Editing Kwashiorkor

{{short description|Severe protein malnutrition}}
{{Use dmy dates|date=February 2025}}
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'''Kwashiorkor''' ({{IPAc-en|ˌ|k|w|ɒ|ʃ|i|ˈ|ɔːr|k|ɔːr|,_|-|k|ər}} {{respell|KWOSH|ee|OR|kor|,_-|kər}}, is also  {{respell|KWASH|-}})<ref>{{cite LPD|3}}</ref> is a form of severe [[protein–energy malnutrition|protein malnutrition]] characterized by [[edema]] and an enlarged [[liver]] with [[fat]]ty infiltrates.<ref name="Benjamin & Lappin Kwashiorkor"/> It is thought to be caused by sufficient [[calorie]] intake, but with insufficient [[protein (nutrient)|protein]] consumption (or lack of good quality protein), which distinguishes it from [[marasmus]]. Recent studies have found that a lack of antioxidant micronutrients such as [[β-carotene]], [[lycopene]], other carotenoids, and [[vitamin C]] as well as the presence of [[aflatoxins]] may play a role in the development of the disease.<ref name="Pham Alou Golden et al 2021">{{cite journal |last1=Pham |first1=Thi-Phuong-Thao |last2=Alou |first2=Maryam Tidjani |last3=Golden |first3=Michael H. |last4=Million |first4=Matthieu |last5=Raoult |first5=Didier |title=Difference between kwashiorkor and marasmus: Comparative meta-analysis of pathogenic characteristics and implications for treatment |journal=Microbial Pathogenesis |date=January 2021 |volume=150 |pages=104702 |doi=10.1016/j.micpath.2020.104702 |pmid=33359074 |s2cid=229694345 |url=https://hal-amu.archives-ouvertes.fr/hal-03216130 |access-date=9 February 2023 |archive-date=10 February 2023 |archive-url=https://web.archive.org/web/20230210090745/https://hal-amu.archives-ouvertes.fr/hal-03216130 |url-status=live }}</ref> However, the exact cause of kwashiorkor is still unknown. Inadequate food supply is correlated with kwashiorkor; occurrences in [[Developed country| high-income countries]] are rare.<ref>{{cite journal|display-authors=6|vauthors=Liu T, Howard RM, Mancini AJ, Weston WL, Paller AS, Drolet BA, Esterly NB, Levy ML, Schachner L, Frieden IJ|date=2001|title=Kwashiorkor in the United States: fad diets, perceived and true milk allergy, and nutritional ignorance|url=http://archderm.ama-assn.org/cgi/pmidlookup?view=long&pmid=11346341|journal=Archives of Dermatology|volume=137|issue=5|pages=630–6|pmid=11346341}}{{Dead link|date=February 2020|bot=InternetArchiveBot|fix-attempted=yes}}</ref>  It occurs amongst [[Weaning|weaning children]] to ages of about five years old.<ref name="Benjamin & Lappin Kwashiorkor"/>

Conditions analogous to kwashiorkor were well documented around the world throughout history.<ref name="Nott2021">{{cite journal |last1=Nott |first1=John |title='No one may starve in the British Empire': Kwashiorkor, Protein and the Politics of Nutrition Between Britain and Africa |journal=Social History of Medicine |date=May 2021 |volume=34 |issue=2 |pages=553–576 |doi=10.1093/shm/hkz107|pmc=8162845|pmid= 34084092}}</ref>
The disease's first formal description was published by [[Jamaica]]n [[pediatrician]] [[Cicely Williams]] in 1933. She was the first to research kwashiorkor, and to suggest that it might be a protein deficiency to differentiate it from other dietary deficiencies.<ref name="williams1933">{{cite journal|vauthors=Williams CD|date=1983|orig-year=1933|title=Fifty years ago. Archives of Diseases in Childhood 1933. A nutritional disease of childhood associated with a maize diet|journal=Archives of Disease in Childhood|volume=58|issue=7|pages=550–60|doi=10.1136/adc.58.7.550|pmc=1628206|pmid=6347092}}</ref><ref name=williams1935>{{cite journal | vauthors = Williams CD, Oxon BM, Lond H | title = Kwashiorkor: a nutritional disease of children associated with a maize diet. 1935 | journal = Bulletin of the World Health Organization | volume = 81 | issue = 12 | pages = 912–3 | year = 1935 | pmid = 14997245 | pmc = 2572388 | doi = 10.1016/S0140-6736(00)94666-X | author-link = Cicely Williams }} Reprint: {{cite journal | vauthors = Williams CD, Oxon BM, Lond H | title = Kwashiorkor: a nutritional disease of children associated with a maize diet. 1935 | journal = Bulletin of the World Health Organization | volume = 81 | issue = 12 | pages = 912–3 | year = 2003 | pmid = 14997245 | pmc = 2572388 | doi = 10.1016/S0140-6736(00)94666-X }}</ref>

The name, introduced by Williams in 1935, was derived from the [[Ga language]] of coastal [[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]] from the breast when a younger sibling comes.<ref name=listeningga>{{cite book |doi=10.1163/9789004333390_008 |chapter=Listening to the Ga: Cicely Williams' Discovery of Kwashiorkor on the Gold Coast |title=Women and Modern Medicine |year=2001 |pages=149–171 |pmid=11603151 |isbn=978-90-04-33339-0 |last1=Stanton |first1=J. |series=Clio Medica |volume=61 |chapter-url=https://www.wphna.org/htdocs/downloadsMar2012/Listening%20to%20the%20Ga.pdf |access-date=25 February 2022 |archive-date=1 December 2021 |archive-url=https://web.archive.org/web/20211201013530/http://www.wphna.org/htdocs/downloadsMar2012/Listening%20to%20the%20Ga.pdf |url-status=live }}</ref>
Breast milk contains [[amino acid]]s vital to a child's growth. In at-risk populations, kwashiorkor is most likely to develop after children are weaned from breast milk and begin consuming a diet high in [[carbohydrate]]s, including [[maize]], [[cassava]], or rice.<ref name="Benjamin & Lappin Kwashiorkor"/><ref name=williams1933/>

