Malignancy in scleroderma patients from south west England: a population-based cohort study.

The pathophysiological relationship between scleroderma and malignancy remains poorly understood. Although some previous studies have demonstrated an increased malignancy risk in patients with scleroderma, others have been inconclusive. We aimed to determine if patients with scleroderma had an increased risk of malignancy compared to an age- and sex-matched local South West England population, and if there were any important differences between scleroderma patients with and without malignancy. Methods of this study are as follows. Notes were obtained on all local scleroderma patients (n = 68) locally, and those diagnosed with malignancy verified by contacting each patient's general practitioner. Expected malignancy figures were obtained from age- and sex-stratified regional prevalence data provided by the South West Cancer Intelligence Service registry. Among the patients, 22.1% with scleroderma were identified with concurrent malignancy. Affected sites were of the breast (n = 5), haematological system (n = 5), skin (n = 4), and unknown primary (n = 1). Overall, malignancy risk was found to be increased in scleroderma (RR = 3.15, 95% CI 1.77-5.20, p = 0.01). In particular, this risk was the highest for haematological malignancies (RR = 18.5, 95% CI 6-43, p = 0.03), especially for non-Hodgkin's lymphoma (RR = 25.8, 95% CI 5-75, p = 0.10). The majority of patients (86.7%) developed malignancy after the onset of scleroderma (mean = 6.9 years). Age of >70 and patients with limited scleroderma were significant risk factors for a patient with scleroderma to have a concurrent malignancy; however, no increased risk was found in patients with any particular pattern of organ involvement, cytotoxic usage or serology. To conclude, in this small patient cohort, we have found that scleroderma is associated with an increased risk of malignancy. This risk is statistically significant in patients with limited scleroderma. Patients who are elderly and those with limited disease should be closely scrutinized at follow-up appointments.

Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts.

OBJECTIVES: To assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early rheumatoid arthritis (RA) inception cohorts with a focus on methotrexate (MTX) exposure. DESIGN: Multicentre prospective early RA inception cohort studies; the early RA study (ERAS) and the early RA network (ERAN). SETTING: Secondary care, ERAS nine centres, ERAN 23 centres in England, Wales and Ireland. PARTICIPANTS: Patients with new diagnosis of RA, n=2701. Standardised data including demographics, drug therapies and clinical outcomes including the presence of RA-ILD were collected at baseline, within 3-6 months, at 12 months and annually thereafter. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the association of MTX exposure on RA-ILD diagnosis. Secondary outcomes were the association of demographic, comorbid and RA-specific factors on RA-ILD diagnosis and the association of MTX exposure on time to RA-ILD diagnosis. RESULTS: Of 92 eligible ILD cases, 39 occurred in 1578 (2.5%) MTX exposed and 53 in 1114 (4.8%) non-MTX exposed cases. The primary analysis of RA-ILD cases only developing after any conventional synthetic disease-modifying antirheumatic drug treatment (n=67) showed MTX exposure not to be associated with incident RA-ILD (OR 0.85, 95% CI 0.49 to 1.49, p=0.578) and a non-significant trend for delayed ILD diagnosis (OR 0.54, 95% CI 0.28 to 1.06, p=0.072). In an extended analysis including RA-ILD cases present at RA diagnosis (n=92), MTX exposure was associated with a significantly reduced risk of incident RA-ILD (OR 0.48, 95% CI 0.3 to 0.79, p=0.004) and longer time to ILD diagnosis (OR 0.41, 95% CI 0.23 to 0.75, p=0.004). Other independent baseline associations with incident RA-ILD were higher age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first outpatient visit. CONCLUSIONS: MTX treatment was not associated with an increased risk of RA-ILD diagnosis. On the contrary, evidence suggested that MTX may delay the onset of ILD.

The relationship between psychosocial variables and pain reporting in osteoarthritis of the knee.

