Gout: diagnosis, pathogenesis, and clinical manifestations.

Gout is a common form of arthritis, in which many of the risk factors, pathogenetic mechanisms, and clinical features have been recognized for years. Nevertheless, new information has become available regarding the normal physiologic role of uric acid as an antioxidant, and greater insight has been obtained regarding the inflammatory process in acute gout. New studies have improved our understanding of the role of genetic and environmental factors responsible for hyperuricemia, and we know more about the significance of the association of hyperuricemia with other diseases. Clinically, rare complications and disease manifestations in new populations continue to be discussed, and diagnostic methods continue to be refined.

Methotrexate in the management of immune mediated cochleovesitibular disorders: clinical experience with 53 patients.

OBJECTIVE: To describe our experience with low dose weekly methotrexate (MTX) in the management of immune mediated cochleovestibular disorder (IMCVD). METHODS: Between 1991 and 1999, we treated 53 patients with IMCVD with MTX. Patients were selected on the basis of progressive vestibular symptoms that had responded to corticosteroids and in most cases, relapsed. MTX was initiated at a dose of 7.5 mg weekly and increased to doses up to 25 mg weekly as needed. Response was assessed by audiologic studies and history of change in tinnitus and vertigo. MTX was discontinued after 4-6 mo in patients showing no improvement, and after 12-18 mo in patients with improved and stable symptoms. RESULTS: Three patients were still in early therapy and had not improved. Of the 50 remaining patients, significant improvement was seen in vertigo in 27/39 (69%) patients, hearing loss in 25/47 (53%), and tinnitus in 11/42 (26%). Overall improvement in symptoms was seen in 35/50 (70%) patients. Four patients stopped MTX due to toxicity, and 11 due to lack of response. In 28 patients, MTX was stopped after 12-18 mo when symptoms had stabilized, and restarted in 5 of these after relapse. Seven patients remain on therapy with improved and stable symptoms after 17.3 mo. CONCLUSION: In this open label experience, a majority of patients with IMCVD improved with weekly low dose MTX therapy with minimal toxicity.

Crystal-associated arthritis in the elderly.

The understanding of the clinical syndromes of gout and pseudogout, and the role of basic calcium crystals in arthritis has increased since the original descriptions of the involvement of crystals in arthritis. Gout is usually considered an affliction confined to middle aged males but has an increasing prevalence in older populations, with unique and often atypical features. Calcium pyrophosphate dihydrate crystal deposition disease is common in elderly patients. The diagnosis of these common forms of arthritis and the need to individualize therapy in patients with other medical problems remain important clinical challenges to the practicing physician.

Nutritional supplementation with Chlorella pyrenoidosa for patients with fibromyalgia syndrome: a pilot study.

Fibromyalgia syndrome is a common, chronic musculoskeletal disorder of unknown aetiology. While available therapy is often disappointing, most patients can be helped with a combination of medication, exercise and maintenance of a regular sleep schedule. The objective of the present study was to determine if adding nutritional supplements derived from the unicellular green alga, Chlorella pyrenoidosa, produced any improvements in the clinical and functional status in patients with moderately severe symptoms of fibromyalgia syndrome. Eligible patients had 2+ palpable tenderness at 11 or more of 18 defined tender points and had a tender point index (TPI) of at least 22. Each day for 2 months, participants consumed two commercially available Chlorella-based products, 10 g of 'Sun Chlorella' tablets and 100 mL of liquid 'Wakasa Gold'. Any amelioration of symptoms was validated and quantified using semi-objective and subjective outcome measures systematically administered at clinic visits on days 0, 30 and 60 of the diet therapy. Eighteen of the 20 patients enrolled completed the 2 month trial. The average TPI for the group which at onset was 32, decreased to a mean of 25 after 2 months. This decrease was statistically significant (p = 0.01), representing a 22% decrease in pain intensity. Blood samples taken on each occasion indicated no significant alterations in serum chemistries, formed elements, and circulating lymphocyte subsets. Compilations of the results of patient interviews and self-assessment questionnaires revealed that seven patients felt that the dietary supplement had improved their fibromyalgia symptoms, while six thought they had experienced no change, and five believed the symptoms had worsened over the time of the trial. The results of this pilot study suggest that dietary Chlorella supplementation may help relieve the symptoms of fibromyalgia in some patients and that a larger, more comprehensive double-blind, placebo-controlled clinical trial in these patients is warranted.

