Work productivity loss due to flares in patients with chronic gout refractory to conventional therapy.

OBJECTIVE: Joint pain and swelling during gout flares may lead to considerable morbidity and disability, having an impact on patient work productivity and social participation. The objective of this study was to assess how gout flares affect these activities in patients with chronic gout refractory to conventional therapy. METHODS: A 1-year prospective observational study was conducted among patients with symptomatic disease in the United States in 2001. Inclusion criteria required patients (1) to be age 18 years or older, (2) to have documented, crystal-proven gout, (3) to have symptomatic gout, and (4) to be intolerant or unresponsive to conventional therapy, reflected by SUA ≥ 6.0 mg/dL. Patients were evaluated every 2 months. At each visit, patients completed a gout diary, which included number of flares experienced, duration and severity of each flare, and whether the flare caused: (1) work loss, (2) missed appointments or social events, or (3) impairment of self-care activities. The Short-Form Health Survey (SF-36) was also completed each visit. RESULTS: Analyses were restricted to those who completed the first 6 months of the study (n = 81). Mean number of flares per patient per year was 8.8. Of the patients who were <65 years, 78% reported at least 1 work day lost due to a gout attack during the year. Mean annual work day loss for those <65 years was 25.1 days. A total of 545 of patients reported at least one flare per year that impaired social activities, with a mean of 17.1 social days lost and 52% reported at least one flare per year that compromised normal self-care activities, with a mean of 16.9 days impairment. Correlations between the diary reports and activity-related questions from the SF-36 were significantly positive. LIMITATIONS: The study is limited by small sample size, lack of reference group, and inability to explicitly collect employment information. Age under 65 years was used as a proxy for employment eligibility. CONCLUSION: Flares in patients with chronic gout refractory to conventional therapy significantly affect patient work productivity and social activities.

Toward a valid definition of gout flare: results of consensus exercises using Delphi methodology and cognitive mapping.

OBJECTIVE: To identify, in people known to have gout, the testable, key components of a standard definition of gout flare for use in clinical research. METHODS: Consensus methodology was used to identify key elements of a gout flare. Two Delphi exercises were conducted among different groups of rheumatologists. A cognitive mapping technique among 9 gout experts with hierarchical cluster analysis provided a framework to guide the panel discussion, which identified the final set of items that should be tested empirically. RESULTS: From the Delphi exercises, 21 items were presented to the expert panel. Cluster analysis and multidimensional scaling showed that these items clustered into 5 concepts (joint inflammation, severity of symptoms, stereotypical nature, pain, and gout archetype) distributed along 2 dimensions (objective to subjective features and general features to specific features of gout). Using this analysis, expert panel discussion generated a short list of potential features: joint swelling, joint tenderness, joint warmth, severity of pain, patient global assessment, time to maximum pain, time to complete resolution of pain, an acute-phase marker, and functional impact of the episode. CONCLUSION: A short list of features has been identified and now requires validation against a patient- and physician-defined gout flare in order to determine the best combination of features.

Magnetic resonance imaging in the quantitative assessment of gouty tophi.

Measurements of tophus size can be important in monitoring the course of gout therapy, as tophus resolution is proposed as one measure of success of treatment. This multicentre study assessed the intra- and interreader reproducibility of quantitative tophus volume measurements from magnetic resonance images (MRI) in subjects with palpable gouty tophi. Subjects first underwent radiographic imaging of a selected tophus followed by MRI before and at

Magnetic resonance imaging of tophaceous gout in the hands and wrists.

The objective of this study was to determine the relative usefulness of physical examination, plain radiographs, and magnetic resonance imaging (MRI) using T1- and T2-weighted spin-echo images in evaluating the extent of urate deposition and soft tissue destruction in gouty arthritis. Seven patients with chronic tophaceous gout of the hands and wrists were examined to identify all clinically apparent tophi. Plain radiographs of the hands and wrist were obtained to further quantify soft tissue and osseous changes. MRI was then performed of the involved areas and a comparison made between soft tissue and bony changes observed by clinical examination and plain radiographs and those observed by MRI. Plain radiographs and physical examination markedly underestimate the size and extent of soft tissue and osseous involvement by tophi when compared with the findings of MRI. MRI also detects early, subclinical tophaceous deposits and indicates that urate deposits appear to spread along compartmental and fascial planes as opposed to the traditional view of strict radial growth. MRI is a useful method of determining the extent of disease in tophaceous gout and may provide information regarding the patterns of deposition and spread of monosodium urate crystals.