Psychosocial factors may explain some of the variation in pain reporting among individuals with knee OA. This has important potential implications for management; indeed, several studies (reviewed in ref. 56) have demonstrated that interventions may reduce knee pain without apparent halting or reversing of structural damage. Such interventions have included the simple provision of support by monthly telephone calls (57), self-management programs (58), and cognitive-behavioral approaches designed to teach patients ways of coping with their pain (59). These programs are even more effective if the spouse is involved (60). It should be noted that there may be a large placebo effect in these interventions, and the degree to which patients are responding simply to an interest being taken in them and their problems is unclear; at least one study has shown that formal cognitive-behavioral therapy is no better than didactic education at improving pain and function in knee OA (though both are beneficial) (61). Many studies examining the role of psychosocial factors have suffered from poor design; many, for example, fail to control for radiographic severity. Future studies should define how pain is identified (dichotomous, ever/never/current, severity), differentiate community and hospital subjects, and separate patients by type and location of OA. Studies should also control for other factors potentially associated with pain: obesity, comorbidity, muscle weakness, and aerobic fitness. Prospective studies would allow clarification of the cause and effect relationship between anxiety, depression, and pain, both in the community and in patients who have elected to seek medical help. In this way, we may increase our understanding of the complex interaction between mood, social factors, and pain reporting in knee OA and, thus, improve the effectiveness, already equivalent to many pharmacologic interventions, of treatments designed to address psychosocial factors.

Sustained improvement produced by nonpharmacologic intervention in fibromyalgia: results of a pilot study.

OBJECTIVE: The aim of this pilot study was to examine the practicality of delivering a package of nonpharmacologic, behavioral-based treatment, previously found to be effective in chronic back pain, to patients with fibromyalgia (FM) and to assess the efficacy of the intervention using a range of outcome measures up to 4 months posttreatment. METHODS: Participants with FM (n = 28) formed a single group for 8 sessions at weekly intervals. Each session comprised an education/cognitive-behavioral component, formal relaxation/meditation training, and instruction in a Chinese movement therapy (Qi Gong). RESULTS: Twenty of 28 subjects completed at least 5 of the 8 sessions. Significant improvement was seen in the Fibromyalgia Impact Questionnaire and a range of other outcome measures including tender points and pain threshold. Improvement was sustained 4 months after the end of the intervention. CONCLUSION: A simple behavioral intervention using large groups can be administered to subjects with FM and appears to produce sustained benefit in a range of outcomes. Controlled trials are currently being planned.

The relationship of anxiety and depression with self-reported knee pain in the community: data from the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To investigate the relationship between anxiety and depression and reporting of knee pain in the community. METHODS: Subjects (n = 374) were community volunteers aged 40 years and above who are participants in the Baltimore Longitudinal Study of Aging, a prospective multidisciplinary research study of normative aging. Knee pain was defined by the First National Health and Nutrition Examination Survey question "have you ever had pain in or around your knee on most days for at least one month?"; anxiety and depression were measured by the relevant subscales of the Arthritis Impact Measurement Scales questionnaire. All subjects had standing anteroposterior radiographs, read for Kellgren and Lawrence (K + L) grade. RESULTS: After adjustment for age, women reporting "ever" knee pain had significantly higher anxiety scores than those reporting "never" pain (3.06 +/- 0.26 versus 2.35 +/- 0.17; P = 0.025). Pain reporting was related neither to anxiety scores in men, nor to depression in either sex. Analysis stratified by radiographic severity, adjusted for age and gender, showed that differences in anxiety were confined to those reporting knee pain in the absence of radiographic change (i.e., K + L grade 0). CONCLUSIONS: In the community, women reporting knee pain in the absence of radiographic osteoarthritis have higher anxiety scores than those without pain. Depression was not significantly related to knee pain in this population. Psychosocial factors may explain some of the discrepancy between reported knee pain and structural change as seen on x-ray.

Management of osteoarthritis in older adults.

