Idiopathic hypertrophic pachymeningitis.

BACKGROUND: Hypertrophic pachymeningitis is an uncommon disorder that causes a localized or diffuse thickening of the dura mater and has been associated with rheumatoid arthritis, syphilis, Wegener's granulomatosis, tuberculosis, and cancer. Few series of the idiopathic variety have been described, particularly with respect to MRI correlation to clinical outcome and treatment. OBJECTIVE: To investigate the clinical and laboratory evaluation, course, and treatment of patients with idiopathic hypertrophic pachymeningitis (IHP), to correlate the MRI findings with the clinical course, and to review the literature on IHP. METHODS: Retrospective case series of 12 patients (9 men, 3 women), with a mean age of 55 years (range 39 to 88 years), who had IHP by imaging studies, meningeal or orbital biopsy, or both. The clinical features, laboratory evaluation, contrast-enhanced MRI, treatment, and clinical outcome were documented for each case. The mean duration of follow-up was 3.5 years (range 3 months to 16 years). RESULTS: The main clinical features at presentation were headache (11 cases), loss of vision (7 cases), diplopia (4 cases), papilledema (2 cases), other cranial nerve involvement (3 cases), ataxia (2 cases), and seizures (1 case). On the initial MRI, the location of abnormal enhancement of the dura mater correlated with the clinical findings and the sphenoid wing area was affected in all patients. The sedimentation rate was elevated in five cases. The CSF had increased protein in six cases and lymphocytosis in four cases. Biopsy of the dura mater in five cases and the orbital soft tissue in one case showed infiltrates of small mature lymphocytes, plasma cells, and epithelioid histiocytes, but no neoplasia, vasculitis, or infectious agents. Cultures of the CSF and biopsy material remained sterile. Corticosteroid therapy improved the vision in 7 of 8 cases and controlled headache in 10 of 11 cases. Five cases had partial improvement of other neurologic symptoms and signs. Recurrence developed with steroid tapering in six cases. One case had progressive deterioration and died. In four cases methotrexate or azathioprine was added with reduction of the steroid dose. Follow-up MRI performed in 11 patients correlated 80% with the clinical state (p = 0.01). CONCLUSION: IHP can be suspected on MRI and defined pathologically on biopsy. Untreated, the clinical course is usually marked by severe headache and progressive neurologic deterioration and vision loss. Although initially steroid-responsive, clinical manifestations frequently recur with corticosteroid taper, requiring the addition of immunosuppressive agents in some cases.

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.

Visual function and quality of life among patients with giant cell (temporal) arteritis.

OBJECTIVE: To investigate patient perception of visual and systemic disability associated with giant cell arteritis (GCA) and whether the perceived disability can be correlated with visual performance measures. METHODS: We prospectively evaluated and compared the visual performance and quality of life survey for 20 patients with GCA after 4 to 5 weeks of corticosteroid therapy and after one year of therapy. We measured visual acuity, contrast sensitivity, and threshold perimetry and patients completed the Activities of Daily Vision Scale (ADVS) and the short-form of the Health Survey (SF-36). The results were grouped by GCA affected or unaffected eye or by better or worse eye and reported as a decimal and percent impairment for acuity, log units for contrast, mean deviation and the Advanced Glaucoma Intervention Study (AGIS) score for perimetry. The results for patients with and without visual loss were compared. Correlation analyses between ADVS categories and visual performance measures, SF-36 categories and the presence of visual loss, total corticosteroid dose, systemic symptoms, secondary hypertension or diabetes mellitus, the presence of vertebral fracture, and visual performance were performed. RESULTS: Day driving was the only ADVS category significantly reduced at baseline in patients with visual loss (62.5) compared with those without visual loss (96.3, P = 0.04). Modest to moderate correlations between ADVS categories were most frequent for percent binocular acuity impairment with day driving (r = -0.62, P = 0.017), with distance vision (r = -0.5, P = 0.02), and with glare (r = -0.59, P = 0.006); and the AGIS score of the worse eye with day driving (r = -0.66, P = 0.01), with near vision (r = -0.49, P = 0.03), and with glare (r = -0.48, P = 0.04). The baseline SF-36 scores did not correlate with the presence of vision loss at baseline or systemic complications. The ADVS and SF-36 scores were similar at one year. The total dose of corticosteroids only had a modest correlation with the one-year mental health score (r = -0.45, P = 0.05), but there was no correlation between SF-36 scores and other systemic side effects of steroid therapy. CONCLUSION: Except for the day driving score, the ADVS did not differ between patients with and without visual loss. The SF-36 did not distinguish between patients with and without visual loss and did not reveal significant trends. The ADVS and SF-36 did not reveal significant disability in GCA patients and there were no strong correlations with any visual performance or systemic measures.

Paraneoplastic rheumatic syndromes.

Paraneoplastic rheumatic syndromes are challenging from both a clinical and research standpoint. Progress over the past decade has provided clarification of clinical syndromes. At the same time, our increasing ability to define and quantitate mediators of inflammation is shedding new light on pathogenesis. In turn, this understanding may answer questions regarding more common rheumatic diseases.

Visual performance in giant cell arteritis (temporal arteritis) after 1 year of therapy.