== Classification ==

Kwashiorkor is a type of severe acute malnutrition (SAM). SAM is a category, composed of two conditions: marasmus and kwashiorkor.<ref name="Bhutta Berkley Bandsma 2017"/> Both kwashiorkor and marasmus fall under the umbrella of [[protein–energy malnutrition]] (PEM).<ref name="Odigwe Smedslund Ejemot-Nwadiaro et al 2010"/> These diseases are oftentimes discussed together, but are distinctly separate conditions of malnutrition. Kwashiorkor is marked by an array of metabolic disturbances of uncertain cause. In contrast, marasmus is more clearly an energy deficiency syndrome, marked by weight loss. On physical exam, kwashiorkor is also distinguished from marasmus by the presence of edema. When children present with both kwashiorkor and marasmus, the condition is referred to as "marasmic-kwashiorkor".<ref name=":4">{{Cite web|date=2017|title=Malnutrition (Kwashiorkor and Marasmus) — Symptoms and Treatment|url=https://www.lecturio.com/magazine/malnutrition/|access-date=27 July 2021|website=The Lecturio Online Medical Library|language=en|archive-date=27 October 2021|archive-url=https://web.archive.org/web/20211027095329/https://www.lecturio.com/magazine/malnutrition/|url-status=live}}</ref><ref name="Pham Alou Golden et al 2021"/> In general, kwashiorkor is marked by more profound serum depletions of antioxidant molecules and minerals, relative to marasmus.<ref name="Pham Alou Golden et al 2021"/>

===Wellcome's classification===
Wellcome classification<ref>{{Cite web|title=Protein energy malnutrition classification - wikidoc|url=https://www.wikidoc.org/index.php/Protein_energy_malnutrition_classification|access-date=29 July 2021|website=www.wikidoc.org|language=en|archive-date=15 September 2022|archive-url=https://web.archive.org/web/20220915031438/https://www.wikidoc.org/index.php/Protein_energy_malnutrition_classification|url-status=live}}</ref> is a system for classifying protein-energy malnutrition in children based on weight for their age and based on presence of edema. Other classifications include Gomez classification and Waterlow classification.<ref>{{cite book |chapter=Wellcome classification |chapter-url=https://www.oxfordreference.com/view/10.1093/oi/authority.20110803121717631 |editor1-last=Bender |editor1-first=David A. |title=A Dictionary of Food and Nutrition |date=29 January 2009 |publisher=OUP Oxford |isbn=978-0-19-157975-2 |access-date=30 July 2021 |archive-date=21 July 2022 |archive-url=https://web.archive.org/web/20220721164536/https://www.oxfordreference.com/view/10.1093/oi/authority.20110803121717631 |url-status=live }}</ref><ref>{{cite journal |last1=Gernaat |first1=H. |last2=Voorhoeve |first2=HW |title=A new classification of acute protein-energy malnutrition |journal=Journal of Tropical Pediatrics |date=1 April 2000 |volume=46 |issue=2 |pages=97–106 |doi=10.1093/tropej/46.2.97 |pmid=10822936 |doi-access=free }}</ref>
{| class="wikitable"
!Weight for age
!With edema
!Without edema
!General considerations
|-
|65-85%
|Kwashiorkor
|Undernutrition
| rowspan="2" |
* Weight for age +/- oedema
* Reference standard (50th percentile)
|-
|<60%
|Marasmic kwashiorkor
|Marasmus
|}

== Signs and symptoms ==
The defining sign of kwashiorkor in children is bilateral [[edema]] in the feet. Edema may also involve the hands, trunk, and face. Kwashiorkor is characterized by a fatty liver. This fatty liver of the undernutrition phenotype is often accompanied by evidence of inflammation and fibrosis. Whereas a fatty liver of undernutrition is a consistent feature of kwashiorkor, it is only encountered sometimes in children with marasmus. In addition to this characteristic [[hepatic steatosis]], kwashiorkor is marked by a parallel pattern of multi-organ dysfunction. Organs often affected in children with kwashiorkor include the kidneys, pancreas, heart, and nervous system.<ref name="Pham Alou Golden et al 2021"/>  Other findings that may be encountered on physical exam include a distended [[abdomen]], hair thinning, loss of teeth, skin or hair depigmentation, and [[dermatitis]]. Children with kwashiorkor often develop irritability and [[Anorexia (symptom)|anorexia]]. Generally, kwashiorkor is treated by introducing a high-quality source of protein to the diet. Ready-to-use therapeutic food (RUTF) as well as [[F-100 and F-75 (foods)|F-100 and F-75 milk powders]], which both include skim milk powder, are recommended for the treatment of kwashiorkor. These products are designed for use in low-resource settings. The 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 [[Amino acid-based formula|elemental enteral formulas]], with parenteral nutrition provided in extreme cases.