Management of osteoarthritis (OA) is directed primarily towards relief of pain and functional limitation. This article discusses a range of nonpharmacologic modalities, including education, social support, weight reduction, and exercise. Drug treatment should begin with adequate doses of acetaminophen. Guidelines for appropriate use of NSAIDs also are suggested in this article. Intraarticular steroids help a proportion of patients, particularly those with OA of the knee or thumb base; the role of intraarticular therapies remains uncertain. Surgery (total joint replacement) remains an excellent treatment for patients in whom medical treatment has failed to provide adequate symptom relief. Future developments are likely to include earlier intervention using drugs with the potential to modify the course of the disease.

A pilot study of cognitive behavioral therapy in fibromyalgia.

BACKGROUND: Fibromyalgia is a syndrome characterized by widespread musculoskeletal pain and multiple tender points as well as high levels of self-reported disability and poor quality of life. OBJECTIVES: In this pilot study, a mind-body approach (cognitive-behavioral therapy) was tested that has been successful in treating chronic back pain patients to determine whether it would improve function, decrease perceived pain, and improve mood state for fibromyalgia patients. PARTICIPANTS: 28 patients recruited from the greater Baltimore area. INTERVENTION: Eight weekly sessions, 2 1/2 hours each, with three components: an educational component focusing on the mind-body connection, a portion focusing on relaxation response mechanisms (primarily mindfulness meditation techniques), and a qigong movement therapy session. MAIN OUTCOME MEASURES: Data collection instruments were the Fibromyalgia Impact Questionnaire, the Health Assessment Questionnaire, the Beck Depression Inventory, the Coping Strategies Questionnaire, the helplessness subscale of the Arthritis Attitudes Index, the Medical Outcomes Study Short Form General Health Survey, and a double-anchored 100-mm visual analog scale to assess sleep. RESULTS: Twenty patients completed the study. Standard outcome measures showed significant reduction in pain, fatigue, and sleeplessness; and improved function, mood state, and general health following an 8-week intervention. CONCLUSION: A mind-body intervention including patient education, meditation techniques, and movement therapy appears to be an effective adjunctive therapy for patients with fibromyalgia.

Are psychosocial factors related to response to acupuncture among patients with knee osteoarthritis?

CONTEXT: Acupuncture has been found to be beneficial in the treatment of patients with knee osteoarthritis. However, response among such patients is highly variable. Identification of subjects with greater response would facilitate a more rational use of acupuncture. OBJECTIVE: To examine the relationship between demographic and psychosocial variables and response to acupuncture as defined by reduction in pain and disability at the end of an 8-week course of treatment. DESIGN: Retrospective study. SETTING: Outpatients attending rheumatologists or primary care physicians. PATIENTS: 37 patients with symptomatic knee osteoarthritis who had previously participated in a controlled trial using acupuncture were recalled for an interview approximately 1 year later. INTERVENTION: Structured interview, questionnaire completion, and an examination. MAIN OUTCOME MEASURES: Depression, anxiety, helplessness, self-efficacy, and fatigue were measured by standard instruments. Knee examination and assessment of pain threshold were measured by dolorimetry. RESULTS: Response at 8 weeks was significantly related to duration of symptoms. A statistically nonsignificant trend was found for older and more educated subjects to have a better response; anxiety and fatigue were found to be inversely related to response (also statistically nonsignificant). Subjects with localized medial pain had significantly better response in terms of pain and disability than did subjects with generalized knee pain. CONCLUSION: Other than a weak relationship with anxiety (at 8 weeks only), no evidence of a link between psychosocial variables and response to acupuncture was found. Prospective studies are needed to confirm these results.

Spondyloarthropathies.

The spondyloarthropathies are disorders characterised mainly by sacroiliitis (with or without spondylitis), peripheral oligoarthritis, enthesopathy, absence of rheumatoid factor, certain extra-articular features such as iritis, and increased prevalence of HLA-B27. The diagnosis should be considered in patients, especially young people, with low back pain. A history of psoriasis, bowel dysfunction, eye problems and peripheral joint inflammation should point to the diagnosis.

Osteoarthritis pain and its treatment.

