Time to Deal with Rheumatoid Cachexia: Prevalence, Diagnostic Criteria, Treatment Effects and Evidence for Management

Cachexia is an early result of rheumatoid arthritis (RA) (rheumatoid cachexia, RC), characterised mainly by involuntary loss of fat-free mass. RC is apparent in 1–67% of patients with RA, depending on the diagnostic criteria applied and the method used for the assessment of body composition. RC is associated with increased inflammation and disability, lower health perception, and greater mortality risk. These changes in body composition are driven by the inflammation process, the low levels of physical activity, the underlying testosterone deficiency and hypogonadism, and the pharmacotherapy required for RA. Chronic inflammation enhances resting energy expenditure as a response to stress, inducing an energy deficit, further propelling protein turnover. The use of corticosteroids and tumour necrosis factor α (TNF-α) inhibitors tend to increase fat accumulation, whereas other disease-modifying antirheumatic drugs (DMARDs) appear to induce increments in fat-free mass. The present review presents all information regarding the prevalence of RC, diagnostic criteria, and comorbidities, as well as the effects of pharmacotherapy and medical nutrition therapy on body composition of patients with RA.

[1]  H. Kato,et al.  Ameliorating Effects of Coriander on Gastrocnemius Muscles Undergoing Precachexia in a Rat Model of Rheumatoid Arthritis: A Proteomics Analysis , 2021, Nutrients.

[2]  A. Södergren,et al.  Rheumatoid cachexia in early rheumatoid arthritis: prevalence and associated variables , 2021, Scandinavian journal of rheumatology.

[3]  Y. Akhverdyan,et al.  POS0509 PREVALENCE OF RHEUMATOID CACHEXIA AND ITS ASSOCIATION WITH SERUM FETUIN-A LEVELS IN CAUCASIAN PATIENTS WITH RHEUMATOID ARTHRITIS , 2021 .

[4]  A. Erden,et al.  Prevalence of sarcopenia and clinical implications in patients with newly diagnosed rheumatoid arthritis. , 2021, Nutrition.

[5]  L. Gonzalez-Lopez,et al.  Association of myostatin, a cytokine released by muscle, with inflammation in rheumatoid arthritis , 2021, Medicine.

[6]  B. Cortet,et al.  Body composition in patients with rheumatoid arthritis: a narrative literature review , 2021, Therapeutic advances in musculoskeletal disease.

[7]  M. Grammatikopoulou,et al.  Disease Activity, Functional Ability and Nutritional Status in Patients with Rheumatoid Arthritis: An Observational Study in Greece , 2020, Mediterranean journal of rheumatology.

[8]  L. Dai,et al.  Neglected extra-articular manifestations in rheumatoid arthritis patients with normal body mass index: reduced skeletal muscle overlapping overfat , 2020, Therapeutic advances in chronic disease.

[9]  C. Inderjeeth,et al.  The global prevalence of rheumatoid arthritis: a meta-analysis based on a systematic review , 2020, Rheumatology International.

[10]  R. Straub,et al.  Sex steroids and autoimmune rheumatic diseases: state of the art , 2020, Nature Reviews Rheumatology.

[11]  P. Hilliquin,et al.  Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study , 2020, Arthritis Research & Therapy.

[12]  C. Inderjeeth,et al.  SAT0576 THE PREVALENCE OF RHEUMATOID ARTHRITIS: A SYSTEMATIC REVIEW OF POPULATION-BASED STUDIES. , 2020, Annals of the Rheumatic Diseases.

[13]  N. Toroptsova,et al.  AB0267 BODY COMPOSITION IN PATIENTS WITH RHEUMATOID ARTHRITIS , 2020, Annals of the Rheumatic Diseases.

[14]  P. Spritzer,et al.  Cachexia in patients with rheumatoid arthritis: a cohort study , 2020, Clinical Rheumatology.

[15]  N. Aryaeian,et al.  Effects of hydroalcoholic extract of Berberis Integerrima on the anthropometric indices and metabolic profile in active rheumatoid arthritis patients. , 2020, Complementary therapies in medicine.