=== Differential Diagnosis ===
While Kwashiorkor is primarily characterized by edema, growth failure, and dermatitis, it can sometimes be misdiagnosed as [https://www.ncbi.nlm.nih.gov/books/NBK441835/ Acrodermatitis Enteropathica (AE)], as both conditions present with similar dermatological symptoms.<ref name=":0">{{Cite book |last1=Khan Mohammad Beigi |first1=Pooya |url=https://link.springer.com/10.1007/978-3-319-17819-6 |title=Acrodermatitis Enteropathica: A Clinician's Guide |last2=Maverakis |first2=Emanual |date=2015 |publisher=Springer International Publishing |isbn=978-3-319-17818-9 |location=Cham |pages=43–53 |language=en |chapter=Diagnosis |doi=10.1007/978-3-319-17819-6}}</ref><ref>{{Cite journal |last1=Park |first1=Sarah E. |last2=Williams |first2=Madison |last3=Crew |first3=Ashley B. |last4=Hsiao |first4=Jennifer L. |date=2024-12-01 |title=Cutaneous Signs of Nutritional Deficiencies |url=https://link.springer.com/article/10.1007/s13670-024-00425-8 |journal=Current Geriatrics Reports |language=en |volume=13 |issue=4 |pages=189–199 |doi=10.1007/s13670-024-00425-8 |issn=2196-7865|doi-access=free }}</ref> However, AE is caused by zinc deficiency, not protein deficiency, and is associated with a significant decrease in serum zinc levels.<ref name=":0" /><ref>{{Cite journal |last1=Alwadany |first1=Muhannad M. |last2=Wadani |first2=Abdullah F. Al |last3=Almarri |first3=Fatimah H. |last4=Alyami |first4=Hadi S. |last5=Al-Subaie |first5=Muhammad A. |last6=Alwadany |first6=Muhannad M. |last7=Wadani |first7=Abdullah F. Al |last8=Almarri |first8=Fatimah H. |last9=Alyami |first9=Hadi S. |last10=Al-Subaie |first10=Muhammad A. |date=2023-04-18 |title=Acrodermatitis Enteropathica: A Rare Case With Lifelong Implications |journal=Cureus |language=en |volume=15 |issue=4 |pages=e37783 |doi=10.7759/cureus.37783 |doi-access=free |issn=2168-8184 |pmc=10198582 |pmid=37214014}}</ref> Unlike kwashiorkor, which is diagnosed based on clinical signs like [[edema]] and low [[serum albumin]] levels, AE requires additional diagnostic tests, such as zinc uptake tests and genetic screening, to differentiate it from other disorders with similar symptoms.<ref name=":0" /><ref>{{Cite journal |last1=Alwadany |first1=Muhannad M. |last2=Wadani |first2=Abdullah F. Al |last3=Almarri |first3=Fatimah H. |last4=Alyami |first4=Hadi S. |last5=Al-Subaie |first5=Muhammad A. |last6=Alwadany |first6=Muhannad M. |last7=Wadani |first7=Abdullah F. Al |last8=Almarri |first8=Fatimah H. |last9=Alyami |first9=Hadi S. |last10=Al-Subaie |first10=Muhammad A. |date=2023-04-18 |title=Acrodermatitis Enteropathica: A Rare Case With Lifelong Implications |journal=Cureus |language=en |volume=15 |issue=4 |pages=e37783 |doi=10.7759/cureus.37783 |doi-access=free |issn=2168-8184 |pmc=10198582 |pmid=37214014}}</ref> Therefore, while both conditions can present with [[dermatitis]], the underlying etiology helps distinguish the two.<ref name=":0" /><ref>{{Cite journal |last1=Alwadany |first1=Muhannad M. |last2=Wadani |first2=Abdullah F. Al |last3=Almarri |first3=Fatimah H. |last4=Alyami |first4=Hadi S. |last5=Al-Subaie |first5=Muhammad A. |last6=Alwadany |first6=Muhannad M. |last7=Wadani |first7=Abdullah F. Al |last8=Almarri |first8=Fatimah H. |last9=Alyami |first9=Hadi S. |last10=Al-Subaie |first10=Muhammad A. |date=2023-04-18 |title=Acrodermatitis Enteropathica: A Rare Case With Lifelong Implications |journal=Cureus |language=en |volume=15 |issue=4 |pages=e37783 |doi=10.7759/cureus.37783 |doi-access=free |issn=2168-8184 |pmc=10198582 |pmid=37214014}}</ref> 

== Causes ==
The precise etiology of kwashiorkor remains unclear.<ref name=":1">{{Cite web|url=https://www.ennonline.net/attachments/2314/Kwashiorkor-still-an-enigma-CMAM-Forum-Dec-2014.pdf|title=Kwashiorkor: still an enigma – the search must go on|last=Briend|first=Andre|name-list-style=vanc|date=2014|website=Emergency Nutrition Network|access-date=2 August 2019|archive-date=15 February 2022|archive-url=https://web.archive.org/web/20220215095457/https://www.ennonline.net/attachments/2314/Kwashiorkor-still-an-enigma-CMAM-Forum-Dec-2014.pdf|url-status=live}}</ref><ref name="G. Coulthard 2015"/><ref name="Smith Yatsunenko Manary 2013">{{cite journal |last1=Smith |first1=Michelle I. |last2=Yatsunenko |first2=Tanya |last3=Manary |first3=Mark J. |last4=Trehan |first4=Indi |last5=Mkakosya |first5=Rajhab |last6=Cheng |first6=Jiye |last7=Kau |first7=Andrew L. |last8=Rich |first8=Stephen S. |last9=Concannon |first9=Patrick |last10=Mychaleckyj |first10=Josyf C. |last11=Liu |first11=Jie |last12=Houpt |first12=Eric |last13=Li |first13=Jia V. |last14=Holmes |first14=Elaine |last15=Nicholson |first15=Jeremy |last16=Knights |first16=Dan |last17=Ursell |first17=Luke K. |last18=Knight |first18=Rob |last19=Gordon |first19=Jeffrey I. |title=Gut Microbiomes of Malawian Twin Pairs Discordant for Kwashiorkor |journal=Science |date=February 2013 |volume=339 |issue=6119 |pages=548–554 |doi=10.1126/science.1229000 |pmid=23363771 |pmc=3667500 |bibcode=2013Sci...339..548S }}</ref> Several hypotheses have been proposed that are associated with and explain some, but not all aspects of the pathophysiology of kwashiorkor. They include, but are not limited to protein deficiency causing hypoalbuminemia, amino acid deficiency, oxidative stress, and gut microbiome changes.<ref name=":1" /><ref name="Smith Yatsunenko Manary 2013"/><ref>{{cite journal|vauthors=Velly H, Britton RA, Preidis GA|date=2017|title=Mechanisms of cross-talk between the diet, the intestinal microbiome, and the undernourished host|journal=Gut Microbes|volume=8|issue=2|pages=98–112|doi=10.1080/19490976.2016.1267888|pmc=5390823|pmid=27918230}}</ref>

=== Low protein intake ===
[[File:Protein-energy malnutrition world map - DALY - WHO2002.svg|thumb|upright=1.2|[[Disability-adjusted life year]]s per 100,000&nbsp;inhabitants for protein-energy malnutrition in 2002:<ref>{{cite web |url=https://www.who.int/entity/healthinfo/statistics/bodgbddeathdalyestimates.xls |title=Mortality and Burden of Disease Estimates for WHO Member States in 2002 |format=xls |work=World Health Organization |year=2002 |access-date=5 October 2020 |archive-date=16 January 2013 |archive-url=https://web.archive.org/web/20130116174540/http://www.who.int/healthinfo/statistics/bodgbddeathdalyestimates.xls |url-status=live }}</ref>{{Div col|small=yes|colwidth=10em}}
{{legend|#b3b3b3|no data}}
{{legend|#ffff65|fewer than 10}}
{{legend|#fff200|10–100}}
{{legend|#ffdc00|100–200}}
{{legend|#ffc600|200–300}}
{{legend|#ffb000|300–400}}
{{legend|#ff9a00|400–500}}
{{legend|#ff8400|500–600}}
{{legend|#ff6e00|600–700}}
{{legend|#ff5800|700–800}}
{{legend|#ff4200|800–1000}}
{{legend|#ff2c00|1000–1350}}
{{legend|#cb0000|more than 1350}}
{{div col end}}]]
Kwashiorkor is a severe form of [[malnutrition]] associated with a low-protein diet.<ref name="Benjamin & Lappin Kwashiorkor"/> The extreme lack of protein causes an osmotic imbalance in the [[Human gastrointestinal tract|gastrointestinal system]] causing swelling of the gut diagnosed as an [[edema]] or retention of water.<ref name="williams1935" />

