William S. Wilke

Low-dose Methotrexate Therapy for Ocular Inflammatory Disease

BACKGROUND Methotrexate is a second-line anti-inflammatory agent used in the treatment of rheumatic diseases. At low doses (12.5 mg/week), it is associated with few serious side effects. METHODS Twenty-two patients (5 men, 17 women) with chronic noninfectious ocular inflammatory disease, who had not responded to or who had become intolerant of corticosteroid or alternate cytotoxic agents, were treated weekly with oral low-dose, pulse methotrexate. Treated diseases included chronic uveitis-vitreitis (9), scleritis (4), inflammatory pseudotumor (3), orbital myositis (3), and retinal vasculitis (3). RESULTS Follow-up ranged from 2 to 39 months (mean, 11 months). Response time ranged from 3 to 9 weeks (mean, 5 weeks) after implementation of methotrexate therapy. Sixteen of 22 patients had reduction of inflammatory activity. Fourteen of these 16 patients were able to taper or discontinue corticosteroid therapy. Five patients had complete remission of their disease; six patients did not respond to methotrexate. CONCLUSION Treatment with low-dose methotrexate appears to be effective therapy for steroid-resistant ocular inflammatory disease.

Low dose oral methotrexate in rheumatoid arthritis: An uncontrolled trial and review of the literature☆

New therapeutic alternatives are needed for patients with progressive RA unresponsive to gold or D-penicillamine. Azathioprine and cyclophosphamide can be effective but have been linked with the development of lymphoreticular malignancies. In an effort to exploit a less toxic agent, we have been impressed by the results and minimal toxicity of low dose oral MTX. Extensive application of this regimen in psoriasis and psoriatic arthritis indicates that low dose MTX does not have an unusual risk for developing cancer. In addition, prior experience with other rheumatic disorders and preliminary studies on the mechanism of action suggest a potential value in RA. We present our initial retrospective results in 28 patients with refractory RA given low dose oral MTX over the past 2.5 yr. An apparent positive response was noted in 19 of these patients (67%) and is similar to the experience of other clinicians. At the same time, the toxicity has been low and, with one exception, amenable to dose modification. Methotrexate in various regimens is being increasingly employed in refractory RA. Issues concerning the pharmacology and potential toxicity are, therefore, important. These topics are reviewed with emphasis on low dose therapy and hepatotoxicity. Despite the encouraging preliminary results it is unclear whether MTX can prevent erosions or improve long-term function and quality of life in RA. There are still no controlled perspective studies comparing MTX to placebo or other immunosuppressive agents in RA. Although short-term toxicity is low, long-term toxicity, especially hepatic, is uncertain. As a result, a controlled, long-term prospective study is necessary.

Folate supplementation in methotrexate-treated rheumatoid arthritis patients

Two hundred rheumatoid arthritis (RA) patients taking low dose methotrexate (MTX) were evaluated for adverse effects. During a mean follow up of 41.5 months, the mean cell volume (MCV) was elevated at some time during the course of treatment in 42 patients. The MCV was normal in the remaining 158 patients. One hundred ninety-eight patients were treated simultaneously with oral folic acid. With the exception of heartburn, which was seen more often in the high MCV group, there was no difference in the frequency of adverse effects attributable to MTX between groups. Severity of side effects and the frequency of MTX dose reduction and MTX discontinuation due to toxicity were also similar between groups. This analysis suggests that elevation of MCV in RA patients treated simultaneously with MTX and folate does not predict MTX toxicity. The authors also discuss the mechanism of action of MTX with regard to folate metabolism.

5 Large vessel vasculitis (giant cell arteritis, Takayasu arteritis)

Giant cell arteritis and Takayasu arteritis are separate but similar idiopathic diseases clinically characterized by constitutional symptoms, shared surrogate markers of systemic inflammation and indistinguishable granulomatous pan-arteritis of large vessels. This review emphasizes and analyses changing perceptions about the diseases. Recent series suggest that aortic involvement in giant cell arteritis may be more common than was previously appreciated. The case for and against inflammatory arthritis in giant cell arteritis is discussed. Ethnic new geographical variation in Takayasu arteritis-disease expression is reviewed. New philosophies of treatment are presented for both diseases. Prognosis in giant cell arteritis and its relationship to treatment is analysed. The utility of the laboratory for diagnosis and monitoring disease activity is appraised for each.

Pilot study to assess the frequency of fibromyalgia, depression, and sleep disorders in patients with granulomatosis with polyangiitis (Wegener's)

To assess the frequency of fibromyalgia syndrome (FMS), depression, and sleep disorders in patients with granulomatosis with polyangiitis (Wegeners) (GPA).

Diagnosis, etiology, and therapy of fibromyalgia.

