Cachexia has only one meaning

Abstract

Cachexia means any general reduction in vitality and strength of body and mind resulting from any debilitating chronic disease. Cachexia is defined as loss of weight, muscle atrophy, fatigue, weakness, and loss of appetite in someone who is not actively trying to lose weight. These features markedly distinguish cachexia from starvation. Cachexia can be a sign of various underlying disorders. Physicians confronted with cachexia generally consider the possibility of cancer, certain infectious diseases such as tuberculosis or AIDS, parasitic diseases, autoimmune disorders, or chronic heart failure. Cachexia physically weakens patients to a state of immobility stemming from loss of appetite, asthenia, and anemia. The response to standard treatments is poor [1]. The above sounds straightforward enough. However, in PubMed, about 4,500 papers have been published on cachexia; interestingly, >1,000 of these papers are reviews. Such a relationship raises suspicion that little is known about the subject. Weber et al. [2], in this issue, introduce a novel inverse marker of clinical muscle wasting, namely, the measurement of plasma myoglobin concentration. Their report is immediately disconcerting, as the title of their paper ends in a question mark, implying a lack of self-confidence on behalf of the authors. However, the entire cachexia field is riddled with question marks. Weber et al. studied 17 cancer patients, the prototype patients exhibiting cachexia. The patients had lost >20% of their body mass without intending to do so. A suitable matched control group of 27 subjects was recruited who had lost no weight. Plasma myoglobin, creatine kinase, quadriceps muscle cross-sectional area (by magnetic resonance imaging), muscle morphology from biopsies of the Vastus lateralis, body cell mass by impedance, and maximal oxygen uptake (VO2 max) were all measured in these patients and control subjects. To no surprise, myoglobin, muscle cross-sectional area, body cell mass, and VO2 max were all lower in cachexic cancer patients than in healthy controls. However, in a multiple-regression analysis, myoglobin (hypomyoglobinemia) won out over other indicators (27 μg/dl vs 42 μg/dl); or did it? The authors found that myoglobin was directly correlated with cross-sectional muscle mass and was better than reduced creatine kinase in this regard, although the magnitude of the creatine kinase reduction was greater. The fact that creatine kinase and myoglobin were not elevated is of some mechanistic interest, since active muscle destruction would have featured elevation of both myoglobin and creatine kinase. Weber et al. [2] performed muscle biopsies on 11 patients and 15 control subjects. A marked size reduction in type 1 and 2 fibers occurred in the cachexic patients that corresponded to the reduction in cross-sectional area and correlated significantly with the reduced myoglobin levels. What causes cachexia anyway? Are the diverse chronic (or not so chronic) cachexia conditions related? The cachexic patients presented by Weber et al. [2] all had cancer. Skipworth et al. [3] recently reviewed cancer cachexia. They stressed the role of host–tumor interaction, particularly pro-inflammatory cytokines. Tumor cells release cytokines and other factors locally to promote inflammation and thereby activate a local response. For instance, proteolysis-inducing factor (PIF) is a sulphated glycoprotein that produces muscle wasting in tumor-free mice when injected. The material has been identified in patients with pancreatic, breast, ovarian, lung, colon, rectum, and liver J Mol Med (2007) 85:783–785 DOI 10.1007/s00109-007-0231-0