Low-dose oral methotrexate management of patients with bilateral Ménière's disease.

In this retrospective clinical trial, we evaluated the effectiveness of low-dose oral methotrexate in the management of bilateral Ménière's disease of immune-mediated origin. At our tertiary-care referral center, we evaluated ten men and eight women who had longstanding bilateral Ménière's disease that had been unresponsive to traditional conservative medical management. Sixteen of these patients had steroid-responsive bilateral Ménière's disease. Two patients had contraindications to steroids, but their clinical and laboratory evaluations were consistent with an immune-mediated process. Patients were treated with 7.5 to 20 mg/week of oral methotrexate. The mean duration of treatment was 16.7 months (range: 8 to 35), with a mean followup of 2 years (range: 9 mo to 5 yr). Changes in clinical symptoms (vertigo, hearing loss, tinnitus, and aural fullness), audiometric changes, and side effects of therapy were evaluated. Vertigo resolved in 14 patients (78%), was substantially alleviated in three patients (17%), and remained unchanged in one patient (6%). Hearing improved in five patients (28%) and stabilized in seven patients (39%). Tinnitus and aural fullness resolved or was relieved in 11 of 17 (65%) and 13 of 14 (93%) patients, respectively. Side effects were minimal and reversible. We conclude that low-dose oral methotrexate is effective and safe for treating bilateral Ménière's disease of immune-mediated origin. In this study, methotrexate alleviated vertiginous symptoms and improved or stabilized hearing in most patients. Low-dose methotrexate can be considered for patients with immune-mediated bilateral Ménière's disease when long-term treatment is required or when a steroid or cyclophosphamide is contraindicated.

Crystal-associated arthritis.

Since the original descriptions of the involvement of crystals in arthritis, understanding of the clinical syndromes of gout and pseudogout and the role of basic calcium crystals in arthritis has increased. Gout is a common problem in middle-aged males but has an increasing prevalence in older patients, particularly women. Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is now a well-recognized problem in older patients. The diagnosis of both of these common forms of arthritis and the need to individualize therapy in patients with other medical problems remain important clinical challenges to the practicing physician.

Diagnosis and management of complicated gout.

Although a diagnosis of gout can be confirmed by the presence of monosodium urate crystals in synovial fluid, arriving at the suspected diagnosis and managing the disease can be a challenge for primary care physicians and specialists alike. Symptoms of gout can mimic other forms of inflammatory arthritis such as rheumatoid arthritis, pseudogout, or septic arthritis. Treatment can be complicated by the patient's need for drugs that contribute to hyperuricemia. Once other diagnoses are ruled out and urate crystals are detected under polarized light microscopy, treatment to end the acute attack and follow-up treatment designed to lower serum urate levels can be undertaken.

Methotrexate management of immune-mediated cochleovestibular disorders.

Immune-mediated cochleovestibular disorders continue to present a management challenge to the otolaryngologist. The traditional treatment of these disorders, corticosteroids and/or cyclophosphamide (Cytoxan), has been associated with serious and occasionally life-threatening complications. In this study we report our experience in treating 25 patients with immune-mediated cochleovestibular disorders with methotrexate, a less toxic immunosuppressive agent that has been used extensively in patients with rheumatoid arthritis. Mean duration of treatment was 12.9 months, and adverse reactions were acceptable and reversible. Hearing improved in 69.6% of patients, and vestibular symptoms subsided or improved in 80% of patients. The results of this study suggest that methotrexate treatment is effective in a substantial number of patients with immune-mediated cochleovestibular disorders and has acceptable adverse reactions. A prospective, randomized study is needed to compare the efficacy of methotrexate with that of other immunosuppressive agents.

