{"history":[],"article":{"id":"e3641ae1-b7ef-4162-aa45-147330e2a947","title":"Kwashiorkor","slug":"kwashiorkor","content":":::summary\n![A young girl with kwashiorkor in a relief camp during the Nigerian Civil War](https://upload.wikimedia.org/wikipedia/commons/4/47/Starved///girl.jpg)\n**Field:** [Pediatrics](https://bliptext.com/articles/pediatrics) \n:::\n\n# \n**Kwashiorkor** (, is also ) is a form of severe [protein malnutrition](https://bliptext.com/articles/protein-energy-malnutrition) characterized by [edema](https://bliptext.com/articles/edema) and an enlarged [liver](https://bliptext.com/articles/liver) with [fatty](https://bliptext.com/articles/fat) infiltrates.\nIt is thought to be caused by sufficient [calorie](https://bliptext.com/articles/calorie) intake, but with insufficient [protein](https://bliptext.com/articles/protein-nutrient) consumption (or lack of good quality [protein](https://bliptext.com/articles/protein-nutrient)), which distinguishes it from [marasmus](https://bliptext.com/articles/marasmus).\nRecent studies have found that a lack of antioxidant micronutrients such as [β-carotene](https://bliptext.com/articles/carotene), [lycopene](https://bliptext.com/articles/lycopene), other carotenoids, and [vitamin C](https://bliptext.com/articles/vitamin-c) as well as the presence of [aflatoxins](https://bliptext.com/articles/aflatoxins) may play a role in the development of the disease.\nHowever, the exact cause of kwashiorkor is still unknown.\nInadequate food supply is correlated with occurrences of kwashiorkor; occurrences in [high income countries](https://bliptext.com/articles/developed-country) are rare.\nIt occurs amongst [weaning children](https://bliptext.com/articles/weaning) to ages of about five years old.\nConditions analogous to kwashiorkor were well documented around the world throughout history.\nHowever, [Jamaican](https://bliptext.com/articles/jamaica) [pediatrician](https://bliptext.com/articles/pediatrician) [Cicely Williams](https://bliptext.com/articles/cicely-williams) introduced the term in 1935, two years after she published the disease's first formal description.\nWilliams was the first to conduct research on kwashiorkor and differentiate it from other dietary deficiencies.\nShe was the first to suggest that this might be a deficiency of protein.\nThe name is derived from the [Ga language](https://bliptext.com/articles/ga-language) of coastal [Ghana](https://bliptext.com/articles/ghana), translated as \"the sickness the baby gets when the new baby comes\" or \"the disease of the deposed child\", and reflecting the development of the condition in an older child who has been [weaned](https://bliptext.com/articles/weaned) from the breast when a younger sibling comes.\nBreast milk contains [amino acids](https://bliptext.com/articles/amino-acid) vital to a child's growth.\nIn at-risk populations, kwashiorkor may develop after children are weaned from breast milk and begin consuming a diet high in [carbohydrates](https://bliptext.com/articles/carbohydrate), including [maize](https://bliptext.com/articles/maize), [cassava](https://bliptext.com/articles/cassava) or rice.\n\n# Classification\nKwashiorkor is a type of severe acute malnutrition (SAM).\nSAM is a category, composed of two conditions: marasmus and kwashiorkor.\nBoth kwashiorkor and marasmus fall under the umbrella of [protein–energy malnutrition](https://bliptext.com/articles/protein-energy-malnutrition) (PEM).\nThese diseases are oftentimes discussed together, but are distinctly separate conditions of malnutrition.\nKwashiorkor is marked by an array of metabolic disturbances of uncertain etiology.\nIn contrast, marasmus is more clearly a syndrome of energy deficiency, which is marked by weight loss.\nOn physical exam, kwashiorkor is also distinguished from marasmus by the presence of edema.\nWhen children present with both kwashiorkor and marasmus, the condition is referred to as \"marasmic-kwashiorkor\".\nIn general, kwashiorkor is marked by more profound serum depletions of antioxidant molecules and minerals, relative to marasmus.\n\n## Wellcome's classification\nWellcome classification is a system for classifying protein-energy malnutrition in children based on weight for their age and based on presence of edema.\nOther classifications include Gomez classification and Waterlow classification.\n\n# Signs and symptoms\nThe defining sign of kwashiorkor in children is bilateral [edema](https://bliptext.com/articles/edema) in the feet.\nEdema may also involve the hands, trunk, and face.\nKwashiorkor is characterized by a fatty liver.\nThis fatty liver of undernutrition phenotype is often accompanied by evidence of inflammation and fibrosis.\nWhereas a fatty liver of undernutrition is a consistent feature of kwashiorkor, it is only encountered sometimes in children with marasmus.\nIn addition to this characteristic [hepatic steatosis](https://bliptext.com/articles/hepatic-steatosis), kwashiorkor is marked by a parallel pattern of multi-organ dysfunction.\nOrgans often affected in children with kwashiorkor include the kidneys, pancreas, heart, and nervous system.\nOther findings that may be encountered on physical exam include a distended [abdomen](https://bliptext.com/articles/abdomen), hair thinning, loss of teeth, skin or hair depigmentation, and [dermatitis](https://bliptext.com/articles/dermatitis).\nChildren with kwashiorkor often develop irritability and [anorexia](https://bliptext.com/articles/anorexia-symptom).\nGenerally, kwashiorkor is treated by introducing a high quality source of protein to the diet.\nReady to use therapeutic food (RUTF) as well as [F-100 and F-75 milk powders](https://bliptext.com/articles/f-100-and-f-75-foods), which both include skim milk powder, are recommended for the treatment of kwashiorkor.\nThese products are designed for use in low resource settings.