Clinical pathogenesis and diagnosis of osteoarthritis.

New insights into the metabolism of cartilage have increased respect for efforts designed to prevent osteoarthritis. The aging of the population adds to the desire to diagnose and manage the disease before patients become seriously disabled.

Axial skeletal changes in paralysed patients may mimic ankylosing spondylitis.

Patients with paralysis may develop radiographic changes in the axial skeleton and sacroiliac joints that resemble those seen in ankylosing spondylitis. These similarities can result in confusion when evaluating paralysed patients with back pain. We report on a patient with paralysis secondary to amyotrophic lateral sclerosis who developed back pain, apparent sacroiliac joint fusion, and a 'bamboo spine', leading to the misdiagnosis of ankylosing spondylitis. Serial radiographs of the bony changes in our patient are presented, along with a brief review of the literature on axial skeletal abnormalities in paralysis and a discussion of the subtle changes that distinguish immobilization spondyloarthropathy from ankylosing spondylitis.

A cooperative interaction between NF-kappa B and Sp1 is required for HIV-1 enhancer activation.

The human immunodeficiency virus (HIV-1) long terminal repeat (LTR) contains two binding sites for NF-kappa B in close proximity to three binding sites for the constitutive transcription factor, Sp1. Previously, stimulation of the HIV enhancer in response to mitogens has been attributed to the binding of NF-kappa B to the viral enhancer. In this report, we show that the binding of NF-kappa B is not by itself sufficient to induce HIV gene expression. Instead, a protein-protein interaction must occur between NF-kappa B and Sp1 bound to an adjacent site. Cooperativity both in DNA binding and in transcriptional activation of NF-kappa B and Sp1 was confirmed by electrophoretic mobility shift gel analysis, DNase footprinting, chemical cross-linking and transfection studies in vivo. With a heterologous promoter, we find that the interaction of NF-kappa B with Sp1 is dependent on orientation and position, and is not observed with other elements, including GATA, CCAAT or octamer. An increase in the spacing between the kappa B and Sp1 elements virtually abolishes this functional interaction, which is not restored when these sites are brought back into the same helical position. Several other promoters regulated by NF-kappa B also contain kappa B in proximity to Sp1 binding sites. These findings suggest that an interaction between NF-kappa B and Sp1 is required for inducible HIV-1 gene expression and may serve as a regulatory mechanism to activate specific viral and cellular genes.

Multicentric reticulohistiocytosis: systemic macrophage disorder.

Multicentric reticulohistiocytosis is a rare multisystem disorder that reflects a reactive inflammatory response to an undetermined stimulus. While the disease is characterized as a dermatoarthritis, multiple organ systems including cardiac and skeletal muscle, the pleura and gastrointestinal tract have been involved in reported cases. The synovitis can be quite destructive with arthritis mutilans developing in a substantial percentage. The dermatitis may be particularly disfiguring when the face is involved. This chapter describes the clinical and laboratory features of the 33 cases of MRH previously reviewed by Barrow and Holubar and an additional 33 cases that have appeared in the medical literature since that report. We note an apparent decline in frequency of some manifestations of MRH. This may be due in part to the nature of the recent reports which often present a brief clinical report and focus primarily on specific disease associations, unusual manifestations, new organ system involvement or treatment regimens. The primary cell involved in the reactive inflammatory response of MRH is the phagocytic tissue histiocyte (macrophage). While uncontrolled proliferation of these reticulohistiocytes is seen in several infectious and malignant conditions there is presently no direct evidence of a particular organism or neoplasm involved in the aetiopathogenesis of MRH. There is evidence of tuberculosis exposure in one third of cases with active tuberculosis present in 5%. Likewise, malignancies are reported concomitantly with MRH in 15-28% of cases. The therapeutic trend in MRH is to treat early and aggressively to prevent the devastating arthropathy and disfiguring cutaneous sequelae. This recommendation, however, is largely based on anecdotal reports and thus the physician encountering a case of MRH needs to proceed with circumspection.