ConclusionFMS is an entity and an illness. The symptoms, and the mechanisms responsible for them, are very real. Recognition that these mechanisms are important in all distressed patients results in proper diagnosis and treatment. Study of FMS has provided better understanding of a variety of symptoms experienced by distressed patients, and legitimizes its existence. Incorporation of cognitive-behavioral training into treatment programs may improve outcome.

Fibromyalgia and bipolar disorder: a potential problem?

OBJECTIVE To screen patients with fibromyalgia for bipolar disorder and to determine if there were any clinical clues, other than the Mood Disorders Questionnaire (MDQ), which might suggest a diagnosis of comorbid bipolar disorder. METHODS A total of 128 consecutive new fibromyalgia patients referred to a tertiary care center rheumatology practice were enrolled and assessed using a standard clinical protocol that included the completion of four screening questionnaires: (i) MDQ for bipolar disorder, (ii) Beck Depression Inventory (BDI) for depression, (iii) Epworth Sleepiness Scale (ESS) for daytime sleepiness, and (iv) Fibromyalgia Impact Questionnaire Disability Index (FIQ-DI) to assess for functional capacity. RESULTS A quarter of the fibromyalgia subjects, 25.19%, had a positive screen for bipolar disorder (MDQ >or= 7); 78.12% were clinically depressed (BDI >or= 10); and 52.13% reported daytime sleepiness (ESS >or= 10). Fibromyalgia subjects who screened positive for bipolar disorder had more severe depression than those with a negative screen [median BDI: 26.0 (19.0, 32.0) versus 15.0 (9.0, 24.0), p < 0.001]. CONCLUSIONS We report a high prevalence of positive testing for bipolar disorder in this fibromyalgia cohort. Clinical data and questionnaire instruments other than nonspecific high depression severity failed to identify these patients. Since the norepinephrine serotonin reuptake inhibitors duloxetine and milnacipran have been recently approved by the U.S. Food and Drug Administration for the treatment of fibromyalgia, and because patients with bipolar disorder may experience destabilization of mood when treated with such agents, patients with fibromyalgia should be systematically screened for bipolar disorder prior to treatment.

Spondyloarthropathy and Hidradenitis Suppurativa

Excerpt To the editor: Rosner and associates (1) recently reported ten patients with spondyloarthropathy associated with hidradenitis suppurativa and acne conglobata. We report a case that is simil...

Non-surgical synovectomy

Summary Rheumatoid patients with intractable knee effusions may benefit from medical or radio-isotopic synoviorthesis. These offer more convenient, less costly alternatives to surgery with similar long-term outcome. Temporary symptomatic relief may be obtained, but disease progression is unaffected. Potential adverse effects include development of osteoarthrosis with osmic acid and teratogenicity and mutagenicity with alkylating agents and radioisotopes.

Fibromyalgia and Obesity: The Association Between Body Mass Index and Disability, Depression, History of Abuse, Medications, and Comorbidities.

AimThe aim of this study was to determine the frequency of increasing body mass index (BMI) in fibromyalgia (FM) and to understand the impact of increasing BMI on FM. MethodsPatients with FM were divided into 3 BMI classifications: normal weight, overweight, and obese. We then sought relationships of increasing BMI to core process FM variables and symptoms and disability, as well as medical comorbidities and demographic, socioeconomic, psychiatric, and treatment data. ResultsOf 224 patients, 0.4% were underweight; 25.9%, normal weight; 29.9%, overweight; 43.8%, obese. We found no differences within groups with regard to age, gender, demographics, FM symptoms, FM impact questionnaire scores, and meeting the American College of Rheumatology 1990 criteria and FM survey criteria. Patients with FM who are obese, compared with normal-weight patients, have higher depression scores measured by Patient Health Questionnaire 9 (13.2 [6.6] vs 10.5 [6], P = 0.03), report increased disability by Health Assessment Questionnaire Disability Index scores (1.3 [0.6] vs 0.9 [0.6], P < 0.001), exercise less (8.4% vs 25.4%, P = 0.003), have more medical comorbidities (1.5 [1.3] vs 0.7 [0.9], P < 0.001), take more medications for FM (3.5 [2.2] vs 2.1 [1.8], P < 0.001), and report higher prevalence of abuse (48% vs 33.9%, P = 0.016) and sexual abuse (17.3% vs 6.8%, P = 0.01). ConclusionsCompared with normal-weight patients, obese FM patients are more disabled, report more medical comorbidities, exercise less, have a higher incidence of abuse, report increased depressive symptoms, and take more medications for FM. Bivariate analysis showed association of increasing BMI with the Health Assessment Questionnaire Disability Index (not FM impact questionnaire) and depression. We confirm that the prevalence of overweight and obesity is high in FM and believe that physicians treating FM should be aware of our bivariate linear correlations and discuss weight loss with their FM patients. Even if increasing BMI is not intrinsic to FM, it contributes to poor mood and functional outcome and should be a treatment goal.