =10, and ESR < or =30 mm/h during at least six months. Cox regression analysis was used to determine baseline clinical, demographic, and treatment predictors of remission. RESULTS: Mean follow up duration was 62 months. Thirty six per cent achieved at least one period of remission. Median duration between diagnosis and the first remission period was 15 months for the intramuscular gold group, 18 months for the methotrexate and hydroxychloroquine groups, and 24 months for the pyramid group (NS). Predictors of remission were early response to initial treatment, less pain, rheumatoid factor negativity, and lower joint score at baseline. CONCLUSIONS: After a mean follow up duration of 62 months, only 36% of the patients had fulfilled the remission criteria at least once. A good response to treatment during the first year seems to be independently associated with remission rather than initial treatment alone.

[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.

Treatment of primary Sjögren's syndrome with D-penicillamine: a pilot study.

BACKGROUND: Up to now no satisfying systemic treatment is available for patients with primary Sjögren's syndrome. METHODS: In a prospective, open study we investigated the effect of D-penicillamine (first three months 250 mg/day, next three months 500 mg/day) on clinical and immunological parameters in 19 patients with primary Sjögren's syndrome and a mean disease duration of 3.8 years. RESULTS: Eight patients had to stop treatment mainly due to severe (reversible) loss of taste. Clinically, a statistically significant increase in basal salivary flow was observed after three months (p<0.05). In addition, improvement was noted in the Schirmer test and stimulated parotid salivary flow after six months, but these differences were not statistically significant. Laboratory values showed a decrease in ESR (p<0.05) and levels of IgA and IgM (both p<0.02) after six months, a decrease in levels of IgA-Rf and IgM-Rf after three months (both p<0.05), and an increase in haemoglobin level (p<0.05). CONCLUSION: From this pilot study we conclude that the treatment of primary Sjögren's syndrome with D-penicillamine has only marginal beneficial effects. Together with its clear side effects this means that D-penicillamine is unsuitable for this indication.

Aggressive treatment in early rheumatoid arthritis: a randomised controlled trial. On behalf of the Rheumatic Research Foundation Utrecht, The Netherlands.

OBJECTIVES: To compare three therapeutic strategies using slow acting antirheumatic drugs (SAARDs) in early rheumatoid arthritis (RA), for their disease modifying properties, toxicity, and lag time until treatment effect. METHODS: Patients with recent onset RA from six hospitals were randomly assigned to immediate initiation of one of three treatment strategies: (I) a "mild SAARD with a long lag time" (hydroxychloroquine, if necessary replaced by auranofin); (II) a "potent SAARD with a long lag time" (intramuscular gold, if necessary replaced by D-penicillamine); (III) a "potent SAARD with a short lag time" (methotrexate, if necessary replaced by sulfasalazine). Comparisons included two years of follow up. RESULTS: All SAARD strategies reduced mean disease activity. A greater percentage of patients improved clinically with strategies II and III than with strategy I: percentages of patients improved on joint score with strategies II and III (79% and 82%, respectively), which was statistically different from strategy I (66%). The same was true for remission percentages: 31% and 24% v 16%, respectively). Longitudinal analysis showed significantly less disability with strategy III, and a lower erythrocyte sedimentation rate with strategy II than with strategy I. In addition, radiological damage after one and two years, was significantly lower in strategies II and III (at two years median scores were 11 and 10 v 14 in strategy I, p<0.05). Toxicity was increased in strategy II compared with the other strategies. CONCLUSION: Strategy III, comprising methotrexate or sulfasalazine, produced the best results weighing effectiveness and toxicity. Strategy I (hydroxychloroquine or auranofin) was slightly less effective, and strategy II (intramuscular gold or D-penicillamine) was associated with increased toxicity.

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.

Direct cost of rheumatoid arthritis during the first six years: a cost-of-illness study.

