54 ~o}21:i1J- : All 8l':! All 1 ~ 2002';1 Vo l. 8. No. 1. June 2002

Hirschsprung's Disease~ {}~ {l B-

Differential Diagnosis of Hirschsprung's Disease

Soo-Young Yoo, M.D.

Department of Surgery, Yonsei University Wonju College of Medicine

Wonju, Korea

Hirschsprung's disease (Hn) is usually diagnosed in the newborn period and early infancy.

The common presentation of HD in newborns consists of a history of delayed passage of

meconium within the first 48 hours of life. The differential diagnosis in newborns is one of

the clinical challenges of this disorder . A number of medical conditions which cause

functional obstruction of the intestines are easily excluded. Neonates with meconium ileus, meconium plug syndrome, distal ileal atresia and low imperforate anus often present in a

manner similar to those with HD in the first few days of life. Abdominal radiographs may

help to diagnose complete obstruction such as intestinal atresia. Microcolon on contrast

enema can be shown in cases with total colonic aganglionosis, ileal atresia or meconium

ileus. Suction rectal biopsy or frozen section biopsy at operation is essential for differential diagnosis in such cases. HD is also considered in any child who has a history of constipation

regardless of age. Older children with functional constipation may have symptoms that

resemble those of HD and contrast enema is usually diagnostic. However, children with other

motility disorders generally referred to as chronic idiopathic intestinal pseudoobstruction

present with very similar symptoms and radiographic findings. These disorders are classified according to their histologic characteristics.; visceral myopathy, visceral neuropathy, in-

testinal neuronal dysplasia (IND) , hypoganglionosis, immature ganglia, internal sphincter

achalasia. Therefore, the workup for motility disorders should include rectal biopsy not only to confirm the presence of ganglion cells but also evaluate the other pathologic conditions. (J Kor Assoc Pediatr Surg 8(1):54-61), 2002.

Index Words: Hirschsprung's disease, Differential diagnosis, Motility disorder

AJ-Q.] {l~~A~]~ -¥-A~oJ] Q.]~ AJ--&-% AJ-0~£ ~J,~~~ IID~ J "6'--"J- ~~ 0] ll~q- qOJ=-o}oj t:J1 7~~ {l;.~0}1-J- %o}

7] oj] ~7,1~ A]1i!- ~~71] ;

I Delayed meconium passing I I l

I Mechanical obstructions l Functional obstructions I I T

• Meconium ileus • Prematurity • Meconium plug syndrome • Small left colon syndrome • Distal ileal or colonic atresia • Sepsis & electrolyte imbalance • Low imperforate anus • Intestinal neuronal dysplasia

• Achalasia of anal sphincter • Hypothyroidism

Fig . 1. Differntial diagmosis of Hirschsprung's disease in neonates.

Pi~ :~:!A%oJ1 A1 ~-3] {lA}AJ- {l~~AiL'V} ~A~ ~oJl s:. ~~

i5}Jl 7-J--8:-% 7-J- on7} 71t:11 ~7-J-% ~?ll w 7-js:.S!- {lztw ~-9-oJ]-c 01 oj] t:11 ~ {ltl~% ~{li5] Aji5}71 oiD1-8:- ~-9-7} t:11 lf-

{f°lq. rrj- c.}A1 o ] ~ ~~~ ~~ q OJi5}oj 7}Aj lID (pseu-

doHirschsprung's disease), ;,}).j ~l~Fj 7-J- 7H:llll] ~%

(chronic idiopathic intestinal pseudoobstuction; eIPS), 1(! % lID (variant lID), -~A lID (allied lID) .2i oJl s:. ~-3]~:jAJ

~).j % rrj-c.} 7-J-{l ~ tl!f1 ~ ).j ~-o~ (intestinal neuronal dys-

plasia; IND), {l7cl7-JAi] '±~~% (hypoganglionosis), o] ).j ~

{l ~ ~ (immature ganglia), 7-J-{l7cl ~ If-~ % (intestinal

dysganglionosis), l.·W~-Q.j:-2- ° 1 ~~~% (internal sphincter

achalasia), 7-J-{l ~ tl!f1 71 ~ (intestinal neuronal malfor-

mations) %~ ~~01 A}%~Jl 'U L}. ~QjAJ- lID~ ~~Zl

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~q.