Comparison of factor VIII-related antigen and erythrocyte sedimentation rate in outpatient management of vasculitis.

Electroimmunodiffusion (Laurell rocket) determinations of factor VIII-related antigen in plasma were ordered to determine the cost/benefit ratio for factor VIII-related antigen as a putative test for endothelial damage in suspected vasculitis. Twenty-seven consecutive patients referred for vasculitis or suspected vasculitis were identified and followed up for an average of 9.1 +/- months (range: one to thirty-three months) in a prospective, unblinded study performed in a clinic, associated with a 1054-bed inner-city university hospital. There was no difference in Westergren erythrocyte sedimentation rate (WESR) in patients with final diagnosis of systemic vasculitis (SV) (38 +/- 12 mm/hour) compared to those without vasculitis (NV) (27 +/- 7) as the final diagnosis. The mean plasma concentration of factor VIII-related antigen was significantly elevated in SV (344 +/- 100%) when compared with NV (147 +/- 39%) (P < 0.016). The factor VIII-related antigen test in this study was 2.56 times more likely (crude odds ratio) than the WESR to contribute to a change in diagnosis or therapy (P = 0.016). Positive and negative predictive values (PPV and NPV) for factor VIII-related antigen (abnormal at greater than 220% of the normal value) were both 70%. PPV and NPV for WESR were 56% and 86%, respectively. The factor VIII-related test was less cost-effective than the WESR in the follow-up period unless it was important to define complete remission or differentiate vasculitis flare from infection. The authors conclude that factor VIII-related antigen is a useful test in the initial diagnosis of vasculitis.

Methotrexate in nonrenal lupus and undifferentiated connective tissue disease--a review of 36 patients.

OBJECTIVE: To determine the efficacy, tolerability, and steroid sparing effect of methotrexate (MTX) in patients with systemic lupus erythematosus (SLE) in clinical practice. METHODS: From a database of 467 patients, we identified all patients with SLE and undifferentiated connective tissue disease (UCTD, 2-3 criteria for SLE) who had received MTX. Details of previous therapy, indications for MTX, efficacy, toxicity, and steroid reduction during MTX therapy were recorded. RESULTS: 21 patients with SLE who had been treated with MTX were identified. The mean weekly MTX dose rose from 7.5 mg at initiation to 13.6 mg at 6 mo and 17.1 mg at 12 mo. A response was seen in 12 of 21 patients, and 7 patients had a sustained 50% reduction in disease activity at the final evaluation. Response was best in patients with dermatitis (5/6), arthritis (6/13), and myositis (1/1), but minimal in patients with central nervous system dysfunction (1/4), serositis (1/3), and isolated fatigue (0/1). Toxicity was noted in 62% of patients, but only 33% discontinued due to toxicity. MTX was continued in 74% of patients at 6 mo and 40% at 12 mo. Steroid dosage was reduced to half the original dose in 9 of 16 patients. A similar pattern of MTX efficacy and toxicity was observed in 15 patients with UCTD. CONCLUSION: MTX is useful in the treatment of some patients with mild manifestations of SLE, with an acceptable toxicity profile, but only modest steroid sparing potential. Patients with dermatitis and arthritis appear to have the best chance of responding to MTX therapy.

Gouty arthritis and uric acid metabolism.