Drugs to lower uric acid levels. How to avoid misuse in gouty arthritis.

Several points regarding the use of drugs to lower uric acid levels deserve emphasis. First, these agents are not useful in the management of acute gout. Second, all forms of the drugs should be initiated at low dose with gradual increments to achieve a serum uric acid level between 5 and 6 mg/dL. There are no data to support the widely presumed notion that dropping the uric acid level to a very low range (1 to 3 mg/dL) hastens resorption of tophi or improves joint function. Third, the uricosuric agents probenecid (Benemid) and sulfinpyrazone (Anturane) interact with a number of drugs, and both the patient and physician should be aware of this. Finally, and most important, careful and frequent monitoring is needed during the first several months of therapy with these drugs.

Magnetic resonance imaging in patients with inflammatory arthritis of the knee.

Magnetic resonance imaging (MRI) permits visualization of anatomic structures not appreciated by conventional radiographic imaging and may quantify inflammatory disease and its progression with greater sensitivity than available techniques. We therefore compared MRI with clinical evaluation and with radiographic examination of 17 patients with inflammatory arthritis of the knee. We sought to determine anatomic integrity of bone, cartilage, menisci, and ligaments, and to quantify joint effusion and synovial proliferation. Patients studied had rheumatoid arthritis (10 patients), juvenile rheumatoid arthritis (4 patients), ankylosing spondylitis (1 patient), and monoarticular arthritis (2 patients). In all patients MRI revealed clinically important abnormalities not detected by physical or conventional radiographic exams. These included proliferative synovitis (13 patients), cartilage thinning (2 patients), cartilage erosion (8 patients), bone infarction (1 patient), meniscal injury (1 patient), and synovial invagination into bone (1 patient). Also MRI indicated inflammatory disease to be quantitatively greater than had been appreciated on clinical examination or routine X-ray studies--proliferative synovitis (12 patients), erosion (7 patients), effusion (8 patients), cartilage thinning (11 patients), and ligamentous/meniscal damage (1 patient). These findings led to reassessment of anatomic staging and influenced therapeutic decision for these patients. Thus MRI provides clinically important information about joint integrity and inflammatory disease, with a sensitivity and resolution considerably beyond conventional techniques.

Profile of a meeting: how abstracts are written and reviewed.

We analyzed submissions to a recent scientific program to determine (1) how abstracts were reviewed and (2) what constituted a successful abstract. We found that (1) reviewers' gradings varied from 2-29%, in some instances differing significantly; (2) many (<74%) abstracts had inadequacies in form, title, introduction, aims, methods, results, and conclusions(collectively termed "content") or lacked numerical or statistical data; (3) accepted abstracts had fewer inadequacies and better "content"; and (4) abstract grades correlated closely with "content". The quality of preparation and of individual features of abstracts led to favorable review. This information is of potential value to scientists preparing and reviewing abstracts and planning programs.

Vasculitis associated with malignancy. Experience with 13 patients and literature review.

Vasculitis is a syndrome which may complicate certain infectious, rheumatic, and allergic diseases. We identified 13 patients, over the past 17 years, who had both vasculitis and lympho- or myeloproliferative disorders and relate their clinical, laboratory, histologic, and immunologic features, course, therapy, and outcome. Nine patients were male, 4 female; ages ranged from 28 to 82 years. Ten of 13 patients presented with cutaneous vasculitis antedating malignancy by an average of 10 months. Three of 13 developed cutaneous vasculitis after malignancy. A statistically significant association between cutaneous vasculitis and lympho- or myeloproliferative malignancies was noted when compared with all other tumors. Dermatologic manifestations included palpable purpura (5 patients), maculopapular eruptions (4), urticarial and petechial lesions (3), and ulcers (1). Hepatitis B surface antigen, Coombs antibodies, rheumatoid factor and antinuclear antibodies were not found. Serum cryoglobulins were detected in 3 patients; serum C3 and C4 were normal in 8 of 9 patients evaluated. Histologic examinations revealed necrotizing leukocytoclastic vasculitis with disruption of endothelial integrity, destruction of endothelium, and neutrophil infiltration. Occasional perivascular mononuclear cell invasion was also noted in 4 patients. Immunofluorescent staining for IgG, IgA, IgM, C3, and C4 was negative in all patients studied. Symptoms were, in general, poorly responsive to therapy, which included nonsteroidal antiinflammatory drugs, antihistamines, antiserotonin agents, and corticosteroids. Chemotherapy directed at the underlying malignancy was also generally ineffective, although the vasculitis appeared to lessen in severity. Vasculitis appeared to lessen in severity as bone marrow function deteriorated. Ten patients died, all as a direct result of their malignancy. We have described a unique clinical syndrome of lympho- and myeloproliferative disease presenting with small-vessel vasculitis. Recognition that rheumatic symptoms may reflect or antedate malignancy may permit early diagnosis, aggressive treatment, and elucidation of pathogenesis.