Extreme fluid retention observed in individuals suffering from kwashiorkor is accompanied by irregularities in the [[lymphatic system]] as well as disruptions of capillary exchange. The lymphatic system serves three major purposes: fluid recovery, immunity, and [[lipid]] absorption. Victims of kwashiorkor commonly exhibit reduced ability to recover fluids, immune system failure, and low lipid absorption. Fluid recovery by the lymphatic system is accomplished by the re-vascularization of fluid and macromolecules from the interstitial space, allowing these constituents of whole blood to be returned to the venous circulation. Compromised fluid recovery may contribute to the phenomenon of extravascular fluid accumulation in kwashiorkor.<ref>{{cite journal | year = 1950 | title =  Nova et Vetera| journal = The British Medical Journal | volume = 2 | issue = 4673| page = 284 | doi = 10.1136/bmj.2.4673.267 | s2cid = 220181068}}</ref>

The 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. Proteins, mainly albumin, are responsible for creating the COP observed in the blood and tissue fluids. The difference in the COP of the blood and tissue tends to favor the reentry of fluid from the extravascular space, into the circulatory system. This tendency is opposed by the venous hydrostatic pressure, which tends to favor the exit of fluid from small vessels, into the interstitial space. The 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. It has been taught that this is what accounts for the accumulation of extravascular fluid in kwashiorkor, and the subsequent pedal edema and abdominal distension.<ref>{{cite book |last=Saladin |first=Kenneth | name-list-style = vanc |title=Anatomy and Physiology |edition=6th |location=New York |publisher=McGraw Hill |year=2012 |pages=766–767, 809–811 |isbn=978-0-07-337825-1 }}</ref>

The 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. What it does not explain, however, is the entire array of disturbances that define the kwashiorkor syndrome. These 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]] disturbances, diffuse DNA hypomethylation, immune dysfunction, decreased transmethylation activity, and sulfated [[glycosaminoglycan]] deficiencies. It is now generally acknowledged that by itself, the low protein theory does not adequately account for the pathogenesis of kwashiorkor. More complex deficiencies are at work. These have still not been established. <ref>{{cite journal|vauthors=Tierney EP, Sage RJ, Shwayder T|date=2010|title=Kwashiorkor from a severe dietary restriction in an 8-month infant in suburban Detroit, Michigan: case report and review of the literature|journal=International Journal of Dermatology|volume=49|issue=5|pages=500–6|doi=10.1111/j.1365-4632.2010.04253.x|pmid=20534082|s2cid=13050691}}</ref>

Social factors are also relevant. Ignorance of nutrition can be a cause. A case was described where parents who fed their child [[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.<ref>{{cite web|title=Malnutrition in Third World Countries|url=http://www.religion-online.org/showarticle.asp?title=1405.|website=www.religion-online.org|access-date=2 March 2017|archive-url=https://web.archive.org/web/20150919024954/http://www.religion-online.org/showarticle.asp?title=1405.|archive-date=19 September 2015|url-status=dead}}</ref>

=== Aflatoxins ===
Recent studies have attempted to pinpoint a relationship between kwashiorkor and high levels of [[aflatoxin]]s. Aflatoxins are naturally occurring toxins produced by the mold ''[[Aspergillus flavus]]'', a fungus found in areas with hot and humid climates.<ref name="Kumar Mahato Kamle et al 2017">{{cite journal |last1=Kumar |first1=Pradeep |last2=Mahato |first2=Dipendra K. |last3=Kamle |first3=Madhu |last4=Mohanta |first4=Tapan K. |last5=Kang |first5=Sang G. |title=Aflatoxins: A Global Concern for Food Safety, Human Health and Their Management |journal=Frontiers in Microbiology |date=17 January 2017 |volume=07 |page=2170 |doi=10.3389/fmicb.2016.02170 |pmid=28144235 |pmc=5240007 |doi-access=free }}</ref> These toxins tend to grow and can be found in agricultural crops such as millet, maize, and rice.<ref name="Kumar Mahato Kamle et al 2017"/> An 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).<ref name="Soriano Rubini Morales-Suarez-Varela et al 2020">{{cite journal |last1=Soriano |first1=Jose M. |last2=Rubini |first2=Ana |last3=Morales-Suarez-Varela |first3=María |last4=Merino-Torres |first4=Juan F. |last5=Silvestre |first5=Dolores |title=Aflatoxins in organs and biological samples from children affected by kwashiorkor, marasmus and marasmic-kwashiorkor: A scoping review |journal=Toxicon |date=October 2020 |volume=185 |pages=174–183 |doi=10.1016/j.toxicon.2020.07.010 |pmid=32693007 |bibcode=2020Txcn..185..174S |s2cid=220698925 }}</ref><ref>{{cite journal |last1=Watson |first1=Sinead |last2=Gong |first2=Yun Yun |last3=Routledge |first3=Michael |title=Interventions Targeting Child Undernutrition in Developing Countries May Be Undermined by Dietary Exposure to Aflatoxin |journal=Critical Reviews in Food Science and Nutrition |date=15 July 2015 |volume=57 |issue=9 |pages=1963–1975 |doi=10.1080/10408398.2015.1040869 |pmid=26176888 |s2cid=24089209 |url=http://eprints.whiterose.ac.uk/124824/3/Interventions%20targeting%20child%20undernutrition%20in%20developing%20countries%20may%20be%20undermined%20by%20dietary%20exposure%20to%20aflatoxin%207th%20JAN%20SW%20%282%29.pdf }}</ref> In particular, biological samples showed greater levels of aflatoxins in the brain, heart, kidney, liver, lungs, serum, stool, and urine.<ref name="Soriano Rubini Morales-Suarez-Varela et al 2020"/> Aflatoxins were not found in liver samples of individuals with marasmus.<ref name="Soriano Rubini Morales-Suarez-Varela et al 2020"/> It has been known that the liver organ is the main target of aflatoxins and chronic toxicity can result in immunosuppressive and carcinogenic effects.<ref name="Soriano Rubini Morales-Suarez-Varela et al 2020"/> However, there is currently conflicting evidence to pinpoint a connection between kwashiorkor and aflatoxins. Studies have shown that not all children with kwashiorkor present with detectable aflatoxin levels.<ref name="Pham Alou Golden et al 2021"/> It 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.<ref name="Pham Alou Golden et al 2021"/>

