Tropical enteropathy and tropical sprue’

8/3/2019 Tropical enteropathy and tropical sprue

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T rop ica l en te ropa th y and trop ica l sp rue 2

Th e A m er ica ,z Jo ,,r,,a l o f C /in /ca l N u tr ition 25 : O C T O B E R 1972 , pp . 1 047-1 055 . P rin ted in U .S .A . 1047

S . J . B a ker, M .D ., F .R .A .C .P ., and V . I . M a tha n , M .D ., P h .D .

A sy n d ro m e o f u n k n ow n etio logy , ch arac-ter ized b y in te stina l m a lab so rp tio n , ch ron icd ia rrhea , and m ultip le n u tr itiona l d iso rde rs ,w as recog n ized in Ind ia a num ber o f cen -tu rie s B .C . b y C araka (1 ) . S in ce tha t tim e,th e synd rom e has b een docum en ted by m anyin vestiga to rs in d iffe ren t pa rts o f the coun tryin bo th end em ic an d ep idem ic fo rm s. M anyn am es h av e been g iven to th is synd rom e , b u tg rad ua lly the te rm trop ica l sp rue w as g en -e rally ad op ted fo r it. M uch o f th e n in eteen thand ea rly tw en tie th cen tu ry litera tu re onsp rue in Ind ia h as been rev iew ed by O B rien(2 ) . O the r m ore recen t inv es tiga tions h av eb een carried ou t by w orke rs in d iffe ren tp arts o f In d ia such as C alcu tta (3 ) , B om bay(4 ) , D e lh i (5) , L udh iana (6 ), and V e llo re (7 ,8 ) . I t th ere fo re ap pears p ro bab le th at trop i-ca l sp rue is p reva len t th roug hou t m os t o fth e Ind ian su bcon tinen t.

In th e past d ecade , w ith th e in tro duc tiono f new er techn iq ues fo r the in vestiga tion ofth e gastro in te stin al trac t, the re has a lso com ea recogn ition tha t in th e trop ic s , in add itionto p atien ts w ith cla ssica l trop ica l sp ru e , the reare m any asym ptom atic su b jects w ho hav e am ilde r fo rm o f sm a ll in te stina l d iso rde r. T h ism ay be m an ife sted by m ino r h isto log ica l ab -no rm a litie s o f the jeju na l m u co sa o r abn or-m alitie s in abso rp tio n tes ts , o r bo th . Th is d is-o rd e r m ay be te rm ed trop ica l je jun itis , o r ,m ore ap tly , trop ica l en te ropa thy .

Th is comm unica tion com pares an d co n-tra sts so -called no rm al sub jec ts , m any o fw hom hav e trop ica l en te ro pa thy , w ith su b-jec ts su ffer ing from tro p ical sp rue .

S u b jec ts an d m eth od sThe following three groups of subjects we r e

studied:1 ) W ard c on tro ls. This group cons isted o f 71

ap paren tly hea lth y , asym ptom atic , sou thern Ind ianadult vo lun tee rs w ho w ere m a in ly from the low ersocioeconomic group and who were admitted to theho sp ita l fo r p eriods of one to sev eral w eek s fo r de-

ta iled m etabo lic s tu d ies . T h eir ages rang ed from 17to 70 years w ith a m ean of 3 2 .1 y ears.

2) V il lag e co n tro ls . In ord er to ob ta in a sta tisti-ca lly va lid p opu latio n sam p le o f a sou th ern Ind ianv illage , a census w as carried ou t in th e v illag e ofM a, and 94 famil ies (29% of the po pu la tio n ) w erecho sen fo r s tu dy by stra tified random sam pling .T he hea lth s ta tus o f th is g ro up has been recordedov e r a 2-year period , and a sub sam ple o f th is g rou phad variou s ab sorp tion stud ies d one-47 o f w hichw ere fat excre tio n , 308 xy lose absorp tion , an d 205v itam in B12 abso rp tion tests in a ll.

