SevereAcuteMalnutrition(ProteinEnergyMalnutrition)

Deficiencyofasinglenutrientisanexampleofundernutritionormalnutrition,but
deficiencyofasinglenutrientusuallyisaccompaniedbyadeficiencyofseveralother
nutrients.Proteinenergymalnutrition(PEM)ismanifestedprimarilybyinadequate
dietaryintakesofproteinandenergy,eitherbecausethedietaryintakesofthese2
nutrientsarelessthanrequiredfornormalgrowthorbecausetheneedsforgrowthare
greaterthancanbesuppliedbywhatotherwisewouldbeadequateintakes.PEMis
almostalwaysaccompaniedbydeficienciesofothernutrients.
Historically, the most severe forms of malnutrition, marasmus (nonedematous
malnutritionwithseverewasting)andkwashiorkor(edematousmalnutrition),were
considered distinct disorders. Nonedematous malnutrition was believed to result
primarilyfrominadequateenergyintakeorinadequateintakesofbothenergyand
protein, whereas edematous malnutrition was believed to result primarily from
inadequateproteinintake.Athirddisorder,marasmickwashiorkor,hasfeaturesof
both disorders (wasting and edema). The 3 conditions have distinct clinical and
metabolic features, but they also have a number of overlapping features. A low
plasma albumin concentration, often believed to be a manifestation of edematous
malnutrition, is common in children with both edematous and nonedematous
malnutrition.
IntheUSA,severemalnutritionhasbeenreportedinfamilieswhouseunusualand
inadequate foods tofeed infants whom the parents believe to be at riskfor milk
allergiesandalsoinfamilieswhobelieveinfaddiets.Manycasesareassociatedwith
ricemilkdiets,aproductthatisverylowinproteincontent.Inaddition,protein
caloriemalnutritionhasbeennotedinchronicallyillpatientsinneonatalorpediatric
intensivecareunitsaswellasamongpatientswithburns,HIV,cysticfibrosis,failure
to thrive, chronicdiarrheasyndromes,malignancies,bone marrow transplantation,
andinbornerrorsofmetabolism.

ClinicalManifestationsofSevereProteinCalorieMalnutrition
Nonedematousmalnutrition(marasmus)ischaracterizedbyfailuretogainweightand
irritability,followedbyweightlossandlistlessnessuntilemaciationresults.Theskin
losesturgorandbecomeswrinkledandlooseassubcutaneousfatdisappears.Lossof
fatfromthesuckingpadsofthecheeksoftenoccurslateinthecourseofthedisease;
thus,theinfantsfacemayretainarelativelynormalappearancecomparedwiththe
restofthebody,butthis,too,eventuallybecomesshrunkenandwizened.Infantsare
oftenconstipated,buttheycanhavestarvationdiarrhea,withfrequentsmallstools
containingmucus.Theabdomenmaybedistendedorflat,withtheintestinalpattern
readilyvisible.Thereismuscleatrophyandresultanthypotonia.Asthecondition
progresses,thetemperatureusuallybecomessubnormalandthepulseslows(Table
434).
TABLE434ClinicalSignsofMalnutrition
SITE

SIGNS

Face

Moonface(kwashiorkor),simianfacies(marasmus)

Eye

Dryeyes,paleconjunctiva,Bitotspots(vitaminA),periorbitaledema

Mouth

Angularstomatitis,cheilitis,glossitis,spongybleedinggums(vitaminC),paro

Teeth

Enamelmottling,delayederuption

Hair

Dull,sparse,brittlehair,hypopigmentation,flagsign(alternatingbandsofligh
normalcolor),broomstickeyelashes,alopecia

Skin

Looseandwrinkled(marasmus),shinyandedematous(kwashiorkor),dry,foll
hyperkeratosis,patchyhyperandhypopigmentation(crazypavingorflakypa
dermatoses),erosions,poorwoundhealing