AIMS: To determine if patients with giant cell arteritis (GCA) treated with corticosteroids develop delayed visual loss or drug related ocular complications. METHODS: In a multicentre prospective study patients with GCA (using precise diagnostic criteria) had ophthalmic evaluations at predetermined intervals up to 1 year. The dose of corticosteroid was determined by treating physicians, often outside the study, with the daily dose reduced to the equivalent of 30-40 mg of prednisone within 5 weeks. Subsequently, treatment guidelines suggested that the dose be reduced as tolerated or the patient was withdrawn from steroids in a period not less than 6 months. RESULTS: At presentation, of the 22 patients enrolled, seven patients had nine eyes with ischaemic injury. Four eyes had improved visual acuity by two lines or more within 1 month of starting corticosteroids. No patients developed late visual loss as the steroid dose was reduced. At 1 year the visual acuity, contrast sensitivity, colour vision, and threshold perimetry were not significantly different from the 4-5 week determinations. At 1 year, there were no significant cataractous or glaucomatous changes. At 2 months, there was no difference in systemic complications between patients who received conventional dose (60-80 mg per day) or very high doses (200-1000 mg per day) of corticosteroids at the start or early in the course. CONCLUSIONS: Patients with GCA related visual loss can improve with treatment. Corticosteroids with starting doses of 60-1000 mg per day, with reduction to daily doses of 40-50 mg per day given for 4-6 weeks, and gradual dose reduction thereafter, as clinically permitted, did not result in delayed visual loss. There were no significant drug related ophthalmic complications.

Insufficiency fracture of the femoral head: MR imaging in three patients.

OBJECTIVE: The purpose of this report is to describe three patients in whom a presumptive diagnosis of insufficiency fracture of the femoral head was made on the basis of clinical and MR imaging findings. CONCLUSION: Femoral head insufficiency fracture should be included in the differential diagnosis of hip pain in the osteopenic elderly patient.

Inhibition of methotrexate-induced rheumatoid nodulosis by colchicine: evidence from an in vitro model and regression in 7 of 14 patients.

Methotrexate is one of the most effective and widely used medications in the treatment of rheumatoid arthritis. One poorly understood side effect of methotrexate is increased rheumatoid nodule formation, a phenomenon which has been reported to occur in some patients despite suppression of synovial inflammation. Using an in vitro model of nodulosis, induction of monocyte differentiation into multinucleated giant cells, we previously found that methotrexate promotes this inflammatory response by a mechanism dependent on adenosine A1 receptor stimulation. In the current study, we tested the effects of an A1 signal inhibitor, the commonly available anti-inflammatory medication colchicine, and found that it markedly inhibited nodulosis in vitro as well as in seven of fourteen patients in a clinical series.

Behçet-type vasculopathy in a patient without the diagnostic features of Behçet's disease.

Behçet's disease is a multisystem inflammatory disorder which may involve the vascular system. The vasculopathy of Behçet's disease is distinctive among the vasculitides in that it involves both arteries and veins, and vessels of all sizes. Most published diagnostic criteria for Behçet's disease include the classic triad of orogenital ulceration and ocular inflammation. In this report, we describe a patient who had a vasculopathy fitting the Behçet's disease type, but who lacked the other characteristic or diagnostic features of Behçet's disease. This case illustrates an unusual presentation and natural history of a complex vasculitic disease.

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.

Recovery from pulmonary hypertension in an adolescent with mixed connective tissue disease.

This paper describes the case of an 11 year old girl who presented with mixed connective tissue disease which was complicated by the development of pulmonary hypertension. This case is unique with respect to the young age of onset, the serial non-invasive method used to follow the disease process, and the favourable response to treatment with vasodilator and anti-inflammatory drugs.

Antemortem diagnosis of giant cell aortitis.

A 67-year-old man well while receiving steroid therapy for giant cell arteritis, developed symptoms of ischemic heart disease and was found to have critical left main coronary stenosis. An aortic biopsy at the time of bypass grafting revealed giant cell aortitis. We discuss the finding of clinically discordant aortitis; the etiology of the concurrent coronary stenosis and therapy with prednisone-dapsone.

Autoimmune optic neuropathy: evaluation and treatment.

Fourteen patients, 12 of whom were women, with an age range from 26 to 56 years, presented with progressive or recurrent optic neuropathy, despite conventional doses of corticosteroid, and laboratory evidence of collagen vascular disease. The visual loss was severe and most had an acuity less than 20/200. Megadose corticosteroid therapy improved the vision in 11 of the 12 patients. Continued oral prednisone and cytotoxic drugs were necessary to maintain vision in nine patients. Patients with autoimmune optic neuropathy must be differentiated from cases with idiopathic optic neuritis or multiple sclerosis to facilitate the appropriate therapy.

Proliferative changes of the hip in juvenile rheumatoid arthritis.

A ring of proliferative osteophytes at the junction of the femoral head and neck has been described as a characteristic finding in patients with ankylosing spondylitis. A review of 55 cases of juvenile rheumatoid arthritis, without evidence of sacroiliitis, revealed an identical ridge of osteophytes in 5.

Fate of antigen after intravenous and intraarticular injection into rabbits.

To determine the manner in which small protein antigens enter the synovium and are localized, horseradish peroxidase (molecular weight 40,000) was injected by intravenous and intraarticular routes. Passage of antigen from capillary lumen to joint space and vice versa occurred primarily across fenestrated vessels. Antigen localized to collagen fibers and lining cells. At low concentrations of antigen, antigen was taken up predominantly by marcophages, whereas at higher concentrations both macrophages and fibroblast-like lining cells accumulated antigen.