Cachexia · What It Is, Causes, Signs and Symptoms, and More

Cachexia is a complex, hypercatabolic state that is driven by a chronic inflammatory response and is characterized by the progressive loss of skeletal muscle with or without loss of fat. Cachexia typically occurs in individuals with cancer (especially gastric and pancreatic cancer) but can also be seen in individuals with chronic conditions, such as chronic kidney disease (CKD), congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and acquired immunodeficiency syndrome (AIDS). People with cachexia may experience low appetite, unintentional weight loss, and muscle wasting.

It is hypothesized that cachexia is caused by a hypermetabolic state, where excess cytokines (i.e., proteins that are responsible for controlling the growth and activity of other cells) and polypeptides are released by immune cells. The release of cytokines leads to an increase in resting energy expenditure and energy deficits, leading to muscle and fat wasting. Specifically, cancer cachexia is a complex syndrome that increases the severity and risk of side effects in those who are also receiving cancer treatment. These side effects may include dysphagia, nausea, vomiting, diarrhea, and mucositis (i.e., inflammation of the mucous membranes lining the mouth and gastrointestinal tract). 

In individuals without cancer, the etiologies are multifactorial and are not solely related to inflammation or changes in metabolism. For example, in CKD, fluctuations in hormone and vitamin D levels may play a role. In CHF, activation of the renin-angiotensin-aldosterone system and changes in catecholamine levels also influence cachexia. In COPD, malnutrition and tissue hypoxia contribute to pathogenesis. Other contributing medical conditions include hypogonadism (i.e., testosterone deficiency in males may experience decreased muscle mass); adrenal insufficiency (i.e., insufficient mineralocorticoids and glucocorticoids can present with anorexia and weight loss); and thyroid abnormalities (i.e., which may lead to unintentional weight loss).

Individuals with cachexia may lose weight and muscle mass unintentionally, without any changes to their diet, and have poor appetite and/or caloric intake. Although loss of appetite may also be a side effect from cancer treatment, cachexia does not resolve with caloric supplementation. Additionally, the excessive weight loss seen in cachexia may result in psychosocial distress, manifesting as anxiety or depression. 

Diagnosis of cachexia begins with a thorough review of symptoms and medical history focused on nutritional status, including risk factors that may interfere with one’s ability to take in nutrition (e.g., mucositis). Subjective measures of nutritional status and psychosocial distress can be ascertained using questionnaires, such as quality of life (QoL) assessments. Individuals should be evaluated for reversible medical conditions (e.g., hypogonadism, adrenal insufficiency, thyroid abnormalities) or medications (e.g., cancer treatment, androgen deprivation therapy) that can contribute to cachexia. A focused physical exam can show loss of subcutaneous fat and muscle wasting in the temporal region and upper and lower body muscles.

Diagnostic criteria for cachexia are met when weight loss is greater than 5% of total body weight. Refractory cachexia is defined as weight loss greater than 15% of total body weight when body mass index (BMI) is less than 23 kg/m² or when weight loss is greater than 20% with BMI less than 27 kg/m². Body mass and composition can be assessed via different methods including dual-energy X-ray absorptiometry (DEXA), computed tomography (CT), or magnetic resonance imaging (MRI).

Additional laboratory testing may be helpful in differentiating non-cancer etiologies of cachexia and aid in identifying reversible medical conditions (i.e., thyroid function tests to assess for thyroid abnormalities, HIV screening, pulmonary function tests to assess for pulmonary disease). 

Treatment of cachexia involves a combination of dietary and lifestyle modifications and pharmacologic therapies. Examples of dietary and lifestyle modifications include eating small, frequent meals dense in calories and using a straw to facilitate intake of fluids. For cancer cachexia, appetite stimulants such as low-dose olanzapine (i.e., atypical antipsychotic agent), progesterone, and steroids have been shown to improve appetite. While individuals may benefit from nutritional supplements, increasing caloric intake will not reverse cachexia since it is typically a metabolic syndrome driven by chronic inflammation. For non-cancer etiologies of cachexia, treatment is aimed at addressing the underlying medication condition. For example, individuals with HIV/AIDS respond rapidly to antiretroviral therapy. Finally, consultation with a nutritionist or dietician should be offered to individuals with cachexia to help with nutrition optimization. 

Cachexia is a complex, hypercatabolic syndrome that is driven by a chronic inflammatory response and is characterized by the progressive loss of skeletal muscle with or without loss of fat. Cachexia typically occurs in individuals with cancer but can also be seen in individuals with chronic illnesses, such as chronic kidney disease, congestive heart failure, chronic obstructive pulmonary disease, and AIDS. Cachexia is hypothesized to be a result of excess cytokines and polypeptides released by immune cells, leading to an increase in resting energy expenditure and muscle and fat wasting. Diagnostic criteria for cachexia are met when weight loss is greater than 5% of total body weight. It is important to incorporate several types of therapy when treating cachexia, which includes a variety of dietary and lifestyle modifications (e.g., small, frequent, nutrient-dense meals) and appetite stimulants (e.g., low-dose olanzapine, progesterone, steroids). Referral to a nutritionist or dietician may also help optimize nutrition status.