Important observations have continued to expand our understanding of gout. The increased risk of gout in black Americans has been linked more closely with the development of hypertension, and an increasing prevalence in African blacks and in England may have a similar association, possibly through the use of diuretics. The association of gout and insulin resistance appears to be related to fat distribution, and the link with hyperlipidemia may be related to genetic factors. The relationship between gout and renal disease and the frequency of gout in patients with renal failure continue to be areas of controversy. The mechanism and a possible therapeutic approach to the hyperuricemia associated with cyclosporine therapy are better understood. The potential for antibodies against urate crystals to potentiate further crystallization may explain some of the uncertainties about gouty attacks. Unusual manifestations of gout, including more cases of spinal involvement, were reported. The role of formalin in dissolving urate crystals in pathologic specimens was further clarified, and the use of atomic force microscopy to detect crystals was reported. Corticosteroids are increasingly accepted in treating acute gout, and the role of colchicine in acute and intercritical gout has come under increasing scrutiny. Urate-lowering drugs appear to be cost effective in patients with more than one or two attacks per year.

More Aggressive Drug Treatment of Rheumatoid Arthritis in a University-based Practice.

We sought to assess the impact of recent observations and recommendations on the treatment of rheumatoid arthritis in a university-based rheumatology practice over a recent 6-year period. Data was collected from information recorded in a database by physicians treating patients in outpatient rheumatology clinics. The treatment regimens of all patients with rheumatoid arthritis seen during the first half of 1987 and 1993 were compared. The populations were similar in age, race, and sex distribution, disease duration, and seropositivity. Nonsteroidal anti-inflammatory drug use decreased from 85% to 74%, while corticosteroid use increased from 31% to 44% of patients. Second-line agent use increased from 46% to 65% of patients, all of which could be accounted for by the increase in methotrexate use from 11% to 32%. The use of other second-line agents remained stable (hydroxychloroquine, auranofin, azathioprine), declined (intramuscular gold, penicillamine), or increased slightly (sulfasalazine). An increase in combination second-line drug therapy from 2% to 6% was noted. This study shows that between 1987 and 1993, our drug therapy for rheumatoid arthritis has become more aggressive: we have increased steroid use, decreased nonsteroidal use, and more frequently used second-line agents, particularly methotrexate.

Gonococcal arthritis in an era of increasing penicillin resistance. Presentations and outcomes in 41 recent cases (1985-1991).

BACKGROUND: To assess the impact of recent reports of disseminated gonococcal infection caused by penicillin-resistant organisms, we reviewed the presenting features, clinical course, and outcomes of a group of patients with gonococcal arthritis treated in recent years. METHODS: We reviewed the records of all cases of acute arthritis associated with a culture positive for Neisseria gonorrhoeae at our institution from July 1985 through December 1991. RESULTS: Forty-one cases were identified. Patients included 34 women and 38 blacks; the mean age was 22.6 years. Duration of symptoms averaged 4.8 days at presentation. Other features included migratory arthralgias (n = 27), urogenital symptoms or signs (n = 26), fever (n = 21), and skin lesions (n = 16). Comorbid conditions included intravenous drug use (n = 8) and systemic lupus erythematosus (n = 3). The knee was the most commonly affected joint. Positive culture results were obtained from 32 urogenital samples (86%), 14 synovial fluid samples (44%), seven rectal samples (39%), four blood samples (12%), and two throat samples (7%). All synovial fluid samples with positive culture results had white blood cell counts higher than 20.0 x 10(9)/L. Response to therapy with penicillin and/or ceftriaxone was prompt, and mean duration of hospitalization was 5.8 days. Patients who required longer hospitalization had a higher mean erythrocyte sedimentation rate and higher frequencies of positive synovial fluid culture results and comorbid conditions. Penicillin sensitivity could be determined in 30 patients on the basis of clinical response or in vitro testing. Among these patients, two cases of penicillin-resistant organisms were identified, one beta-lactamase positive and one beta-lactamase negative. CONCLUSIONS: The clinical features of patients with gonococcal arthritis have changed very little since the last large reported series over a decade ago. Underlying conditions appear to be more common, but response to antibiotic therapy and eventual outcome remain excellent. The finding of penicillin-resistant organisms in at least 5% of patients reinforces recent recommendations that third-generation cephalosporin agents be used as initial therapy for disseminated gonococcal infections until drug susceptibilities are known.