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1111 ~% ~.2-~ 'T 'U -c ~ '?l.2-S!--c 311] 7111] ~ 7-J-llll ~ J!} 7]

55

Dysmotility Disorders (Chr. idiopathic intestinal pseudo-obstruction)

• Visceral myopathy ·Intest neuronal dysplasia • Visceral neuropathy • Hypoganglionosis • Drug~nduced • Immature ganglia • Chagas's disease · Int. sphincter achalasia

Fig. 2. Differntial diagmosis of Hirschsprung's disease in other age groups.

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(meconium ileus)~ ~ 7-J- wtllf-oJjAi Ejj 1(! oJl Qj ~ AJ-lll] ~ 01

~oit-J-u9 t:11 4'-{f0] l..-J-.±Aj --ilil-% (cystic fibrosis).Qj ~ ~

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conium plug syndrome)~ AJ-t~ ~ AJ-J!} :9il t~ ~7-J- If-!f1 oJl Ell

1(!0] ~} 'U-c ~:j% .!i!.0]u9 't.±).j --ilil-%J!} '?1:t!-).j~ ~~

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s:. i5}Jl ~7-J-.Qj e}t.1% ~OJ~ AJ- ~~7-J- (microcolon)Qj ~

Ejj~ %% .!i!.0171 rrJl~oJl %~7-J- .!j!-{l~7-J Ail.±%J!} ~i51 )}

~ % li ~ q. ~!f1lf- ~ AJ- .!j!-i?-% s:. %~ 7-J- .!j!-{l7cl ~ Ail'± %

J!} il-A}~ ~ Ejj ~ .!i!.°171 rrJl~ oJ] -3]7-J- ~-3] {lA}t-J- 7~ -l!},Al

'T~ ~:j ~-C ~7-J-~ ~-3] {lA}S!- ~~% lii5}ll] ~ u9 ~

%If- -'fi?-% %lfr~ 15J-~ 317-J- 71 ~Qj ~-9-s:. i5}lf- ~7-J-Qj

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S!- )}~01 %o] ~ ~ol q.

{l-,,~0} 71 01 ~Qj )}~ Zltl~ 71 111 ~ 7-J-llll~% .!i!.q-c

7-J-.Qj 71 ~~ -8:-% ~-on (dysmotility disorder)~ ~.2--1] -C ~

56

%%JJj-Qj {}~ ~li±o] ~xt}q (:::Lii:J 2). 7 ] .'g-~ ~% ~JoH

01] QjtH ~J}ijl~ '6'-AJol 1114i- ~ 78Jf- %-fJ'~~~ ~Acl ~~

J-cl 7Fcl ~J}ijl ~ '6'-4-r 0]c.J- ~~t}9 ~~L}8 ~~011-i::- 0]

%~ ~AH1~ ~ S£:-i::- ~eJ5:-3j~-3:j l:~~~ **t}9 ~~ t }il ~q?,l0

1. ~~ ~~ (degenrative disorders)

7r. tlJAJ- -2'op.J-%- (visceral myopathy) : Sfl ~H!- ~% ~Qj ~Acl011 QjtH ~~o] {l%5:-3j:& ~1i'!A1 ~'\~~-i::- ~~

~~ 0]C1~ ~%~ ~J-cl°l llJ%lJ}7.] {l~~ 78Jf- megacy-

stismicrocolon-intestinal hypoperistalsis synclrome~ ~~71

711 ~qll.

Y-. tJlAJ- {l~oP'J-%- (visceral neuropathy) : 1:J1 7H A}OJ 4- lJL:tJAJ ~~~-i::- ~~~~ l::&71-t!-Qj ~J~ {l78%

(myenteric plexus)Qj ~J-cl°] L}E.}L}-i::- [1112 {}~ q~Acl 1.-]1*

tll {l'\~% type 2 9-} '?:!-t!-~o1 L}E.}L}71s:. ~q.

q.. ~% 'it% : ~1i'!-'11A1N ~t}-'11 Qj Jlj-s:.~ 'J%~~ 1-H ~J ~~Acl°] i cJl~o1 ~'\~~q.