[16]  U. Kujala,et al.  Muscle and bone mass in middle‐aged women: role of menopausal status and physical activity , 2020, Journal of cachexia, sarcopenia and muscle.

[17]  K. Põlluste,et al.  Factors Associated with Low Lean Mass in Early Rheumatoid Arthritis: A Cross-Sectional Study , 2019, Medicina.

[18]  I. Rosner,et al.  Effects of Tocilizumab, an Anti-Interleukin-6 Receptor Antibody, on Serum Lipid and Adipokine Levels in Patients with Rheumatoid Arthritis , 2019, International journal of molecular sciences.

[19]  A. Winkvist,et al.  Dietary Habits of Women with Rheumatoid Arthritis Differ from that of Women without the Disease: Results from a Population-Based Study , 2019, Journal of Rheumatic Diseases and Treatment.

[20]  P. Sfikakis,et al.  Low rates of remission with methotrexate monotherapy in rheumatoid arthritis: review of randomised controlled trials could point towards a paradigm shift , 2019, RMD Open.

[21]  Christopher A. Taylor,et al.  Dietary patterns and nutrient intake of individuals with rheumatoid arthritis and osteoarthritis in the United States. , 2019, Nutrition.

[22]  N. Cherbuin,et al.  Fat mass changes during menopause: a metaanalysis. , 2019, American journal of obstetrics and gynecology.

[23]  J. Cauley,et al.  Changes in body composition and weight during the menopause transition. , 2019, JCI insight.

[24]  J. Alcocer-Varela,et al.  Body composition evaluated by body mass index and bioelectrical impedance vector analysis in women with rheumatoid arthritis. , 2018, Nutrition.

[25]  R. Xavier,et al.  Prevalence of rheumatoid cachexia in rheumatoid arthritis: a systematic review and meta‐analysis , 2018, Journal of cachexia, sarcopenia and muscle.

[26]  A. Tokarev,et al.  AB0347 Body composition in patients with rheumatoid arthritis kazakh nationality , 2018, Rheumatoid arthritis – comorbidity and clinical aspects.

[27]  Robert Dantzer,et al.  The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure , 2018, Front. Behav. Neurosci..

[28]  H. Kautiainen,et al.  Decreasing muscle performance associated with increasing disease activity in patients with rheumatoid arthritis , 2018, PloS one.

[29]  W. Lems,et al.  An unfavorable body composition is common in early arthritis patients: A case control study , 2018, PloS one.

[30]  D. Bogdanos,et al.  The Role of Flavonoids in Inhibiting Th17 Responses in Inflammatory Arthritis , 2018, Journal of immunology research.

[31]  George D Kitas,et al.  University of Birmingham Sedentary behaviour in rheumatoid arthritis: definition, measurement and implications for health , 2017 .

[32]  L. Castillo-Martínez,et al.  Prevalence of rheumatoid cachexia assessed by bioelectrical impedance vector analysis and its relation with physical function , 2018, Clinical Rheumatology.

[33]  R. Straub The brain and immune system prompt energy shortage in chronic inflammation and ageing , 2017, Nature Reviews Rheumatology.

[34]  F. Dutheil,et al.  Changes in body composition and metabolic profile during interleukin 6 inhibition in rheumatoid arthritis , 2017, Journal of cachexia, sarcopenia and muscle.

[35]  P. Kerstens,et al.  The short-term effects of two high-dose, step-down prednisolone regimens on body composition in early rheumatoid arthritis. , 2016, Rheumatology.

[36]  A. Lemmey Rheumatoid cachexia: the undiagnosed, untreated key to restoring physical function in rheumatoid arthritis patients? , 2016, Rheumatology.

[37]  M. Raji,et al.  Hypogonadism and the risk of rheumatic autoimmune disease , 2016, Clinical Rheumatology.

[38]  T. Wilkinson,et al.  Can Creatine Supplementation Improve Body Composition and Objective Physical Function in Rheumatoid Arthritis Patients? A Randomized Controlled Trial , 2016, Arthritis care & research.

[39]  L. D. de Groot,et al.  Differences in Nutrient Intake and Biochemical Nutrient Status Between Sarcopenic and Nonsarcopenic Older Adults-Results From the Maastricht Sarcopenia Study. , 2016, Journal of the American Medical Directors Association.

