Anti-CCP antibody testing as a diagnostic and prognostic tool in rheumatoid arthritis.

Rheumatoid arthritis is both common and chronic, with significant consequences for multiple organ systems. Better understanding of its pathophysiology has led to the development of targeted therapies that have dramatically improved outcomes. The key to therapeutic success lies in identifying individuals who will have severe destructive disease as early as possible, so that effective treatment can be initiated before irreversible damage occurs. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing is particularly useful in the diagnosis of rheumatoid arthritis, with high specificity, presence early in the disease process, and ability to identify patients who are likely to have severe disease and irreversible damage. However, its sensitivity is low, and a negative result does not exclude disease. Anti-CCP antibodies have not been found at a significant frequency in other diseases to date, and are more specific than rheumatoid factor for detecting rheumatoid arthritis. We discuss anti-CCP antibody testing in rheumatoid arthritis, with an emphasis on diagnostic performance, prognostic capability, and relevance to pathogenesis and new treatment paradigms in rheumatoid arthritis.

Methotrexate use in rheumatoid arthritis is associated with few clinically significant liver function test abnormalities.

OBJECTIVE: To determine the frequency of liver function tests (LFT) abnormalities associated with methotrexate (MTX) use in the treatment of rheumatoid arthritis (RA). METHODS: A retrospective chart review for demographic information, RA-specific history, medication history, complications of therapy, results of all available blood tests (specifically aspartate aminotransferase (AST), alanine aminotransferase (ALT), complete blood count (CBC), albumin, creatinine), and liver biopsy reports was conducted for RA patients, who were currently using or have used MTX in the past. RESULTS: A total of 2791 LFTs were performed among 182 RA patients with 94 abnormal results. 152 patients (83.5%) with 2007 LFT evaluations demonstrated no abnormal results, compared with 30 patients (16.5%) who had at least one abnormal LFT in 784 tests. Twenty-two of the 30 patients with at least one LFT abnormality (73.3%) continued treatment despite the elevation without further evaluation or change in therapy, and subsequent LFT assessments were within normal limits. 128 patients (70.3%) remained on MTX at the time of our study. The most common reason for discontinuation was inadequate response. CONCLUSIONS: MTX appears to be associated with very few clinically significant hepatic side effects. In view of these data, consideration as to revision of the current MTX monitoring guidelines in the direction of less frequent monitoring, especially in patients with no risk factors for liver disease, may be considered.

A prospective, double-blind, randomized, placebo controlled trial of methotrexate in the treatment of giant cell arteritis (GCA).

OBJECTIVE: To determine if methotrexate has disease-controlling and corticosteroid (cs)-sparing effects in the treatment of giant cell arteritis (GCA). METHODS: This was a randomized, controlled, double-blind trial comparing methotrexate versus placebo in addition to corticosteroid therapy in patients with newly diagnosed giant cell arteritis. Patients with giant cell arteritis were enrolled and treated with high dose corticosteroids as well as methotrexate starting at 7.5 mg/week or placebo. Corticosteroids were tapered by the treating physician as guided by the clinical picture, with methotrexate or placebo dose increased by 2.5 mg/week for disease flare with a maximum allowable dose of 20 mg/week. After a clinically-defined remission and steroid discontinuation, methotrexate or placebo was tapered monthly to zero by 2.5 mg/week. RESULTS: Twenty-one patients were enrolled, 12 randomized to methotrexate, 9 to placebo. Baseline characteristics (age, height, weight, sedimentation rate, bone mineral density, total corticosteroid dose prior to randomization, and quality of life as measured by SF-36 and function as measured by AIMS) were comparable between groups. At completion, there was no significant difference between methotrexate- and placebo-treated patients with regard to the cumulative corticosteroid dose (6469 mg and 5908 mg respectively, p = 0.6), number of weeks to completion of steroids (68 and 60 respectively, p = 0.5), time (weeks) to taper prednisone to less than 10 mg prednisone/day (23 and 25 respectively, p = 0.5), bone mineral density in lumbar spine (p = 0.2) or hip (p = 0.4) at one year, or functional status as measured by AIMS and quality of life as measured by SF36. There was no late vision loss in either group, and only one major treatment-responsive relapse in a methotrexate-treated patient. There were few major corticosteroid-related side effects and these did not significantly differ between groups. CONCLUSION: With this study design, no corticosteroid-sparing benefit could be attributed to the combination of methotrexate with corticosteroid therapy for the treatment of patients with giant cell arteritis. Both groups did well, with few major corticosteroid-related side effects, and most patients were safely tapered off corticosteroids sooner than reported in many series. The shorter overall duration of steroid treatment in this study probably contributed to the remarkably low frequency of side effects, without increased ischemic risk for the patient.