\nThe limited number of kwashiorkor cases that occur in high resource settings, where there is good access to advanced therapeutic tools, are typically treated with partially hydrolyzed or [elemental enteral formulas](https://bliptext.com/articles/amino-acid-based-formula), with parenteral nutrition provided in extreme cases.\n\n# Causes\nThe precise etiology of kwashiorkor remains unclear.\nSeveral hypotheses have been proposed that are associated with and explain some, but not all aspects of the pathophysiology of kwashiorkor.\nThey include, but are not limited to protein deficiency causing hypoalbuminemia, amino acid deficiency, oxidative stress, and gut microbiome changes.\n\n## Low protein intake\nKwashiorkor is a severe form of [malnutrition](https://bliptext.com/articles/malnutrition) associated with a low protein diet.\nThe extreme lack of protein causes an osmotic imbalance in the [gastrointestinal system](https://bliptext.com/articles/human-gastrointestinal-tract) causing swelling of the gut diagnosed as an [edema](https://bliptext.com/articles/edema) or retention of water.\nExtreme fluid retention observed in individuals suffering from kwashiorkor is accompanied by irregularities in the [lymphatic system](https://bliptext.com/articles/lymphatic-system) as well as disruptions of capillary exchange.\nThe lymphatic system serves three major purposes: fluid recovery, immunity, and [lipid](https://bliptext.com/articles/lipid) absorption.\nVictims of kwashiorkor commonly exhibit reduced ability to recover fluids, immune system failure, and low lipid absorption.\nFluid recovery by the lymphatic system is accomplished by re-vascularization of fluid and macromolecules from the interstitial space, allowing these constituents of whole blood to be returned to the venous circulation.\nCompromised fluid recovery may contribute to the phenomenon of extravascular fluid accumulation in kwashiorkor.\nThe low protein theory for the pathogenesis of kwashiorkor has been used to teach that capillary exchange between the lymphatic system and circulating blood is impaired by a reduced oncotic (i.e. colloid osmotic pressure, COP) in the blood, as a consequence of inadequate protein intake, so that the hydrostatic pressure gradient, which favors extravasation of fluid from small vessels, is not overcome.\nProteins, mainly albumin, are responsible for creating the COP observed in the blood and tissue fluids.\nThe difference in the COP of the blood and tissue tends to favor the reentry of fluid from the extravascular space, into the circulatory system.\nThis tendency is opposed by the venous hydrostatic pressure, which tends to favor the exit of fluid from small vessels, into the interstitial space.\nThe low protein theory for the pathogenesis of kwashiorkor held that a deficiency of serum proteins, caused by inadequate protein intake, disrupted this balance, and thus impaired the return flow of fluid from the interstitium into the capillary and venous structures.\nIt has been taught that this is what accounts for the accumulation of extravascular fluid in kwashiorkor, and the subsequent pedal edema and abdominal distension.\nThe low protein theory, which relies heavily upon Starling's theory for the movement of fluid in biological systems, provided a compelling rationale for the pathogenesis of edema in kwashiorkor.\nWhat it does not explain however, is the entire array of disturbances that define the kwashiorkor syndrome.\nThese include, irritability, anorexia, skin desquamation, skin depigmentation, hair discoloration, reduced mitochondrial respiration, impaired lipid export from the liver without an accompanying reduction of lipoprotein synthesis, 'oxidative stress', glutathione depletions, [transsulfuration](https://bliptext.com/articles/transsulfuration) disturbances, diffuse DNA hypomethylation, immune dysfunction, decreased transmethylation activity, and sulfated [glycosaminoglycan](https://bliptext.com/articles/glycosaminoglycan) deficiencies.\nIt is now generally acknowledged that by itself, the low protein theory does not adequately account for the pathogenesis of kwashiorkor.\nMore complex deficiencies are at work.\nThese have still not been established.\nSocial factors are also relevant.\nIgnorance of nutrition can be a cause.\nA case was described where parents who fed their child [cassava](https://bliptext.com/articles/cassava) failed to recognize malnutrition because of the edema caused by the syndrome and believed the child was well-nourished despite the development of kwashiorkor.\n# [Disability-adjusted life years per 100,000 inhabitants for protein–energy malnutrition in 2002: \n{{legend|#b3b3b3|no data}}\n{{legend|#ffff65|fewer than 10}}\n{{legend|#fff200|10–100}}\n{{legend|#ffdc00|100–200}}\n{{legend|#ffc600|200–300}}\n{{legend|#ffb000|300–400}}\n{{legend|#ff9a00|400–500}}\n{{legend|#ff8400|500–600}}\n{{legend|#ff6e00|600–700}}\n{{legend|#ff5800|700–800}}\n{{legend|#ff4200|800–1000}}\n{{legend|#ff2c00|1000–1350}}\n{{legend|#cb0000|more than 1350}} | upload.wikimedia.org/wikipedia/commons/6/69/Protein-energy///malnutrition///world///map///-///DALY///-///WHO2002.svg]\n\n## Aflatoxins\nRecent studies have attempted to pinpoint a relationship between kwashiorkor and high levels of [aflatoxins](https://bliptext.com/articles/aflatoxin).\nAflatoxins are naturally occurring toxins produced by the mold [Aspergillus flavus](https://bliptext.com/articles/aspergillus-flavus), a fungus found in areas with hot and humid climates.\nThese toxins tend to grow and can be found in agricultural crops such as millet, maize, and rice.\nAn analysis found that the presence of aflatoxins was found more frequently and in higher concentrations in individuals with kwashiorkor when compared to individuals with marasmus (another form of severe acute malnutrition).\nIn particular, biological samples showed greater levels of aflatoxins in the brain, heart, kidney, liver, lungs, serum, stool, and urine.