Chest wall syndromes.

Chest pain of musculoskeletal origin has not been reviewed on an annual basis in Current Opinion in Rheumatology because of the relative infrequency of important contributions in this area. Over the past 5 years, several studies have contributed to our knowledge of the epidemiology of musculoskeletal chest wall pain, particularly in the setting of noncardiac chest pain. In addition, a growing body of literature has further defined the various syndromes involving the sternum and its articulations, with particular emphasis on the seronegative spondyloarthropathies and arthropathy associated with pustular skin disease. Finally, small series and reviews have continued to address special syndromes of the anterior and posterior chest wall that are of interest to clinicians dealing with patients with pain in this area.

Minor salivary gland biopsies in patients investigated for primary Sjögren's syndrome. A review of 187 patients.

OBJECTIVE: To correlate presenting features and indication for biopsy with results in patients undergoing minor salivary gland biopsy for the diagnosis of primary Sjögren's syndrome (SS). METHODS: The charts of 187 patients undergoing minor salivary gland biopsy for primary SS over a 9-year period were reviewed. RESULTS: 76 patients had a focus score > 1, 111 had a focus score < or = 1. No difference between the 2 groups was noted in most features, including frequency of symptomatic dry eyes or mouth, or Schirmer test results. Patients with focus score > 1 had significant increases in frequency of salivary gland swelling (25 vs 9%), antinuclear antibodies > 1:100 (68 vs 32%), rheumatoid factor > 1:160 (63 vs 22%), anti-SSA (46 vs 9%), anti-SSB (32 vs 4%), or any serologic marker (87 vs 46%). Abnormal biopsies were more frequent in those biopsied for serologic abnormalities (53%) than for sicca symptoms (33%) or systemic illness (29%). CONCLUSION: Serologic markers are better predictors of results than clinical features in patients undergoing minor salivary gland biopsy for primary SS. The frequency of a positive biopsy is increased in patients in whom unexplained serologic markers are being evaluated.

Oral lesions in systemic lupus erythematosus. Do ulcerative lesions represent a necrotizing vasculitis?

BACKGROUND: It has been suggested that oral lesions in patients with systemic lupus erythematosus (SLE) may be grouped clinically as erythema, discoid lesions, or oral ulcerations. Oral ulcerations have been said to foretell a severe systemic disease flare and the proposal that oral ulcers represent a mucosal vasculitis has been suggested to explain this hypothesis. OBJECTIVE: Our objective was to test the hypothesis that oral ulcers in patients with SLE result from vasculitis. METHODS: We studied 10 patients with American College of Rheumatology (ACR) criteria for a diagnosis of SLE who had oral lesions of lupus (six prospectively and four retrospectively) clinically and by routine and immunofluorescence microscopy. Biopsy specimens were reviewed in a single-blinded fashion. RESULTS: In our patients, no oral lesion, regardless of morphology, demonstrated vasculitis histologically. All lesions demonstrated an interface mucositis. CONCLUSION: Our data strongly contradict the hypothesis that leukocytoclastic vasculitis explains a possible unproven correlation between oral ulceration and disease flares in patients with SLE.

Presenting features and outcomes in patients undergoing temporal artery biopsy. A review of 98 patients.

