From the Guidelines
Cachexia is a complex wasting syndrome primarily caused by advanced cancer, chronic infections, and other chronic diseases, which trigger systemic inflammation, disrupt normal metabolism, and promote protein breakdown in muscles, and its management should prioritize early intervention with nutritional support, anti-inflammatory medications, and exercise programs to preserve muscle mass and improve quality of life 1.
Causes of Cachexia
The primary causes of cachexia include:
- Advanced cancer (cancer cachexia)
- Chronic infections like HIV/AIDS and tuberculosis
- Chronic heart failure
- Chronic kidney disease
- Chronic obstructive pulmonary disease (COPD)
- Rheumatoid arthritis
- Inflammatory bowel diseases These conditions trigger systemic inflammation through pro-inflammatory cytokines such as TNF-alpha, IL-1, and IL-6, which disrupt normal metabolism, increase energy expenditure, and promote protein breakdown in muscles.
Pathophysiology of Cachexia
Cachexia involves hormonal imbalances affecting insulin, cortisol, and ghrelin, as well as neurological pathways that suppress appetite. Malnutrition from reduced food intake worsens the condition, creating a vicious cycle. The systemic inflammatory reaction is assumed to be involved in and causing loss of appetite and body weight, and may facilitate tumor progression 1.
Management of Cachexia
Treatment approaches must address the underlying disease while providing nutritional support, anti-inflammatory medications, appetite stimulants like megestrol acetate (400-800 mg daily) or dexamethasone (2-4 mg daily for short periods), and exercise programs to preserve muscle mass. Early intervention is crucial as cachexia becomes increasingly difficult to reverse as it progresses. A combination therapy approach may yield the best possible outcomes for patients with cancer cachexia, including medroxyprogesterone, megestrol acetate, eicosapentaenoic acid and L-carnitine supplementation, and thalidomide 1.
Recent Guidelines
The American Society of Clinical Oncology (ASCO) guideline on the management of cancer cachexia recommends a multidisciplinary approach to diagnosis and treatment, including assessment of weight loss, appetite, and muscle mass, as well as provision of nutritional support, anti-inflammatory medications, and exercise programs 1.
From the Research
Causes of Cachexia
- Cachexia is a serious medical consequence of various chronic illnesses, including malignant cancer, chronic heart failure (CHF), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), cystic fibrosis, rheumatoid arthritis, Alzheimer's disease, infectious diseases, and many other chronic illnesses 2.
- The pathogenesis of cachexia is not fully understood, but it is thought to be multifactorial, involving interactions between decreased caloric intake, malabsorption, and alterations in energy expenditure secondary to hormonal and/or metabolic abnormalities 3.
- Cancer cachexia is characterized by decreased skeletal muscle mass and weight loss, and is associated with reduced chemotherapeutic effects, increased side effects and treatment interruptions, and poorer survival 4.
- Cachexia can be caused by factors of catabolism produced by tumors in the systemic circulation, as well as physiological factors such as imbalanced inflammatory activation, proteolysis, autophagy, and lipolysis 5.
- HIV-related cachexia is a frequent complication of acquired immune deficiency syndrome (AIDS), and is likely to be multifactorial, resulting from interactions between decreased caloric intake, malabsorption, and alterations in energy expenditure secondary to hormonal and/or metabolic abnormalities 3.
Diseases Associated with Cachexia
- Cachexia is commonly associated with:
Prevalence of Cachexia
- The prevalence of cachexia is high, ranging from 5% to 15% in CHF or COPD to 60% to 80% in advanced cancer 2.
- In industrialized countries, the overall prevalence of cachexia is growing and currently about 1%, i.e., about nine million patients 2.
- Cachexia is also a significant problem in Asia, South America, and Africa, although data are scarce in some of these regions 2.