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The Anorexia-Cachexia Syndrome: Definitions, Evaluation, and Non-Pharmacologic Management

  • Ryan Jozwiak MD
  • Katherine Recka MD

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Introduction:  Anorexia-cachexia encompasses a broad, multi-organ 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 non-pharmacologic 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 which can be psychogenic (anorexia nervosa) or secondary to an underlying advanced illness (3). 

Cachexia: >5% weight loss over 6 months in absence of starvation or BMI <20 and weight loss >2%; or appendicular skeletal muscle index consistent with sarcopenia and weight loss >2% (4,5).

Pre-cachexia:  < 5% weight loss and presence of anorexia (4).

Refractory cachexia: usually described in the published literature in the context of a progressive, incurable non-cancer 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. IL-1, IL-6, IL-10, and TNF-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 like testosterone, insulin-like growth factor, and myostatin cause the ACS via a) intracellular oxidative stress leading to catabolism and the breakdown of proteins (proteolysis); b) resistance of the hypothalamus to respond to orexigenic (appetite-stimulating) neurologic signals; and c) 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: e.g. stomatitis, refractory dyspnea, odynophagia, pain.
  • Swallowing deficits:  e.g. a localized tumor from head and neck.
  • GI symptoms: both diarrhea from chemotherapy-induced bowel ischemia and opioid-related constipation are common culprits. 
  • Endocrine or metabolic disorders: e.g. hyperthyroidism, diabetes mellitus, uremia, hypercalcemia.
  • Infections: e.g. HIV, occult abscess, parasitic infections, osteomyelitis.
  • Dental issues:  e.g. dental caries, thrush, poorly fitting dentures.
  • Social issues: food insecurity, poor nutritional literacy, and social isolation, especially in patients with functional impairments who require feeding assistance. Involve social workers as appropriate. 
  • Mental health disorders: e.g. depression, bulimia, anorexia nervosa, untreated anxiety. 
  • Medications: numerous drug classes (e.g. chemotherapeutics, antibiotics, anticonvulsants, cardiovascular medications, antidepressants) have been associated with altered taste, early satiety, dry mouth, dysphagia, and nausea. Involving a clinical pharmacist can help identify potential culprits.

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 (17) Additionally, 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 non-cancer illnesses (18-20). 

Non-pharmacologic 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. While a separate Fast Factwill review the utility of pharmacotherapies and supplements for ACS, patient counseling is the cornerstone to the clinical management of ACS.

  • Education that ACS is not a patient choice, but rather a manifestation of a hormonally-advanced, underlying illness may be the most crucial aspect of ACS care. In fact, experts suggest that the presence of refractory cachexia should prompt a goals of care discussion and nutritional refocusing away from weight gain and caloric intake and more towards alleviating hunger and thirst (5). 
  • Most experts do not recommend enteral nor parenteral artificial nutrition for refractory cachexia, as neither meaningfully improve quality of life or survival (17).
  • Controlled studies in patients undergoing cancer treatment suggest that consultation with a licensed nutritionist may offer quality-of-life benefits in the pre-cachexia phase via improved dietary intake from fortified food, nutritional supplementation, and counseling (21,22). The nutritional counseling often involves liberalizing diet restrictions and encouraging patients to eat frequent, small meals with preferably the bulk of calorie intake occurring the morning. Additionally, some patients may wish to limit exposure to strong aromas and spicy flavors.  However, the evidence underlying this nutritional counseling and/or consultation, is not established in patients with more advanced illness (5,23).

