Which group is most likely to suffer from protein deficiency in developing countries?

Background

The World Health Organization (WHO) defines malnutrition as "the cellular imbalance between the supply of nutrients and energy and the body's demand for them to ensure growth, maintenance, and specific functions." [1]  The term protein-energy malnutrition (PEM) applies to a group of related disorders that include marasmus, kwashiorkor (see the images below), and intermediate states of marasmus-kwashiorkor.

Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. [2]  Studies suggest that marasmus represents an adaptive response to starvation, whereas kwashiorkor represents a maladaptive response to starvation. Children may also present with a mixed picture of marasmus and kwashiorkor or with milder forms of malnutrition. 

Which group is most likely to suffer from protein deficiency in developing countries?
This photograph shows children and a nurse attendant at a Nigerian orphanage in the late 1960s. Note that four of the children have gray-blond hair, a symptom of the protein-deficiency disease kwashiorkor. Image courtesy of Dr Lyle Conrad and the Centers for Disease Control and Prevention Public Health Image Library.

Which group is most likely to suffer from protein deficiency in developing countries?
This late 1960s photograph shows a seated, listless child who was among many individuals found with kwashiorkor in Nigerian relief camps during the Nigerian-Biafran war. Kwashiorkor is a disease that develops due to a severe dietary protein deficiency. This child, whose diet fit such a deficiency profile, presented with symptoms including edema of the legs and feet; light-colored, thinning hair; anemia; a pot-belly; and shiny skin. Image courtesy of Dr Lyle Conrad and the Centers for Disease Control and Prevention Public Health Image Library.

Protein-energry malnutition is a global issue, seen primarily in resource-limited countries. Overall, malnutrition has decreased worldwide, but the rates vary by region. For example, Asia has seen declines in this condition, whereas there has been a continued increase in African nations. [3]

Malnutrition can be classified as acute versus chronic. Features of chronic malnutrition include stunted growth, mental apathy, developmental delay, and poor weight gain. [4, 5]  Acute malnutition manifests itself in two major forms: marasums (the most common form) and kwashiorkor, although some patients' condition may manifest as a combination of both forms (marasmic kwashiorkor).

Children with marasmus are often low weight-for-height and have a reduced mid-upper arm circumference, as well as a head that appears large relative to the rest of their body. Other findings include dry skin, thin hair, and irritability. Kwashiorkor is characterized by peripheral pitting edema, as well as "moon facies," hepatomegaly, and a pursed mouth.

Pathophysiology

In general, marasmus occurs when there is an insufficient energy intake to match the body's requirements. As a result, the body draws on its own stores, resulting in emaciation. In kwashiorkor, adequate carbohydrate consumption and decreased protein intake lead to decreased synthesis of visceral proteins. The resulting hypoalbuminemia contributes to extravascular fluid accumulation. Impaired synthesis of B-lipoprotein produces a fatty liver.

Protein-energy malnutrition also involves an inadequate intake of many essential nutrients. Low serum levels of zinc have been implicated as the cause of skin ulceration in many patients. In a 1979 study of 42 children with marasmus, Golden and Golden found that only those with low serum levels of zinc developed skin ulceration. [6] Serum zinc levels correlated closely with the presence of edema, stunted growth, and severe wasting. The classic "mosaic skin" and "flaky paint" dermatosis of kwashiorkor bears considerable resemblance to the skin changes of acrodermatitis enteropathica, the dermatosis of zinc deficiency.

In 2007, Lin et al stated that "a prospective assessment of food and nutrient intake in a population of Malawian children at risk for kwashiorkor" found "no association between the development of kwashiorkor and the consumption of any food or nutrient." [7]

Marasmus and kwashiorkor can both be associated with impaired glucose clearance that relates to dysfunction of pancreatic beta-cells. [8] In utero, plastic mechanisms appear to operate, adjusting metabolic physiology and adapting postnatal undernutrition and malnutrition to define whether marasmus and kwashiorkor will develop. [9]

A 2013 report from Texas noted an 18-month-old infant with type 1 glutaric acidemia who had extensive desquamative plaques, generalized nonpitting edema, and red-tinged sparse hair, with low levels of zinc, alkaline phosphatase, albumin, and iron. [10] This patient had a variation of kwashiorkor, and the authors suggested that it be termed acrodermatitis dysmetabolica. [10]

For complex reasons, sickle cell anemia can predispose sufferers to protein malnutrition. [11]

Protein-energy malnutrition ramps up arginase activity in macrophages and monocytes. [12]

Derangements to the gut microbiome in undernourished hosts also appear to play a role in the pathophysiology that results in persistent growth impairment in children. [13]

Etiology

Worldwide, the most common cause of malnutrition is inadequate food intake. Preschool-aged children in developing countries are often at risk for malnutrition because of their dependence on others for food, increased protein and energy requirements, immature immune systems causing a greater susceptibility to infection, and exposure to nonhygienic conditions.

