Cachexia

Cachexia is a complex metabolic syndrome characterized by involuntary weight loss, with loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support. It often occurs in the context of chronic diseases such as cancer, chronic heart failure, chronic obstructive pulmonary disease, chronic kidney disease, HIV/AIDS, and inflammatory conditions. It is distinguished from starvation by its association with systemic inflammation, elevated energy expenditure, and persistent catabolism driven by illness.

Pathophysiology: Inflammation triggers cytokines such as tumor necrosis factor alpha, interleukin-6, and interferon-gamma, promoting muscle proteolysis via the ubiquitin-proteasome pathway and reduced muscle protein synthesis. Hormonal changes, insulin resistance, and adipose tissue wasting contribute to energy imbalance. Appetite loss (anorexia) compounds undernutrition, and physical activity is often reduced, accelerating weakness.

Clinical features: unintentional weight loss, diminished muscle strength, fatigue, and decreased functional ability. Weight loss may be accompanied by reduced appetite, edema, and low albumin in advanced cases. Diagnosis relies on weight loss criteria and assessment of body composition, as values are not captured by weight alone; imaging and functional tests help identify sarcopenia.

Management: address the underlying disease, optimize nutrition with adequate protein and energy intake, and incorporate resistance exercise. Pharmacologic options include agents to stimulate appetite and, in some cases, anabolic therapies; anti-inflammatory approaches and several investigational drugs (eg, ghrelin mimetics, myostatin inhibitors) are under study. Palliative and supportive care are integral.

Prognosis: cachexia is associated with worse outcomes and poorer survival across diseases, underscoring the importance of early recognition and multimodal management.