Increased cervical dysplasia in intravenous cyclophosphamide-treated patients with SLE: a preliminary study.

To determine if intravenous cyclophosphamide (IV-C) causes an excess of cervical dysplasia and/or cancer in systemic lupus erythematosus (SLE) patients, a retrospective review was conducted. Patients with SLE who received IV-C between 1988-98 (study group) were compared with a group of SLE patients who had not received IV-C (control group). Of the 79 IV-C-treated SLE patients identified, we excluded 18 because of absence of pertinent data. We found 10 cases of cervical dysplasia in the remaining 61 patients, compared to 2 in 49 non-exposed patients (P<0.04). Comparison of the two groups revealed no difference in: mean years of disease duration, months of follow-up and age. The non-exposed patients were more likely to be on estrogen and hydroxychloroquine but less often on steroids and azathioprine. The study group with and without dysplasia were assessed; we found no difference in the mean, or total IV-C dose, smoking and estrogen use. There was a significant decrease in time to dysplasia in those, given IV-C, with previous dysplasia compared to those without. These preliminary data suggests that IV-C causes an increased number of abnormal Papanicolaou (Pap) smears in SLE patients, particularly those with previous dysplasia.

Elderly-onset rheumatoid arthritis.

It is appreciated that age has a modifying effect on the clinical presentations of disorders such as hyperthyroidism and systemic lupus erythematosus. Similarly in EORA, there seems to be a change in the disease phenotype when it is compared to YORA. These differences are significant not only in highlighting the importance of the aging process on the immune system but also because they have medical and therapeutic implications. Improved classification has greatly improved our understanding and treatment of systemic lupus erythematosus, juvenile chronic arthritis, and seronegative spondyloarthropathies. Similarly, appreciating the differences, and similarities, between YORA and EORA should advance the choice of therapeutic options and potentially move closer to defining pathogenesis and origin.

Sarcoidosis presenting with large vessel vasculitis and osteosclerosis-related bone and joint pain.

A 34-year-old African-American female diagnosed earlier with idiopathic thrombocytopenic purpura (ITP), lymphadenopathy, splenomegaly, uveitis, and pulmonary nodules, developed a subclavian artery aneurysm, and generalized annular osteosclerotic lesions with disabling arthralgias. Biopsies from bone and lymph node revealed non-caseating granulomas and no evidence of malignancy or infection, confirming the clinical impression of sarcoidosis.

Adaptations made by rheumatoid arthritis patients to continue working: a pilot study of workplace challenges and successful adaptations.

OBJECTIVES: The goals of this pilot study were to use qualitative research techniques in a group of currently employed patients with rheumatoid arthritis (RA) to develop categories of challenges encountered in maintaining employment and categories of successful adaptations made to continue working; and to identify obstacles considered to be persistent threats to continued employment. METHODS: Patients were interviewed by telephone with a questionnaire composed of structured-response format and open-ended response format questions focusing on specific challenges and adaptations in the workplace. RESULTS: Of the 22 patients interviewed, 96% were women, mean age was 50 years, 84% were college graduates, and the majority had light physical job demands and high autonomy over their work and hours worked. Patients encountered diverse challenges, such as fatigue, pain, typing, writing, physical requirements, maintaining a pleasant disposition, working overtime, traveling for business, commuting, being on time, not being able to choose rest periods, and environmental issues. Patients also made multiple adaptations to continue working, the most helpful being changing job or altering career path (36%), altering work hours (32%), using more disease-modifying antirheumatic drugs (27%), using car service (23%), sleeping more (18%), and working at home (14%). Patients were not at all confident in their ability to continue working because of RA, and perceived the following persistent threats to continued employment: fatigue (45%), not being able to use hands (45%), not being able to choose rest periods (27%), and commuting problems (18%). In addition, patients confronted psychological stresses, such as dealing with coworkers and supervisors and balancing job and personal roles. These challenges and adaptations included unfavorable work-related occurrences, or "negative work-role events." CONCLUSIONS: Seemingly successfully employed patients with RA faced multiple challenges and made major adaptations to maintain employment and still perceived their employment to be in jeopardy because of RA. The findings of this study have important implications for screening patients at risk for negative work-role events and for possible work-related and social support interventions aimed at preserving employment.