Another significant factor is ineffective weaning secondary to ignorance, poor hygiene, economic factors, and cultural factors. The prognosis is worse when protein-energy malnutrition occurs with human immunodeficiency virus (HIV) infection. Gastrointestinal infections can and often do precipitate clinical protein-energy malnutrition because of associated diarrhea, anorexia, vomiting, increased metabolic needs, and decreased intestinal absorption. In addition, parasitic infections play a major role in many parts of the world.

In developed nations, inadequate food intake is a less common cause of malnutrition than that caused by decreased absorption or abnormal metabolism. Thus, diseases, such as cystic fibrosis, chronic renal failure, childhood malignancies, congenital heart disease, and neuromuscular diseases contribute to malnutrition in developed countries. Fad diets, inappropriate management of food allergies, and psychiatric diseases (eg, anorexia nervosa) can also lead to severe protein-energy malnutrition.

Populations in both acute- and long-term facilities are at risk for clinically significant involuntary weight loss (IWL) that can result in protein-energy malnutrition. IWL is defined as a loss of 4.5 kg or greater than 5% of the usual body weight over a period of 6-12 months. Protein-energy malnutrition occurs when weight loss of greater than 10% of normal body weight occurs.

Elderly patients are often at risk for protein-energy malnutrition because of inadequate nutrition, which has been determined to be a common comorbid factor for increased morbidity and mortality in elderly burn victims. [14]

Anorexia of aging, defined as the loss of appetite and/or decreased food intake in late life, is used to describe multifaceted clinical conditions that are common among frail older persons but not easily grouped into specific diseases or syndrome categories. Common causes of resulting malnutrition include decreased appetite, dependency on help for eating, impaired cognition and/or communication, poor positioning, frequent acute illnesses with gastrointestinal losses, medications that decrease appetite or increase nutrient losses, polypharmacy, decreased thirst response, decreased ability to concentrate urine, intentional fluid restriction due to fear of incontinence or choking if dysphagic, psychosocial factors such as isolation and depression, monotony of diet, higher nutrient density requirements, and other demands of age, illness, and disease on the body. [15]

Protein-energy malnutrition is one of the most common complications in liver cirrhosis patients, with reported rates of 25.1% to 65.5%.

Patients on long-term hemodialysis also may develop protein-energy malnutrition; this is associated with increased morbidity and mortality.

Patients with squamous cell carcinoma of the esophagus are at risk for protein-energy malnutrition.

Bariatric surgery can be associated with iatrogenic kwashiorkor. [16, 17]

Epidemiology

United States data

Protein-energy malnutrition is the most common form of nutritional deficiency among patients who are hospitalized in the United States. Up to half of all patients admitted to the hospital have malnutrition to some degree. In a survey of a large children's hospital, the prevalence of acute and chronic protein-energy malnutrition was more than 50%.

Protein-energy malnutrition is very much a disease that occurs in 21st century, even in the United States and other developed nations. [18, 19]  The case of an 8-month-old child with kwashiorkor in suburban Detroit, Michigan, was reported in 2010, [20]  and additional US cases of kwashiorkor have been noted, such as that of a baby in 2013 with a clinical picture imitating Stevens-Johnson syndrome but who in fact had kwashiorkor. [21] Babies solely fed on rice milk can also develop kwashiorkor.

In a survey focusing on low-income areas of the United States, 22-35% of children aged 2-6 years were below the 15th percentile for weight. Another survey showed that 11% of children in low-income areas had height-for-age measurements below the 5th percentile. Poor growth is seen in 10% of children in rural populations.

In hospitalized elderly persons, up to 55% are undernourished. Up to 85% of institutionalized elderly persons are undernourished. Studies have shown that as many as 50% have vitamin and mineral intake that is less than the recommended dietary allowance, and up to 30% of elderly persons have below-normal levels of vitamins and minerals.

International data

In 2000, the World Health Organization (WHO) estimated that malnourished children numbered 181.9 million (32%) in developing countries. [22]  In addition, approximately 149.6 million children younger than 5 years were malnourished when measured in terms of weight for age. In south central Asia and eastern Africa, about half the children had growth retardation due to protein-energy malnutrition. This figure was five times the prevalence in the western world.

More recent data (2016) indicate that severe acute malnutrition including kwashiorkor and marasmus affects more than 18 million children each year, most living in low-income settings. [2]  According to 2018 WHO data, 52 million children younger than 5 years are wasted (low weight-for-height), 17 million are severely wasted, and 155 million are stunted (low height-for-age). [23]

A 2018 systematic review and meta-analysis of 1989-2017 data regarding the prevalence of underweight and wasting in Iranian children younger than 5 years found regional differences, which the investigators believed could be attributed to the varying level of development in these areas. [24] The prevalence of underweight among children at the national level was 6%, with the lowest at 5% in western Iran and the highest in central Iran. The prevalence of pediatric wasting was 4% at the national level, with the lowest at 4% in western Iran and the highest in southen Iran. [24]

A cross-sectional study of Palestinian adolescents found inadequate energy intake in 55.66% of boys and 64.81% of girls, and inadequate protein intake in 15.07% of boys and 43.08% of girls. [25]  The recommended daily allowance for micronutrients was met by less than 80% of the study subjects.