\nAflatoxins were not found in liver samples of individuals with marasmus.\nIt has been known that the liver organ is the main target of aflatoxins and chronic toxicity can result in immunosuppressive and carcinogenic effects.\nHowever, there is currently conflicting evidence to pinpoint a connection between kwashiorkor and aflatoxins.\nStudies have shown that not all children with kwashiorkor present with detectable aflatoxin levels.\nIt has also been proposed that damage done by aflatoxins may be due to glutathione depletion (another proposed mechanism of the disease) in children with kwashiorkor.\n\n# Mechanisms\n\n## Peripheral edema and hypoalbuminemia\nKwashiorkor is a form of protein deficiency, which can result in both osmotic imbalances and irregularities in the lymphatic system.\nKwashiorkor is most notable for peripheral edema.\nThe presence of edema in kwashiorkor is correlated with very low albumin concentration ([hypoalbuminemia](https://bliptext.com/articles/hypoalbuminemia)).\nEdema results from a loss of fluid balance between the hydrostatic and oncotic pressures across the capillary blood vessel walls due to the lack of protein which affects the body's ability to draw fluid from the tissues into the bloodstream.\nLow albumin concentration influences negatively the strength of oncotic pressure.\nFailure leads to the fluid buildup in the abdomen, resulting in edema and belly distension.\nFurthermore, the release of antidiuretic hormone is stimulated by hypovolemia, also leading to the development of peripheral edema.\nPlasma [renin](https://bliptext.com/articles/renin) is also stimulated, promoting sodium retention.\nIt is important to distinguish the pathophysiology of marasmus and kwashiorkor when it comes to treating malnourished children who may have hypovolemic shock that is cause by an acute loss of salt and water.\nChildren with severe albumin deficiency struggle physiologically to maintain their blood volume.\n\n## Low glutathione levels\nKwashiorkor is also marked by low [glutathione](https://bliptext.com/articles/glutathione) levels.\nGlutathione is used in many of the body processes on a molecule level.\nIt is believed to be related to high oxidant levels commonly seen in people who suffer from starvation and rarely in chronic inflammation.\nGlutathione serves vital functions including management of oxidative stress which is an imbalance that plays a key role in the pathogenesis of many diseases.\nEvidence indicates that amino acid balance has an important effect on protein nutrition and therefore on glutathione homeostasis.\nCysteine is an essential amino acid that acts as the limiting amino acid for glutathione synthesis in humans.\nFactors that increase demand for glutathione may increase demand for cysteine, and hence methionine.\nSuch demands have been hypothesized to increase risk for kwashiorkor.\n\n## Others\nA proposed experimental theory suggests that alterations in the microbiome/virone contributes to edematous malnutrition, but further studies are required to understand the mechanism.\n\n# Diagnosis\nKwashiorkor, or edematous malnutrition, like many other malnutrition diseases, is indirectly assessed using [anthropometry](https://bliptext.com/articles/anthropometry).\nKwashiorkor is a subtype of severe acute malnutrition (SAM) characterized by bilateral peripheral pitting edema.\nAccording to the World Health Organization, the SAM diagnosis parameters are a \"mid-upper arm circumference (MUAC) of < 115 mm, weight-for-height/length Z-score (WHZ) of < -3Z and nutritional edema or any combination of these parameters.\"\nAdditional clinical findings on physical exam include marked muscle atrophy, abdominal distension, dermatitis, and hepatomegaly.\nWHO criteria for clinical assessment of malnutrition are based on the degree of wasting (MUAC), stunting (weight-for-height Z-score), and the presence of edema (mild to severe).\n\n# Screening\nBecause it can be difficult to measure weight-for-height Z scores (WHZ) frequently, screening is performed by physical exam, with careful examination of the child's feet to detect the presence of bilateral pitting edema.\nScreening for edema is essential for the diagnosis of kwashiorkor, since nearly two thirds of kwashiorkor cases do not have evidence of acute wasting (i.e. mid-upper arm circumference (MUAC) < 125 mm, or WHZ < -2) when diagnosed with kwashiorkor.\n\n# Prevention\nAs for the prevention of childhood malnutrition, there needs to be public health changes such as improving agriculture and improving access to healthcare to effectively reduce the rates of malnutrition in children.\nBy educating individuals of childbearing age on proper nutrition and health during and after pregnancy, they can provide their children with the appropriate nutrients from a young age.\nBy ensuring they are equipped with the proper education and resources, caretakers and infants are in better health, ultimately preventing childhood malnutrition.\nBecause edema can hide decreased muscle mass, it can be hard to diagnose kwashiorkor in young children; however, if cases are overlooked, children become more susceptible to infections and can ultimately lead to morbidity and mortality.\nTo prevent this from happening, parents can be educated on proper nutrition and the importance of breastfeeding infants to ensure they receive all the nutrients they need.\nA diet rich in carbohydrates, fats that make up 10% of the total caloric needs, and proteins that make up 15% of the caloric needs can prevent kwashiorkor.\nProteins can be found in the following foods\n\n# Treatment\n[WHO](https://bliptext.com/articles/who) guidelines outline 10 general principles for the inpatient management of severely malnourished children.\nBoth clinical subtypes of severe acute malnutrition (kwashiorkor and marasmus) are treated similarly.