Durable medication-free remission of sarcoidosis following discontinuation of anti-tumor necrosis factor-α therapy.

BACKGROUND: Monoclonal antibodies against tumor necrosis factor-alpha (TNF-α) have been used successfully in the treatment of sarcoidosis, but optimal duration of their use is unclear. Published studies have consistently suggested that withdrawal of therapy typically results in prompt disease relapse. The aim of this study is to identify and characterize patients with sarcoidosis in whom medication-free disease remissions were induced and sustained following treatment with and subsequent discontinuation of anti-TNF-α antibodies. METHODS: A retrospective chart review was conducted to identify patients satisfying three criteria: (1) histopathological documentation of sarcoidosis; (2) disease remission induced by anti-TNF-α antibodies, since discontinued; and (3) subsequent maintained clinical, radiological, and laboratory remission for at least one year without ongoing immunomodulatory medications. RESULTS: Eight patients whose sarcoidosis remained in medication-free remissions were identified. The duration of remissions ranged from 22 to 132 months. All patients had previously had inadequate response to corticosteroid therapy and at least one steroid-sparing agent, prompting the use of anti-TNF-α antibodies. Before anti-TNF-α therapy was discontinued, all eight patients had been able to remain off systemic corticosteroid therapy for at least a year (range 12-130 months). CONCLUSIONS: These observations suggest that in select sarcoidosis patients, anti-TNF-α antibodies may induce prolonged medication-free remissions. The sustained capacity to remain off corticosteroids during anti-TNF-α therapy may be a favorable prognostic indicator for maintained disease remission. These findings may help to develop principles for optimal utilization of these agents and to shed light onto the potential pathogenic role of TNF-α in this disease.

Pilot study of a multidisciplinary gout patient education and monitoring program.

OBJECTIVE: Gout patient self-management knowledge and adherence to treatment regimens are poor. Our objective was to assess the feasibility and acceptability of a multidisciplinary team-based pilot program for the education and monitoring of gout patients. METHODS: Subjects completed a gout self-management knowledge exam, along with gout flare history and compliance questionnaires, at enrollment and at 6 and 12 months. Each exam was followed by a nursing educational intervention via a structured gout curriculum. Structured monthly follow-up calls from pharmacists emphasized adherence to management programs. Primary outcomes were subject and provider program evaluation questionnaires at 6 and 12 months, program retention rate and success in reaching patients via monthly calls. RESULTS: Overall, 40/45 subjects remained in the study at 12 months. At 12 months, on a scale of 1 (most) to 5 (least), ratings of 3 or better were given by 84.6% of subjects evaluating the usefulness of the overall program in understanding and managing their gout, 81.0% of subjects evaluating the helpfulness of the nursing education program, and 50.0% of subjects evaluating the helpfulness of the calls from the pharmacists. Knowledge exam questions that were most frequently answered incorrectly on repeat testing concerned bridge therapy, the possibility of being flare-free, and the genetic component of gout. CONCLUSIONS: Our multidisciplinary program of gout patient education and monitoring demonstrates feasibility and acceptability. We identified variability in patient preference for components of the program and persistent patient knowledge gaps.

Sarcoidosis: Rheumatology perspective.

Sarcoidosis is a systemic inflammatory granulomatous disease for which rheumatologists are uniquely trained and qualified to treat. Historically, sarcoidosis has been managed within silos of medical subspecialties, but with increased appreciation of the systemic nature of this disorder and the availability of more therapeutic options, it is clear that a multidisciplinary approach, with the rheumatologist as a key component, can offer more optimal care. This manuscript reviews clinically relevant immunology and pathophysiology, diagnostic issues, management decision-making, and therapeutics in the care of patients with sarcoidosis. Issues particularly relevant to rheumatologists are highlighted. These include aiding in establishing diagnosis; recognition of disease manifestations involving bone, joint, and muscle; management of calcium metabolism and metabolic bone disease; and formulation and implementation of anti-inflammatory and immunomodulatory therapies.

The CY domain of the Fcgamma RIa alpha-chain (CD64) alters gamma-chain tyrosine-based signaling and phagocytosis.

Although the cytoplasmic domain of the human FcgammaRIa alpha-chain lacks tyrosine-based phosphorylation motifs, it modulates receptor cycling and receptor-specific cytokine production. The cytoplasmic domain of FcgammaRIa is constitutively phosphorylated, and the inhibition of dephosphorylation with okadaic acid, an inhibitor of type 1 and type 2A protein serine/threonine phosphatase, inhibits both receptor-induced activation of the early tyrosine phosphorylation cascade and receptor-specific phagocytosis. To explore the basis for these effects of the cytoplasmic domain of FcgammaRIa, we developed a series of human FcgammaRIa molecular variants, expressed in the murine macrophage cell line P388D1, and demonstrate that serine phosphorylation of the cytoplasmic domain is an important regulatory mechanism. Truncation of the cytoplasmic domain and mutation of the cytoplasmic domain serine residues to alanine abolish the okadaic acid inhibition of phagocytic function. In contrast, the serine mutants did not recapitulate the selective effects of cytoplasmic domain truncation on cytokine production. These results demonstrate for the first time a direct functional role for serine phosphorylation in the alpha-chain of FcgammaRIa and suggest that the cytoplasmic domain of FcgammaRI regulates the different functional capacities of the FcgammaRIa-receptor complex.