Remission of juvenile rheumatoid arthritis after infection with parvovirus B19.

A 22-year-old Caucasian woman with a 6 year history of persistently active, systemic onset juvenile rheumatoid arthritis (JRA) developed symptoms of headache, dry cough, nausea, vomiting, abdominal pain, diarrhea, and dehydration associated with a high fever, elevated liver enzymes, and lymphopenia. Subsequent investigation revealed acute infection with parvovirus B19. Following clinical improvement over 10-14 days solely with supportive care, her underlying disease remained in remission for about 7 months.

Lymphoma in patients with rheumatoid arthritis: what is the evidence of a link with methotrexate?

An increasing number of instances of lymphoma in patients with rheumatoid arthritis who are treated with methotrexate continue to appear. The majority of patients with lymphoproliferation have features of immunosuppression-associated lymphoma. Rheumatoid arthritis itself and the actions of methotrexate concur in leading to a immunosuppressed state. Possible oncogenic mechanisms and the risk factors for patients with rheumatoid arthritis to develop lymphoma while receiving methotrexate include: (i) intense immunosuppression and severe disease in combination with genetic predisposition and; (ii) an increased frequency of latent infection with prooncogenic viruses like Epstein-Barr virus. The aetiological role of methotrexate in the development of these lymphomas is supported by the spontaneous remission of these malignancies in some of patients with rheumatoid arthritis after methotrexate has been stopped. The physicians caring for patients with rheumatoid arthritis receiving methotrexate should be vigilant about signs and symptoms suggestive of lymphoma, mostly in those patients with significant comorbidity, long standing and severe disease who are more likely to be immunosuppressed. If a lymphoma appears in these patients, methotrexate should be stopped. Spontaneous remission may occur and a period of observation is advisable when clinically possible. If functional deterioration appears or there are signs of lymphoproliferative organ invasion after several months then specific antineoplastic treatment should be instituted.

Adventitial stripping: a digit saving procedure in refractory Raynaud's phenomenon.

OBJECTIVE: To assess the efficacy and role of adventitial stripping (i.e., digital sympathectomy) in patients with severe digital ischemia secondary to refractory Raynaud's phenomenon (RP). METHODS: A retrospective chart review of 13 consecutive cases of adventitial stripping in 9 patients with severe secondary RP was performed, examining patient characteristics, previous therapeutic interventions, and postoperative outcomes. An illustrative case is presented. RESULTS: All identified patients had evidence of systemic disease. After adventitial stripping, sustained longterm improvement was achieved in all 13 ischemic digits, 8 of which showed amelioration of symptoms immediately after surgery. In 2 patients, sustained improvement was noted despite progressive ischemia in nonoperated digits. The mean followup time was 28 months (range 10 to 47). No postoperative complications were observed. Pre-operative sympathetic nerve blockade was performed in 12 of the cases, of which 10 showed no clinical response. Pathologic specimens revealed adventitial fibrosis that caused extrinsic compression of the digital arteries. CONCLUSION: Adventitial stripping of digital arteries is an extremely effective and safe option for patients with severe digital ischemia secondary to refractory RP. The efficacy of this procedure results not only from sympathetic denervation but also from decompression of the ischemic vessel through removal of a fibrotic and noncompliant adventitia. Because of the effects of this extrinsic vascular compression, lack of response to pre-operative sympathetic nerve blockade is not predictive of postoperative outcomes.

Users evaluate LupusLine, a telephone peer counseling service.

OBJECTIVE: To assess the impact of LupusLine during its pilot phase of operation by determining patterns of utilization and user satisfaction. LupusLine is a peer counseling service designed to provide ongoing emotional support from home to home by telephone appointment. METHODS: One hundred fifty-three respondents were surveyed, using a 72-item structured questionnaire administered over the telephone by interviewers separately trained and hired specifically for this purpose. The questionnaire was pilot tested on 10 volunteers with systemic lupus erythematosus (SLE), and a panel of related health professionals reviewed the questionnaire for face validity. RESULTS: Most users were women (94.5%) who had SLE themselves (87.5%) and who called the service because of recent changes in their physical functioning and reported feelings of depression and anxiety about their illness. Forty-one percent of respondents made 6 or more calls to their assigned peer counselor. Respondents reported high levels of satisfaction across 5 highly correlated measures, with 92% of callers reporting at least moderate satisfaction with the service. Over 60% of respondents who reported a change in 6 "feeling" categories attributed this change to using LupusLine. Fewer users reported a change in 4 specific behaviors since using the service, but more respondents attributed changes, when they occurred, to LupusLine. CONCLUSIONS: Based on these initial findings, we believe that telephone networks similar to the LupusLine model may be able to offer substantial benefit to people coping with the complex, ongoing psychosocial challenges of SLE. Further, the at-home accessibility and low cost of such volunteer-based interventions may play an ever more needed role in the present health care environment.