BACKGROUND: Although temporal arteritis is a well-recognized syndrome, controversy still exists regarding the optimal approach to diagnosis and treatment of this condition. We undertook this review to further define the spectrum of presenting features and outcomes of patients undergoing temporal artery biopsy. METHODS: We reviewed the records of all patients undergoing temporal artery biopsy over a 5-year period. Presenting features were compared in biopsy-positive and biopsy-negative patients. In patients with positive biopsy specimens, treatment regimens, disease, treatment-related morbidity, and outcomes were recorded. Alternative diagnoses and therapy were reviewed in biopsy-negative patients. RESULTS: Of 98 patients, 30 had positive and 68 had negative biopsy specimens. Biopsy-positive patients had an increased incidence of headache (93% vs 62%), jaw claudication (50% vs 18%), and prior polymyalgia rheumatica (23% vs 3%), but the sensitivity and specificity of these indicators were relatively low. Other clinical and laboratory parameters, including prior steroids and erythrocyte sedimentation rate, were similar between the two groups. In 30 patients with positive biopsy specimens, response to initial high-dose steroid was excellent. Serious manifestations after initial treatment were not seen, but mild flares were common after 1 year of therapy. Steroid-related morbidity was common, and steroids were seldom discontinued (0/22 patients at 1 year, 6/19 patients at 2 years, 5/11 patients at 3 years). In 68 patients with negative biopsy specimens, alternative diagnoses included neurologic diseases (15 patients), "pure" polymyalgia rheumatica (14 patients), and other inflammatory rheumatologic diseases (10 patients). Fourteen patients with negative biopsy specimens were treated for temporal arteritis, and were similar to biopsy-positive patients. CONCLUSIONS: Temporal arteritis remains a challenging condition to diagnose and to treat. Presenting features are seldom helpful in predicting biopsy results. Initial treatment is effective but frequently toxic. Although late disease-related complications are rare, most patients continue to take long-term low-dose steroid therapy.

Musculoskeletal chest wall syndromes in patients with noncardiac chest pain: a study of 100 patients.

One hundred patients with chest pain and negative coronary arteriography were evaluated for musculoskeletal chest wall findings. Sixty-nine patients had chest wall tenderness. Typical chest pain was evoked by palpation in 16 patients. Tender areas were not found in a control group of patients without chest pain. A diagnosis of fibrositis could be made in five patients, including two in whom chest palpation reproduced typical chest pain. The sternal and xiphoid area, left costosternal junctions, and left anterior chest wall were the areas where tenderness was most common, but no significant differences were found comparing locations of tenderness in those with reproduction of typical pain. There was no significant difference in location, exacerbating factors, or other musculoskeletal symptoms among different groups of patients. Thus, most patients with noncardiac chest pain have chest wall tenderness that is not found in a control group without chest pain. However, reproduction of pain by palpation, a more specific diagnostic finding, is found in a minority of these patients.

Osteoarthritis of the knee: effects on gait, strength, and flexibility.

This study examined the differences in gait mechanics, isokinetic knee strength, and flexibility between a group of adults with symptomatic osteoarthritis (OA) of the knee (n = 15) and an age-, mass-, and gender-matched group of control subjects (n = 15). Both groups performed under similar environmental conditions. Our results suggest that patients with symptomatic OA of the knee have poorer flexibility in both the affected and unaffected legs and demonstrate significantly less (p less than .05) knee angular velocity and, to a lesser extent, knee range of motion during gait. They have an increased loading rate in the unaffected leg after heel strike, exert less peak vertical force during pushoff, and are significantly weaker in both the dominant and nondominant legs compared to adults with no lower extremity disease.

Temporal arteritis with low erythrocyte sedimentation rate: a review of five cases.

We compared 5 patients who had biopsy-proven temporal arteritis and erythrocyte sedimentation rates (ESR) less than 50 mm/hour with 25 patients who had temporal arteritis and high ESR and with 10 patients who had negative temporal artery biopsy results and low ESR. Patients with low-ESR temporal arteritis were similar to the other groups, except that they had a higher mean hemoglobin level than the high-ESR group and a significant increase in the percentage of patients (4 of 5) who had a previous diagnosis of polymyalgia rheumatica or had received steroid therapy compared with either of the other groups. The latter finding suggests that even low-dose steroid therapy can lower the ESR in patients with temporal arteritis. We conclude that the ESR is low in only a small percentage of patients with temporal arteritis, and that most of these patients have a history of polymyalgia rheumatica or steroid therapy.