Understanding Cachexia, Diagnosis, and Medical Supports

Understanding cachexia

Cachexia, often referred to as the “wasting syndrome,” is a complex metabolic condition characterised by severe muscle loss and weight loss, frequently observed in patients with chronic illnesses such as cancer, heart failure, and HIV/AIDS. 

This syndrome goes beyond simple weight loss, it involves alterations in the body’s protein and energy balance driven by a systemic inflammatory response. Understanding cachexia is crucial for improving patient outcomes and quality of life, as it significantly impacts their strength and survival.

What Is Cachexia?

Cachexia is a complex metabolic syndrome associated with underlying illness and characterised by the loss of muscle mass with or without the loss of fat mass. It commonly occurs in patients with cancer, heart failure, renal failure, and other chronic conditions. 

The syndrome is marked by weight loss, anorexia, inflammation, insulin resistance, and increased muscle protein breakdown. Cachexia is distinct from starvation, age-related muscle loss, and other similar conditions due to its association with increased morbidity and specific biochemical changes driven by the illness.

Diagnosis And Symptoms Of Cachexia

Most common symptoms of cachexia
Most common symptoms of cachexia

The diagnosis of cachexia, particularly in the context of cancer, is based on a combination of clinical criteria that aim to capture the multifactorial nature of this syndrome. Here are the key diagnostic criteria used for cachexia, based on recent consensus and studies:

Weight Loss

A primary indicator of cachexia is significant weight loss, typically more than 5% over six months or 2% in individuals who are already considered lean (BMI <20 kg/m²). This is the hallmark symptom of cachexia. People with cachexia can lose a significant amount of weight in a short period, even if they are eating enough calories. The weight loss is primarily due to the loss of muscle mass, rather than fat.

Muscle Mass Loss

Loss of skeletal muscle mass, with or without loss of fat mass, is a critical feature. This loss is not fully reversible by conventional nutritional support.

Additional Metabolic Indicators

The presence of anorexia or decreased food intake and evidence of systemic inflammation (e.g., increased CRP levels) are often associated with cachexia. Chronic inflammation is a central feature of cachexia. Inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 (IL-1) are elevated in cachexia and contribute to the suppression of erythropoietin production. This suppression leads to anaemia by reducing red blood cell production in the bone marrow. Additionally, these cytokines directly induce muscle catabolism, resulting in muscle wasting and associated weakness 

Functional Impairment

Progressive functional impairment, often measured by decreased muscle strength or fatigue, is a common diagnostic criterion, reflecting the clinical impact of muscle degradation and metabolic changes. 

Anaemia and Weakness

Anaemia and weakness in cachexia, particularly in patients with cancer, are driven by multiple intertwined mechanisms, primarily revolving around systemic inflammation, metabolic dysregulation, and nutritional deficiencies.

These criteria help to diagnose cachexia and differentiate it from other conditions that also lead to weight loss and muscle wasting, ensuring that appropriate interventions can be implemented to manage this complex condition.

Understanding Different Types Of Cachexia

Each type of cachexia is influenced by a unique interplay of metabolic changes, inflammatory responses, and the specific pathology of the underlying disease. Currently, these are the known types of cachexia: 

Cancer Cachexia

This type is most commonly seen in patients with cancers of the lung, pancreas, and gastrointestinal tract. Cancer cachexia is marked by severe muscle wasting, weight loss, and systemic inflammation driven by both tumour-secreted factors and the host immune response. This form of cachexia significantly affects patient survival and response to cancer therapies

The profound loss of body mass and strength leads to significant impairments in physical function, fatigue, and a diminished quality of life. Cachexia also increases the toxicity of cancer treatments and reduces treatment efficacy, complicating clinical management and prognosis.

Is cancer cachexia deadly? Currently, studies inform that on average, around 20% of patients die due to cancer cachexia.

Cardiac Cachexia

Cardiac cachexia is a severe complication often seen in patients with chronic heart failure (CHF). It represents a significant clinical challenge due to its multifactorial nature and substantial impact on prognosis and quality of life. 

Cardiac cachexia is characterised by a progressive loss of muscle mass and fat, which is not solely due to malnutrition but is a direct consequence of the heart failure condition itself. The condition typically manifests after significant weight loss, specifically more than 6% of non-edematous weight over a period of six months. Patients may also experience fatigue, weakness, and a reduced exercise capacity due to the loss of muscle strength and respiratory capacity.

The morbidity associated with cardiac cachexia includes not only an increased risk of mortality but also a marked decline in the quality of life and increased hospitalisation rates. It is estimated that the mortality rate of cardiac cachexia is at 20% – 40% yearly.

COPD-Associated Cachexia

COPD-associated cachexia is a serious and complex condition that often occurs in patients with chronic obstructive pulmonary disease (COPD). It involves significant weight loss, muscle wasting, and a decrease in fat mass, impacting patient morbidity and mortality. Understanding the mechanisms and management strategies for COPD-associated cachexia is crucial for improving patient outcomes.

Approximately 25% of patients with COPD develop cachexia. This condition is associated with a roughly 50% reduction in median survival, underscoring its severity and the need for effective management strategies.