4. Chagas ~ ~ : Jf-eJ L}c.J-011 -i::- 0}-3j .!2..il'El tl} ~.2.. L} Try]Xll1osorna cruzi 011 7f}~ ~ 78 Jf- ~J~{l78 %Qj ~ ~ ~

i cJl t }9 :::L lJL*Qj 1JL*~ ~~J~ ~.2..71r9 ~J~% ~JoH~

2. ~% HD .9:e ~A~ HD HD9-} uH-9- %A}~ '15-AJ~ L}E.}1.-]11-} HD9-} q~ 1:1-& ::t.

-3j :tJAPJ {l781i A11.¥.-i::- ~AHt}~ ~J~~ol L} {l78% ::t.-3j

011 9 cl q~ ~ EllQj ~~~ L}E.}1.-]1 -i::- ~~%% ~~ HDIO

Table 1. Characteristics of Intestinal Neuronal Dysplasia

Type A Type B

Incidence < 5 % > 95%

Pathology Ganglion cells'+' Ganglion cells'+'

Increased AchE activity Increased AchE activity

Hypoplasia of sym. Hyperganglionosis innervation

Increase parasym. nerve fiber

Symptom Neonatal period

Obstruction

Diarrhea

Bloody stool

HD; Hirschsprung s disease

Giant ganglia

Similar with HD

Milder Sx

(Fadda et ai, 19835)

S£:-i::- %"'} HD13~ ~~t}il :::L ::t.-3j~~ ~AcJ011 u:j-ct ~7}

7.1 ~~~~ T*t}il ~q.

7t. AJ {l7f:l\1~ ~J-dAJ-()fl (IND) : IND-i::- 1971~

Meier-Ruge14011 QjtH ;iH- l:7H ~ ~~.2..~ ~cJ 5:-3j~~

l:~011 utc.J- Type A, B ~ ~* ~q 01 n IND~ ;illi.-c Jlj-71 HD9-} %"'}t}711 'T~~ ;iP17r ~xt}qil A~Zf~~~

L} ~~ .!i!.il011 ut.s1i'! INDQj 7f:lJf--i::- HD011 tll3Jl l A11 °l AJ

011"'1 ~li±~-i::- 78Jf-7} 50 % 01 AJ olil16,J7 '15-AJ ol H0011 tll'8'H 78 ul t}E..~ ~J {l 78::t.-3j %01 % [:1 Ad4i-~-i::- "']71lJ}7.1 'T~

% "'Pf~ ~X7} ~qil t}~q. Gillick %-&16 33oJl~ IND

%A}'15- 21oJl(64%)7r 'T~ ~ol ~]%~ ~qil .!i!.ilt}~q. 1-}. {l7f:l1i 1JL~%- : {l781iA11 .¥.7} ~AH'O}~ :::L 'T7} {}

l:~o1 ~qE-Al S£:-i::- ulAcJ4i- {l781i A11 '¥'7} L}E.}L}-i::- 78Jf-

%01]"'1 HD9-} %",}~ %-AJO] L}E.}'€t 'T ~q. q.. 1.-]1~~-2' °l~~:og.%- : 5:-3j~~~~-i::- ~l:{l:&~

(nitregeric) {l7f:l ~ {j 0 1 ~.2..1i'!"'1 tJ-lf--3j AJ~ 11l~AJ ~!A~

1.-]1 ~~~ °1~01

~, iH!~ %Qj qOJ~ '?lA}%O] -l!}~~.2-S'- ~%-o]-Y- ~;:;

::r ~'?l% ~~-o] '?l y 'ict 'c ~1flAcl ~1:I ] ~0] 7}AJ- ~~ t;:l EHO]q. HD9.\- ~Acl 1(11:1] ~Qj O,:P'J-~ ~Acl-€:- K 2'4 ~-c}.