Pain is the most important symptom of osteoarthritis (OA) and the reason why individuals seek medical treatment. The anatomic cause is unclear and is likely to vary between individuals. Recent work confirms the heterogeneity of pain in OA with differences in severity, location, precipitating and relieving factors, and response to intra-articular anesthetic. Nonpharmacologic treatment of OA is important and evidence is now accumulating for interventions such as aerobic exercise, quadriceps exercises, footwear modification, education, and social support. Analgesia remains the first choice drug therapy: compounds more potent than acetaminophen are now available and effective. New cyclooxygenase-2 (COX-2) inhibitors may have a role in subjects for whom simple analgesia is inadequate. Glucosamine is a simple, safe product that appears to have a weak pain-relieving effect, and intra-articular hyaluronate injections may also have a limited role. Recent community studies confirm the benefit of joint replacement in OA, though a number of questions remain about the timing, indications, and alternatives to surgery.

Intra-articular corticosteroid treatment in osteoarthritis.

Intra-articular corticosteroids remain widely used for symptomatic treatment of peripheral joint osteoarthritis (OA). Several studies in knee OA have indicated a significant benefit compared with placebo, although the effect appears to last for only 1 to 3 weeks. Two placebo-controlled studies have confirmed these findings. A further uncontrolled study has examined the effect of intra-articular corticosteroid at the hip. Attention is increasingly focused on a possible disease-modifying role for steroids in OA. Although a beneficial effect can be demonstrated in some animal models, caution should be exercised when extrapolating to human cartilage. Osteoarthritis is increasingly viewed as a phasic condition in which organ damage occurs intermittently. An ability to detect these phases of increased disease activity, perhaps with new imaging or biochemical techniques, could lead to a more rational approach to the use of intra-articular steroids in OA.

Seronegative systemic lupus erythematosus.

We have presented a patient with severe clinical SLE but negative serological tests. This diagnostic difficulty, together with a presentation limited to the skin and an initial response to high dose steroids probably lead to a delay in starting immunosuppression. The finding of a retinopathy was important in deciding on therapy. An excellent response to immunosuppression was seen, with full recovery.

Quantitation of IL-2Rp75 (CD122) expression on mononuclear cells in rheumatic disease.

OBJECTIVE: To compare expression of the p75 chain of the interleukin-2 receptor (IL-2Rp75, CD122) on peripheral and synovial mononuclear cells in rheumatoid and non-rheumatoid inflammatory arthritis. METHODS: Peripheral blood (PBMC) and synovial (SFMC) mononuclear cells were isolated from subjects with rheumatoid arthritis (n = 16) and non-rheumatoid inflammatory arthritis (n = 12). PBMC were isolated from six healthy controls. Expression of CD122 was examined using indirect immunofluorescence and quantitative flow cytometry. RESULTS: There was no difference in IL-2Rp75 expression on PBMC from rheumatoid arthritis patients, non-rheumatoid arthritis patients, and controls. In subjects with rheumatoid arthritis there was no difference in IL-2Rp75 expression on PBMC and SFMC. However, in the non-rheumatoid arthritis group there was an increase in IL-2Rp75 expression on SFMC compared with PBMC (P = 0.0032). On SFMC there was a greater expression of IL-2Rp75 in non-rheumatoid arthritis than in rheumatoid arthritis (P = 0.0007). Expression was greater on CD8 positive cells and in subjects with shorter duration of disease. CONCLUSIONS: The p75 chain of the IL-2 receptor, an important T cell activation antigen, is not upregulated in synovial fluid. This appears to be a disease specific defect and provides further support for the concept of "frustrated" or incomplete T cell activation in this disease.

Pain mechanisms in osteoarthritis of the knee: effect of intraarticular anesthetic.