Dermatologic findings appear more significant and occur more frequently among darker-skinned peoples. This finding is likely explained by the greater prevalence and the increased severity of protein-energy malnutrition in developing countries and not to a difference in racial susceptibility.

Marasmus most commonly occurs in children younger than 5 years. This period is characterized by increased energy requirements and increased susceptibility to viral and bacterial infections. Weaning (the deprivation of breast milk and the commencement of nourishment with other food) occurs during this high-risk period. Weaning is often complicated by geography, economy, hygiene, public health, culture, and dietetics. It can be ineffective when the foods introduced provide inadequate nutrients, when the food and water are contaminated, when the access to health care is inadequate, and/or when the patient cannot access or purchase proper nourishment.

In some studies, the protein-energy malnutrition prevalence among elderly persons is estimated to be as high as 4% for those living in the community, 50% for those hospitalized in acute care units or geriatric rehabilitation units, and 30-40% for those in long-term care facilities. A 2019 systematic review, meta-analysis, and meta-regression of the prevalence of protein-energy malnutrition among the elderly found that rural communities were affected twice as much as urban communities and women were affected more than males. [26] Other recent studies of geriatric patients hospitalized for orthopedic conditions [27] or heart failure [28] also note protein-energy malnutrition is prevalent in this population.

Prognosis

The extent of growth failure and the severity of hypoproteinemia, hypoalbuminemia, and electrolyte imbalances are predictors of a poorer prognosis. Additionally, underlying human immunodeficiency virus (HIV) infection is associated with a poor prognosis. 

Approximately 45% deaths each year in developing countries occur because of malnutrition in children younger than 5 years. [2, 13, 23] In kwashiorkor, mortality tends to decrease as the age of onset increases.

Protein-energy malnutrition has also been found to be a primary factor of poor prognosis in elderly persons. In a study designed to assess the quality of care in nursing home residents, there was a direct association between mortality and anorexia in elderly residents of both genders with an almost two-fold higher risk of death for all causes in patients with anorexia. [29] In a separate propensity-matched study of 32,771 elderly patients hospitalized for heart failure, protein-match malnutrition was associated with higher mortality, cardiogenic shock, cardiac arrest, acute kidney failure, acute respiratory failure, and mechanical ventilation. [28]

Patients with liver cirrhosis are also at risk for protein-energy malnutrition, [30] which portends a poor prognosis for survival. [31] Protein-energy malnutrition is associated with an increased risk of liver cirrhosis complications, including ascites, variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome. [30, 32]

Complications

Complications of protein-energy malnutrition can be many, including the following [33] :

  • Hypothermia

  • Hypoglycemia

  • Encephalopathy

  • Diarrhea

  • Heart failure

  • Infection

Another important complication of malnutrition is micronutrient defiencies. Vitamin deficiencies can be seen, with deficiencies in the fat-soluble vitamins (A, D, E, and K) being more common. Vitamin A deficiency can have ocular effects, causing night blindness among other problems; vitamin D deficiency can have bony effects; vitamin E deficiency can cause neuropathy and ataxia; and vitamin K deficiency can cause bleeding.

Deficiencies in the water-soluble vitamins has a multitude of effects. Folic acid (vitamin B9) and cobalamin (vitamin B12) deficiency can both cause megaloblastic anemia. Deficiency in thiamine (vitamin B1) can cause beriberi and high-output heart failure, whereas deficiency riboflavin (vitamin B2) can cause glossitis and seborrheic dermatitis. Niacin (vitamin B3) deficiency can result in pellagra, leading to dermatitis, dementia, diarrhea, and weakness. Pyridoxine (vitamin B6) deficiency can lead to neuropathy, irritability, and weight loss. 

Minerals or trace elements such as phosphorus, iron, and zinc can also be deficient in protein-energy malnutrition. Phosphate deficiency, if severe, can cause rhabdomyolysis, bone pain, or osteomalacia. Iron deficiency can lead to microcytic anemia and, if severe, can result in cardiomegaly, lethargy, and impaired psychomotor and mental development. Zinc deficiency can lead to growth failure, increased infections, and cognitive dysfunction.

Patient Education

Education regarding adequate nutrition starts with the mother, often prior to childbirth. It is important to educate the mother to be healthy during pregnancy to meet the nutritional demands not only of her child, but also herself. Educating these women regarding the importance of breastfeeding and how to adequately nourish a child is also essential.

  1. Onis M de, Monteiro C, Clugston G. The worldwide magnitude of protein-energy malnutrition: an overview from the WHO Global Database on Child Growth. Bulletin of the World Health Organization. 1993. 71(6):

  2. Di Giovanni V, Bourdon C, Wang DX, et al. Metabolomic changes in serum of children with different clinical diagnoses of malnutrition. J Nutr. 2016 Dec. 146 (12):2436-44. [QxMD MEDLINE Link]. [Full Text].

  3. Levels and trends in child malnutrition: UNICEF – WHO – World Bank Group joint child malnutrition estimates. Key findings of the 2016 edition. Available at http://www.who.int/nutgrowthdb/jme_brochure2016.pdf?ua=1. 2016; Accessed: August 27, 2018.