== Mechanisms ==
=== Peripheral edema and hypoalbuminemia ===
Kwashiorkor is a form of protein deficiency, which can result in both osmotic imbalances and irregularities in the lymphatic system.<ref name="Pham Alou Golden et al 2021"/>

Kwashiorkor is most notable for peripheral edema. The presence of edema in kwashiorkor is correlated with very low albumin concentration ([[hypoalbuminemia]]). Edema results from a loss of fluid balance between the hydrostatic and oncotic pressures across the capillary blood vessel walls<ref name="Benjamin & Lappin Kwashiorkor"/> due to the lack of protein which affects the body's ability to draw fluid from the tissues into the bloodstream. Low albumin concentration influences negatively the strength of oncotic pressure. Failure leads to fluid buildup in the abdomen, resulting in edema and belly distension.<ref name="Pham Alou Golden et al 2021"/>

Furthermore, the release of antidiuretic hormone is stimulated by hypovolemia, also leading to the development of peripheral edema. Plasma [[renin]] is also stimulated, promoting sodium retention.<ref name="Benjamin & Lappin Kwashiorkor">{{cite book |last1=Benjamin |first1=Onecia |last2=Lappin |first2=Sarah L. |chapter=Kwashiorkor |id={{NCBIBook2|NBK507876}} |title=StatPearls |date=2022 |publisher=StatPearls Publishing |pmid=29939653 }}</ref>

It is important to distinguish the pathophysiology of marasmus and kwashiorkor when it comes to treating malnourished children who may have hypovolemic shock that is caused by an acute loss of salt and water.<ref name="G. Coulthard 2015">{{cite journal |last1=G. Coulthard |first1=Malcolm |title=Oedema in kwashiorkor is caused by hypoalbuminaemia |journal=Paediatrics and International Child Health |date=13 May 2015 |volume=35 |issue=2 |pages=83–89 |doi=10.1179/2046905514Y.0000000154 |pmid=25223408 |pmc=4462841 }}</ref> Children with severe albumin deficiency struggle physiologically to maintain their blood volume.<ref name="G. Coulthard 2015"/>

=== Low glutathione levels ===
Kwashiorkor is also marked by low [[glutathione]] levels. Glutathione is used in many of the body processes on a molecule level.<ref name=":02">{{cite journal |last1=Wu |first1=Guoyo |last2=Fang |first2=Yun-Zhong |last3=Yang |first3=Sheng |last4=Lupton |first4=Joanne R |last5=Turner |first5=Nancy D. |date=2004 |title=Glutathione Metabolism and Its Implications for Health |journal=The Journal of Nutrition |doi=10.1093/jn/134.3.489 |doi-access=free |pmid=14988435 |volume=134 |issue=3 |pages=489–492 |url=https://academic.oup.com/jn/article/134/3/489/4688681 |access-date=29 July 2021 |archive-date=19 June 2022 |archive-url=https://web.archive.org/web/20220619192840/https://academic.oup.com/jn/article/134/3/489/4688681 |url-status=live }}</ref>

It is believed to be related to high oxidant levels commonly seen in people who suffer from starvation and rarely in chronic inflammation.<ref name="Benjamin & Lappin Kwashiorkor"/> Glutathione serves vital functions including management of oxidative stress which is an imbalance that plays a key role in the pathogenesis of many diseases.

Evidence indicates that amino acid balance has an important effect on protein nutrition and therefore on glutathione homeostasis.<ref>{{cite journal |last1=Gould |first1=Rebecca L. |last2=Pazdro |first2=Robert |title=Impact of Supplementary Amino Acids, Micronutrients, and Overall Diet on Glutathione Homeostasis |journal=Nutrients |date=11 May 2019 |volume=11 |issue=5 |pages=1056 |doi=10.3390/nu11051056 |pmid=31083508 |pmc=6566166 |doi-access=free }}</ref>

Cysteine is an essential amino acid that acts as the limiting amino acid for glutathione synthesis in humans. Factors that increase demand for glutathione may increase demand for cysteine, and hence methionine. Such demands have been hypothesized to increase the risk for kwashiorkor.

=== Others ===
A proposed experimental theory suggests that alterations in the microbiome/virome contribute to edematous malnutrition, but further studies are required to understand the mechanism.<ref name="Benjamin & Lappin Kwashiorkor"/>

== Diagnosis ==
Kwashiorkor, or edematous malnutrition, like many other malnutrition diseases, is indirectly assessed using [[anthropometry]].<ref name="Bhutta Berkley Bandsma 2017">{{cite journal |last1=Bhutta |first1=Zulfiqar A. |last2=Berkley |first2=James A. |last3=Bandsma |first3=Robert H. J. |last4=Kerac |first4=Marko |last5=Trehan |first5=Indi |last6=Briend |first6=André |title=Severe childhood malnutrition |journal=Nature Reviews Disease Primers |date=21 December 2017 |volume=3 |issue=1 |pages=17067 |doi=10.1038/nrdp.2017.67 |pmid=28933421 |pmc=7004825 }}</ref> Kwashiorkor is a subtype of severe acute malnutrition (SAM) characterized by bilateral peripheral pitting edema. According 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."<ref>{{cite book |last1=Roberfroid |first1=Dominique |last2=Hammami |first2=Naïma |last3=Mehta |first3=Pankti |last4=Lachat |first4=Carl |last5=Verstraeten |first5=Roosmarijn |last6=Weise Prinzo |first6=Zita |last7=Huybregts |first7=Lieven |last8=Kolsteren |first8=Patrick |title=Management of oedematous malnutrition in infants and children aged >6 months: a systematic review of the evidence |date=2013 |hdl=1854/LU-5700347 |hdl-access=free |citeseerx=10.1.1.655.6549 }}</ref><ref name="Benjamin & Lappin Kwashiorkor"/><ref>{{cite journal |last1=Grellety |first1=Emmanuel |last2=Golden |first2=Michael H. |title=Severely malnourished children with a low weight-for-height have similar mortality to those with a low mid-upper-arm-circumference: II. Systematic literature review and meta-analysis |journal=Nutrition Journal |date=December 2018 |volume=17 |issue=1 |pages=80 |doi=10.1186/s12937-018-0383-5 |pmid=30217196 |pmc=6138903 |doi-access=free }}</ref> Additional clinical findings on physical exam include marked muscle atrophy, abdominal distension, dermatitis, and hepatomegaly.<ref name="Benjamin & Lappin Kwashiorkor"/><ref>{{cite journal |last1=Heilskov |first1=S. |last2=Rytter |first2=M.J.H. |last3=Vestergaard |first3=C. |last4=Briend |first4=A. |last5=Babirekere |first5=E. |last6=Deleuran |first6=M.S. |title=Dermatosis in children with oedematous malnutrition (Kwashiorkor): a review of the literature |journal=Journal of the European Academy of Dermatology and Venereology |date=August 2014 |volume=28 |issue=8 |pages=995–1001 |doi=10.1111/jdv.12452 |pmid=24661336 |s2cid=24731334 }}</ref>