4) 7~~ Ail~ (interstitial cells of Caial : ICC)2~

~~~ M ~~ MOH ICC'c -'fVJ-{l-Qj IiJ~24101] ~An-o}o:j AJ- '?1%~%% {l-AJ-

-o}'c -?;I~S'- ~?jA~ *~y-19-21 1992\1 Maeda %22 01] QjtH

ICC7} C-Kit immunoreactivity~ L-j·E}';!!C}'c -?;I 0] ~?jtl

0] 4-S'- 0]01] {l-~ '?:! T7} ~1fl-o] tlt~£] oj*~o:j :1]2 AJ-~

% 7.J-°n~ ~~7']'c ~~%Qj ~-¥-7} 0] A~1 ~Qj o]AJ-01] QjtH ::tiQl'8.qJl ~JlS1Jl ~q (1f. 3)13,23-30

~Acl 1(11:1] EE'c £\11(1 tlH~Qj ;z]~, -l!}-¥- ll§uJ %Q) HD ~AJ

% L-}E}1-H'c ~;z}01]Ai 7}AJ- ~1l71] tll -ft y ~'c ~~ tll(!-llHl -€:- .6j:AJ- yA] {jA}S'- yA] {jA}AJ .6jAJ41 -l:t1(1Q) ~A]

~-¥-9} .6j7.JQ) ll§r1l ~-¥- % ~S'- HDQ) 7}'6- Acl% E}~tll -ft Y ~rl {)),~o}Qj ~i'-'c s:.{}% iiJ~01\ 1l-0Ji;}~ AJOJA\

:AJ- 0 1l 7} ~'c ~i'-'c iiJ-~ ~3} o]y- .6jAJ- 4'--tt~Q) 7}'6- Acl % A~ZftH -ft y ~Jl s:.{l-% *-l:t-o] ~'iJ4-s:. 5:-{l- ~t:Pf-01] -l:t1(10] %oj A~ y-~A] ?J-% ~-1'-'c 7]1l]~ :AJ- lfj]~~o]y- HD

~ Qj{Jtll -ft y ~lq. HD l1l~0 ] fJ- -€:- ~o]oJl ;:;-~£\oj ~ % ~-1'-01] 'c 15J-~ ~{l-o]y- y A] l,:lA}},] -l:t1(1 x} -tt7]7} ~~

0] -l:t~S1 oj Y-~1?1 Ai -l!}-¥- ll§J?!-0] :§:1\ S1715:- -o}E-S'- ~~

57

tll(!-oJ1 5:-%% Y'c 5::;:! 01 c1-. c1-% l(!-1l1oJ)Ai A 1 t~ ~ Y ~ 'c {jAt'c ~A}~ -l!}9}-'f1 S'- ~Jl ft l;J}-¥-~ %c:j ~~ AJ-EN

)'1 ~-l!}-¥- l(!-~ ~Oa% A1'i;~-o} o-~ .6j7.J- ~ S A} ~:AJ-Q) -tt71

%oa_~S'- 0 ] t~ -¥--'f1 7}

58

Fig. 3. Diffemtial diagmosis of Hirschsprungs Disease in patients with microcolon. A. Case 1 (total intestinal aganglionosis, 5day-old female). The barium study shows microcolon (A-1) and transition zone was not found at operation (A-2). Neither ganglion cells nor nerve plexus are present in the entire small and large intestines. B. Case 2 (ileal atresia, 2 day-old male): The barium study shows microcolon similar to case 1 (B-1) and the operative finding shows ileal atresia type III-a(B-2). C. Case 3 (total colonic aganglionosis: 3day-old female): Microcolon is seen in the contrast study (C-1) and ganglion cells are absent in entire colon and the transition zone is shown in the terminal ileum (C-2). D. Case 4 (meconium obstruction without cystic fibrosis: 2day-old male): The contrast study shows microcolon (0-1) and ganglion cells are present in the colon. The terminal ileum is filled with sticky meconium (0-2).