\nUpon initial treatment, children with kwashiorkor may experience weight loss as their edema resolves.\nTherefore, after concerns of [refeeding syndrome](https://bliptext.com/articles/refeeding-syndrome) have passed, children may require 120-140% of their estimated caloric needs in order to achieve catch-up growth.\nThe cause, type, and severity of malnutrition determines what type of treatment would be most appropriate.\nFor primary acute malnutrition, children with no complications are treated at home and are encouraged to either continue breastfeeding (for infants) or start using ready-to-use therapeutic foods (for children).\nFor secondary acute malnutrition, the underlying cause needs to be identified to appropriately treat children.\nOnly after the primary disease is determined can an appropriate dietary plan be made, as fluid, vitamins, and macronutrients may need to be considered to not exacerbate the cause of the malnutrition.\n[Ready-to-use therapeutic foods](https://bliptext.com/articles/therapeutic-food) (RUTFs) and [F-75 and F-100 milks](https://bliptext.com/articles/f-100-and-f-75-foods) were created to provide appropriate nutrition and caloric intake to those experiencing malnutrition.\nF-75 milk would be ideal when trying to reintroduce food into a malnourished person, and F-100 milk would be used to aid in weight gain.\nWhile RUTFs and F-100 milk were made to have the same nutritional value, RUTFs are beneficial as they are dehydrated and do not require much preparation.\n\n# Prognosis\nKwashiorkor is associated with a high risk of mortality and long-term complications.\nTreatment under the guidelines of the World Health Organization has proven to reduce this mortality risk and affected children tend to recover faster than children with other severe malnutrition diseases.\nHowever, physical and intellectual capabilities are not fully restored.\nGrowth stunting and chronic disruption of microbiota are commonly observed after recovery.\nA high risk of death is identified by a brachial perimeter < 11 cm or by a weight-for-age threshold < −3 z-scores below the median of the WHO child growth standards.\nIn practice, malnourished children with edema are suffering from potentially life-threatening severe malnutrition.\n\n# Epidemiology\nKwashiorkor is rare in high income countries.\nIt is mostly observed in low-income and middle income nations and regions such as Southeast Asia, Central America, Congo, Ethiopia, Puerto Rico, Jamaica, South Africa, and Uganda, where poverty is prominent.\nOccurrences of severe malnutrition also tend to trend higher under conditions of food insecurity, higher prevalence of infectious diseases, lack of access to appropriate care, and poor living situations with inadequate sanitation.\nCommunities experiencing famine are affected the most especially during the rainy season.\nPrevalence varies, but it affects children of either sex commonly under five years old.\n\"Globally, kwashiorkor indirected accounted for 53% of deaths among children under five between 2000 and 2003 when associated with other common childhood diseases like acute respiratory infections, malaria, measles, HIV/AIDS and other causes of perinatal deaths.\"\nWhen compared to marasmus in developing countries, kwashiorkor typically has a lower prevalence, \"0.2%-1.6% for kwashiorkor and 1.2%-6.8% for marasmus.\"\nFactors such as \"diet, geographical locations, climate and aflatoxin exposure\" have been invoked as potential causes for observed differences in the prevalence for kwashiorkor and marasmus.\nIn general, in areas where Severe Acute Malnutrition (SAM) is prevalent, marasmus is more often the dominant SAM condition.\nHowever, in certain areas kwashiorkor may be more common than marasmus.\n\n# History\nKwashiorkor was present in the world long before 1933, when Cecily Williams published research which took the [Ga](https://bliptext.com/articles/ga-language) name for the disease.\nThere were already many names for the illness which referenced the cessation of breastfeeding, or the consumption of monotonous diets high in [starch](https://bliptext.com/articles/starch).\nHowever, Williams was the first to suggest that this might be a deficiency of protein or an amino acid.\nDespite publishing in 1933, it was only in 1949 that the World Health Organization officially recognized kwashiorkor as a public health concern.\nThis period also correlated with the promotion of [infant formula](https://bliptext.com/articles/infant-formula), often by [European colonial powers](https://bliptext.com/articles/european-colonial-powers).\nThe substitution of formula for breastmilk contributed significantly to the increasing visibility of kwashiorkor throughout the twentieth century.\nCicely Williams later described the promotion of formula as \"the most criminal form of sedition, and that those deaths should be regarded as murder.\"\nThese arguments underpinned the 1970s [Nestlé boycott](https://bliptext.com/articles/nestl-boycott).\n\n# Effects on pharmacokinetics\nThose experiencing poverty-related infectious diseases (PRDs) such as malaria and tuberculosis are also likely to be malnourished.\nMalnutrition can affect the pharmacokinetics of various drugs used to treat PRDs by changing a drug's bioavailability, distribution, and elimination.\nTo optimize treatment of those diseases, there needs to be more research into how severe malnutrition, specifically kwashiorkor, can affect treatment response.\n\n# Research directions\nCurrent research and recommendations to manage severe acute malnutrition (SAM), such as kwashiorkor, in children are largely based on expert opinions.\nOnly one-third of the WHO guidelines for management of SAM are based on epidemiological and clinical research.\nFurther studies are needed in order to \"improve treatment outcomes in the large number of children with SAM.