WHO 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).<ref name="WHO 10665/95584">{{cite book |title=Guideline: updates on the management of severe acute malnutrition in infants and children |date=2013 |publisher=World Health Organization |isbn=978-92-4-150632-8 |hdl=10665/95584 |hdl-access=free }}{{pn|date=February 2022}}</ref>

In addition to anthropometric measures, laboratory tests can be critical for diagnosing kwashiorkor.<ref>{{Cite journal |last1=Bunker |first1=Sarah |last2=Pandey |first2=Jyotsna |date=2021-01-01 |title=Educational Case: Understanding Kwashiorkor and Marasmus: Disease Mechanisms and Pathologic Consequences |journal=Academic Pathology |language=English |volume=8 |doi=10.1177/23742895211037027 |issn=2374-2895 |pmc=8392804 |pmid=34458565}}</ref> Low serum albumin levels ([[hypoalbuminemia]]) are a hallmark of protein deficiency, and elevated [[Liver function tests|liver enzymes]] may indicate liver dysfunction.<ref>{{Cite journal |last1=Bunker |first1=Sarah |last2=Pandey |first2=Jyotsna |date=2021-01-01 |title=Educational Case: Understanding Kwashiorkor and Marasmus: Disease Mechanisms and Pathologic Consequences |journal=Academic Pathology |language=English |volume=8 |doi=10.1177/23742895211037027 |issn=2374-2895 |pmc=8392804 |pmid=34458565}}</ref> [[Electrolyte]] imbalances and blood tests may also be used to assess the degree of organ involvement and complications.<ref>{{Cite journal |last1=Bunker |first1=Sarah |last2=Pandey |first2=Jyotsna |date=2021-01-01 |title=Educational Case: Understanding Kwashiorkor and Marasmus: Disease Mechanisms and Pathologic Consequences |journal=Academic Pathology |language=English |volume=8 |doi=10.1177/23742895211037027 |issn=2374-2895 |pmc=8392804 |pmid=34458565}}</ref>

Specifically in children, severe malnutrition, such as kwashiorkor, can lead to notable changes in brain function and behavior.<ref>{{Cite journal |last1=Bhutta |first1=Zulfiqar A. |last2=Berkley |first2=James A. |last3=Bandsma |first3=Robert H. J. |last4=Kerac |first4=Marko |last5=Trehan |first5=Indi |last6=Briend |first6=André |date=2017-09-21 |title=Severe childhood malnutrition |journal=Nature Reviews Disease Primers |language=en |volume=3 |issue=1 |page=17067 |doi=10.1038/nrdp.2017.67 |issn=2056-676X |pmc=7004825 |pmid=28933421}}</ref> Children with kwashiorkor tend to be irritable and may develop [[cerebral atrophy]], whereas those with severe wasting frequently show [[apathy]], reduced movement, and speech delays.<ref name="Bhutta Berkley Bandsma 2017" /> These neurological and behavioral changes are key factors in the clinical assessment of malnutrition.<ref name="Bhutta Berkley Bandsma 2017" />

==  Screening ==
Because 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. Screening 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.

==Prevention==
As 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. By 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. By ensuring they are equipped with the proper education and resources, caretakers and infants are in better health, ultimately preventing childhood malnutrition.<ref name="Bhutta Berkley Bandsma 2017"/>

Because 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.<ref name="Kamaruzaman Jamani Said 2020">{{cite journal |last1=Kamaruzaman |first1=NA |last2=Jamani |first2=NA |last3=Said |first3=AH |title=An infant with kwashiorkor: The forgotten disease |journal=Malaysian Family Physician |date=6 July 2020 |volume=15 |issue=2 |pages=46–49 |pmid=32843945 |pmc=7430309 }}</ref> To 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.<ref name="Kamaruzaman Jamani Said 2020"/>

A diet rich in carbohydrates, fats that provide 10% of the total caloric needs, and proteins that provide 15% of the caloric needs can prevent kwashiorkor.

Proteins can be found in the following foods
* Seafood
* Peas
* Nuts
* Seeds
* Eggs
* Lean meat or fish
* Beans<ref name="Pham Alou Golden et al 2021"/>

== Treatment ==
[[WHO]] guidelines outline 10 general principles for the inpatient management of severely malnourished children.<ref name="WHO 10665/95584"/><ref>{{Cite web|url=https://www.who.int/nutrition/publications/guide_inpatient_text.pdf|archive-url=https://web.archive.org/web/20060327201732/http://www.who.int/nutrition/publications/guide_inpatient_text.pdf|url-status=dead|archive-date=27 March 2006|title=Guidelines for the inpatient treatment of severely malnourished children|last=Ashworth|first=Ann| name-list-style = vanc |date=2003|website=WHO}}</ref>

# Treat/prevent [[hypoglycemia]]
# Treat/prevent [[hypothermia]]
# Treat/prevent [[dehydration]]
# Correct [[electrolyte imbalance]]
# Treat/prevent [[infection]]
# Correct [[micronutrient deficiencies]]
# Start cautious [[refeeding syndrome|feeding]]
# Achieve [[catch-up growth]]
# Provide sensory stimulation and emotional support
# Prepare for follow-up after recovery