  4. Bergen DC. Effects of poverty on cognitive function: a hidden neurologic epidemic. Neurology. 2008. 71:447-451. [QxMD MEDLINE Link].

  5. Horta BL, Victora CG, de Mola CL, et al. Associations of linear growth and relative weight gain in early life with human capital at 30 years of age. J Pediatr. 2017 Mar. 182:85-91.e3. [QxMD MEDLINE Link]. [Full Text].

  6. Golden BE, Golden MH. Plasma zinc and the clinical features of malnutrition. Am J Clin Nutr. 1979 Dec. 32 (12):2490-4. [QxMD MEDLINE Link].

  7. Lin CA, Boslaugh S, Ciliberto HM, et al. A prospective assessment of food and nutrient intake in a population of Malawian children at risk for kwashiorkor. J Pediatr Gastroenterol Nutr. 2007 Apr. 44 (4):487-93. [QxMD MEDLINE Link].

  8. Spoelstra MN, Mari A, Mendel M, et al. Kwashiorkor and marasmus are both associated with impaired glucose clearance related to pancreatic beta-cell dysfunction. Metabolism. 2012 Mar 2. [QxMD MEDLINE Link].

  9. Forrester TE, Badaloo AV, Boyne MS, et al. Prenatal factors contribute to the emergence of kwashiorkor or marasmus in severe undernutrition: evidence for the predictive adaptation model. PLoS One. 2012. 7(4):e35907. [QxMD MEDLINE Link].

  10. Ma L, Savory S, Agim NG. Acquired protein energy malnutrition in glutaric acidemia. Pediatr Dermatol. 2013 Jul-Aug. 30(4):502-4. [QxMD MEDLINE Link].

  11. Hyacinth HI, Adekeye OA, Yilgwan CS. Malnutrition in sickle cell anemia: implications for infection, growth, and maturation. J Soc Behav Health Sci. 2013 Jan 1. 7(1):7(1). [QxMD MEDLINE Link].

  12. Corware K, Yardley V, Mack C, et al. Protein energy malnutrition increases arginase activity in monocytes and macrophages. Nutr Metab (Lond). 11(1). 2014 Oct 24:51. [QxMD MEDLINE Link].

  13. Velly H, Britton RA, Preidis GA. Mechanisms of cross-talk between the diet, the intestinal microbiome, and the undernourished host. Gut Microbes. 2017 Mar 4. 8 (2):98-112. [QxMD MEDLINE Link].

  14. Demling RH. The incidence and impact of pre-existing protein energy malnutrition on outcome in the elderly burn patient population. J Burn Care Rehabil. 2005 Jan-Feb. 26(1):94-100. [QxMD MEDLINE Link].

  15. Landi F, Calvani R, Tosato M, et al. Anorexia of aging: risk factors, consequences, and potential treatments. Nutrients. 2016 Jan 27. 8 (2):69. [QxMD MEDLINE Link]. [Full Text].

  16. William JH, Tapper EB, Yee EU, Robson SC. Secondary kwashiorkor: a rare complication of gastric bypass surgery. Am J Med. 2015 May. 128(5):e1-2. [QxMD MEDLINE Link].

  17. Ghorbel HH, Broussard JF, Lacour JP, Passeron T. Iatrogenic kwashiorkor developing after bypass surgery. Clin Exp Dermatol. 2014 Jan;. 39(1):113-4. [QxMD MEDLINE Link].

  18. Barker LA, Gout BS, Crowe TC. Hospital malnutrition: prevalence, identification and impact on patients and the healthcare system. Int J Environ Res Public Health. 2011 Feb. 8 (2):514-27. [QxMD MEDLINE Link].

  19. McCarthy A, Delvin E, Marcil V, et al. Prevalence of malnutrition in pediatric hospitals in developed and in-transition countries: the impact of hospital practices. Nutrients. 2019 Jan 22. 11 (2):[QxMD MEDLINE Link].

  20. Tierney EP, Sage RJ, Shwayder T. Kwashiorkor from a severe dietary restriction in an 8-month infant in suburban Detroit, Michigan: case report and review of the literature. Int J Dermatol. 2010 May. 49(5):500-6. [QxMD MEDLINE Link].

  21. Boyd KP, Andea A, Hughey LC. Acute inpatient presentation of kwashiorkor: not just a diagnosis of the developing world. Pediatr Dermatol. 2013 Nov-Dec. 30(6):e240-1. [QxMD MEDLINE Link].

  22. World Health Organization. Nutrition for Health and Development: A Global Agenda for Combating Malnutrition. WHO/NHD/00.6. Geneva, Switzerland: WHO; 2000. [Full Text].

  23. World Health Organization. Malnutrition fact sheet. Available at https://www.who.int/news-room/fact-sheets/detail/malnutrition. February 16, 2018; Accessed: March 8, 2019.