\"","current_revision":null,"created_by":"kACnuQmH5k9Nr5VNVEpVeg7XpvUmMctD","created_at":"2025-01-25T17:21:57.403Z","updated_at":"2025-01-25T17:21:57.403Z","search_vector":"'kwashiorkor':1","search_content":" \n \n**Field:** [Pediatrics](https://bliptext.com/articles/pediatrics) \n \n\n# \n**Kwashiorkor** (, is also ) is a form of severe [protein malnutrition](https://bliptext.com/articles/protein-energy-malnutrition) characterized by [edema](https://bliptext.com/articles/edema) and an enlarged [liver](https://bliptext.com/articles/liver) with [fatty](https://bliptext.com/articles/fat) infiltrates.\nIt is thought to be caused by sufficient [calorie](https://bliptext.com/articles/calorie) intake, but with insufficient [protein](https://bliptext.com/articles/protein-nutrient) consumption (or lack of good quality [protein](https://bliptext.com/articles/protein-nutrient)), which distinguishes it from [marasmus](https://bliptext.com/articles/marasmus).\nRecent studies have found that a lack of antioxidant micronutrients such as [β-carotene](https://bliptext.com/articles/carotene), [lycopene](https://bliptext.com/articles/lycopene), other carotenoids, and [vitamin C](https://bliptext.com/articles/vitamin-c) as well as the presence of [aflatoxins](https://bliptext.com/articles/aflatoxins) may play a role in the development of the disease.\nHowever, the exact cause of kwashiorkor is still unknown.\nInadequate food supply is correlated with occurrences of kwashiorkor; occurrences in [high income countries](https://bliptext.com/articles/developed-country) are rare.\nIt occurs amongst [weaning children](https://bliptext.com/articles/weaning) to ages of about five years old.\nConditions analogous to kwashiorkor were well documented around the world throughout history.\nHowever, [Jamaican](https://bliptext.com/articles/jamaica) [pediatrician](https://bliptext.com/articles/pediatrician) [Cicely Williams](https://bliptext.com/articles/cicely-williams) introduced the term in 1935, two years after she published the disease's first formal description.\nWilliams was the first to conduct research on kwashiorkor and differentiate it from other dietary deficiencies.\nShe was the first to suggest that this might be a deficiency of protein.\nThe name is derived from the [Ga language](https://bliptext.com/articles/ga-language) of coastal [Ghana](https://bliptext.com/articles/ghana), translated as \"the sickness the baby gets when the new baby comes\" or \"the disease of the deposed child\", and reflecting the development of the condition in an older child who has been [weaned](https://bliptext.com/articles/weaned) from the breast when a younger sibling comes.\nBreast milk contains [amino acids](https://bliptext.com/articles/amino-acid) vital to a child's growth.\nIn at-risk populations, kwashiorkor may develop after children are weaned from breast milk and begin consuming a diet high in [carbohydrates](https://bliptext.com/articles/carbohydrate), including [maize](https://bliptext.com/articles/maize), [cassava](https://bliptext.com/articles/cassava) or rice.\n\n# Classification\nKwashiorkor is a type of severe acute malnutrition (SAM).\nSAM is a category, composed of two conditions: marasmus and kwashiorkor.\nBoth kwashiorkor and marasmus fall under the umbrella of [protein–energy malnutrition](https://bliptext.com/articles/protein-energy-malnutrition) (PEM).\nThese diseases are oftentimes discussed together, but are distinctly separate conditions of malnutrition.\nKwashiorkor is marked by an array of metabolic disturbances of uncertain etiology.\nIn contrast, marasmus is more clearly a syndrome of energy deficiency, which is marked by weight loss.\nOn physical exam, kwashiorkor is also distinguished from marasmus by the presence of edema.\nWhen children present with both kwashiorkor and marasmus, the condition is referred to as \"marasmic-kwashiorkor\".\nIn general, kwashiorkor is marked by more profound serum depletions of antioxidant molecules and minerals, relative to marasmus.\n\n## Wellcome's classification\nWellcome classification is a system for classifying protein-energy malnutrition in children based on weight for their age and based on presence of edema.\nOther classifications include Gomez classification and Waterlow classification.\n\n# Signs and symptoms\nThe defining sign of kwashiorkor in children is bilateral [edema](https://bliptext.com/articles/edema) in the feet.\nEdema may also involve the hands, trunk, and face.\nKwashiorkor is characterized by a fatty liver.\nThis fatty liver of undernutrition phenotype is often accompanied by evidence of inflammation and fibrosis.\nWhereas a fatty liver of undernutrition is a consistent feature of kwashiorkor, it is only encountered sometimes in children with marasmus.\nIn addition to this characteristic [hepatic steatosis](https://bliptext.com/articles/hepatic-steatosis), kwashiorkor is marked by a parallel pattern of multi-organ dysfunction.\nOrgans often affected in children with kwashiorkor include the kidneys, pancreas, heart, and nervous system.\nOther findings that may be encountered on physical exam include a distended [abdomen](https://bliptext.com/articles/abdomen), hair thinning, loss of teeth, skin or hair depigmentation, and [dermatitis](https://bliptext.com/articles/dermatitis).\nChildren with kwashiorkor often develop irritability and [anorexia](https://bliptext.com/articles/anorexia-symptom).\nGenerally, kwashiorkor is treated by introducing a high quality source of protein to the diet.\nReady to use therapeutic food (RUTF) as well as [F-100 and F-75 milk powders](https://bliptext.com/articles/f-100-and-f-75-foods), which both include skim milk powder, are recommended for the treatment of kwashiorkor.\nThese products are designed for use in low resource settings.