The Anorexia-Cachexia Syndrome: Definitions,Evaluation,and Nonpharmacological Management #386

Introduction

Anorexia-cachexia encompasses a broad, multiorgan syndrome seen in several chronic diseases. ¹ The purpose of this Fast Fact is to review the anorexia-cachexia syndrome (ACS), its clinical evaluation, and its nonpharmacological management. See other Fast Facts for related information: #10 (the role of enteral nutrition in serious illness), #100 (megestrol acetate); #190 (the role of parenteral nutrition for advanced cancer), #279 (cannabinoids), #314 (mirtazapine), and #315 (olanzapine).

Definitions

Sarcopenia: diffuse muscle loss often associated with an increase in fat mass and abdominal circumference. ²

Anorexia: appetite reduction that can be psychogenic (anorexia nervosa) or secondary to an underlying advanced illness. ³

Cachexia: >5% weight loss for 6 months in absence of starvation or body mass index <20 and weight loss >2%; or appendicular skeletal muscle index consistent with sarcopenia and weight loss >2%.^4,5

Precachexia: <5% weight loss and presence of anorexia. ⁴

Refractory cachexia: usually described in the published literature in the context of a progressive incurable noncancer illness at an advanced stage or an untreatable cancer.^4,5

Pathophysiology and Associated Disease Processes

Typically, ACS involves more than just a loss of appetite and is also associated with nausea, glucose intolerance, meat aversion, early satiety, and/or an unpleasant change in taste and smell.^4,5 Increases in cytokine release and other inflammatory mediators (e.g., interleukin [IL]-1, IL-6, IL-10, and tumor necrosis factor-alpha) brought upon by an underlying illness are thought to be the primary culprit across many chronic illnesses, including cancer, chronic kidney disease, COPD, AIDS, rheumatoid arthritis, cirrhosis, and congestive heart failure.^6–13 These inflammatory mediators along with hormonal mediators such as testosterone, insulin-like growth factor, and myostatin cause the ACS through (1) intracellular oxidative stress leading to catabolism and the breakdown of proteins (proteolysis); (2) resistance of the hypothalamus to respond to orexigenic (appetite-stimulating) neurological signals; and (3) increases in total and resting energy expenditure.^3,6–8 The Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire and the North Central Cancer Treatment Group (NCCTG) Anorexia/Cachexia questionnaire are validated tools to assess ACS. ³

Clinical Evaluation

ACS is a clinical diagnosis encountered in a patient with the appropriate degree of weight loss and in the context of an advanced illness. Typically, no additional testing is necessary to confirm the diagnosis; however, clinicians should be aware of potentially reversible ACS etiologies or cofactors and consider targeted testing and/or interventions as appropriate^14,15:

Uncontrolled disease-related symptoms: for example, stomatitis, refractory dyspnea, odynophagia, and pain.

Prognostication

ACS is incorporated into numerous prognostication scales and is considered a common manifestation on the terminal illness pathway. ¹⁶ Refractory cachexia is associated with a prognosis <3 months.^4,5,16 The clinical recognition of ACS can help clinicians assess where a patient may be at on an illness trajectory (see Fast Fact #326). Hence, clinicians should utilize the presence of ACS to improve their prognostic disclosure and clinical recommendations regarding the role of pleasure feeding over artificial nutrition especially for refractory cachexia. ¹⁶ In addition, the Glasgow prognostic index, which involves a simple 0, 1, 2 scoring system based on the presence of elevated c-reactive protein levels and/or low albumin levels, has been validated to assess the extent of disease-related inflammation and offer reliable prognostic information for cancer and noncancer illnesses.^17–19

Nonpharmacological Management

ACS can be very distressing given the lack of efficacious therapies. Patient-family strife may result as loved ones may not understand why previously cherished foods lovingly prepared are not being eaten. Although a separate Fast Fact will review the utility of pharmacotherapies and supplements for ACS, patient counseling is the cornerstone to the clinical management of ACS.