  24. Moradi Y, Shadmani FK, Mansori K, Hanis SM, Khateri R, Mirzaei H. Prevalence of underweight and wasting in Iranian children aged below 5 years: a systematic review and meta-analysis. Korean J Pediatr. 2018 Aug. 61 (8):231-8. [QxMD MEDLINE Link].

  25. Jildeh C, Papandreou C, Abu Mourad T, et al. Assessing the nutritional status of Palestinian adolescents from East Jerusalem: a school-based study 2002-03. J Trop Pediatr. 2011 Feb. 57(1):51-8. [QxMD MEDLINE Link].

  26. Crichton M, Craven D, Mackay H, Marx W, de van der Schueren M, Marshall S. A systematic review, meta-analysis and meta-regression of the prevalence of protein-energy malnutrition: associations with geographical region and sex. Age Ageing. 2019 Jan 1. 48 (1):38-48. [QxMD MEDLINE Link].

  27. Rosenberger C, Rechsteiner M, Dietsche R, Breidert M. Energy and protein intake in 330 geriatric orthopaedic patients: Are the current nutrition guidelines applicable?. Clin Nutr ESPEN. 2019 Feb. 29:86-91. [QxMD MEDLINE Link].

  28. Adejumo AC, Adejumo KL, Adegbala OM, et al. Protein-energy malnutrition and outcomes of hospitalizations for heart failure in the USA. Am J Cardiol. 2019 Mar 15. 123 (6):929-35. [QxMD MEDLINE Link].

  29. Landi F, Lattanzio F, Dell'Aquila G, et al. Prevalence and potentially reversible factors associated with anorexia among older nursing home residents: results from the ULISSE project. J Am Med Dir Assoc. 2013 Feb. 14 (2):119-24. [QxMD MEDLINE Link].

  30. Shergill R, Syed W, Rizvi SA, Singh I. Nutritional support in chronic liver disease and cirrhotics. World J Hepatol. 2018 Oct 27. 10 (10):685-94. [QxMD MEDLINE Link].

  31. Yao CK, Fung J, Chu NHS, Tan VPY. Dietary interventions in liver cirrhosis. J Clin Gastroenterol. 2018 Sep. 52 (8):663-73. [QxMD MEDLINE Link].

  32. Nishikawa H, Yoh K, Enomoto H, et al. Factors associated with protein-energy malnutrition in chronic liver disease: analysis using indirect calorimetry. Medicine (Baltimore). 2016 Jan. 95 (2):e2442. [QxMD MEDLINE Link]. [Full Text].

  33. Wharton B. Protein energy malnutrition: problems and priorities. Acta Paediatr Scand Suppl. 1991. 374:5-14. [QxMD MEDLINE Link].

  34. Jen M, Yan AC. Syndromes associated with nutritional deficiency and excess. Clin Dermatol. 2010 Nov-Dec. 28(6):669-85. [QxMD MEDLINE Link].

  35. Hon KL, Nip SY, Cheung KL. A tragic case of atopic eczema: malnutrition and infections despite multivitamins and supplements. Iran J Allergy Asthma Immunol. 2012 Sep. 11 (3):267-70. [QxMD MEDLINE Link].

  36. Mori F, Serranti D, Barni S, et al. A kwashiorkor case due to the use of an exclusive rice milk diet to treat atopic dermatitis. Nutr J. 2015 Aug 21. 14:83. [QxMD MEDLINE Link].

  37. Henrique de S B Xavier M, De Magalhaes E, Ferraz Oliveira G, Keltke Magalhaes M, Prates de Almeida E Oliveira C, Braganca Oliveira N. A child with kwashiorkor misdiagnosed as atopic dermatitis. Dermatol Online J. 2017 May 15. 23 (5):[QxMD MEDLINE Link].

  38. Lewandowski H, Breen TL, Huang EY. Kwashiorkor and an acrodermatitis enteropathica-like eruption after a distal gastric bypass surgical procedure. Endocr Pract. 2007 May-Jun. 13(3):277-82. [QxMD MEDLINE Link].

  39. Al-Mubarak L, Al-Khenaizan S, Al Goufi T. Cutaneous presentation of kwashiorkor due to infantile Crohn's disease. Eur J Pediatr. 2010 Jan. 169(1):117-9. [QxMD MEDLINE Link].

  40. Sander CS, Hertecant J, Abdulrazzaq YM, Berger TG. Severe exfoliative erythema of malnutrition in a child with coexisting coeliac and Hartnup's disease. Clin Exp Dermatol. 2009 Mar. 34(2):178-82. [QxMD MEDLINE Link].

  41. Franco G, Calcaterra R, Valenzano M, Padovese V, Fazio R, Morrone A. Cupping-related skin lesions. Skinmed. 2012 Sep-Oct. 10(5):315-8. [QxMD MEDLINE Link].

  42. Nafzger S, Fleury LA, Uehlinger DE, Plüss P, Scura N, Kurmann S. Detection of malnutrition in patients undergoing maintenance haemodialysis: a quantitative data analysis on 12 parameters. J Ren Care. 2015 Sep. 41 (3):168-76. [QxMD MEDLINE Link].