Fig. 4. Differntial diagmosis of Hirschsprungs Disease in patients with transition zone in the sigmoid colon at contrast study. E. Case 5 (rectosigmoid aganglionsis: 15day-old male) : The barium study shows transition zone in the sigmoid colon (E-1) which is grossly identified at operation field (E-2). F. Case 6 (Meconium obstruction: 11-day old female): The contrast study shows a similar finding with the Case 5 (F-1). Grossly, the transition area is seen in the terminal ileum (F-2, arrow) was confirmed by frozen section biopsy and C-kit+ cells are not seen in the colon at ileostmy time. C-kit immunoreactivity (F-3b, arrow; red stained area) appears 83 days later at the time of ileostomy closure.

Fig . 5. Differntial diagmosis of Hirschsprungs Disease in patients with segmental dilatation of colon . G. Case 7 (total colonic aganglionosis: 5-day old female): The contrast study shows segmental dilatation of transverse colon (G-2). However, ganglion cells are absent in entire colon. H. Case 8 (segmental dilatation of transeverse colon: 15-month old male): The contrast material is not passed through the dilated segment of transeverse colon (H-1) and operative finding shows isolated segmental dilatation of transeverse colon (H-2). Ganglion cells are present in the colon including the dilated segment.

T %A}~~Y. -T~4- ~Bol AJolt}111 l..-}.2_:C 78.q-~01 % % ~q . ..::rt(:l 3A-D:c {l )'~0}011Ai CdAJ %AJ ~ tl}c1% ::t.

OJ~AJ l:~~JQ] %AH!' l:7,j% ~;i;(~y. 7fl*~ Al t~ 4- ~

B~ol Ai~ qiO..l1] y.,g- 78.q-~~ ~?1] 1 (..::rt(:l 3A-l,2).g.

~AJ ~'il 0}L1c1- l:~J ~~~]oJl ~~ -¥-{l78~ ),il.¥.~~ ~7Jl]

~JLJ1 ~AJt-~ %~t- A}olQ] {l78% :E~' ~~ ~~~Oi ~

Al ?io} LJ1 ~J {l7801AJ~01 %~ ¥! HD ~ ).~Z{~~~u:j ~

o}:c ~AJ ::t.if-~ Alt~4- 40~ ~011 ~1* ~7}~~~ {l-Aa£l

Oi ~~t};i;(q. %?1] 2 (..::rt(:l 3B-l,2):c -T~ l:7,jAJ §l~J -¥-~~ (Type III-a)~~ ~l(l'~~Jl ~?1] 3 (..::rt(:l 3C-l ,2).g.

-T~ l:7,jAJ ~~~ E11I(! Aa ~Jlljl~ ~Q] l:7,j% y.Ej-LJ1~~y.

L-J.¥.).j Jclit~~:c -¥-t}t};i;(Jl ~~} §lAJ::t.if-~ Alt~Al ~~J

::t.~ 7d AVJ {l78~ )'i].¥.:C ~:Afl~ ~Tt!011 ~J ~%-8:-%% ::t.

~t}:c 7}~),i].¥.:C l..-}Ej-y.Al ?i~q. §l~J ::t.if- *~~.g. ~

!fi-¥- ~Jt}Q] t}AJ% IT?,]~~~Alt~t}erj ~J -8:-%01 AaAJ~~ s- §l*~~% uJ1~ ).~ 4- 87~01] Alt~t};i;(~u:j ..::r uJ1 Alt~

~ ::t.~ ~A} ~~:c 7}~),i].¥.Q] AaAJ~~ ~.¥.% y.Ej-1-B~

59

cj'. ~?1] 4 (..::rt(:l 3D-l,2):c ~AJ ~~~191- ~P'J '?J'B-¥-01] -¥-{l

78~ ),i].¥.~ol ~)~1{i HD~~s- ~~} ~l~J ::t.if-~ Alt~4-

).~4- 47H~~n I(!~ Martin ~~01 Alt~~~ct. Jt(:l 4E, F:c

{l),~OHAi *-¥- ll~'il ~ [HI(! l:IH~ A]~O] 'V.Oi tl}2-]% ::t. °8 ~ A]t~ ~~ ~ojl .2.~ S-7.} ~AJ011 °ltE -¥-!fi~ ~:c I-ID~ ).~Z{sq~~y. %?11 5 (Jt(:l 4E-l,2):c S-7.} ~~J01I 01

t~-¥-!fi% ~:c ~~~ HD~ ~B¥! ~Tt!01] ~?1] 6 (Jt(:l

4F- l,2,3) .g. A}~oj] Q]{l~~1{i olt~-¥-!fi:c -T~ ~~VJ ~

% -T ~~~u:j ~lAJ 9lB-¥-011 °lt~-¥-~l~HJ y.Ej-lJ -¥-!fi7}

