Hypercalcemia from sarcoidosis successfully treated with infliximab.

Sarcoidosis is a systematic inflammatory condition with a variable clinical course. While many patients have a benign, indolent illness, some patients have more severe manifestations. Therapy is determined by an individual patient's disease manifestations and the response to treatment. We report a case of sarcoidosis beginning with lymphadenopathy, initially controlled with steroids and immunosuppressive therapy. Our patient tolerated treatments poorly and developed severe hypercalcemia with progressive renal insufficiency. Intravenous infliximab was given with prompt resolution of hypercalcemia and very gradual improvement in renal function. Discontinuation of therapy resulted in immediate elevation of serum calcium. This patient has now responded for four years to infliximab treatment with no serious adverse events and continued improvement in renal function. Prompt infliximab therapy should be considered for patients with severe hypercalcemia from sarcoidosis unresponsive to steroids or other more conventional treatments.

The 6-month safety and efficacy of abatacept in patients with rheumatoid arthritis who underwent a washout after anti-tumour necrosis factor therapy or were directly switched to abatacept: the ARRIVE trial.

OBJECTIVE: To assess the safety, tolerability and efficacy of abatacept in patients with rheumatoid arthritis (RA) who had failed anti-tumour necrosis factor (TNF) therapy and were switched to abatacept directly or after completing washout. METHODS: In this international, 6-month, open-label trial, patients had active RA, an inadequate response to anti-TNF therapy for 3 months or longer and a disease activity score in 28 joints (DAS28 (C-reactive protein; CRP) of 5.1 or greater. "Washout" patients discontinued anti-TNF therapy 2 months or longer pre-screening; "direct-switch" patients began abatacept ( approximately 10 mg/kg) at their next scheduled anti-TNF therapy dose. RESULTS: 1046 patients were treated (449 washout, 597 direct-switch; baseline characteristics were similar between groups). At 6 months, adverse events (AE; 78.0% vs 79.2%), serious AE (11.1% vs 9.9%) and discontinuations due to AE (3.8% vs 4.0%) and serious AE (2.0% vs 1.3%) were comparable in washout versus direct-switch patients. There were no opportunistic infections. At 6 months, in washout versus direct-switch patients, similar clinically meaningful improvements were seen in DAS28 (CRP) (> or =1.2 unit improvement, 59.5% vs 53.6%, respectively; low disease activity state, 22.5% vs 22.3%; DAS28-defined remission, 12.0% vs 13.7%), physical function (health assessment questionnaire disability index > or =0.22 improvement; 46.3% vs 47.1%) and health-related quality of life (mean change in short-form 36 scores: physical component summary, 5.5 vs 6.1; mental component summary, 4.8 vs 5.4). CONCLUSION: Abatacept demonstrated acceptable safety and tolerability and clinically meaningful efficacy over 6 months in patients with inadequate response to anti-TNF therapy. Results were comparable with or without a washout, supporting direct switching from anti-TNF therapy to abatacept as an option in clinical practice. TRIAL REGISTRATION NUMBER: NCT00124982.

A modified scleroderma skin scoring method.

The extent of skin thickness in scleroderma has been reported to correlate with the degree of internal organ involvement. An objective method for the clinical evaluation of skin involvement (skin score) in scleroderma is described. In this preliminary study, the method was tested in twenty scleroderma patients. An acceptable degree of inter-observer reproducibility was noted. This method is proposed as a means of monitoring the degree of skin involvement and the overall disease activity.

Cellular immunity to collagen and laminin in scleroderma.

Peripheral blood mononuclear cells (PBMC) obtained from scleroderma patients and normal controls were cultured in the presence of types I and IV collagen, intima collagen, laminin, and phytohemagglutinin. PBMC from 9 of 19 patients (47%) demonstrated lymphocyte transformation in response to laminin, and those from 2 of 17 patients (12%) demonstrated reactivity to type IV collagen. None of the patient PBMC were responsive to type I collagen or to intima collagen. Healthy controls failed to demonstrate lymphocyte transformation in response to laminin or collagens. Analysis of clinical data, including age, disease duration, and degree of skin thickening and internal organ involvement, failed to predict the response to laminin or type IV collagen. The significance and disease specificity of this cellular immunity to laminin and, with lower frequency, to type IV collagen, that occurs in some scleroderma patients are unknown.