  43. Katalinic L, Premuzic V, Basic-Jukic N, Barisic I, Jelakovic B. Hypoproteinemia as a factor in assessing malnutrition and predicting survival on hemodialysis. J Artif Organs. 2019 Mar 9. [QxMD MEDLINE Link].

  44. Tavarela Veloso F. Review article: skin complications associated with inflammatory bowel disease. Aliment Pharmacol Ther. 2004 Oct. 20 Suppl 4:50-3. [QxMD MEDLINE Link].

  45. Harima Y, Yamasaki T, Hamabe S, et al. Effect of a late evening snack using branched-chain amino acid-enriched nutrients in patients undergoing hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma. Hepatol Res. 2010 Jun. 40(6):574-84. [QxMD MEDLINE Link].

  46. World Health Organization, United Nations Children's Fund. WHO child growth standards and the identification of severe acute malnutrition in infants and children. Available at http://apps.who.int/iris/bitstream/handle/10665/44129/9789241598163_eng.pdf?sequence=1. 2009; Accessed: August 29, 2018.

  47. Thavaraj V, Sesikeran B. Histopathological changes in skin of children with clinical protein energy malnutrition before and after recovery. J Trop Pediatr. 1989 Jun. 35(3):105-8. [QxMD MEDLINE Link].

  48. McKenzie CA, Wakamatsu K, Hanchard NA, Forrester T, Ito S. Childhood malnutrition is associated with a reduction in the total melanin content of scalp hair. Br J Nutr. 2007 Jul. 98(1):159-64. [QxMD MEDLINE Link].

  49. Odabas D, Caksen H, Sar S, Unal O, Tuncer O, Atas B, et al. Cranial MRI findings in children with protein energy malnutrition. Int J Neurosci. 2005 Jun. 115 (6):829-37. [QxMD MEDLINE Link].

  50. Writing Group for the ISCD Position Development Conference. Diagnosis of osteoporosis in men, premenopausal women, and children. J Clin Densitom. 2004 Spring. 7 (1):17-26. [QxMD MEDLINE Link].

  51. [Guideline] World Health Organization. Updates on the Management of Severe Acute Malnutrition in Infants and Children. Available at http://apps.who.int/iris/bitstream/handle/10665/95584/9789241506328_eng.pdf?sequence=1. 2013; Accessed: September 6, 2018.

  52. Kabalo MY, Seifu CN. Treatment outcomes of severe acute malnutrition in children treated within Outpatient Therapeutic Program (OTP) at Wolaita Zone, Southern Ethiopia: retrospective cross-sectional study. J Health Popul Nutr. 2017 Mar 9. 36 (1):7. [QxMD MEDLINE Link]. [Full Text].

  53. Chung SH, Stenvinkel P, Lindholm B, Avesani CM. Identifying and managing malnutrition stemming from different causes. Perit Dial Int. 2007 Jun. 27 suppl 2:S239-44. [QxMD MEDLINE Link].

  54. Dorner TE, Lackinger C, Haider S, et al. Nutritional intervention and physical training in malnourished frail community-dwelling elderly persons carried out by trained lay "buddies": study protocol of a randomized controlled trial. BMC Public Health. 2013 Dec. 13(1):1232. [QxMD MEDLINE Link].

  55. [Guideline] US Department of Health and Human Services, US Department of Agriculture. Dietary Guidelines for Americans: 2015-2020. 8th ed. Washington, DC: HHS, USDA; December 2015. [Full Text].

  56. Bekele A, Janakiraman B. Physical therapy guideline for children with malnutrition in low income countries: clinical commentary. J Exerc Rehabil. 2016 Aug. 12 (4):266-75. [QxMD MEDLINE Link].

  57. Walmsley RS. Refeeding syndrome: screening, incidence, and treatment during parenteral nutrition. J Gastroenterol Hepatol. 2013 Dec. 28 Suppl 4:113-7. [QxMD MEDLINE Link].

  58. Al Sharkawy I, Ramadan D, El-Tantawy A. 'Refeeding syndrome' in a Kuwaiti child: clinical diagnosis and management. Med Princ Pract. 2010. 19 (3):240-3. [QxMD MEDLINE Link].

  59. Melchior JC. From malnutrition to refeeding during anorexia nervosa. Curr Opin Clin Nutr Metab Care. 1998 Nov. 1(6):481-5. [QxMD MEDLINE Link].

  60. Garber AK, Mauldin K, Michihata N, Buckelew SM, Shafer MA, Moscicki AB. Higher calorie diets increase rate of weight gain and shorten hospital stay in hospitalized adolescents with anorexia nervosa. J Adolesc Health. 2013 Nov. 53 (5):579-84. [QxMD MEDLINE Link].

  61. Takeda E, Ikeda S, Nakahashi O. [Lack of phosphorus intake and nutrition] [Japanese]. Clin Calcium. 2012 Oct. 22 (10):1487-91. [QxMD MEDLINE Link].

  62. Williams PCM, Berkley JA. Guidelines for the treatment of severe acute malnutrition: a systematic review of the evidence for antimicrobial therapy. Paediatr Int Child Health. 2018 Nov. 38 (sup1):S32-S49. [QxMD MEDLINE Link].

