Cachexia
Cachexia | |
---|---|
Other names | Wasting syndrome |
Physical Medicine and Rehabilitation | |
Symptoms | sudden weight loss, altered eating signals |
Prognosis | very poor |
Frequency | 1% |
Deaths | 1.5 to 2 million people a year |
Cachexia (
The term is from Greek κακός kakos 'bad' and ἕξις hexis 'condition'.
Causes
Cachexia can be caused by diverse medical conditions, but is most often associated with end-stage cancer, known as cancer cachexia. About 50% of all cancer patients develop cachexia. Those with upper gastrointestinal and pancreatic cancers have the highest frequency of developing a cachexic symptom. Prevalence of cachexia rises in more advanced stages and is estimated to affect 80% of terminal cancer patients.[2]
Mechanism
The exact mechanism in which these diseases cause cachexia is poorly understood, and likely is multifactorial with multiple disease pathways involved.
Although many different tissues and cell types may be responsible for the increase in circulating cytokines, evidence indicates tumors themselves are an important source of factors that may promote cachexia in cancer. Tumor-derived molecules such as lipid mobilizing factor,
There is also evidence of alteration in feeding control loops in cachexia. High levels of
Diagnosis
Diagnostic guidelines and criteria to differentiate from sarcopenia have only recently[when?] been proposed despite the prevalence of cachexia and varying criteria; the primary features of cachexia include progressive depletion of muscle and fat mass, reduced food intake, abnormal metabolism of carbohydrate, protein, and fat, reduced quality of life, and increased physical impairment.[9]
Historically, body weight changes were used as the primary metrics of cachexia, including low body mass index and involuntary weight loss of more than 10%. Using weight alone is limited by the presence of edema, tumor mass and the high prevalence of obesity in the general population.[10] Weight-based criteria do not take into account changes in body composition, especially loss of lean body mass.
In the attempt to include a broader evaluation of the burden of cachexia, diagnostic criteria using assessments of laboratory metrics and symptoms in addition to weight have been proposed. The criteria included weight loss of at least 5% in 12 months or low body mass index (less than 22 kg/m2) with at least three of the following features: decreased muscle strength, fatigue, anorexia, low fat‐free mass index, or abnormal biochemistry (increased inflammatory markers, anemia, low serum albumin).[11] In cancer patients, cachexia is diagnosed from unintended weight loss of more than 5%. For cancer patients with a body mass index of less than 20 kg/m2, cachexia is diagnosed after the unintended weight loss of more than 2%. Additionally, it can be diagnosed through sarcopenia, or loss of skeletal muscle mass.[12]
Laboratory markers are used in evaluation of people with cachexia, including
In the effort to better classify cachexia severity, several scoring systems have been proposed including the Cachexia Staging Score (CSS) and Cachexia Score (CASCO). The CSS takes into account weight loss, subjective reporting of muscle function, performance status, appetite loss, and laboratory changes to categorize patients into non-cachexia, pre-cachexia, cachexia, and refractory cachexia. The Cachexia SCOre (CASCO) is another validated score that includes evaluation of body weight loss and composition, inflammation, metabolic disturbances, immunosuppression, physical performance, anorexia, and quality of life.[10]
Evaluation of changes in body composition is limited by the difficulty in measuring muscle mass and health in a non-invasive and cost-effective way. Imaging with quantification of muscle mass has been investigated including bioelectrical impedance analysis, computed tomography, dual-energy X-ray absorptiometry (DEXA), and magnetic resonance imaging but are not widely used.[10]
Definition
Identification, treatment, and research of cachexia have historically been limited by the lack of a widely accepted definition of cachexia. In 2011, an international consensus group adopted a definition of cachexia as "a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that can be partially but not entirely reversed by conventional nutritional support."[13]
Cachexia differs from weight loss due to malnutrition from malabsorption, anorexia nervosa, or anorexia due to major depressive disorder. Weight loss from inadequate caloric intake generally causes fat loss before muscle loss, whereas cachexia causes predominantly muscle wasting. Cachexia is also distinct from sarcopenia, or age-related muscle loss, although they often co-exist.[11]
Treatment
The management of cachexia depends on the underlying cause, the general prognosis, and the needs of the person affected.