\nThe limited number of kwashiorkor cases that occur in high resource settings, where there is good access to advanced therapeutic tools, are typically treated with partially hydrolyzed or [elemental enteral formulas](https://bliptext.com/articles/amino-acid-based-formula), with parenteral nutrition provided in extreme cases.\n\n# Causes\nThe precise etiology of kwashiorkor remains unclear.\nSeveral hypotheses have been proposed that are associated with and explain some, but not all aspects of the pathophysiology of kwashiorkor.\nThey include, but are not limited to protein deficiency causing hypoalbuminemia, amino acid deficiency, oxidative stress, and gut microbiome changes.\n\n## Low protein intake\nKwashiorkor is a severe form of [malnutrition](https://bliptext.com/articles/malnutrition) associated with a low protein diet.\nThe extreme lack of protein causes an osmotic imbalance in the [gastrointestinal system](https://bliptext.com/articles/human-gastrointestinal-tract) causing swelling of the gut diagnosed as an [edema](https://bliptext.com/articles/edema) or retention of water.\nExtreme fluid retention observed in individuals suffering from kwashiorkor is accompanied by irregularities in the [lymphatic system](https://bliptext.com/articles/lymphatic-system) as well as disruptions of capillary exchange.\nThe lymphatic system serves three major purposes: fluid recovery, immunity, and [lipid](https://bliptext.com/articles/lipid) absorption.\nVictims of kwashiorkor commonly exhibit reduced ability to recover fluids, immune system failure, and low lipid absorption.\nFluid recovery by the lymphatic system is accomplished by re-vascularization of fluid and macromolecules from the interstitial space, allowing these constituents of whole blood to be returned to the venous circulation.\nCompromised fluid recovery may contribute to the phenomenon of extravascular fluid accumulation in kwashiorkor.\nThe low protein theory for the pathogenesis of kwashiorkor has been used to teach that capillary exchange between the lymphatic system and circulating blood is impaired by a reduced oncotic (i.e. colloid osmotic pressure, COP) in the blood, as a consequence of inadequate protein intake, so that the hydrostatic pressure gradient, which favors extravasation of fluid from small vessels, is not overcome.\nProteins, mainly albumin, are responsible for creating the COP observed in the blood and tissue fluids.\nThe difference in the COP of the blood and tissue tends to favor the reentry of fluid from the extravascular space, into the circulatory system.\nThis tendency is opposed by the venous hydrostatic pressure, which tends to favor the exit of fluid from small vessels, into the interstitial space.\nThe low protein theory for the pathogenesis of kwashiorkor held that a deficiency of serum proteins, caused by inadequate protein intake, disrupted this balance, and thus impaired the return flow of fluid from the interstitium into the capillary and venous structures.\nIt has been taught that this is what accounts for the accumulation of extravascular fluid in kwashiorkor, and the subsequent pedal edema and abdominal distension.\nThe low protein theory, which relies heavily upon Starling's theory for the movement of fluid in biological systems, provided a compelling rationale for the pathogenesis of edema in kwashiorkor.\nWhat it does not explain however, is the entire array of disturbances that define the kwashiorkor syndrome.\nThese include, irritability, anorexia, skin desquamation, skin depigmentation, hair discoloration, reduced mitochondrial respiration, impaired lipid export from the liver without an accompanying reduction of lipoprotein synthesis, 'oxidative stress', glutathione depletions, [transsulfuration](https://bliptext.com/articles/transsulfuration) disturbances, diffuse DNA hypomethylation, immune dysfunction, decreased transmethylation activity, and sulfated [glycosaminoglycan](https://bliptext.com/articles/glycosaminoglycan) deficiencies.\nIt is now generally acknowledged that by itself, the low protein theory does not adequately account for the pathogenesis of kwashiorkor.\nMore complex deficiencies are at work.\nThese have still not been established.\nSocial factors are also relevant.\nIgnorance of nutrition can be a cause.\nA case was described where parents who fed their child [cassava](https://bliptext.com/articles/cassava) failed to recognize malnutrition because of the edema caused by the syndrome and believed the child was well-nourished despite the development of kwashiorkor.\n# [Disability-adjusted life years per 100,000 inhabitants for protein–energy malnutrition in 2002: \n{{legend|#b3b3b3|no data}}\n{{legend|#ffff65|fewer than 10}}\n{{legend|#fff200|10–100}}\n{{legend|#ffdc00|100–200}}\n{{legend|#ffc600|200–300}}\n{{legend|#ffb000|300–400}}\n{{legend|#ff9a00|400–500}}\n{{legend|#ff8400|500–600}}\n{{legend|#ff6e00|600–700}}\n{{legend|#ff5800|700–800}}\n{{legend|#ff4200|800–1000}}\n{{legend|#ff2c00|1000–1350}}\n{{legend|#cb0000|more than 1350}} | upload.wikimedia.org/wikipedia/commons/6/69/Protein-energy///malnutrition///world///map///-///DALY///-///WHO2002.svg]\n\n## Aflatoxins\nRecent studies have attempted to pinpoint a relationship between kwashiorkor and high levels of [aflatoxins](https://bliptext.com/articles/aflatoxin).\nAflatoxins are naturally occurring toxins produced by the mold [Aspergillus flavus](https://bliptext.com/articles/aspergillus-flavus), a fungus found in areas with hot and humid climates.\nThese toxins tend to grow and can be found in agricultural crops such as millet, maize, and rice.\nAn analysis found that the presence of aflatoxins was found more frequently and in higher concentrations in individuals with kwashiorkor when compared to individuals with marasmus (another form of severe acute malnutrition).\nIn particular, biological samples showed greater levels of aflatoxins in the brain, heart, kidney, liver, lungs, serum, stool, and urine.