Case Presentation: Cachexia or wasting syndrome is characterized by loss of weight, muscle atrophy, fatigue, weakness, loss of appetite and unintentional weight loss. It is most commonly seen in malignancy and may also be the clinical presentation of rheumatoid arthritis.Case Report:
A 50 year old female presented because of fifty pound weight loss and loss of appetite over the last 2 years. She also complained of fatigue, bilateral wrist and knee pain since the last few months. On admission she was also found to have elevated blood sugar (409) and was diagnosed with new onset diabetes with HgA1c 14.2%. Next, immunologic work up showed elevated Anti-CCP (>250) and elevated rheumatoid factor. Patient was diagnosed with rheumatoid arthritis and new onset diabetes. She was started on appropriate medical therapy consisting of methotrexate and steroids for rheumatoid arthritis and she was started on insulin/metformin for diabetes. Over the course of few months she had improvement of joint pain and her A1C was 5.9. However despite her well controlled diabetes, patient had no changes in weight and was still cachectic, with no other signs of malignancy. Plan was made to start trial of TNF antagonist in addition to methotrexate.
Discussion: Rheumatoid cachexia (RC) is primarily TNF mediated and is more common in patients with diabetes. Several potential mechanisms have been investigated, and the etiology is probably multifactorial including excessive cytokine production, physical inactivity, and increased peripheral insulin resistance. The inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß) are thought to be centrally involved in the pathogenesis of RA. Concentrations of TNF and IL-1ß are high in patients with active RA. Peripheral insulin action is reduced in patients with RA. Insulin acts to inhibit muscle protein degradation, thus making it a potent anabolic hormone. Therefore, decrease in insulin action causes muscle loss in RA. The etiology of reduced peripheral insulin action in RA is not known, but TNF-α may interfere with insulin receptor signaling and may be a contributing factor. Due this mechanism, patients with rheumatoid arthritis may be more prone to developing diabetes with cachexia.
Conclusions: It is known that RC increases morbidity and mortality in patients with RA. It is therefore important to prevent or at least slow the advance of this complication. As physicians we focus on the joints and their protection in RA, but we should step back and evaluate the muscle and fat mass as well, and seek to protect our patients from the metabolic complications of RA in addition to its rheumatic sequelae. Available therapeutic methods include increasing physical activity and maintaining a diet adequate in protein. Anti-TNF-α therapy is an intervention that seems to improve RC, but more investigation is needed to prove its efficacy and safety.