Nails

Koilonychia,thinandsoftnailplates,fissuresorridges

Musculature

Musclewasting,particularlybuttocksandthighs;ChvostekorTrousseausigns

Skeletal

Deformities,usuallyasaresultofcalcium,vitaminD,orvitaminCdeficiencie

Abdomen

Distended:hepatomegalywithfattyliver;ascitesmaybepresent

Cardiovascular

Bradycardia,hypotension,reducedcardiacoutput,smallvesselvasculopathy

Neurologic

Globaldevelopmentaldelay,lossofkneeandanklereflexes,impairedmemory

Hematologic

Pallor,petechiae,bleedingdiathesis

Behavior

Lethargic,apathetic,irritableonhandling

FromGroverZ,EeLC:Proteinenergymalnutrition, PediatrClinNAm 56:1055

1068,2009.
Edematousmalnutrition(kwashiorkor)canoccurinitiallyasvaguemanifestationsthat
includelethargy,apathy,and/orirritability.Whenkwashiorkorisadvanced,thereis
lack of growth, lack of stamina, loss of muscle tissue, increased susceptibility to
infections,vomiting,diarrhea,anorexia,flabbysubcutaneoustissues,andedema.The
edemausuallydevelopsearlyandcanmaskthefailuretogainweight.Itisoften
present in internal organs before it is recognized in the face and limbs. Liver
enlargementcanoccurearlyorlateinthecourseofdisease.Dermatitisiscommon,
withdarkeningoftheskininirritatedareas,butincontrasttopellagra(Chapter46)
notinareasexposedtosunlight.Depigmentationcanoccurafterdesquamationin
theseareas,oritmaybegeneralized(Figs.433,434,435).Thehairissparseand
thin,andindarkhairedchildren,itcanbecomestreakyredorgray.Eventually,there
isstupor,coma,anddeath(seeTable434).

FIGURE433 A, Kwashiorkorina2yroldboy.Notethegeneralizededema,the
typicalskinlesions,andthestateofprostration.B,Closeupviewofthesamechild
showingthehairchangesandpsychicalterations(apathyandmisery);theedemaof
thefaceandskinlesionscanbeseenmoreclearly.(Photographsmadeavailableby
theInstituteofNutritionofCentralPanama,Guatemala,courtesyofMoisesBehar,
MD.)

FIGURE 434 A and B, A 7mo old boy with diffuse erythematous papules and
plaques,somescaly,andedemaoftheextremities.(FromKatzKA,MahlbergMH,
HonigPJ,etal:Ricenightmare:kwashiorkorin2PhiladelphiaareainfantsfedRice
Dreambeverage,JAmAcadDermatol52[5Suppl1]:S69S72,2005.)

PathophysiologyofSevereProteinCalorieMalnutrition
Why edematous malnutrition develops in some children and nonedematous
malnutritiondevelopsinothersisunknown.Onefactormaybethevariabilityamong

infantsinnutrientrequirementsandinbodycompositionatthetimethedietarydeficit
isincurred.Italsohasbeenproposedthatgivingexcesscarbohydratetoachildwith
nonedematous malnutrition reverses the adaptive responses to low protein intake,
resulting in mobilization of body protein stores. Eventually, albumin synthesis
decreases, resulting in hypoalbuminemia with edema. Fatty liver also develops
secondary,perhaps,tolipogenesisfromtheexcesscarbohydrateintakeandreduced
apolipoprotein synthesis. Other causes of edematous malnutrition are aflatoxin
poisoningaswellasdiarrhea,impairedrenalfunctionanddecreasedNa +/K+ATPase
activity. Free radical damage has been proposed as an important factor in the
developmentofedematousmalnutrition.Thisproposalissupportedbylowplasma
concentrationsofmethionine,adietaryprecursorofcysteine,whichisneededfor
synthesis of the major antioxidant factor, glutathione. This possibility also is
supported by lower rates of glutathione synthesis in children with edematous
comparedwithnonedematousmalnutrition.