[40]  H. Gin,et al.  Energy expenditure and nutritional complications of metabolic syndrome and rheumatoid cachexia in rheumatoid arthritis: an observational study using calorimetry and actimetry. , 2016, Rheumatology.

[41]  M. Sampaolesi,et al.  Role of Inflammation in Muscle Homeostasis and Myogenesis , 2015, Mediators of inflammation.

[42]  M. Tierney,et al.  Profile of energy expenditure in people with rheumatoid arthritis. , 2015, Disability and health journal.

[43]  A. El Maghraoui,et al.  Does Rheumatoid Cachexia Predispose Patients with Rheumatoid Arthritis to Osteoporosis and Vertebral Fractures? , 2015, The Journal of Rheumatology.

[44]  G. Melino,et al.  The interplay between inflammation and metabolism in rheumatoid arthritis , 2015, Cell Death and Disease.

[45]  L. Caplan,et al.  Predictors of Longterm Changes in Body Mass Index in Rheumatoid Arthritis , 2015, The Journal of Rheumatology.

[46]  A. Laviano,et al.  Cachexia: clinical features when inflammation drives malnutrition , 2015, Proceedings of the Nutrition Society.

[47]  P. Katz,et al.  Are Men at Greater Risk of Lean Mass Deficits in Rheumatoid Arthritis? , 2015, Arthritis care & research.

[48]  K. Masuko Rheumatoid Cachexia Revisited: A Metabolic Co-Morbidity in Rheumatoid Arthritis , 2014, Front. Nutr..

[49]  J. Choe,et al.  Resting energy expenditure is not associated with disease activity in women with rheumatoid arthritis: cross-sectional study , 2014, The Korean journal of internal medicine.

[50]  J. Visser,et al.  Body composition of rheumatoid arthritis patients in the City of Cape Town, South Africa , 2014, Clinical Rheumatology.

[51]  Chih‐Yen Chen,et al.  Long-term etanercept therapy favors weight gain and ameliorates cachexia in rheumatoid arthritis patients: roles of gut hormones and leptin. , 2013, Current pharmaceutical design.

[52]  W. Lems,et al.  Relevance of the new pre-cachexia and cachexia definitions for patients with rheumatoid arthritis. , 2012, Clinical nutrition.

[53]  M. Tierney,et al.  Physical activity in rheumatoid arthritis: a systematic review. , 2012, Journal of physical activity & health.

[54]  Frank Buttgereit,et al.  Energy metabolism and rheumatic diseases: from cell to organism , 2012, Arthritis Research & Therapy.

[55]  C. McCall,et al.  NAD+-dependent Sirtuin 1 and 6 Proteins Coordinate a Switch from Glucose to Fatty Acid Oxidation during the Acute Inflammatory Response* , 2012, The Journal of Biological Chemistry.

[56]  C. Mendoza,et al.  Análisis de la composición corporal en mujeres adultas con lupus eritematoso sistémico , 2012 .

[57]  V. De Rosa,et al.  Intracellular metabolic pathways control immune tolerance. , 2012, Trends in immunology.

[58]  Samuel Hernández-Baldizón [How to effectively use methotrexate in rheumatoid arthritis?]. , 2012, Reumatologia clinica.

[59]  C. Hsieh,et al.  When T Cells Run Out of Breath: The HIF-1α Story , 2011, Cell.

[60]  A. Herrick,et al.  The effect of disease activity on body composition and resting energy expenditure in patients with rheumatoid arthritis , 2011, Journal of inflammation research.

[61]  I. Hafström,et al.  Low level of physical activity in women with rheumatoid arthritis is associated with cardiovascular risk factors but not with body fat mass - a cross sectional study , 2011, BMC musculoskeletal disorders.

[62]  M. Laudes,et al.  Effects of Inhibition of Interleukin-6 Signalling on Insulin Sensitivity and Lipoprotein (A) Levels in Human Subjects with Rheumatoid Diseases , 2010, PloS one.

[63]  J. Thom,et al.  Skeletal muscle properties in rheumatoid arthritis patients. , 2010, Medicine and science in sports and exercise.