~~~y. %~~l{1 7d A}AJ ~~J ~ §l~J01] {l78~ ).i] .¥.7} ~

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).~ 4- 94~;Y:H §l~J- ::t.if- *~~01 Alt~~~J:}. ~7.}:C QcjAl

\l-.¥.).a 1l*~~:c -¥-t}t};i;(~u:j %?1] 3~ p}{}7}7.]~ §l~J

::t.if-~ Alt~Al 7}~ ).il.¥.7} ~{l~Oi ~~~y. (Jt(:l 4F-3a)

*~~ A]t~A]:C 7}~ ).i] .¥.Q] ~.¥.7} Aj).J% y.Ej-LJ1~~u:j

(Jt(:l 4F-3b) -T~4- ~J-8:-%S=- A,PJ% y.Ej-LJ1~q. Jt(:l

5G,H:c tl}c1% ::t.°8~ AJ §dt~ ~~J01] °lt~-¥-!fi7} 'V.:C HD

s- ).~Z{~~1{i %?1] ~s- ~?1] 7 (Jt(:l 5G-1,2).g. -T~AHs:.

~"'E~AJoJl 0ltE-¥-!fi7} ~):c ~~.£ ).~z)-£l~~l+ -T~).l %

~AJl{1 ::t.~ ~AVJ %?,PJQ] -¥-{l78~).il.¥.~~~ §l~J::t.-'f

~o] Alt~£mJl ~?1] 8 (Jt(:l 5H-1,2).g. §dtE ~AJQj ~~

.~~~~ -¥-~~~~ ~'4- ~~~ ~~~~~ Jt(:l 6I-KQj ).i] ~?1]:c Z{Z{ 9).il, 7).il, lO).il¥! 'J0}~ 'il).j I(!tl]

~ ~ *-¥- ~'il0l ~Oi LJ1~t};i;(~u:j tl}c1% ::t.OJ~AJ .2.~

7ltJ1 ~AJO] {l~ HD~ ).~Z{t};i;(~y. %?1] 9 (Jt(:l 61-1,2) 'il S-7.} ~~Jojl °lt~-¥-!fi7} ~:c ~~~ HD ;i;(Jl ~?1] 10

(Jt(:l 6J-1,2).g. ~ t~~~JQj ~J%*~om~u:j ~?11 11 (Jt(:l

6Kl,2,3).g. J:l:lc1 ::t.~~~ l:7,jAJ {l78~ ).i].¥.:C ~:AHt}~ ~J

Qj t-% tl}~~ ~~ ° 1l: {l78 ~ (ectopic ganglia)Qj l:7,j ~

~7Jll {l78% tll4- ~ achtylcholine esterase activity Qj ~7}

l:7,j0l ~Oi IND~ ~B ~~q.

HD:c l:0}Ql Oi ~ ~ ~ %01Vi y. y.Ej-\t -T ~Jl tJ1-¥-~ .g. -T~~ %olt}l1] ~B£l:c 't1°1y. !fiQ] 78.q-~~ ~01 7H

*~ Al t~4-011 -T~ l:7,j0ly. ::t.~~~ l:7,jojl QjiiH ~B LJ1

aj7.1:C -T7} %% ~)~E.~ -T~~ ~~J ::t.~ 7d A}7} Al t~~

A] ?i.g. 78 .q-c1-Tt! -T~Al 01 t~-¥-!fi % *~~~ .~ ~ -T ~ q t}1:1c1-S=- ~£Al %~~'t1 ::t.~ ~A}% Alt~t}erj {l78~

)'i] .¥.Q] ~)\H it-¥-% .~iiHoF ~J:}. :E~ {l78 ~ ),il.¥.7} ~

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,B,i5}u:j itA} HDQl 7}~).cl% Jlaji5}erj achtylcholine esterase

60

Fig. 6. Differntial diagmosis of Hirschsprungs Disease in patients with huge megacolon. I. Case 9 (HD with short segment: 9-year old male): The contrast study shows huge megacolon (1-1) and operative findging shows the same picture (1-2). Ganglion cells are not present in the distal narrowed segment. J. Case 10 (colon dupication: 7-year old male): the contrast study shows huge megacolon ad distal marrowing segment (J-1). The distended loop is duplicated transverse colon (J-2, arrow). K. Case 11 (intestinal neuronal dysplasia: 10-year old male): The contrst study shows distened colon without definite transition zone (K-1) and operative finding shows markedly distended colon (K-2). Microscopically, ganglion cells are present with hyperplasia of nerve plexus (K-3a, arrow), ectopic ganglia (K-3b, arrow) and increased acetylcholine esterase activity (K-3c).

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