The objective was to estimate the annual direct disease-related cost of rheumatoid arthritis (RA) during the first 6 yr and to determine which socio-demographic and clinical characteristics relate to these costs. The study population consisted of 424 RA patients who had participated in a (population-based) trial on therapeutic strategies for early RA since 1990 and were not lost to follow-up in April 1996. A questionnaire on costs due to RA was sent to these patients; 363 (86%) completed questionnaires were analysed. The total annual direct cost per patient was estimated by adding up the costs of health care workers, days admitted to care facilities, medication, monitoring for side-effects, alternative medicine, adaptations in the home, devices, and other direct costs such as travelling expenses. The mean annual direct cost due to RA was estimated to be Dfl. 11,550 per patient. An obvious increase in direct cost with increasing disease duration was not found. Patients with higher disease activity exhibited significantly higher costs compared to patients with lower disease activity. A multiple logistic regression model showed that greater disability and lower age increased the odds for high costs. The annual direct cost of RA averaged out at Dfl. 11,550 per patient (i.e. Pound Sterling 3680). A high total direct cost in the first 6 yr of disease is related to severe functional disability and lower age.

Cerebellitis as an uncommon complication of infectious mononucleosis.

Cerebellitis is an uncommon complication of infectious mononucleosis. We describe such a patient with infectious mononucleosis and cerebellitis as a major feature of a more global encephalitis. In the discussion the cerebral complications are reviewed.

Is addition of sodium fluoride to cyclical etidronate beneficial in the treatment of corticosteroid induced osteoporosis?

OBJECTIVE: To investigate whether administration of sodium fluoride (NaF) in addition to cyclical etidronate has a positive effect on bone mineral density (BMD) in patients with established osteoporosis during continued treatment with corticosteroids. PATIENTS AND METHODS: 47 patients who were receiving treatment with corticosteroids were included in a two year randomised, double blind, placebo controlled trial. Established osteoporosis was defined as a history of a peripheral fracture or a vertebral deformity, or both, on a radiograph. All patients were treated with cyclical etidronate, calcium, and either NaF (25 twice daily) or placebo. Vitamin D was supplemented in the case of a low serum 25 (OH) vitamin D concentration. BMD of the lumbar spine and hips was measured at baseline and at 6, 12, 18, and 24 months. RESULTS: After two years of treatment, the BMD of the lumbar spine in the etidronate/NaF group had increased by +9.3% (95% confidence intervals (CI): +2.3% to +16.2%, p < 0.01), while the BMD in the etidronate/placebo group was unchanged: +0.3% (95% CI: -2.2% to +2.8%). The difference in the change in BMD between groups was +8.9% (95% CI: +1.9% to +16.0%, p < 0.01). For the hips, no significant changes in BMD were observed in the etidronate/NaF group after two years: -2.5% (95% CI: -6.8% to +1.8%); in the etidronate/placebo group BMD had significantly decreased: -4.0% (95% CI: -6.6% to -1.4%; p < 0.01). The difference between the groups was not significant: +1.5% (95% CI: -3.4% to +6.4%). No significant differences in number of vertebral deformities and peripheral fractures were observed between the two groups. CONCLUSION: The effect of combination treatment with NaF and etidronate on the BMD of the lumbar spine in corticosteroid treated patients with established osteoporosis is superior to that of etidronate alone.

Aortitis, aortic valve incompetence, and left coronary ostium stenosis in a patient with C-ANCA-associated necrotizing vasculitis.

Aortitis with involvement of the aortic valve is rarely associated with vasculitis syndromes. We present a patient with antibodies to a neutrophil cytoplasmic antigen-associated (ANCA) vasculitis with renal failure who developed aortic incompetence as a result of aortitis which involved the aortic valve. Thickening of the aortic wall also caused stenosis of the left coronary ostium.

Effect of sodium fluoride on the prevention of corticosteroid-induced osteoporosis.

