Opinion PaperConsensus 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”
Introduction
The close association between chronic illnesses and the deterioration of nutritional status, impaired quality of life and increased risk for morbidity and mortality has been long recognised.1 Indeed, as early as in the third century B.C., the Greek physician Hippocrates from Koos very neatly described the wasting syndrome associated with terminal disease: “The flesh is consumed and becomes water,… the abdomen fills with water, the feet and the legs swell, the shoulders, clavicles, chest and thighs melt away… This illness is fatal”.2
The spectrum of metabolic and nutritional abnormalities secondary to chronic diseases is indeed wide and multifactorial in origin.3, 4 Consensus exists, however, that the pathogenesis of malnutrition shares analogies and bear diversities among the causative underlying conditions.5 The progressive knowledge of the negative impact of malnutrition on patients’ prognosis has led to the development of simple but effective tools which allow for the accurate screening, diagnosis and treatment of malnutrition.6, 7 This notwithstanding, the prevalence of malnutrition in hospital and the community still remains disappointingly high,1, 8 underdiagnosed and frequently left untreated until extreme pictures may develop, which are currently referred to as ‘cachexia’, ‘cachectic states’ or ‘severe wasting’. On the other hand, it is well recognized that such advanced clinical pictures are scarcely responsive to the available nutritional and pharmacological treatments,9, 10 suggesting that once a critical point is reached, the complex interplay between underlying disease, metabolic alterations and reduced availability of nutrients will eventually and ineluctably cause the patient's death. This underscores the urgent need for the development of early and effective interventions aimed at preventing rather than treating those abnormalities ultimately leading to the clinical picture of cachexia.
Based on these premises, in 2005, the Special Interest Group (SIG) on cachexia-anorexia in chronic wasting diseases was created within ESPEN. The main aims of this SIG are the development and diffusion of knowledge on the basic and clinical aspects of cachexia and anorexia. The secondary aims are to increase the awareness of cachexia among health professionals and caregivers and to develop clinical guidelines for the prevention/treatment of cachexia. This would ultimately allow to promote appropriate interventions at the institutional and political levels.
The definition, the assessment and the staging of cachexia, was identified as a priority by the SIG. The lack of a simple and commonly accepted definition for cachexia still represents a main clinical issue, leading to clinically relevant mistakes, lack or delay in identification, inadequate prevention and frequently ineffective treatments.
This consensus paper reports the definition of cachexia and pre-cachexia. Moreover, the criteria for the differentiation between cachexia and other conditions associated with sarcopenia (i.e. loss of muscle mass) are reported, which have been developed in cooperation with the ESPEN SIG on nutrition in geriatrics.
The SIG nutrition in geriatrics was created in 2006 to focus on nutritional disorders of specific relevance for the elderly. Age-related sarcopenia is a concept that describes the loss of muscle mass and muscle strength associated with aging. In its advanced stages it causes disability and dependence. In order to implement diagnostic and therapeutic strategies, a definition for this entity is urgently needed. For that purpose, the SIG joined forces with the SIG on cachexia-anorexia in chronic wasting diseases for a common ESPEN position paper.
Section snippets
How to define sarcopenia?
The term sarcopenia is derived from the Greek words sarx (flesh) and penia (poverty). Sarcopenia is a condition characterized by loss of muscle mass and muscle strength.11, 12 Muscle accounts for 60% of the body's protein stores. Muscle mass decrease is directly responsible for functional impairment with loss of strength, increased likelihood of falls, and loss of autonomy.13, 14 Respiratory function is also impaired with a reduced vital capacity.15 During a metabolic stress situation muscle
What is age-related sarcopenia?
Age-related sarcopenia is the loss of muscle mass and muscle strength that is associated with aging.11, 12 Features of sarcopenia include: decreased muscle mass and cross-sectional area, infiltration of muscle by fat and connective tissue, decrease of type 2 fiber size and number, but also of type 1 fibers, accumulation of internal nuclei, ring fibers and ragged fibers, disarrangement of myofilaments and Z-lines, proliferation of the sarcoplasmic reticulum and t-tubular system, accumulation of
How to diagnose sarcopenia?