'Rhupus' syndrome.

Occasionally patients with overlapping features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), termed "rhupus," have been encountered. We wanted to ascertain the frequency of such patients and determine whether they represent a unique overlap syndrome. Of approximately 7000 new patients evaluated over 11 years, we identified six patients who had, on the average, 6.7 American Rheumatism Association criteria for RA and 4.2 criteria for SLE. Criteria for RA included chronic symmetric arthritis with morning stiffness (six patients); subcutaneous nodules (two patients); positive rheumatoid factors test (four patients); and radiologic erosions (four patients). The criteria for SLE included malar rash (three patients); discoid lupus erythematosus (two patients); biopsy-proved nephritis (one patient); photosensitivity (one patient); leukopenia/thrombocytopenia (four patients); positive antinuclear antibodies or lupus erythematosus cell test (six patients); hypocomplementemia (two patients); and abnormal results from skin biopsy (two patients). During observations of up to ten years, the conditions of three patients were stable or improved, one died, and two were unavailable for follow-up. Patients usually did not have conditions that evolved to classic rheumatic disease patterns. Rhupus was not common and did not occur more frequently (0.09% prevalence among our patients) than expected from chance concurrence of SLE and RA (calculated at 1.2%). These observations confirm that rhupus indeed exists as a syndrome manifested by patients sharing features of probable coincidental concurrence of RA and SLE, but not as a unique clinical pathologic or immunologic syndrome. Appreciation of these patients with rhupus is important since their therapy and outcome differ from those having RA or SLE alone.

Silicone and rheumatic diseases.

Silicone generally has been regarded as a biologically inert material. However, recent reports suggest that inflammatory responses to silicone occur. There is some experimental and clinical evidence of a direct inflammatory response to the presence of liquid or particulate silicone. These include granulomatous skin reaction to injected silicone, synovitis around silicone prosthetic joints, and lymphadenopathy proximal to silicone prostheses. There are case reports of systemic rheumatic disease following silicone prostheses, but no definitive proof of a direct relationship between silicone prostheses and systemic disease. The clinical features of the reported cases following breast augmentation include breast tenderness, axillary adenopathy, sclerodermatous skin changes, arthritis, Raynaud's phenomenon, rheumatoid factors, and ANAs. Prior epidemiologic evidence and the number and consistency of our own and others' clinical findings suggest that silicone may indeed be associated with inflammatory processes and rheumatic diseases.

Technetium pyrophosphate muscle scans in inflammatory muscle disease.

Technetium-99M pyrophosphate (TcPYP) nuclear scans of extremities were performed on 15 patients at 10 minutes and 2 hours after isotope injection. Scans were carried out both to confirm the diagnosis of myositis and to direct subsequent muscle biopsy. Five of six patients with clinical features strongly suggestive of inflammatory muscle disease had positive scans. All muscle biopsies performed at areas of increased isotope uptake showed inflammatory muscle disease. All nine patients not suspected of active inflammatory muscle disease had negative scans. Two of these underwent muscle biopsy with negative results. Our observations suggest that TcPYP muscle scans may be useful both to confirm the clinical suspicion of inflammatory muscle disease and in directing the choice of site for muscle biopsy.