\nAflatoxins were not found in liver samples of individuals with marasmus.\nIt has been known that the liver organ is the main target of aflatoxins and chronic toxicity can result in immunosuppressive and carcinogenic effects.\nHowever, there is currently conflicting evidence to pinpoint a connection between kwashiorkor and aflatoxins.\nStudies have shown that not all children with kwashiorkor present with detectable aflatoxin levels.\nIt has also been proposed that damage done by aflatoxins may be due to glutathione depletion (another proposed mechanism of the disease) in children with kwashiorkor.\n\n# Mechanisms\n\n## Peripheral edema and hypoalbuminemia\nKwashiorkor is a form of protein deficiency, which can result in both osmotic imbalances and irregularities in the lymphatic system.\nKwashiorkor is most notable for peripheral edema.\nThe presence of edema in kwashiorkor is correlated with very low albumin concentration ([hypoalbuminemia](https://bliptext.com/articles/hypoalbuminemia)).\nEdema results from a loss of fluid balance between the hydrostatic and oncotic pressures across the capillary blood vessel walls due to the lack of protein which affects the body's ability to draw fluid from the tissues into the bloodstream.\nLow albumin concentration influences negatively the strength of oncotic pressure.\nFailure leads to the fluid buildup in the abdomen, resulting in edema and belly distension.\nFurthermore, the release of antidiuretic hormone is stimulated by hypovolemia, also leading to the development of peripheral edema.\nPlasma [renin](https://bliptext.com/articles/renin) is also stimulated, promoting sodium retention.\nIt is important to distinguish the pathophysiology of marasmus and kwashiorkor when it comes to treating malnourished children who may have hypovolemic shock that is cause by an acute loss of salt and water.\nChildren with severe albumin deficiency struggle physiologically to maintain their blood volume.\n\n## Low glutathione levels\nKwashiorkor is also marked by low [glutathione](https://bliptext.com/articles/glutathione) levels.\nGlutathione is used in many of the body processes on a molecule level.\nIt is believed to be related to high oxidant levels commonly seen in people who suffer from starvation and rarely in chronic inflammation.\nGlutathione serves vital functions including management of oxidative stress which is an imbalance that plays a key role in the pathogenesis of many diseases.\nEvidence indicates that amino acid balance has an important effect on protein nutrition and therefore on glutathione homeostasis.\nCysteine is an essential amino acid that acts as the limiting amino acid for glutathione synthesis in humans.\nFactors that increase demand for glutathione may increase demand for cysteine, and hence methionine.\nSuch demands have been hypothesized to increase risk for kwashiorkor.\n\n## Others\nA proposed experimental theory suggests that alterations in the microbiome/virone contributes to edematous malnutrition, but further studies are required to understand the mechanism.\n\n# Diagnosis\nKwashiorkor, or edematous malnutrition, like many other malnutrition diseases, is indirectly assessed using [anthropometry](https://bliptext.com/articles/anthropometry).\nKwashiorkor is a subtype of severe acute malnutrition (SAM) characterized by bilateral peripheral pitting edema.\nAccording to the World Health Organization, the SAM diagnosis parameters are a \"mid-upper arm circumference (MUAC) of < 115 mm, weight-for-height/length Z-score (WHZ) of < -3Z and nutritional edema or any combination of these parameters.\"\nAdditional clinical findings on physical exam include marked muscle atrophy, abdominal distension, dermatitis, and hepatomegaly.\nWHO criteria for clinical assessment of malnutrition are based on the degree of wasting (MUAC), stunting (weight-for-height Z-score), and the presence of edema (mild to severe).\n\n# Screening\nBecause it can be difficult to measure weight-for-height Z scores (WHZ) frequently, screening is performed by physical exam, with careful examination of the child's feet to detect the presence of bilateral pitting edema.\nScreening for edema is essential for the diagnosis of kwashiorkor, since nearly two thirds of kwashiorkor cases do not have evidence of acute wasting (i.e. mid-upper arm circumference (MUAC) < 125 mm, or WHZ < -2) when diagnosed with kwashiorkor.\n\n# Prevention\nAs for the prevention of childhood malnutrition, there needs to be public health changes such as improving agriculture and improving access to healthcare to effectively reduce the rates of malnutrition in children.\nBy educating individuals of childbearing age on proper nutrition and health during and after pregnancy, they can provide their children with the appropriate nutrients from a young age.\nBy ensuring they are equipped with the proper education and resources, caretakers and infants are in better health, ultimately preventing childhood malnutrition.\nBecause edema can hide decreased muscle mass, it can be hard to diagnose kwashiorkor in young children; however, if cases are overlooked, children become more susceptible to infections and can ultimately lead to morbidity and mortality.\nTo prevent this from happening, parents can be educated on proper nutrition and the importance of breastfeeding infants to ensure they receive all the nutrients they need.\nA diet rich in carbohydrates, fats that make up 10% of the total caloric needs, and proteins that make up 15% of the caloric needs can prevent kwashiorkor.\nProteins can be found in the following foods\n\n# Treatment\n[WHO](https://bliptext.com/articles/who) guidelines outline 10 general principles for the inpatient management of severely malnourished children.\nBoth clinical subtypes of severe acute malnutrition (kwashiorkor and marasmus) are treated similarly.