3 ) P a tien ts w ith tro p ica l sp rue . Epidem ics oftrop ica l sp rue in tw o n eig hbo rin g v illag es w eres tud ied . E p idem io log ica lly these tw o ep idem ics ap -p eared to b e sim ila r and , as the re w as no de tec tab led if fe rence be tw een th e c lin ica l m an ifesta tion s inp atien ts from the tw o v illages, they hav e been corn -b in ed . A to ta l o f 90 pa tien ts w ere in vestiga ted ind eta il, a ll o f w hom had d ia rrhea and o ther sym p-tom s such as vom iting , ano rex ia, abdom ina l d is -tens ion , and loud borbo rygm i. O ne-th ird o f thepa tien ts a lso had sym ptom s of defic ien cy sta tessuch as g loss itis , hyperp igm en ta tion , anem ia , andedem a, w hich had deve lop ed during th e course o ft h e ir i l l ne s s .T h e sym p tom s w ere su ffic ien tly sev ereso that the patients agreed to come to the hosp italf or i nv es ti ga ti on .The w ard co n tro ls and the sp ru e p atien ts w eres tu d ied in a m etabo lic w ard w here they rece ived as tan dard d ie t con ta in ing 50 to 6 0 g fa t. T h e v illagecontrols were brought into the metabolic ward for1 day fo r xy lose and v itam in B absorption tests,b ut s to ol c ol le ct io ns f or estim ation of feca l fa t ex -c re tion w ere don e a t hom e w hile the su b jec ts w erecon sum ing a d ie t con ta in ing approx im ate ly 20 gfa t /day .

T he xy lose abso rp tion test w as carried ou t usinga 5 -g d ose D -x y lose . U r in e w as co llec ted fo r the 0to 2- and 2 to 5-h r periods fo llow in g adm in istra tio nof the dose . T he xy lose in the u rin e w as m easuredby the m ethod of R oe and R ice (9 ). Th e resu ltsw ere ex pressed bo th as to ta l excre tion in 5 h r andas the ra tio o f the 0 to 2 /0 to 5-h r excre tion (10 ).S too l fa t w as m easured d aily b y the m ethod of vande K am er e t a l. (11 ), and the resu lts expressed as a3-day m ean . A n ex cre tion o f 6 or m o re p er day w as

F rom the W eilcom e R esearch U n it, C h ristianM ed ica l C o llege H osp ita l V e llo re , T am il N adu ,In d ia, in asso cia tion w ith the W orld H ea lth O r-gan iza t ion .

2 S tudy su pported in p ar t by PL 480 . A gree-m en t N o . 01 329 01 .


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1 0 4 8 B A K E R A N D M A T H A NTA BLE 1X ylo se e xc re tio n am ong d ifferen t age group sof v illag e con tro ls

IPe rcent

A ge g ro up ,yea r s No .Me a npe rcentexcretion so

ofgroup


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II2 0 0 G3 0G R3 O

Fio . 1 . A ge -spec if ic attack rate , in 10 -y ear agegroup s, in on e o f the tw o v illages af f ec ted by ep i-dem ic spru e .

T A B L E 2P a t t e r n o f a b s o r p t i v e d e f e c t s i n 9 0 p a t i e n t swi t h e p i d e mi c s pr u e

a + = p r e s e n t . b - = a b s e n t .

T R O PIC A L E N T E R O PA T H Y A N D T R O PIC A L SPR U E 1 0 4 9

adults and tw o schoolch ild ren) had abnorm alabsorption.

O f the 47 adu lts w ho had all three testsdon e, non e had m alabsorp tion o f three testsubs tan ces; tw o persons (4% ) had m alab-so rp tion o f tw o substances (on e f at andx y lose , on e v itam in B 12 and x y lo se ); and 28( 5 6 % ) had m alabso rp tio n o f one sub stance(2 fat, 25 x y lose , and 1 v itam in B 12 ). T w ohund red f iv e sub jec ts had x y lose and v itam inB12 abso rp tion tests and on ly 6 (3% ) hadm alabsorp tion o f bo th substances. O ne p er-son (0 .5% ) had m alab sorp tion o f v itam inB 12 only and 108 ( 5 4 % ) of x y lose only .T ro p ica l sp rite

T he age-specif ic attack rate in on e o f th etw o epid em ics o f trop ical sprue is show n inFig . 1 . C hildren and adolescen ts are sign if i-can tly less af f ected than adults (P < 0 .0 0 5 ) .A sim ilar pattern has been observed in all theo ther ep idem ics stud ied f rom th is cen ter.