To investigate whether sodium fluoride (NaF) is able to prevent bone loss in patients treated with corticosteroids (Cs), we performed a randomized double-masked, placebo-controlled trial with 44 Cs-treated patients without established osteoporosis, defined as the absence of previous peripheral fractures and vertebral deformities on radiographs. The effects of NaF (25 mg twice daily) and placebo on the bone mineral density (BMD) of the lumbar spine and hips were compared at baseline and at 6, 12, 18 and 24 months. After 2 years, the BMD of the lumbar spine had decreased in the placebo group by 3.0% (95% CI: -4.9% to -1.0%; p < 0.01); in the NaF group there was a statistically insignificant increase in BMD of 2.2% (95% CI: -0.8% to +5.3%). The difference in the changes in BMD between the two groups was +5.2% (95% CI: +1.8% to +8.6%; p < 0.01). In the hips, BMD had decreased after 2 years in both groups: in the placebo group by -3.0% (95% CI: -5.0% to -1.0%; p < 0.05) and in the NaF group by 3.8% (95% CI: -6.1% to -1.5%; p < 0.01). The difference in the changes in BMD between the two groups was not significant: +0.8% (95% CI: -2.1% to +3.8%). Three vertebral deformities were observed in the placebo group and one in the NaF group (insignificant difference), while no peripheral fractures occurred during the study period. It is concluded that in Cs-treated patients without established osteoporosis NaF prevents bone loss in the lumbar spine but does not have a positive effect on the BMD of the hips.

The effectiveness of early treatment with "second-line" antirheumatic drugs. A randomized, controlled trial.

OBJECTIVE: To compare two therapeutic strategies for patients with recent-onset rheumatoid arthritis. DESIGN: Open, randomized clinical trial. SETTING: Outpatient clinics of six clinical centers. PATIENTS: 238 consecutive patients with recently diagnosed rheumatoid arthritis. INTERVENTIONS: Delayed or immediate introduction of treatment with slow-acting antirheumatic drugs (SAARDs). MEASUREMENTS: Primary end points were functional disability, pain, joint score, and erythrocyte sedimentation rate at 6 and 12 months and progression of radiologic abnormalities at 12 months. RESULTS: Statistically significant advantages at 12 months for patients receiving the SAARD strategy (immediate treatment with SAARDs) with regard to all primary end points that may be clinically important are indicated by the differences in improvements from baseline and their 95% CIs. These differences were 0.3 (95% CI, 0.2 to 0.6) for disability (range, 0 to 3), 10 mm (CI, 1 to 19 mm) for pain (range, 0 to 100 mm), 39 (CI, 4 to 74) for joint score (range, 0 to 534), and 11 mm/h (CI, 3 to 19 mm/h) for erythrocyte sedimentation rate (range, 1 to 140 mm/h), all in favor of SAARD treatment. The SAARD strategy also appears to be advantageous at 6 months. Radiologic abnormalities progressed at an equal rate in the SAARD and the non-SAARD groups; the difference in progression (range, 0 to 448) was 1 (CI, -3 to 5). Analyses were based on the intention-to-treat principle and thus included 29% of patients in the non-SAARD group who discontinued the non-SAARD treatment strategy; treatment was usually discontinued because of insufficient effectiveness. The SAARD strategy including two alternative SAARDs could not be continued by 8% of patients, usually because of adverse reactions. CONCLUSIONS: Early introduction of SAARDs may be more beneficial than delayed introduction for patients with recently diagnosed rheumatoid arthritis.

Is it possible to predict the first year extent of pain and disability for patients with rheumatoid arthritis?

OBJECTIVE: To investigate prediction of the extent of suffering during the first year of rheumatoid arthritis (RA) with patient characteristics found to be capable of predicting short term or longterm endpoint disability. METHODS: Ninety-five patients with recently diagnosed RA, participating in a prospective clinical trial, were seen every 3 mo during 1 year. The 12 month and cumulative values of disability (Dutch version of the Health Assessment Questionnaire) and pain (visual analog scale) were related to demographic, clinical, laboratory, and psychological mood variables in correlation and regression analyses. RESULTS: Baseline values of disability and pain were related most strongly to 12 mo and cumulative values of disability; baseline pain was virtually the only important predictor of 12 mo and cumulative pain. Other baseline characteristics had virtually no additional predictive power. CONCLUSION: The short term disease course of RA in terms of disability and pain is most strongly related to the baseline values of these variables, and cannot reliably be predicted with frequently recognized longterm prognostic factors, such as rheumatoid factor status or sex.