Both clinical subtypes of severe acute malnutrition (kwashiorkor and marasmus) are treated similarly.<ref name="Smith Yatsunenko Manary 2013"/><ref name="WHO 10665/95584"/> Upon initial treatment, children with kwashiorkor may experience weight loss as their edema resolves.<ref name="Grover & Ee 2009">{{cite journal |last1=Grover |first1=Zubin |last2=Ee |first2=Looi C. |title=Protein Energy Malnutrition |journal=Pediatric Clinics of North America |date=October 2009 |volume=56 |issue=5 |pages=1055–1068 |doi=10.1016/j.pcl.2009.07.001 |pmid=19931063 }}</ref> Therefore, after concerns of [[refeeding syndrome]] have passed, children may require 120-140% of their estimated caloric needs to achieve catch-up growth.<ref name="Grover & Ee 2009"/>

The cause, type, and severity of malnutrition determine what type of treatment would be most appropriate.<ref name="Dipasquale Cucinotta Romano 2020">{{cite journal |last1=Dipasquale |first1=Valeria |last2=Cucinotta |first2=Ugo |last3=Romano |first3=Claudio |title=Acute Malnutrition in Children: Pathophysiology, Clinical Effects and Treatment |journal=Nutrients |date=12 August 2020 |volume=12 |issue=8 |pages=2413 |doi=10.3390/nu12082413 |pmid=32806622 |pmc=7469063 |doi-access=free }}</ref> For 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).<ref name="Dipasquale Cucinotta Romano 2020"/> For secondary acute malnutrition, the underlying cause needs to be identified to appropriately treat children. Only 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 malnutrition.<ref name="Dipasquale Cucinotta Romano 2020"/> For example, it is important to recognize that supplementation with key micronutrients like vitamin A, zinc, and iron may be necessary for children during recovery.<ref>{{Cite journal |last1=Michael |first1=Husheem |last2=Amimo |first2=Joshua O. |last3=Rajashekara |first3=Gireesh |last4=Saif |first4=Linda J. |last5=Vlasova |first5=Anastasia N. |date=2022-05-02 |title=Mechanisms of Kwashiorkor-Associated Immune Suppression: Insights From Human, Mouse, and Pig Studies |journal=Frontiers in Immunology |language=English |volume=13 |doi=10.3389/fimmu.2022.826268 |doi-access=free |issn=1664-3224 |pmc=9108366 |pmid=35585989}}</ref> Micronutrient deficiencies are common in malnourished children and contribute to immune dysfunction.<ref>{{Cite journal |last1=Michael |first1=Husheem |last2=Amimo |first2=Joshua O. |last3=Rajashekara |first3=Gireesh |last4=Saif |first4=Linda J. |last5=Vlasova |first5=Anastasia N. |date=2022-05-02 |title=Mechanisms of Kwashiorkor-Associated Immune Suppression: Insights From Human, Mouse, and Pig Studies |journal=Frontiers in Immunology |language=English |volume=13 |doi=10.3389/fimmu.2022.826268 |doi-access=free |issn=1664-3224 |pmc=9108366 |pmid=35585989}}</ref> Specific vitamin A supplementation is particularly important for preventing further damage to the liver and skin.<ref>{{Cite journal |last1=Michael |first1=Husheem |last2=Amimo |first2=Joshua O. |last3=Rajashekara |first3=Gireesh |last4=Saif |first4=Linda J. |last5=Vlasova |first5=Anastasia N. |date=2022-05-02 |title=Mechanisms of Kwashiorkor-Associated Immune Suppression: Insights From Human, Mouse, and Pig Studies |journal=Frontiers in Immunology |language=English |volume=13 |doi=10.3389/fimmu.2022.826268 |doi-access=free |issn=1664-3224 |pmc=9108366 |pmid=35585989}}</ref>

[[Therapeutic food|Ready-to-use therapeutic foods]] (RUTFs) and [[F-100 and F-75 (foods)|F-75 and F-100 milks]] were created to provide appropriate nutrition and caloric intake to those experiencing malnutrition. F-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. While 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.<ref name="Bhutta Berkley Bandsma 2017"/>

It is also important to note that infections are common in children with severe malnutrition and can further complicate treatment.<ref>{{Cite journal |last1=Williams |first1=Phoebe C. M. |last2=Berkley |first2=James A. |date=2018-12-21 |title=Guidelines for the treatment of severe acute malnutrition: a systematic review of the evidence for antimicrobial therapy |journal=Paediatrics and International Child Health |language=en |volume=38 |issue=sup1 |pages=S32–S49 |doi=10.1080/20469047.2017.1409453 |issn=2046-9047 |pmc=5972636 |pmid=29790840}}</ref> Routine antibiotics, even in the absence of clinical infection, are generally given as a [[Prophylactic antibiotic|prophylactic]] measure, especially in regions with a high risk of infectious diseases.<ref>{{Cite journal |last1=Williams |first1=Phoebe C. M. |last2=Berkley |first2=James A. |date=2018-12-21 |title=Guidelines for the treatment of severe acute malnutrition: a systematic review of the evidence for antimicrobial therapy |journal=Paediatrics and International Child Health |language=en |volume=38 |issue=sup1 |pages=S32–S49 |doi=10.1080/20469047.2017.1409453 |issn=2046-9047 |pmc=5972636 |pmid=29790840}}</ref> However, due to concerns about antibiotic resistance, there is debate over their routine use.<ref>{{Cite journal |last1=Williams |first1=Phoebe C. M. |last2=Berkley |first2=James A. |date=2018-12-21 |title=Guidelines for the treatment of severe acute malnutrition: a systematic review of the evidence for antimicrobial therapy |journal=Paediatrics and International Child Health |language=en |volume=38 |issue=sup1 |pages=S32–S49 |doi=10.1080/20469047.2017.1409453 |pmid=29790840 |pmc=5972636 |issn=2046-9047}}</ref>

== Prognosis ==

Kwashiorkor is associated with a high risk of mortality and long-term complications. Treatment 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. However, physical and intellectual capabilities are not fully restored. Growth stunting and chronic disruption of microbiota are commonly observed after recovery.<ref name="Pham Alou Golden et al 2021"/>