OBJECTIVE: The causes of pain in osteoarthritis (OA) remain unclear. We examined the effect of intraarticular (IA) local anesthetic (LA) on pain perception in OA knee to test the hypothesis that pain arises from structures in contact with the intraarticular surface. The effect of intervention on one knee on perception of pain in the other was also studied. METHODS: Using a single blind, blind observer design, 20 subjects with bilateral symptomatic OA knee were randomized to receive either IA LA (bupivacaine 0.25%, 5 ml) or placebo into the most painful knee. Pain from both knees was assessed at 1 h, 24 h, and 7 days using a 100 mm visual analog scale (VAS). Pain descriptors using a standardized questionnaire (McGill) were recorded. RESULTS: At 1 h there was a significant fall in pain in LA knees (median VAS 61.5 to 0.0; p = 0.007). The change at VAS was significantly different between knees receiving LA and placebo (median change -45.5 vs +3.5; p = 0.03). 6/10 LA knees scored 0 on VAS at 1 h. Noninjected knees also showed a fall in pain scores. For knees contralateral to those receiving LA, the fall was from median 28.0 to 1.0 (p = 0.08). The reduction in pain was much less in knees contralateral to those receiving placebo (median 43.5 to 38.0), though the difference between the changes did not reach statistical significance. VAS scores remained below baseline for 7 days, though this difference was not significant. McGill pain scores fell in the LA group (for all categories of pain), but did not change in the placebo group. CONCLUSION: Pain in some cases of OA knee can be abolished by IA LA, suggesting that the structures responsible for pain are in contact with the intraarticular environment. As well, interventions in one knee have significant effects on pain perception in the contralateral knee.

Measurement of HLA class I expression in ankylosing spondylitis.

The importance of HLA-B27 in the pathogenesis of ankylosing spondylitis is uncertain: current evidence favours a role for the B27 molecule itself. The possibility that quantitative differences in HLA-B27 expression may exist between patients with ankylosing spondylitis, family members, and control subjects positive for B27 was examined using appropriate monoclonal antibodies, flow cytometry, and a 'model lymphocyte' coated with a known number of mouse immunoglobulin binding sites. No differences were found between the groups. HLA-A2, examined for comparison, was expressed in greater amounts than HLA-B27, but each contributed only 10-20% of the total class I antigens. Homozygotes expressed twice the amount of antigen expressed by heterozygotes. Synovial lymphocytes expressed more class I antigens than peripheral lymphocytes.

Acute inflammatory polyarthritis in association with tamoxifen.

The antioestrogen drug tamoxifen is widely used to treat breast carcinoma. We report three cases in which its use was temporally related to the development of an acute inflammatory polyarthritis resembling RA; a side-effect not previously reported. Possible mechanisms for such an effect are discussed.

Where does it hurt? Pain localization in osteoarthritis of the knee.

OBJECTIVE: To identify the most common sites of pain in symptomatic knee osteoarthritis (OA) and to investigate clinical, radiographic and psychosocial associations of pain occurring in different locations. DESIGN: Sixty-eight outpatients with knee OA were interviewed in detail about their knee pain. Location of pain was recorded on a standard drawing of the knee. Validated instruments were used to measure pain severity, function, depression, anxiety, quality of life, fatigue, helplessness, self efficacy. Pain threshold was measured by dolorimetry and a knee examination performed. Radiographs (anterioposterior and lateral) were viewed if available. RESULTS: Most (85.3%) patients reported either 'generalized' (N = 35, 51.5%) or 'medial' (N = 23, 33.8%) knee pain. There were no differences between groups in pain severity, demographic or psychosocial variables, pain threshold or radiographic location or severity. However, function was significantly worse in the 'generalized' group (WOMAC function score 48.9 +/- 20.8 vs 34.2 +/- 22.3; P = 0.01): this remained significant after adjustment for potential confounding factors. The difference in function was most marked for activities involving knee bending. Early morning stiffness was also greater in the generalized group. CONCLUSIONS: Knee pain is not the same in all individuals with knee OA, confirming the heterogeneity of the condition. Location of pain is usually either generalized or medial. Patients with these patterns do not differ in demographic, radiographic or psychosocial variables but important differences in functional ability can be detected, suggesting differences in the underlying causes of pain and disability between the two groups.