  63. [Guideline] US Health and Human Services, US Department of Agriculture. Dietary Guidelines for Americans: 2015-2020 [Executive summary]. Available at https://health.gov/dietaryguidelines/2015/guidelines/executive-summary/. December 2015; Accessed: March 11, 2019.

  64. [Guideline] Piercy KL, Troiano RP, Ballard RM, et al. The physical activity guidelines for Americans. JAMA. 2018 Nov 20. 320 (19):2020-8. [QxMD MEDLINE Link].

  65. 2018 Physical Activity Guidelines Advisory Committee. 2018 Physical Activity Guidelines Advisory Committee Scientific Report. Washington, DC: US Department of Health and Human Services; November 2018. [Full Text].

  66. Balint JP. Physical findings in nutritional deficiencies. Pediatr Clin North Am. 1998 Feb. 45(1):245-60. [QxMD MEDLINE Link].

  67. Nutritional disorders: malnutrition. Beers MH, Berkow R, eds. The Merck Manual. 17th ed. Whitehouse Station, NJ: Merck Co; 1999. 28-32.

  68. Caksen H, Kendirci M, Kandemir O, Patiroglu T. A case of malignant histiocytosis associated with skin involvement mimicking kwashiorkor. Pediatr Dermatol. 2001 Nov-Dec. 18(6):545-6. [QxMD MEDLINE Link].

  69. Collins N. Protein-energy malnutrition and involuntary weight loss: nutritional and pharmacological strategies to enhance wound healing. Expert Opin Pharmacother. 2003 Jul. 4(7):1121-40. [QxMD MEDLINE Link].

  70. Constans T, Alix E, Dardaine V. [Protein-energy malnutrition. Diagnostic methods and epidemiology] [French]. Presse Med. 2000 Dec 16. 29 (39):2171-6. [QxMD MEDLINE Link].

  71. De Caprio C, Alfano A, Senatore I, Zarrella L, Pasanisi F, Contaldo F. Severe acute liver damage in anorexia nervosa: two case reports. Nutrition. 2006 May. 22(5):572-5. [QxMD MEDLINE Link].

  72. Delahoussaye AR, Jorizzo JL. Cutaneous manifestations of nutritional disorders. Dermatol Clin. 1989 Jul. 7(3):559-70. [QxMD MEDLINE Link].

  73. Golden MHN. Severe malnutrition. In: Weatherall DJ, Ledingham JGG, Warrell DA, eds. Oxford Textbook of Medicine. 3rd ed. Oxford, UK: Oxford University Press; 1996. 1278-96.

  74. Goskowicz M, Eichenfield LF. Cutaneous findings of nutritional deficiencies in children. Curr Opin Pediatr. 1993 Aug. 5(4):441-5. [QxMD MEDLINE Link].

  75. Gupta MA, Gupta AK, Haberman HF. Dermatologic signs in anorexia nervosa and bulimia nervosa. Arch Dermatol. 1987 Oct. 123(10):1386-90. [QxMD MEDLINE Link].

  76. Gurski RR, Schirmer CC, Rosa AR, Brentano L. Nutritional assessment in patients with squamous cell carcinoma of the esophagus. Hepatogastroenterology. 2003 Nov-Dec. 50(54):1943-7. [QxMD MEDLINE Link].

  77. Harris CL, Fraser C. Malnutrition in the institutionalized elderly: the effects on wound healing. Ostomy Wound Manage. 2004 Oct. 50 (10):54-63. [QxMD MEDLINE Link].

  78. Hendricks KM, Duggan C, Gallagher L, et al. Malnutrition in hospitalized pediatric patients. Current prevalence. Arch Pediatr Adolesc Med. 1995 Oct. 149(10):1118-22. [QxMD MEDLINE Link].

  79. Jilcott SB, Masso KL, Ickes SB, Myhre SD, Myhre JA. Surviving but not quite thriving: anthropometric survey of children aged 6 to 59 months in a rural Western Uganda district. J Am Diet Assoc. 2007 Nov. 107(11):1983-8. [QxMD MEDLINE Link].

  80. Kuhl J, Davis MD, Kalaaji AN, Kamath PS, Hand JL, Peine CJ. Skin signs as the presenting manifestation of severe nutritional deficiency: report of 2 cases. Arch Dermatol. 2004 May. 140(5):521-4. [QxMD MEDLINE Link].

  81. Lyder CH. Assessing risk and preventing pressure ulcers in patients with cancer. Semin Oncol Nurs. 2006 Aug. 22(3):178-84. [QxMD MEDLINE Link].

  82. Manguso F, D'Ambra G, Menchise A, Sollazzo R, D'Agostino L. Effects of an appropriate oral diet on the nutritional status of patients with HCV-related liver cirrhosis: a prospective study. Clin Nutr. 2005 Oct. 24(5):751-9. [QxMD MEDLINE Link].