Exercise
Therapy that includes regular physical exercise can be recommended for the treatment of cachexia due to the positive effects of exercise on skeletal muscle but current evidence remains uncertain as to its effectiveness, acceptability and safety for cancer patients.[16] Individuals with cachexia generally report low levels of physical activity and few engage in an exercise routine, owing to low motivation to exercise and a belief that exercising may worsen their symptoms or cause harm.[17]
Medications
Appetite stimulant medications are used to treat cachexia to increase food intake, but are not effective in stopping muscle wasting and may have detrimental side effects.
Nutrition
The increased metabolic rate and appetite suppression common in cachexia can compound muscle loss.[7] Studies using a calorie-dense protein supplementation have suggested at least weight stabilization can be achieved, although improvements in lean body mass have not been observed in these studies.[6]
Supplements
Administration of exogenous amino acids have been investigated to serve as a protein-sparing metabolic fuel by providing substrates for both muscle metabolism and gluconeogenesis. The branched-chain amino acids leucine and valine may have potential in inhibiting overexpression of protein breakdown pathways.[22] The amino acid glutamine has been used as a component of oral supplementation to reverse cachexia in people with advanced cancer[23] or HIV/AIDS.[24]
Epidemiology
Accurate epidemiological data on the prevalence of cachexia is lacking due to changing diagnostic criteria and under-identification of people with the disorder.[27] It is estimated that cachexia from any disease is estimated to affect more than 5 million people in the United States.[9] The prevalence of cachexia is growing and estimated at 1% of the population. The prevalence is lower in Asia but due to the larger population, represents a similar burden. Cachexia is also a significant problem in South America and Africa.[27]
The most frequent causes of cachexia in the United States by population prevalence are: 1) chronic obstructive pulmonary disease (COPD), 2) heart failure, 3) cancer cachexia, 4) chronic kidney disease. The prevalence of cachexia ranges from 15 to 60% among people with cancer, increasing to an estimated 80% in terminal cancer.[2] This wide range is attributed to differences in cachexia definition, variability in cancer populations, and timing of diagnosis.[9] Although the prevalence of cachexia among people with COPD or heart failure is lower (estimated 5% to 20%), the large number of people with these conditions dramatically increases the total cachexia burden.[5][27]
Cachexia contributes to significant loss of function and healthcare utilization. Estimates using the
History
The word "cachexia" is derived from the Greek words "Kakos" (bad) and "hexis" (condition). English ophthalmologist John Zachariah Laurence was the first to use the phrase "cancerous cachexia", doing so in 1858. He applied the phrase to the chronic wasting associated with malignancy. It was not until 2011 that the term "cancer-associated cachexia" was given a formal definition, with a publication by Kenneth Fearon. Fearon defined it as "a multifactorial syndrome characterized by ongoing loss of skeletal muscle (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment".[12]
Research
Several medications are under investigation or have been previously trialed for use in cachexia but are currently not in widespread clinical use:
- Thalidomide[30]
- Cytokine antagonists[19]
- Cannabinoids[19]
- Omega-3 fatty acids, including eicosapentaenoic acid (EPA)[19][31]
- Non-steroidal anti-inflammatory drugs[19]
- Prokinetics[19]
- ghrelin receptor agonist[3]
- Anabolic catabolic transforming agents such as MT-102[3]
- Selective androgen receptor modulators[3]
- Cyproheptadine[32]
- Hydrazine sulfate[32]
Multimodal therapy
Despite the extensive investigation into single therapeutic targets for cachexia, the most effective treatments use multi-targeted therapies. In Europe, a combination of non-drug approaches including physical training, nutritional counseling, and
See also
- Sarcopenia
- Muscle atrophy
- Marasmus
- Cancer
- Progressive disease
- Journal of Cachexia, Sarcopenia and Muscle
References
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