A high risk of death is identified by a brachial perimeter < 11&nbsp;cm or by a weight-for-age threshold < −3 z-scores below the median of the WHO child growth standards. In practice, malnourished children with edema are suffering from potentially life-threatening severe malnutrition.<ref>{{Cite web|title=Management of moderate malnutrition in under-5 children by the health sector|url=https://www.who.int/nutrition/topics/MM_consultation_background.pdf|access-date=6 May 2021|archive-date=27 January 2018|archive-url=https://web.archive.org/web/20180127231057/http://www.who.int/nutrition/topics/MM_consultation_background.pdf|url-status=live}}</ref>

== Epidemiology ==
Kwashiorkor is rare in high-income countries. It 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.<ref name="Pham Alou Golden et al 2021"/> Occurrences 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.<ref name="Bhutta Berkley Bandsma 2017"/> Communities experiencing famine are affected the most, especially during the rainy season. Prevalence varies, but it affects children of either sex commonly under five years old.<ref name="Pham Alou Golden et al 2021"/><ref name="Odigwe Smedslund Ejemot-Nwadiaro et al 2010">{{cite journal |last1=Odigwe |first1=Chibuzo C |last2=Smedslund |first2=Geir |last3=Ejemot-Nwadiaro |first3=Regina I |last4=Anyanechi |first4=Chiedozie C |last5=Krawinkel |first5=Michael B |title=Supplementary vitamin E, selenium, cysteine and riboflavin for preventing kwashiorkor in preschool children in developing countries |journal=Cochrane Database of Systematic Reviews |date=14 April 2010 |volume=2010 |issue=4 |pages=CD008147 |doi=10.1002/14651858.CD008147.pub2 |pmid=20393967 |pmc=6599860 }}</ref> "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."<ref name="Odigwe Smedslund Ejemot-Nwadiaro et al 2010"/>

When 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."<ref name="Pham Alou Golden et al 2021"/> Factors such as "diet, geographical locations, climate, and aflatoxin exposure" have been invoked as potential causes for observed differences in the prevalence of kwashiorkor and marasmus.<ref name="Pham Alou Golden et al 2021"/>

In general, in areas where Severe Acute Malnutrition (SAM) is prevalent, marasmus is more often the dominant SAM condition. However, in certain areas, kwashiorkor may be more common than marasmus.

== History ==
Kwashiorkor was present in the world long before 1933 when Cicely Williams published research that took the [[Ga language|Ga]] name for the disease. There were already many names for the illness which referenced the cessation of breastfeeding, or the consumption of monotonous diets high in [[starch]]. However, Williams was the first to suggest that this might be a deficiency of protein or an amino acid. <ref name="williams1935" /><ref name="Nott2021" /> Despite publishing in 1933, it was only in 1949 that the World Health Organization officially recognized kwashiorkor as a public health concern.<ref name="Benjamin & Lappin Kwashiorkor"/> This period also correlated with the promotion of [[infant formula]], often by [[European colonial powers]]. The substitution of formula for breastmilk contributed significantly to the increasing visibility of kwashiorkor throughout the twentieth century. Cicely Williams later described the promotion of formula as "the most criminal form of sedition, and that those deaths should be regarded as murder." These arguments underpinned the 1970s [[Nestlé boycott]].<ref name="Nott2021" />

== Effects on pharmacokinetics ==
Those experiencing poverty-related infectious diseases (PRDs) such as malaria and tuberculosis are also likely to be malnourished.<ref name="Verrest Wilthagen Beijnen 2021">{{cite journal |last1=Verrest |first1=Luka |last2=Wilthagen |first2=Erica A. |last3=Beijnen |first3=Jos H. |last4=Huitema |first4=Alwin D. R. |last5=Dorlo |first5=Thomas P. C. |title=Influence of Malnutrition on the Pharmacokinetics of Drugs Used in the Treatment of Poverty-Related Diseases: A Systematic Review |journal=Clinical Pharmacokinetics |date=September 2021 |volume=60 |issue=9 |pages=1149–1169 |doi=10.1007/s40262-021-01031-z |pmid=34060020 |pmc=8545752 |s2cid=235259789 }}</ref> Malnutrition can affect the pharmacokinetics of various drugs used to treat PRDs by changing a drug's bioavailability, distribution, and elimination.<ref name="Verrest Wilthagen Beijnen 2021"/> To optimize the treatment of those diseases, there needs to be more research into how severe malnutrition, specifically kwashiorkor, can affect treatment response.<ref name="Verrest Wilthagen Beijnen 2021"/>

== Research directions ==
Current research and recommendations to manage severe acute malnutrition (SAM), such as kwashiorkor, in children, are largely based on expert opinions. Only one-third of the WHO guidelines for the management of SAM are based on epidemiological and clinical research. Further studies are needed to "improve treatment outcomes in the large number of children with SAM."<ref>{{cite journal |last1=Kulkarni |first1=Bharati |last2=Mamidi |first2=RajaSriswan |title=Nutrition rehabilitation of children with severe acute malnutrition: Revisiting studies undertaken by the National Institute of Nutrition |journal=Indian Journal of Medical Research |date=2019 |volume=150 |issue=2 |pages=139–152 |doi=10.4103/ijmr.IJMR_1905_18 |pmid=31670269 |pmc=6829782 |doi-access=free }}</ref>

== See also ==
* [[Anemia]]
* [[Emaciation]]
* [[Marasmus]]
* [[Protein poisoning]]
* [[Starvation]]

==References==
{{Reflist}}

== External links ==
* {{cite journal |last1=Picot |first1=J |last2=Hartwell |first2=D |last3=Harris |first3=P |last4=Mendes |first4=D |last5=Clegg |first5=A J |last6=Takeda |first6=A |title=The effectiveness of interventions to treat severe acute malnutrition in young children: a systematic review |journal=Health Technology Assessment |date=2012 |volume=16 |issue=19 |pages=1–316 |id={{NCBIBook2|NBK98566}} |doi=10.3310/hta16190 |doi-access=free |pmid=22480797 |pmc=4781582 }}
* {{Commons category-inline}}
* {{Wiktionary-inline}}
{{Medical resources
| ICD11           = {{ICD11|5B52}}
| ICD10           = {{ICD10|E40}}
}}

{{Nutritional pathology}}

[[Category:Disorders causing edema]]
[[Category:Protein–energy malnutrition]]