\nUpon initial treatment, children with kwashiorkor may experience weight loss as their edema resolves.\nTherefore, after concerns of [refeeding syndrome](https://bliptext.com/articles/refeeding-syndrome) have passed, children may require 120-140% of their estimated caloric needs in order to achieve catch-up growth.\nThe cause, type, and severity of malnutrition determines what type of treatment would be most appropriate.\nFor primary acute malnutrition, children with no complications are treated at home and are encouraged to either continue breastfeeding (for infants) or start using ready-to-use therapeutic foods (for children).\nFor secondary acute malnutrition, the underlying cause needs to be identified to appropriately treat children.\nOnly after the primary disease is determined can an appropriate dietary plan be made, as fluid, vitamins, and macronutrients may need to be considered to not exacerbate the cause of the malnutrition.\n[Ready-to-use therapeutic foods](https://bliptext.com/articles/therapeutic-food) (RUTFs) and [F-75 and F-100 milks](https://bliptext.com/articles/f-100-and-f-75-foods) were created to provide appropriate nutrition and caloric intake to those experiencing malnutrition.\nF-75 milk would be ideal when trying to reintroduce food into a malnourished person, and F-100 milk would be used to aid in weight gain.\nWhile RUTFs and F-100 milk were made to have the same nutritional value, RUTFs are beneficial as they are dehydrated and do not require much preparation.\n\n# Prognosis\nKwashiorkor is associated with a high risk of mortality and long-term complications.\nTreatment under the guidelines of the World Health Organization has proven to reduce this mortality risk and affected children tend to recover faster than children with other severe malnutrition diseases.\nHowever, physical and intellectual capabilities are not fully restored.\nGrowth stunting and chronic disruption of microbiota are commonly observed after recovery.\nA high risk of death is identified by a brachial perimeter < 11 cm or by a weight-for-age threshold < −3 z-scores below the median of the WHO child growth standards.\nIn practice, malnourished children with edema are suffering from potentially life-threatening severe malnutrition.\n\n# Epidemiology\nKwashiorkor is rare in high income countries.\nIt is mostly observed in low-income and middle income nations and regions such as Southeast Asia, Central America, Congo, Ethiopia, Puerto Rico, Jamaica, South Africa, and Uganda, where poverty is prominent.\nOccurrences of severe malnutrition also tend to trend higher under conditions of food insecurity, higher prevalence of infectious diseases, lack of access to appropriate care, and poor living situations with inadequate sanitation.\nCommunities experiencing famine are affected the most especially during the rainy season.\nPrevalence varies, but it affects children of either sex commonly under five years old.\n\"Globally, kwashiorkor indirected accounted for 53% of deaths among children under five between 2000 and 2003 when associated with other common childhood diseases like acute respiratory infections, malaria, measles, HIV/AIDS and other causes of perinatal deaths.\"\nWhen compared to marasmus in developing countries, kwashiorkor typically has a lower prevalence, \"0.2%-1.6% for kwashiorkor and 1.2%-6.8% for marasmus.\"\nFactors such as \"diet, geographical locations, climate and aflatoxin exposure\" have been invoked as potential causes for observed differences in the prevalence for kwashiorkor and marasmus.\nIn general, in areas where Severe Acute Malnutrition (SAM) is prevalent, marasmus is more often the dominant SAM condition.\nHowever, in certain areas kwashiorkor may be more common than marasmus.\n\n# History\nKwashiorkor was present in the world long before 1933, when Cecily Williams published research which took the [Ga](https://bliptext.com/articles/ga-language) name for the disease.\nThere were already many names for the illness which referenced the cessation of breastfeeding, or the consumption of monotonous diets high in [starch](https://bliptext.com/articles/starch).\nHowever, Williams was the first to suggest that this might be a deficiency of protein or an amino acid.\nDespite publishing in 1933, it was only in 1949 that the World Health Organization officially recognized kwashiorkor as a public health concern.\nThis period also correlated with the promotion of [infant formula](https://bliptext.com/articles/infant-formula), often by [European colonial powers](https://bliptext.com/articles/european-colonial-powers).\nThe substitution of formula for breastmilk contributed significantly to the increasing visibility of kwashiorkor throughout the twentieth century.\nCicely Williams later described the promotion of formula as \"the most criminal form of sedition, and that those deaths should be regarded as murder.\"\nThese arguments underpinned the 1970s [Nestlé boycott](https://bliptext.com/articles/nestl-boycott).\n\n# Effects on pharmacokinetics\nThose experiencing poverty-related infectious diseases (PRDs) such as malaria and tuberculosis are also likely to be malnourished.\nMalnutrition can affect the pharmacokinetics of various drugs used to treat PRDs by changing a drug's bioavailability, distribution, and elimination.\nTo optimize treatment of those diseases, there needs to be more research into how severe malnutrition, specifically kwashiorkor, can affect treatment response.\n\n# Research directions\nCurrent research and recommendations to manage severe acute malnutrition (SAM), such as kwashiorkor, in children are largely based on expert opinions.\nOnly one-third of the WHO guidelines for management of SAM are based on epidemiological and clinical research.\nFurther studies are needed in order to \"improve treatment outcomes in the large number of children with SAM.\"","revisionCount":0},"hasMore":false,"nextCursor":null}