[Chronic arthralgia: not a precursor of rheumatoid arthritis, but part of fibromyalgia syndrome]. / Chronische artralgie: geen voorbode van reuma, maar onderdeel van het fibromyalgiesyndroom.

OBJECTIVE: To determine the characteristics and the course of chronic arthralgia (CA) and the differences from newly diagnosed rheumatoid arthritis (RA). DESIGN: Retrospective, with a follow up after 2.5 years. SETTING: Outpatient clinic for rheumatology of the St. Antonius Hospital, Nieuwegein, The Netherlands. METHOD: The diagnosis of CA was made in the period of June 1986-December 1988 in 74 patients. The CA patients were sent a questionnaire after a mean of 2.5 years and invited for another rheumatological examination; 62 patients responded (84%). Data were compared with all 52 RA patients newly diagnosed in the same period by the same specialist. RESULTS: At the first visit CA had been present for 1 year, RA patients had had complaints for 0.6 years (p = 0.02). The RA patients had elevated BSE rates more often (31 vs. 8 mm in CA) (p < 0.0001) and more serious morning stiffness (75 vs. 0 minutes in CA) (p < 0.0001). The diagnosis of RA was made at the first visit in 86% and in 96% within half a year later. None of the CA patients developed an inflammatory joint disease within 2.5 years. In 1 out of 3 CA patients the diagnosis of fibromyalgia was made and more than 50% had complaints. CONCLUSIONS: CA for more than 3 years does not predict inflammatory rheumatic disease. In contrast, RA develops in a short period and the diagnosis is made in 96% within 1 year. CA can be considered a feature of the fibromyalgia syndrome.

Familial IgG subclass imbalance, anti-SS-A antibodies and third-trimester foetal death.

Foetal heart block occurred in the second pregnancy of an apparently healthy 23-yr-old woman. Her mother and sister were known for 10 yr with hypergammaglobulinaemia which was due to a disproportionate polyclonal elevation of serum IgG1 and with a high titre of rheumatoid factors. No associated disease was obvious. A third-trimester foetal death had occurred with each of these patients. In the sera of these three women circulating anti-SS-A (Ro) antibodies were detected, which are known to be associated with congenital heart block. IgG subclass imbalance, consisting of a disproportionate polyclonal elevation of IgG1, has been recognised as being associated with a characteristic autoantibody pattern. Familial occurrence of this syndrome as such has hitherto not been reported.

Controlled trial of hypnotherapy in the treatment of refractory fibromyalgia.

In a controlled study, 40 patients with refractory fibromyalgia were randomly allocated to treatment with either hypnotherapy or physical therapy for 12 weeks with followup at 24 weeks. Compared with the patients in the physical therapy group, the patients in the hypnotherapy group showed a significantly better outcome with respect to their pain experience, fatigue on awakening, sleep pattern and global assessment at 12 and 24 weeks, but this was not reflected in an improvement of the total myalgic score measured by a dolorimeter. At baseline most patients in both groups had strong feelings of somatic and psychic discomfort as measured by the Hopkins Symptom Checklist. These feelings showed a significant decrease in patients treated by hypnotherapy compared with physical therapy, but they remained abnormally strong in many cases. We conclude hypnotherapy may be useful in relieving symptoms in patients with refractory fibromyalgia.

Distal renal tubular acidosis in polyarteritis nodosa.

Distal renal tubular acidosis developed in a patient with polyarteritis nodosa. The acidosis gradually disappeared, together with most of the other symptoms of systemic vasculitis, after treatment with prednisone and cyclophosphamide. Tubular function test results in this patient suggested that the mechanism underlying the acidification disturbance was acid back-leakage.