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Gastrointestinal disturbances in patients with autistic spectrum disorders

problemy gastroenterologiczne pacjentów z zaburzeniami ze spektrum autyzmu

Beata Kazek

1

, Ewa Jamroz

2

, Urszula Grzybowska-Chlebowczyk

2

, Maciej Kajor

3

,

Monika Ciupińska-Kajor

3

, Halina Woś

2

1Klinika Pediatrii i Neurologii Wieku Rozwojowego 2Klinika Pediatrii

3Katedra Morfologii, Zakład Histopatologii

Śląski Uniwersytet Medyczny, Katowice

ABSTRACT

Gastrointestinal problems occur in patients with Autistic Spec-trum Disorders (ASD) more often than in their peers without developmental problems. The most prevalent include abdomi-nal pain, impaired peristaltic reflexes and eating disorders. The study objective was to determine the incidence of gastrointes-tinal disorders in ASD children with gastrointesgastrointes-tinal complaints. Methods: 30 patients with ASD suffering from gastrointestinal complaints were analyzed. Results: All the children had upper gastrointestinal tract endoscopy and four of them colonos-copy. The nutritional condition was normal in 60% of them, 17% displayed malnutrition and 23% were overweight. Chronic abdominal pain was observed in 80% of patients. Impairment in peristaltic reflexes was noted in almost all autistic children. Histopathology of the duodenum revealed changes in 70% of cases. Colitis chronica indeterminata was recognized in all examined children. Conclusions: Autistic children with trointestinal disturbances should be looked after also by a gas-troenterologist. Higher incidence of gastrointestinal pathologies in ASD may have influence on the behavioral patterns of these sufferers.

Key words: Autistic Spectrum Disorders, chronic abdominal pain, chronic inflammation of duodenum, colitis chronica inde-terminata.

STRESZCZENIE

Problemy gastroeneterologiczne dzieci z zaburzeniami spek-trum autyzmu (ASD) występują częściej niż u ich rówieśników. Do najczęstszych należą bóle brzucha, zaburzenia motoryki w obrębie przewodu pokarmowego, problemy żywieniowe. Celem badania było określenie częstości występowania schorzeń gastroenterologicznych u pacjentów ASD zgłaszających dolegli-wości ze strony przewodu pokarmowego. Pacjenci i metoda: przeanalizowano 30 pacjentów ze zdiagnozowanymi zaburze-niami ze spektrum zaburzeń autystycznych u których wystę-powały istotne dolegliwości gastroenterologiczne. Wyniki: U wszystkich badanych pacjentów stwierdzono wskazania do endoskopii górnego odcinka przewodu pokarmowego, ponadto u czterech z nich do kolonoskopii. U 60% stwierdzono prawid-łowy stopień odżywienia, 17% pacjentów z grupy badanej było niedożywionych, natomiast 23% z nadwagą lub otyłych. Przewlekłe bóle brzucha obserwowano u 80 % z nich. U prawie wszystkich pacjentów z zaburzeniami autystycznymi stwier-dzono zaburzenia motoryki w obrębie przewodu pokarmowego. U 70 % pacjentów badanie histopatologiczne wycinka błony śluzowej dwunastnicy uwidoczniło zmiany zapalne, natomiast u dzieci, u których wykonano kolonoskopię, badanie histopatolo-giczne wykazało nieswoiste zapalenie jelita grubego. Wnioski: Pacjenci z ASD, u których występują dolegliwości ze strony przewodu pokarmowego, powinni być konsultowani gastroen-terologicznie. Występowanie zaburzeń gastroenterologicznych może predysponować do nasilania zaburzeń zachowania. Słowa kluczowe: zaburzenia spektrum autyzmu, przewlekłe bóle brzucha, przewlekłe zapalenie dwunastnicy, nieswoiste zapalenie jelita grubego.