Diagnosis of sarcopenia is based on the combined presence of the two following criteria:
I. A low muscle mass, i.e. a percentage of muscle mass ≥2 standard deviations below the mean measured in young adults of the same sex and ethnic background.
Subjects aged 18–39 years in the 3rd NHANES population13 might be used as reference. The suggested T-score-based diagnosis of sarcopenia relates closely to the diagnosis of osteoporosis. Like for osteopenia/osteoporosis, much needed reference values in
How to define cachexia?
The term cachexia is derived from the Greek words kakòs (bad) and héxis (condition). Cachexia may be defined as a multifactorial syndrome characterized by severe body weight, fat and muscle loss and increased protein catabolism due to underlying disease(s). Cachexia is clinically relevant since it increases patients’ morbidity and mortality. Contributory factors to the onset of cachexia are anorexia and metabolic alterations, i.e. increased inflammatory status, increased muscle proteolysis,
Why is the staging of cachexia necessary?
One of the innovative aspects of the present re-appraisal of cachexia in chronic diseases is the attempt to stage cachexia. The SIGs felt the staging of cachexia as necessary, based on a number of reasons that are listed below:
- (a)
late-stage cachexia is substantially untreatable with currently available tools42;
- (b)
increasing the awareness of conditions potentially leading to cachexia is mandatory;
- (c)
staging may facilitate identification of early markers of cachexia;
- (d)
there is emerging consensus that
How to define ‘pre-cachexia’?
Pre-cachexia is defined based on the presence of all the following criteria:
- (a)
underlying chronic disease;
- (b)
unintentional weight loss ≤5% of usual body weight during the last 6 months;
- (c)
chronic or recurrent systemic inflammatory response;
- (d)
anorexia or anorexia-related symptoms.
Pre-cachexia includes therefore patients with a chronic disease, small weight loss, a chronic or recurrent systemic inflammatory response and anorexia. Inflammation is indicated by elevated serum levels of inflammatory markers like
Is cachexia associated with changes in body composition?
Yes. One of the hallmark of cachexia is loss of body weight, which is brought about by loss of both lean and fat mass.47 In advanced cachexia, water retention may occur as a consequence of severe hypoalbuminemia. The water retention may then account for an increase in body weight in spite of severe body wasting.48 The same may occur in patients with severe heart failure, liver cirrhosis or renal failure, in whom loss of body weight may be obscured by fluid retention.49
Loss of skeletal muscle
Can an obese person be defined as pre-cachectic?
Within the frame of our definition of ‘pre-cachexia’, muscle wasting may be frequently observed in obese or overweight patients exhibiting unintentional weight loss and systemic inflammatory response due to underlying disease, such as cancer.61 These patients exhibit significant muscle loss despite fat mass is still increased. This condition is therefore defined as sarcopenic obesity. The current definition of obesity is anthropometric and based on body mass index and does not take into account
Is it possible to differentiate cachexia from other sarcopenic conditions?
Not always. Loss of muscle mass is a feature of cachexia, whereas most sarcopenic subjects are not cachectic. Persons with no weight loss, no anorexia, no measurable systemic inflammatory response may well be sarcopenic. Sarcopenia may be accelerated after an acute inflammatory stress, and may also involve, in the elderly, a low-grade systemic inflammatory response or insulin resistance.66, 67, 68 However, none of these inflammatory conditions match the definition of cachexia. As inflammation
Conclusion
A universally accepted definition of the clinical syndrome of cachexia would represent a major achievement in clinical medicine, allowing for early recognition, prevention and timely-appropriate treatment of this devastating condition. Cachexia has been long considered a late and ineluctable event complicating the natural history of many chronic diseases such as cancer, chronic heart failure, COPD, chronic renal failure, etc. Moreover, the negligible response of cachexia to available
Conflict of interest statement
None declared.
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