[64]  I. Hafström,et al.  Infliximab therapy increases body fat mass in early rheumatoid arthritis independently of changes in disease activity and levels of leptin and adiponectin: a randomised study over 21 months , 2010, Arthritis Research & Therapy.

[65]  A. Silman,et al.  UvA-DARE (Digital Academic Repository) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative Aletaha, , 2010 .

[66]  S. Morgan,et al.  Folate supplementation during methotrexate therapy for rheumatoid arthritis. , 2010, Clinical and experimental rheumatology.

[67]  G. Summers,et al.  Rheumatoid cachexia and cardiovascular disease , 2010, Nature Reviews Rheumatology.

[68]  Y. Kawahito,et al.  Contribution of rheumatoid arthritis disease activity and disability to rheumatoid cachexia , 2010, Modern rheumatology.

[69]  G. Biolo,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". , 2010, Clinical nutrition.

[70]  J. Thom,et al.  Muscle Quality, Architecture, and Activation in Cachectic Patients with Rheumatoid Arthritis , 2010, The Journal of Rheumatology.

[71]  M. Karlsson,et al.  Early rheumatoid arthritis and body composition. , 2009, Rheumatology.

[72]  I. Hafström,et al.  Gonadal Hormones in Men with Rheumatoid Arthritis — From Onset Through 2 Years , 2009, The Journal of Rheumatology.

[73]  I. Hafström,et al.  Rheumatoid cachexia, central obesity and malnutrition in patients with low-active rheumatoid arthritis: feasibility of anthropometry, Mini Nutritional Assessment and body composition techniques , 2009, European journal of nutrition.

[74]  I. Hafström,et al.  Rheumatoid cachexia is associated with dyslipidemia and low levels of atheroprotective natural antibodies against phosphorylcholine but not with dietary fat in patients with rheumatoid arthritis: a cross-sectional study , 2009, Arthritis research & therapy.

[75]  P. Ponikowski,et al.  Cachexia: a new definition. , 2008, Clinical nutrition.

[76]  K. Fontaine,et al.  Association of body composition with disability in rheumatoid arthritis: impact of appendicular fat and lean tissue mass. , 2008, Arthritis and rheumatism.

[77]  I. Hafström,et al.  Malnutrition in women with rheumatoid arthritis is not revealed by clinical anthropometrical measurements or nutritional evaluation tools , 2008, European Journal of Clinical Nutrition.

[78]  G. Summers,et al.  Rheumatoid cachexia: a clinical perspective. , 2008, Rheumatology.

[79]  L. Ferrucci,et al.  Abnormal body composition phenotypes in older rheumatoid arthritis patients: association with disease characteristics and pharmacotherapies. , 2008, Arthritis and rheumatism.

[80]  M. Kontogianni,et al.  Effect of anti-TNF treatment on body composition and serum adiponectin levels of women with rheumatoid arthritis , 2008, Clinical Rheumatology.

[81]  I. Hafström,et al.  Cachexia in rheumatoid arthritis is associated with inflammatory activity, physical disability, and low bioavailable insulin‐like growth factor , 2008, Scandinavian journal of rheumatology.

[82]  A. Nevill,et al.  New resting energy expenditure prediction equations for patients with rheumatoid arthritis. , 2007, Rheumatology.

[83]  A. Nevill,et al.  Blockade of tumour necrosis factor-alpha in rheumatoid arthritis: effects on components of rheumatoid cachexia. , 2007, Rheumatology.

[84]  A. Arshad,et al.  The effect of disease activity on fat-free mass and resting energy expenditure in patients with rheumatoid arthritis versus noninflammatory arthropathies/soft tissue rheumatism , 2007, Modern rheumatology.

[85]  A. Jamurtas,et al.  Redefining overweight and obesity in rheumatoid arthritis patients , 2007, Annals of the rheumatic diseases.

[86]  B. Cronstein,et al.  Understanding the mechanisms of action of methotrexate: implications for the treatment of rheumatoid arthritis. , 2007, Bulletin of the NYU hospital for joint diseases.

[87]  Samuele M. Marcora,et al.  Randomized phase 2 trial of anti-tumor necrosis factor therapy for cachexia in patients with early rheumatoid arthritis. , 2006, The American journal of clinical nutrition.

