Rheumatoid Arthritis: Keen CL

Borchers AT, Selmi C, Cheema G, Keen CL, Shoenfeld Y, Gershwin ME. · Department of Nutrition, USA. · Autoimmun Rev. · Pubmed #16697970 No free full text.

Abstract: One of the most enigmatic problems in rheumatology has been juvenile idiopathic arthritis (JIA). Firstly, the classification has often depended on clinical features that have variations between patients. Secondly, there are different classification schemes in usage and there are few objective serologic tests that help to resolve the differences between the criteria sets. Thirdly, only recently have significant advances been made in understanding the immunology and immunopathology of JIA and, in particular, new treatment options. In this review, we will define the historical basis of JIA and emphasize not only the clinical features, but also the immunological characteristics, the pathogenesis, and treatment options. We will also discuss, in particular, quality of life, psychosocial functioning, socioeconomic outcomes and the difficult area of mortality. Finally, this review will attempt to bridge genetic observations with clinical presentation. JIA represents a relatively common syndrome of pediatric onset rheumatologic disease and a better understanding of the clinical definition, the relationship to autoimmunity, and novel treatments with biologic agents are critical for improved patient care.

Borchers AT, Keen CL, Cheema GS, Gershwin ME. · Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, 95616, USA. · Semin Arthritis Rheum. · Pubmed #15305245 No free full text.

Abstract: OBJECTIVE: To address the long-term efficacy and toxicity issues related to methotrexate (MTX) and compare it with other disease-modifying antirheumatic drugs (DMARDs). METHODS: Review of the international literature on the clinical use of MTX in rheumatoid arthritis (RA) disease. RESULTS: MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival. The toxicity profile of MTX is well established and includes serious and sometimes fatal liver disease, pneumonitis, and cytopenias. Hence, regular and careful monitoring of patients taking MTX is essential, particularly when MTX is combined with other DMARDs. Folate supplementation can reduce some of the most common side effects of MTX, but it has not yet been established whether this translates into a reduced risk of serious disease. Another potential approach to reducing the toxicity of MTX is therapeutic drug monitoring and dose individualization. However, correlations between pharmacokinetics and clinical response have been addressed in only a few studies and with conflicting results. CONCLUSIONS: MTX is an effective DMARD with a relatively safe profile compared with other therapies. Folate supplementation can significantly reduce the risk of MTX toxicity. Finally, it is essential that patients be monitored carefully to reduce the potential serious toxicities of MTX.

Borchers AT, Keen CL, Gershwin ME. · Department of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, TB192, School of Medicine, Davis, Calif. 95616, USA. · Compr Ther. · Pubmed #14606345 No free full text.

Abstract: Corticosteroids are amongst the most common drugs used in clinical medicine. Prudent management of patients is essential to avoid steroid-induced complications.

Borchers AT, Naguwa SM, Keen CL, Gershwin ME. · Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, TB192, School of Medicine, Davis, CA 95616, USA. · Clin Rev Allergy Immunol. · Pubmed #12794264 No free full text.

Abstract: Sjögren's syndrome (SS) is an autoimmune disease characterized by the sicca symptoms of dry eyes and dry mouth. Glandular dysfunction is thought to arise from destruction associated with lymphocytic infiltration. The degree of glandular destruction, however, does not correlate with the severity of sicca symptoms, suggesting that other mechanisms are involved, including abnormalities in parasympathetic neurotransmission. Autoantibodies against the muscarinic acetylcholine receptor have been implicated in this process, but multiple other autoantibodies have been found. Cytokines elaborated in the inflammatory lesions also appear to be involved and dysregulation of apoptosis are also involved in the pathogenesis of SS. A new two-stage model of SS has been proposed. First, there is a lymphocyte-independent phase during which inappropriate apoptosis results in the generation of apoptotic autoantigens which then attract lymphocytes. Subsequently, in the second lymphocyte-dependent phase, an immune attack causes further cell death and salivary dysfunction. Although the disease generally takes a rather stable and benign course, patients with SS have a significant risk of developing B cell lymphoma.