Lymphoma in patients with rheumatoid arthritis: association with the disease state or methotrexate treatment.

Although long-term clinical studies have shown no excessive risk of lymphoma in rheumatoid arthritis (RA) patients treated with methotrexate (MTX), an increasing number of reports of this association continue to appear. We describe two cases, review the cases in the world's literature, and summarize their important characteristics. Possible oncogenic mechanisms are discussed. Most lymphoproliferation cases presented here have features of immunosuppression-associated lymphoma. The immunosuppressed state is attributable to a combination of factors, such as RA itself and the actions of MTX. The risk factors for RA patients to develop lymphoma while on MTX include severe disease, intense immunosuppression, genetic predisposition, and an increased frequency of latent infection with prooncogenic viruses such as Epstein-Barr virus (EBV). The spontaneous remission of lymphomas in eight RA patients after MTX was stopped highlights the likely causative role of the drug in the development of these malignancies. If the clinical situation permits, a period of observation for spontaneous remission after MTX is stopped is advisable. The physicians caring for RA patients on MTX should maintain a high surveillance for signs and symptoms suggestive of lymphoma.

Assessing cost-effectiveness analyses in rheumatoid arthritis and osteoarthritis.

Economic considerations are now a source of great concern to clinicians and policy analysts. Many cost-effectiveness analyses have been published in the area of arthritis, most with substantial methodologic deficiencies. The goal of this article is to outline a method for evaluating cost-effectiveness assessment within the field of rheumatology. We do so by critically evaluating 6 cost-effectiveness analyses--2 in rheumatoid arthritis and 4 in osteoarthritis--as a basis for appraising the literature and developing future studies.

A randomized controlled trial of salmon calcitonin to prevent bone loss in corticosteroid-treated temporal arteritis and polymyalgia rheumatica.

Patients treated with high-dose or long-term corticosteroids are at risk of accelerated osteoporosis and spontaneous vertebral and traumatic fractures. To assess the efficacy of salmon calcitonin in preventing corticosteroid- induced osteoporosis, 48 patients with newly diagnosed polymyalgia rheumatica, temporal arteritis, and other vasculitides were enrolled in a 2-year, double-blind, randomized, controlled trial. Patients were randomized to receive subcutaneous injections t.i.w. of either 100 IU of salmon calcitonin (25 patients) or placebo (23 patients). After 2 years, 19 and 21 patients, respectively, were evaluable. All patients also received supplemental calcium carbonate (1500 mg daily in divided doses) and vitamin D3 (400 IU daily). Baseline and serial radiologic assessments included dual-energy X-ray absorptiometry (DXA) of the lumbar spine and hip, and spine radiographs to detect vertebral fractures. There were no significant baseline differences between the two study groups. The mean within-subject percentage change in DXA lumbar spine density in the two groups over the 2-year period of the study was only -0.1% (calcitonin plus calcium) versus -0.2% (placebo plus calcium) a nonsignificant difference despite the high mean cumulative corticosteroid doses of 5371 mg and 4680 mg, respectively (NS). The incidence of vertebral fracture was 12.5% (calcitonin plus calcium: 11%, versus placebo plus calcium: 14%, NS), with four fractures in the first year and one fracture in the second year. Higher cumulative cortico-steroid dose was associated with a greater loss in bone density. In rheumatic disease patients starting high-dose, long-term corticosteroids, salmon calcitonin with calcium and vitamin D3 provided no greater bone preservation than that observed with calcium and vitamin D3 alone.

Esophageal involvement in Wegener's granulomatosis.

Wegener's granulomatosis (WG) is characterized by granulomatous vasculitis, renal disease, and upper and lower respiratory tract disease. Although most organ systems can be involved, gastrointestinal (GI) manifestations are notably uncommon. We describe a patient with WG whose presentation was unique for the prominence of odynophagia. Esophagoscopy revealed erosive esophagitis, which on biopsy was shown to be due to direct involvement by the underlying vasculitis. This is first antermortem documentation of esophageal disease secondary to WG. The GI manifestations of WG are reviewed.