Rheumatoid Cachexia

Rheumatoid cachexia is a condition commonly associated with rheumatoid arthritis (RA), characterised by muscle wasting and a decrease in fat mass, despite a potentially normal or even increased body mass index (BMI). 

Patients with rheumatoid cachexia experience a reduction in skeletal muscle mass, which is not necessarily linked to a reduction in overall body weight. Instead, there is often a relative increase in fat mass, particularly visceral fat, leading to a condition sometimes referred to as ‘cachectic obesity’.

The altered body composition in rheumatoid cachexia can lead to metabolic syndrome and increased cardiovascular risks. This metabolic impact is crucial as it may compound the already elevated risk of cardiovascular disease associated with RA.

Medical Supports For Cachexia

Unfortunately, there’s no single cure for cachexia. However, there’s a multi-modal approach that can help manage the symptoms and improve a patient’s quality of life.

Nutritional Supports

This is a cornerstone of cachexia management. The aim is to increase calorie and protein intake to counteract muscle wasting. This might involve:

  • Dietary modifications
    A dietician can help create a high-calorie, high-protein diet that’s easy to digest and enjoyable for the patient.
  • Oral nutritional supplements
    These can be liquid shakes or drinks that provide additional calories and protein when dietary intake is insufficient.
  • Enteral or parenteral nutrition
    In some cases, tube feeding or feeding directly into a vein may be necessary if the person cannot consume enough calories orally.

Pharmacological Treatments

While no medications specifically target cachexia, some can help manage specific symptoms and improve outcomes, these treatments are: 

  • Progestagens
    Drugs like megestrol acetate are used to stimulate appetite and weight gain. They are considered one of the effective treatments for cachexia and are approved in Europe for this purpose.
  • Corticosteroids
    While not a long-term solution, corticosteroids can improve appetite and quality of life in the short term.
  • Anti-inflammatory Agents
    Non-steroidal anti-inflammatory drugs (NSAIDs) may help reduce inflammation-associated muscle wasting.
  • Novel Agents
    Drugs under investigation include ghrelin mimetics, selective androgen receptor modulators (SARMs), and agents targeting specific cytokines involved in cachexia.

Exercise and Rehabilitation

Exercise and rehabilitation are essential components in the management of cachexia, particularly in conditions like cancer cachexia, where they help mitigate the muscle wasting and functional impairment associated with the syndrome. Here are the reasons why exercise and rehabilitation are crucial:

  • Modulation of Muscle Metabolism
    Exercise helps maintain muscle mass and function by influencing muscle metabolism. It enhances insulin sensitivity and modifies the levels of inflammation, which are crucial in managing the muscle wasting typical of cachexia.
  • Prevention of Functional Decline
    Regular physical activity can significantly slow down the decline in muscle mass and physical function observed in cachexia. Even in advanced disease stages, peripheral muscles retain the capacity to respond to exercise, thereby improving overall physical function and quality of life.
  • Influence on Inflammation and Catabolism
    Exercise has been shown to reduce systemic inflammation, a key driver of cachexia. By lowering inflammation, exercise can indirectly reduce the catabolic processes leading to muscle degradation. This modulation of the inflammatory response can help preserve muscle mass and improve metabolic health.

Emerging Therapies

Emerging therapies for cachexia are focusing on various mechanisms to combat the multifaceted nature of this syndrome, especially in cancer cachexia. 

Ongoing research is exploring the efficacy of combination therapies involving newer pharmacological agents, such as: 

  • Thalidomide
    It is known for its immunomodulatory and anti-inflammatory properties. It acts by inhibiting the synthesis of tumour necrosis factor-alpha (TNF-α), a cytokine that plays a significant role in inflammation and cachexia. By reducing TNF-α levels, thalidomide may help mitigate the weight loss and muscle wasting associated with cachexia.
  • Selective COX-2 inhibitors
    COX-2 inhibitors target the cyclooxygenase-2 enzyme, which is involved in inflammation pathways. By inhibiting this enzyme, these drugs may reduce the inflammatory processes that contribute to muscle degradation and cachexia.
  • Medical Cannabinoids
    Cannabinoids are known for their appetite-stimulating effects and potential to increase body weight. They interact with the cannabinoid receptors in the brain to potentially boost appetite and reduce nausea, which can be beneficial for cachexia patients struggling with anorexia and weight loss.

However, there are potentially significant risks with these emerging therapies. The use of any of these emerging therapies require significant involvement of an appropriately qualified health practitioner to ensure that they are used appropriately and effectively, and that the patient receives advice for their individual situation before commencing treatment.

The Road Ahead for Cachexia Management

Navigating the complexities of cachexia, whether stemming from cancer, heart failure, COPD, or rheumatoid arthritis, demands a multifaceted approach tailored to each individual’s needs. 

The key to improving outcomes lies not only in recognising the multifactorial nature of cachexia but also in implementing integrated treatment strategies that address both the physiological and psychological facets of the condition. 

By combining nutritional support, pharmacological interventions, and rehabilitative exercise, patients can hope to improve their quality of life and potentially mitigate some of the more severe impacts of cachexia.

Written by

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.

Written by

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.

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