[88]  Bin Huang,et al.  A randomized controlled trial of calcium supplementation to increase bone mineral density in children with juvenile rheumatoid arthritis. , 2006, Arthritis and rheumatism.

[89]  G. Kitas,et al.  Rheumatoid Cachexia: causes, significance and possible interventions , 2006 .

[90]  Samuele M. Marcora,et al.  Dietary treatment of rheumatoid cachexia with beta-hydroxy-beta-methylbutyrate, glutamine and arginine: a randomised controlled trial. , 2005, Clinical nutrition.

[91]  R. Roubenoff,et al.  Rheumatoid cachexia: metabolic abnormalities, mechanisms and interventions. , 2004, Rheumatology.

[92]  J. Kehayias,et al.  Tumor necrosis factor-alpha production is associated with less body cell mass in women with rheumatoid arthritis. , 2004, The Journal of rheumatology.

[93]  R. Straub,et al.  Increased estrogen formation and estrogen to androgen ratio in the synovial fluid of patients with rheumatoid arthritis. , 2003, The Journal of rheumatology.

[94]  T. Seeman,et al.  Homocysteine levels and decline in physical function: MacArthur Studies of Successful Aging. , 2002, The American journal of medicine.

[95]  R. Roubenoff,et al.  Low physical activity reduces total energy expenditure in women with rheumatoid arthritis: implications for dietary intake recommendations. , 2002, The American journal of clinical nutrition.

[96]  I. Hafström,et al.  Bioavailable testosterone in men with rheumatoid arthritis-high frequency of hypogonadism. , 2002, Rheumatology.

[97]  Yi-Ping Li,et al.  Tumor necrosis factor-α and muscle wasting: a cellular perspective , 2001, Respiratory research.

[98]  M. Cutolo,et al.  Different roles for androgens and estrogens in the susceptibility to autoimmune rheumatic diseases. , 2000, Rheumatic diseases clinics of North America.

[99]  J. Schölmerich,et al.  Conversion of dehydroepiandrosterone to downstream steroid hormones in macrophages. , 2000, The Journal of endocrinology.

[100]  A. Doube,et al.  Inadequate calcium, folic acid, vitamin E, zinc, and selenium intake in rheumatoid arthritis patients: results of a dietary survey. , 1997, Seminars in arthritis and rheumatism.

[101]  S. van der Linden,et al.  Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis , 1997, The Lancet.

[102]  J. Dequeker,et al.  Body composition in rheumatoid arthritis. , 1997, British journal of rheumatology.

[103]  J. Kremer,et al.  Nutrient intake of patients with rheumatoid arthritis is deficient in pyridoxine, zinc, copper, and magnesium. , 1996, The Journal of rheumatology.

[104]  J. Kehayias,et al.  Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation. , 1994, The Journal of clinical investigation.

[105]  C. Rivier Neuroendocrine Effects of Cytokines in the Rat , 1993, Reviews in the neurosciences.

[106]  R. Roubenoff,et al.  Rheumatoid cachexia: depletion of lean body mass in rheumatoid arthritis. Possible association with tumor necrosis factor. , 1992, The Journal of rheumatology.

[107]  J. Wang,et al.  Magnitude of body-cell-mass depletion and the timing of death from wasting in AIDS. , 1989, The American journal of clinical nutrition.

[108]  W. Vale,et al.  In the rat, interleukin-1 alpha acts at the level of the brain and the gonads to interfere with gonadotropin and sex steroid secretion. , 1989, Endocrinology.

[109]  C. Werning [Rheumatoid arthritis]. , 1983, Medizinische Monatsschrift fur Pharmazeuten.

[110]  Joseph R. Bertino,et al.  Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. , 1980, The American journal of medicine.

[111]  C. Begg,et al.  Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. , 1980, The American journal of medicine.

[112]  F. D. Moore,et al.  Energy and the maintenance of the body cell mass. , 1980, JPEN. Journal of parenteral and enteral nutrition.

[113]  J. Paget Nervous Mimicry of Organic Diseases , 1874, Atlanta medical and surgical journal.