Treatment
Theusualapproachtothetreatmentofsevereacutemalnutritionincludes3phases
(Table 435 and Fig. 437). The initial phase (17 days) is a stabilization phase.
During this phase, dehydration, if present, is corrected and antibiotic therapy is
initiated to control bacterial or parasitic infection. Because of the difficulty of
estimatinghydration,oralrehydrationtherapyispreferred(Chapters55and332).If
intravenous therapy is necessary,estimates of dehydration should be reconsidered
frequently,particularlyduringthefirst24hroftherapy.Oralfeedingsarealsostarted
withspecializedhighcalorieformula(seeFig.437andTable436),proposedbythe
WorldHealthOrganization,thatcanbemadewithsimpleingredients.Theinitial
phase of oral treatment is with the F75 diet (75kcal or 315kJ/100mL). The
rehabilitationdietiswiththeF100diet(100kcalor420kJ/100mL).Feedingsare
initiated with higher frequency and smaller volumes; over time, the frequency is
reducedfrom12to8to6feedingsper24hr.Theinitialcaloricintakeisestimatedat
80100kcal/kg/day.Indevelopedcountries,2427calorie/ozinfantformulasmaybe
initiatedwiththesamedailycaloricgoals.Ifdiarrheastartsorfailstoresolveand
lactose intolerance is suspected, a nonlactosecontaining formula should be
substituted.Ifmilkproteinintoleranceissuspected,asoyproteinhydrolysateformula
maybeused.
TABLE435TimeFramefortheManagementofaChildwithSevereMalnutrition*
FromWorldHealthOrganization:Managementofseveremalnutrition:amanualfor
physicians and other senior health care workers, Geneva, 1999, World Health
Organization.

FIGURE437 Classificationofsevereacutemalnutritionusedincommunitybased
therapeuticcare.ICMI,integratedmanagementofchildhoodillness;MUAC,mid
upperarmcircumference;WHO,WordHealthOrganization.*Grade1,mildedema
onbothfeetorankles;grade2,moderateedemaonbothfeet,pluslowerlegs,hands,

orlowerarms;grade3,severegeneralizededemaaffectingbothfeet,legs,hands,
arms, and face. IMCI criteria39: 60 respirations/min children age <2mo; 50
respirations/minforage212mo;40respirations/minforages15yr;30respirations
forage>5yr.(FromCollinsS,DentN,BinnsP,etal:Managementofsevereacute
malnutritioninchildren,Lancet368:19922000,2006.)
INGREDIENT

AMOUNT
F75*

F100

Driedskimmilk

25g

80g

Sugar

70g

50g

Cerealflour

35g

Vegetableoil

27g

60g

Mineralmix

20mL

20mL

Vitaminmix

140mg

140mg

Watertomake

1,000mL

1,000mL

TABLE436PreparationofF75andF100Diets
FromWorldHealthOrganization:Managementofseveremalnutrition:amanualfor
physicians and other senior health care workers, Geneva, 1999, World Health
Organization.
Anotherapproachistheuseofreadytousetherapeuticfoods(RUTFs)(Fig.438).
RUTFs reduce mortality in acosteffective manner, in part because they are less
susceptible to spoilage than powdered milkbased supplementary foods. F100 is
waterbasedandsubjecttobacterialcontamination,whereasRUTFisanoilbased
pastethathaslittlewatercontentandasimilarnutrientprofilebutahighercalorie
density and is equally palatable to F100. RUTF is a mixture of powdered milk,
peanuts,sugar,vitamins,andminerals.

FIGURE438 Severeacutemalnutrition(SAM)management.RUTF,readytouse
therapeutic foods. (From World Health Organization and the United Nations
ChildrensFund:WHOchildgrowthstandardsandtheidentificationofsevereacute
malnutrition in infants and children, 2009
(PDF).
www.who.int/nutrition/publications/severemalnutrition/9789241598163/en/index.htm
l.AccessedMay23,2010.)
OneadvantageofRUTFsisthatinmanycasesitcanbeusedincommunitysettings
ratherthaninrehabilitationcenterswherethereisahighriskofinfection.Indeed,it
maybehardtoseparateouttheintrinsicadvantageoftheRUTFproductsfromthe
advantagesofthecommunitybasedmanagementofcare.
Laboratory evaluation (Table 437) and ongoing monitoring (Table 438), when
available, help guide therapy and prevent complications. Fluid status must be
monitoredverycarefullyinanemicpatients,whomightrequireapackedredblood
celltransfusion.
TABLE437LaboratoryFeaturesofSevereMalnutrition
From Mller O, Krawinkel M: Malnutrition and health in developing countries,
CMAJ173(3):279286,2006.2005CanadianMedicalAssociation.Reprintedwith
permissionofthepublisher.
BLOODORPLASMAVARIABLES

INFORMATIONDERIVED

Hemoglobin, hematocrit, erythrocyte count,

meancorpuscularvolume

Degreeofdehydrationandanemia;typeofanemia
(iron/folateandvitaminB12deficiency,hemolysis,malaria)