T he m ean x y lo se ex cretio n in the group of90 patien ts w ith ep idem ic sprue w as 12 .0%(S D 10 .0), and only tw o subjec ts ex cre ted2 5% or m ore o f the do se . T h e m ean stoo l f atexcre t ion w as 13 .0 g /day (S D 7 .5 ) . Fiv e sub -jects had no steato rrhea. V itam in B 12 abso rp -tion w as de term in ed by th e f ecal test in 30patien ts; th e m ean abso rp tion w as 0 .28 ,sg(SD 0 .12 ). E lev en sub jec ts (3 6% ) abso rbed0. 3 or m ore. In 60 patien ts th e S ch illingtest w as used and the m ean ex cre tion w as4 .5% (S D 4 .1 ); 15 sub jec ts (25% ) ex cre tedm ore th an 6% of the do se . T he dif f e ren ce inth e prev alence o f B 12 m alabsorp tio n em p loy -ing th e tw o tests is n o t s ign if ican t.

T he pattern o f absorp tiv e de f ec ts in these90 patien ts is show n in T able 2 . W ith th reetest sub stances there are sev en possib le com -b inations o f abnorm alities. T h e m ost com -m on com bination w as m alab sorp tion o f allth ree tes t substan ces f o llow ed by m alabso rp-tio n o f f at and x y lo se w ith out v itam in B 12m alab sorp tion . T he other com binatio ns w erem uch less com m on, and an iso lated d ef ecto f v itam in B 52 abso rp tion w as no t seen in th isgroup .

D issectin g m icroscop e ex am inatio n o f theje junal b iopsy in these 90 patien ts show ed aleaf - lik e patte rn in 46 (51 % ) and a con -v o lu ted pattern in 44 (49% ). O n h isto lo g ical

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fll

A bsorp tiv e def e ct Patients

Fat X y l o s e V ir n in N o. %

+ + + 60 67+ + - 20 22+ 4 4+ - + 2 2

- + - 2 2+ - - i 2 2- - + 0 0

ex am ination , 9 sub jects (10% ) had grade I,44 (49% ) grade II, and 37 (41% ) grade IIIchanges .

B arium m eal ex am ination w as norm al in 8subjects, sh ow ed grad e I changes in 37 , g radeII in 23 , grade III in 16 , and grad e IV in 6subjec ts .

Discuss ionW a rd co n tro ls

T he m ean 5-hr x y lose ex cre tion in thew ard contro ls is in the low er range of norm alv alues reported by others (16 -19 ) fo r th e 5-gdose (T ab le 3 ), and 19% o f the sub jec ts hadv alues b elow th e accep ted lim it o f no rm al.T h e ratio o f ex cre tion in th e 0 to 2 /0 to 5 hris con siderably low er th an th e v alu e o f 0 .62(S D 0 .10) repo rted by S am m ons e t al. (1 0),and 40% of all v alues f e ll o u tside the rangeof S am m on ss m ean 2 S D . Ex am ination o fthe x y lo se ex cre tion in th e d if f eren t co llec tion


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1050 B A K E R A N D M A T H A N

TA B L E 3Results of 5-g D -X y lose test i n normal subjectsreported by other i nvesti gators

MeanStudies i: S D

tion

Santini et al . (16)Sammons et al . (10)Joske and H a a g e n s e n (17)Butterw orth et al . (18)R inaldo and G luckmann (19)Present study

periods show s that the reason for the low eredratio i s a considerable decrease in excreti on inthe f i rst 2 hr. T his low ered ratio occurred inmany subjects, even in the presence of a 5-hrexcreti on of 25% or more, and suggests aw idespread f unctional impai rment of xy loseabsorption in the upper smal l i ntesti ne (20).