References

  1. Argiles, Josep M., et al. “Cachexia and sarcopenia: mechanisms and potential targets for intervention.” Current opinion in pharmacology 22 (2015): 100-106.Cederholm, Tommy, et al. “Diagnostic criteria for malnutrition–an ESPEN consensus statement.” Clinical nutrition 34.3 (2015): 335-340.
    1. Ebner, Nicole, et al. “Muscle wasting in ageing and chronic illness.” ESC heart failure 2.2 (2015): 58-68.
    1. Muscaritoli, M., et al. “Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG)“cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics”.” Clinical nutrition 29.2 (2010): 154-159.
    1. Fearon, Kenneth, et al. “Definition and classification of cancer cachexia: an international consensus.” The lancet oncology12.5 (2011): 489-495.
    1. Arends, Jann, et al. “ESPEN expert group recommendations for action against cancer-related malnutrition.” Clinical nutrition36.5 (2017): 1187-1196.
    1. Braun, Theodore P., and Daniel L. Marks. “Pathophysiology and treatment of inflammatory anorexia in chronic disease.” Journal of cachexia, sarcopenia and muscle 1.2 (2010): 135-145.
    1. Molfino, Alessio, Alessandro Laviano, and Filippo Rossi Fanelli. “Contribution of anorexia to tissue wasting in cachexia.” Current opinion in supportive and palliative care 4.4 (2010): 249-253.
    1. Morley, John E., David R. Thomas, and Margaret-Mary G. Wilson. “Cachexia: pathophysiology and clinical relevance.” The American journal of clinical nutrition 83.4 (2006): 735-743.
    1. Mitch, William E. “Cachexia in chronic kidney disease: a link to defective central nervous system control of appetite.” The Journal of clinical investigation 115.6 (2005): 1476-1478.
    1. Mak, R. H., et al. “Leptin and inflammation-associated cachexia in chronic kidney disease.” Kidney international 69.5 (2006): 794-797.
    1. Fouque, D., et al. “A proposed nomenclature and diagnostic criteria for protein–energy wasting in acute and chronic kidney disease.” Kidney international 73.4 (2008): 391-398.
    1. Koehler, Friedrich, et al. “Anorexia in chronic obstructive pulmonary disease—association to cachexia and hormonal derangement.” International journal of cardiology 119.1 (2007): 83-89.
    1. LeBlanc, Thomas W., et al. “Correlation between the international consensus definition of the Cancer Anorexia-Cachexia Syndrome (CACS) and patient-centered outcomes in advanced non-small cell lung cancer.” Journal of pain and symptom management 49.4 (2015): 680-689
    1. Jameson J. Unintentional Weight Loss. In: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 20e New York, NY: McGraw-Hill;  http://accessmedicine.mhmedical.com.proxy.lib.mcw.edu/content.aspx?bookid=2129&sectionid=192012939. Accessed April 22, 2019.
    1. Gaddey, Heidi L., and Kathryn Holder. “Unintentional weight loss in older adults.” Am Fam Physician 89.9 (2014): 718-722.
    1. Maltoni, Marco, et al. “Prognostic factors in advanced cancer patients: evidence-based clinical recommendations—a study by the Steering Committee of the European Association for Palliative Care.” American Society of Clinical Oncology (ASCO), 2005.
    1. Maltoni, Marco, et al. “Prognostic factors in advanced cancer patients: evidence-based clinical recommendations—a study by the Steering Committee of the European Association for Palliative Care.” American Society of Clinical Oncology (ASCO), 2005.
    1. De Paula Pantano N, et al Validation of the modified Glasgow Prognostic Score in advanced cancer patients receiving palliative care. J of Pain and Sympt Manage 2016; 51(2): 270-77.
    1. Miyamoto T, Fujitani M, et al.  The c-reactive protein/albumin ratio is useful for predicting short-term survival in cancer and noncancer patients. J of Pall Med  2019; 22(5): 532-537.
    1. Proctor MJ, Morrison DS, et al.  An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study.  British Journal of Cancer 2011; 104:726-734.
    1. Ravasco P, Monteiro-Grillo I, Vidal PM, et al.  Dietary counseling improves patient outcomes: a prospective, randomized controlled trial in colorectal cancer patients undergoing radiotherapy. J Clin Oncol 2005; 23:1431-1438. 
    1. Rvasco P, Monteiro-Grill I, Marques Vidal P, et al.  Impact of nutrition on outcome: a prospective randomized controlled trial in patients with head and neck cancer undergoing radiotherapy. Head Neck 2005;27:659-668.
    1. Balstad, Trude R., et al. “Dietary treatment of weight loss in patients with advanced cancer and cachexia: a systematic literature review.” Critical reviews in oncology/hematology 91.2 (2014): 210-221. 

Conflicts of Interest: None reported

Authors’ Affiliations: Medical College of Wisconsin; Milwaukee WI

Version History: First electronically published in October 2019; originally edited by Sean Marks MD.