Glucose

Hypoglycemia

Electrolytesandalkalinity
Sodium

Hyponatremia,typeofdehydration

Potassium

Hypokalemia

Chloride,pH,bicarbonate

Metabolicalkalosisoracidosis

Totalprotein,transferrin,(pre)albumin

Degreeofproteindeficiency

Creatinine

Renalfunction

Creactiveprotein,lymphocytecount,serology,
thickandthinbloodfilms

Presenceofbacterialorviralinfectionormalaria

Stoolexamination

Presenceofparasites

TABLE438ElementsintheManagementofSevereProteinEnergyMalnutrition
PROBLEM

MANAGEMENT

Hypothermia

Warmpatientup;maintainandmonitorbodytemperature

Hypoglycemia

Monitorbloodglucose;provideoral(orintravenous)glucose

Dehydration

Rehydratecarefullywithoralsolutioncontaininglesssodiumandmorepotass
thanstandardmix

Micronutrients

Providecopper,zinc,iron,folate,multivitamins

Infections

Administerantibioticandantimalarialtherapy,evenintheabsenceoftypicals

Electrolytes

Supplyplentyofpotassiumandmagnesium

Starternutrition

Keepproteinandvolumeloadlow

Tissuebuilding
nutrition

Furnisharichdietdenseinenergy,protein,andallessentialnutrientsthatis
digest

Stimulation

Preventpermanentpsychosocialeffectsofstarvationwithpsychomotorstimul

Preventionofrelapse

Startearlytoidentifycausesofproteinenergymalnutritionineachcase;invol
thefamilyandthecommunityinprevention

From Mller O, Krawinkel M: Malnutrition and health in developing countries,

CMAJ173(3):279286,2006.2005CanadianMedicalAssociation.Reprintedwith
permissionofthepublisher.

Thesecondrehabilitationphase(wk26)mayincludecontinuedantibiotictherapy
with appropriate changes, if the initial combination was not effective, and
introductionoftheF100orRUTFdiet(Tables436and439)withagoalofatleast
100kcal/kg/day.Thisphaseusuallylastsanadditional4wk.Atanytime,iftheinfant
isunabletotakethefeedingsfromacup,syringe,ordropper,administrationbya
nasogastric tube rather than by the parenteral route is preferred. Bottles may be
contaminated in certain locales, and their use is discouraged unless cleanliness is
assured.Onceadlibitumfeedingsareallowed,intakesofbothenergyandproteinare
oftensubstantial.Irontherapyusuallyisnotstarteduntilthisphaseoftreatment;iron
caninterferewiththeproteinshostdefensemechanisms.Therealsoisconcernthat
free iron during the early phase of treatment might exacerbate oxidant damage,
precipitatinginfections(malaria),clinicalkwashiorkor,ormarasmickwashiorkorina
childwithclinicalmarasmus.Somerecommendtreatmentwithantioxidants.
TABLE439CompositionofF75andF100Diets
FromWorldHealthOrganization:Managementofseveremalnutrition:amanualfor
physicians and other senior health care workers, Geneva, 1999, World Health
Organization.

CONSTITUENT

AMOUNTPER100mL
F75

F100

Energy

75kcalth(315kJ)

100kcalth(420kJ)

Protein

0.9g

2.9g

Lactose

1.3g

4.2g

Potassium

3.6mmol

5.9mmol

Sodium

0.6mmol

1.9mmol

Magnesium

0.43mmol

0.73mmol

Zinc

2.0mg

2.3mg

Copper

0.25mg

0.25mg

Protein

5%

12%

Fat

32%

53%

Percentageofenergyfrom:

Osmolarity

333mOsmol/L

419mOsmol/L

Bytheendofthe2ndphase,anyedemathatwaspresenthasusuallybeenmobilized,
infections are under control, the child is becoming more interested in his or her
surroundings,andhisorherappetiteisreturning.Thechildisthenreadyforthefinal
followup phase, which consists of feeding to cover catchup growth as well as
providingemotionalandsensorystimulation.Thechildshouldbefedadlibitum.
Indevelopingcountries,thisfinalphaseisoftencarriedoutathome.Inallphases,
parentaleducationiscrucialforcontinuedeffectivetreatmentaswellaspreventing
additionalepisodes.