The mean f at excreti on of thi s group (4.2g) i s higher than those reported by others,w ho give values of 2. 5 g (SD 2.0) (21) and 2.6g (SD 1.7) (22) for subjects on a 50 to 60 gf a t i n ta k e. Seven subjects had an excretion of6 g or more p e r day , even i f these are arbi -trar i l y excluded, the mean excretion (3.7 g) i ssti l l elevated, suggesting that in thi s group ofpatients f at absorption may not be as com-plete as in subjects l iv ing in temperate re-gions.T h e g r a d in g o f t h e d eg r ee o f abnormalityof i ntesti nal biopsies i s a subjecti ve process,vary ing w i th di f ferent observers. N everthe-less, the jejunal biopsies in the majori ty ofthe control subjects w ere qui te di f ferent f romthose reported f rom normal subjects in tem-perate regions (23-25).

I t may be concluded that the majori ty ofthe w ard control subjects had f unctional andstructural abnormal i ti es of the jejunum , orboth, and must theref ore be considered ashav ing tropical enteropathy . On the otherhand, i l eal function as measured by thev i tam in B12 absorption test w as normal in al lbut one subject, i ndi cating a relati ve sparingof the i l eum. A sim i lar relati ve sparing of thei l eum has been noti ced in a postmortemmorphological study of the intesti ne in sub-jects dy ing of non-gastrointesti nal di seases(26).

Village contro lsT h e p r ev a len ce o f x y lo se m a la b sor p t io n

among the adul ts in the v i l l age control s w assigni f i cantly higher than in the w ard control s.T he reasons f or thi s are not clear, but thi sincrease suggests that the prevalence of enter-

36 6 opathy may di f fer i n di f f erent groups of sub-35 6 j ects w i thin the general populati on. L inden-35 9 baum (27) has observed di f f erences in the 1 prevalence of xy lose malabsorption betw een30 8 subjects l i v ing in urban and rural env i ron-

------- m e n t s , and sim i lar factors may be operatingbetween these tw o control groups. O f con-siderable interest i s the f inding of a highp r e v a l e n c e of xy lose malabsorption in thep re sc h o o l c h ild re n. Some of thi s increasedprevalence may perhaps be accounted f or bythe f act that al l subjects w ere given a 5-g dosei r r e sp ec t i v e of thei r w eight. H owever, corn-pari son of our data w i th those of Polonovsk iand Gombaul t (28) suggests that the majori tyof the chi l dren w ould sti l l have had xy losemalabsorption even i f the dose had been ad-justed f or body w eight or surface area.

The overal l f i gure f or steatorrhea in theadul ts in thi s group is sim i lar to that in thew ard control group, but the tw o are notstri ctl y comparable because of the low er f ati ntake in the v i l l age control s. I t i s probablethat a higher f at i ntake w ould have brought tol i ght more subjects w i th increased fat excre-tion.

T he low prevalence of v i tam in B 12 malab-sorption i s in sharp contrast to the resul ts ofthe xy lose absorption test and, as in the wardcontrol s, suggests a relati ve sparing of thedistal smal l i ntesti ne.Tropica l sprite

T h e r e la t iv e ly low er in c id en ce o f t r o p ica lsprue among chi ldren compared w i th adul tsin the tw o epidem ics has been a constantf eature in al l epidem ics of sprue that havebeen studied. There are no data avai l able onthe incidence of endem ic sprue in the com -muni ty . H ospi tal stati sti cs suggest i t has a pat-tern of incidence sim i lar to that of epidem icsprue, but such compari sons may be fal l a-cious. Over the past year, studies have beenconducted in a group of 25 v i l l ages covering21,000 people. T he incidence of chronic


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F I G . 2. T he in cid en ce, in 10 -y ear age g roups ,of chron ic d iarrhea c lin ically resem bling endem ictro pic al sp ru e.

XYLO SE # {1 6 3 }XC T iO N % DO S C

T R O P I C A L E N T E R O P A T H Y A N D T R O PI C A L SPR U E 1 0 5 1

diarrhea (contin u ing f or m o re than 1 m onth )c lin ically suggestiv e o f tro p ical sprue , isshow n in Fig . 2 . A gain , the low er inc idencein ch ildren and adolescen ts is strik ing . B ak erand M athan (29) hav e show n that no c lin ical,b iochem ical, or patho log ical d if f e ren ces canbe de tec ted be tw een epid em ic and endem icspru e, ex cep t that patien ts f rom epidem icshav e a high er p rev alence o f v itam in B 12 m al-abso rp tion . I t there f ore seem s p robable thatendem ic and epid em ic sprue are sim ilar, ifno t id en tical, condition s.