  83. McLaren DS. Skin in protein energy malnutrition. Arch Dermatol. 1987 Dec. 123(12):1674-1676a. [QxMD MEDLINE Link].

  84. Miller SJ. Nutritional deficiency and the skin. J Am Acad Dermatol. 1989 Jul. 21(1):1-30. [QxMD MEDLINE Link].

  85. Neldner KH. Nutrition, aging and the skin. Geriatrics. 1984 Feb. 39(2):69-82, 87-8. [QxMD MEDLINE Link].

  86. Pelly TF, Santillan CF, Gilman RH, et al. Tuberculosis skin testing, anergy and protein malnutrition in Peru. Int J Tuberc Lung Dis. 2005 Sep. 9(9):977-84. [QxMD MEDLINE Link].

  87. Prendiville JS, Manfredi LN. Skin signs of nutritional disorders. Semin Dermatol. 1992 Mar. 11(1):88-97. [QxMD MEDLINE Link].

  88. Roongpisuthipong C, Sobhonslidsuk A, Nantiruj K, Songchitsomboon S. Nutritional assessment in various stages of liver cirrhosis. Nutrition. 2001 Sep. 17(9):761-5. [QxMD MEDLINE Link].

  89. Ryan AS, Goldsmith LA. Nutrition and the skin. Clin Dermatol. 1996 Jul-Aug. 14(4):389-406. [QxMD MEDLINE Link].

  90. Schneider JB, Norman RA. Cutaneous manifestations of endocrine-metabolic disease and nutritional deficiency in the elderly. Dermatol Clin. 2004 Jan. 22(1):23-31, vi. [QxMD MEDLINE Link].

  91. Shah S, Kannikeswaran N, Kamat D. A rash. Clin Pediatr (Phila). 2007 Sep. 46 (7):650-4. [QxMD MEDLINE Link].

  92. Soni BP, McLaren DS, Sherertz EF. Skin lesions in nutritional, metabolic and heritable disorders: cutaneous changes in nutritional disease. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz S, eds. Fitzpatrick's Dermatology in General Medicine. 5th ed. New York, NY: McGraw-Hill; 1999. Vol 2: 1725-37.

  93. Tirmentajn-Jankovic B, Dimkovic N. [Simple methods for nutritional status assessment in patients treated with repeated hemodialysis] [Serbian]. Med Pregl. 2004 Sep-Oct. 57 (9-10):439-44. [QxMD MEDLINE Link].

  94. Wilmer WA, Magro CM. Calciphylaxis: emerging concepts in prevention, diagnosis, and treatment. Semin Dial. 2002 May-Jun. 15(3):172-86. [QxMD MEDLINE Link].

  95. Wong MMY, Thijssen S, Wang Y, et al. Prediction of mortality and hospitalization risk using nutritional indicators and their changes over time in a large prevalent hemodialysis cohort. J Ren Nutr. 2019 Mar 6. [QxMD MEDLINE Link].

Author

Coauthor(s)

Thomas L Abell, MD Professor and Arthur M Shoen MD Chair in Gastroenterology, Division of Gastroenterology, Hepatology and Nutrition, Faculty, Uro-Gynecology Fellowship, University of Louisville School of Medicine; Director of GI Motility Clinic at Jewish Hospital/U of Louisville Physicians; Former Director of Nutritional Support, Medical Staff, University of Mississippi Medical Center; Former Medical Staff, Mississippi Methodist Rehabilitation Center

Thomas L Abell, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Neurogastroenterology and Motility Society, American Society for Gastrointestinal Endoscopy, International Society for Quality-of-Life Studies

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: ADEPT-GI<br/>Received research grant from: Theravance; Vanda; Allergan<br/>Have a 5% or greater equity interest in: ADEPT-GI<br/>Received income in an amount equal to or greater than $250 from: Theravance<br/>GI Editor for MedStudy for: Reviewer for UpToDate.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP (Retired) Professor, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Noah S Scheinfeld, JD, MD, FAAD † Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Anusuya Mokashi, MD, MS Resident Physician, Department of Radiology, Staten Island University Hospital

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Dr. Dino Santoro, to the development and writing of this article.

What population is most at risk for protein deficiency?

Protein deficiency is more likely to affect vegans, vegetarians, those over the age of 70, and anyone with a digestive issue like celiac or Crohn's disease. To treat a protein deficiency, increase your intake of high-protein foods like eggs, salmon, and lentils.

Is protein deficiency common in developing countries?

Although severe protein deficiency is rare in the developed world, it is a leading cause of death in children in many poor, underdeveloped countries. There are two main syndromes associated with protein deficiencies: Kwashiorkor and Marasmus. Kwashiorkor affects millions of children worldwide.

What group is most affected by protein

Protein–energy malnutrition affects children the most because they have less protein intake. The few rare cases found in the developed world are almost entirely found in small children as a result of fad diets, or ignorance of the nutritional needs of children, particularly in cases of milk allergy.

Which groups are at risk for deficiency?

But some of us are at a greater risk than others..
Vegetarians (especially vegans) ... .
Prenatal. ... .
The Elderly. ... .
Post-Op. ... .
The Obese..