T h e d if f erences in sev erity and duratio n ofillness and in th e pattern o f absorp tiv e de f ec tsseen in d if f e ren t ind iv iduals raises the ques-tion o f w he ther o r no t all th ese patien ts hav ethe sam e illness. T h e ep idem io log ical patte rnin patien ts w ith an illn ess lasting less than am onth w as iden tical w ith that in patien tsw ith an illness o f longer duration (30 ). A naly -ses o f th e patien ts in th is study w ith m alab-sorp tio n o f f at, x y lose, and v itam in B 12 andtho se w ith only fat and x y lose m alabso rp tio nshow no s ign if ican t d if f e ren ces b etw een th em ,e ither in the sev erity o f th eir illness, th e d e-gree o f f at or x y lose m alab sorp tio n , o r in b i-opsy o r rad io lo g ical f ind in gs. T he oth er com -binatio ns o f absorp tiv e d ef ects w ere f ound insuch sm all num bers th at it is no t possib le toanaly z e them m eaning f u lly . H ow ev er, allo f them had sim ilar sy m ptom s and , inasm uchas they becam e ill at the sam e tim e as o thersin the v illag e, they presum ably had the sam edisease.C om parison be tw een con tro ls an d pa t ien tsw ith trop ica l sprue

T he pattern o f x y lo se ex cre tion in th esp ru e patien ts is com pared w ith that o f thew ard and the v illag e contro ls (Fig . 3 ) . T h esp ru e patien ts and the w ard contro ls are tw od istinc t pop ulation s (P < 0 .001), w ith onlya sm all area of o v erlap be tw een th em . T hev illage contro ls occupy an in term ed iate po si-tion w ith a m uch w id er ov erlap; n ev erthe less,s tatistically they rep resen t a popu latio n d if f er-en t f rom either the sprue g roup o r the w ardcontrols (P < 0 .001 and P < 0.00 5 , respec-t ive ly ) .

T he fat ex cre tion o f the sprue patien ts andth e w ard contro ls is show n in Fig . 4 . T h esef orm tw o dif f e ren t population s (P < 0 .001),

Fio. 3 . Pattern o f x y lo se ex cre tion in the th reegro ups o f sub jects . T he he igh t o f each co lum n rep -resen ts the percen t o f th e group w ith urinary x y lo seex cre tio n w ith in that particu lar 5% range . O penco lum ns , w ard con tro ls ; b lack , v illage con tro ls ;s h a de d , t r o pi c a l s p r ue .

alth ough a few sp ru e patien ts had no rm al f atex cre tion and a few contro ls ex cre ted 6 g orm ore o f f at per day . T h e adu lts f rom thev illage M a are not inc lud ed in th is chart be -cau se f at in tak es d if f e red , so the resu lts arenot stric tly com parab le w ith those o f stu d iesconduc ted in the w ard . In another ep idem ico f sprue , sim ilar estim ation s o f f at ex cre tionw ere m ade w h ile the patien ts w ere liv ing athom e and consum ing the ir o rd inary d ie t;7 2% w ere f ound to hav e steato rrhea (31 ).

V itam in B 12 abso rp tio n in the patien ts w ithsprue and in th e w ard contro ls w as m easu red


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60

40

20

O Co n t r o l s# { 149 }p r u e .

c I Ii . . .6 0 4 5 22 26 30

S T O O L AT EXC S IT ION q / d o y

Fio. 4 . Patte rn o ftro ls and in patien tsFig . 3 .

f at ex cre tion in w ard con-w ith sprue . S y m bo ls as in

1 J c 0 T 1 1 0 %

1052 B A K E R A ND M A T H A N

4 ) and of h is to log ical appearances o f the je-junal b iops ies (T ab le 5) show sign if ican td i f f e r e n c e s be tw een th e s p r u e and w ard con-tro l g roups (P < 0 .00 1 and P < 0 .0005 , re -spectiv ely ). T he resu lts o f the barium m ealex am ination are com pared in T ab le 6 . T hetw o groups are sig n if ican tly d if f e ren t (P

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Tropical enteropathy and tropical sprue’