According to ICD – 10 Au��sm belo�gs �o a group of

per-vas�ve developme��al d�sorders. �ymp�oms occur before 3 years of age a�d co�s�s� of ab�ormal fu�c��o� �� �hree spheres of developme��: soc�al ���erac��o�, commu��ca-��o� behav�oral pa��er�s, a�d ���eres�s. If ab�ormal a�d/or �mpa�red developme�� �s exh�b��ed pas� �he age of 3yrs, a�d/ or �f symp�oms co�cer���g o�e or �wo of �he areas �ecessary �o recog���e ��fa���le au��sm are m�ss��g, A�yp�cal Au��sm �s d�ag�osed. �o�h I�fa���le Au��sm �IA� a�d A�yp�cal Au��sm

�AA� are referred �o as Au��s��c �pec�rum D�sorders �A�Ds�. The ra�ge of d�sab�l���es see� amo�g ch�ldre� �� A�D �s co�s�derable. A�Ds do �o� have a�y e��olog�cal fac�or �� commo�. A hered��ary bas�s �s suppor�ed �� ma�y cases by a h�gh co�corda�ce �� mo�o�ygo��c �w��s, a broader au��s��c phe�o�ype �� �he fam�l�es of proba�ds a�d assoc�a��o� w��h a �umber of ge�e��c d�sorders. I� A�Ds pa��e��s ab�ormal levels of �euro�ra�sm���ers have bee� observed, ��clud��g gamma-am��obu�yr�c ac�d, op�a�es, glu�am��e ac�d a�d

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ca�-echolam��es. The co�cep� of d�sorders �� sero�o�erg�c �ra�s-m�ss�o� �s �he mos� prevale�� a�d bes� ��ves��ga�ed; pla�ele� hypersero�o�em�a has bee� de�ec�ed �� 25-60% of au��s��c ch�ldre� [1].1].

The ��c�de�ce �s es��ma�ed a� 7 per 10,000 ch�ldre�, a�d 20 per 10,000 for A�yp�cal Au��sm [2]. Accord��g �o The U�A Depar�me�� of Heal�h a�d Huma� �erv�ces Ce�-�ers for D�sease Co��rol a�d �reve���o� �he average A�D prevale�ce was abou� 1 �� 150 ch�ldre� �� some commu-����es [3].

�es�des �he ma�� ab�ormal���es, au��s��c ch�ldre� d�s-play �umerous �europhys�olog�cal d�sorders – �� recep��o� of se�sor�c s��mul�, mo�or ac��v��y pla����g, a�d c�rcad�a� rhy�hm regula��o�. Over �he las� years a��e���o� has bee� pa�d �o �he h�gher ��c�de�ce of gas�ro���es���al problems �� au��s��c ch�ldre� compared �o �ha� of �he heal�hy ch�ld popula��o�. The mos� prevale�� ��clude abdom��al pa��, �mpa�red per�s�al��c reflexes a�d ea���g d�sorders [4–9].

The Study Objective was to determine the incidence

of gas�ro���es���al d�sorders �� A�D ch�ldre� w��h gas�ro-intestinal complaints and undertake to link them with pat-hology observed �� e�doscop�c exam��a��o�s.

pATIENTS AND METHOD

Dur��g las� 6 years we hosp��al��ed 30 pa��e��s: �yp�cal au��sm �17 ch�ldre�� or au��s��c fea�ures �13 ch�ldre��, all suffer��g from gas�ro���es���al compla���s such as abdom�-�al pa��, �mpa�red per�sabdom�-�al��c reflexes a�d/or bleed��g; 4 of �he ch�ldre� had already had surg�cal ���erve���o� for al�-me��ary �rac� problems.

The pa��e��s were aged 3yrs up �o 13yrs �mea�: 7 years 6 mo��hs�; �here were 12 g�rls �40%� a�d 18 boys �60%�. I� �he ch�ldre�, subjec� �o �he s�udy, ��fec��o�s were exclu-ded, �based o� phys�cal exam��a��o� a�d b�ochem�cal para-me�ers of ��flamma�ory co�d���o�s�, a�d so were orga��c cha�ges w��h�� �he abdom��al cav��y �ul�rasou�d�. The�r phys�cal developme�� was assessed accord��g �o Cole’s ��dex. D�ag�os��c �mmu�olog�cal �es�s for �he prese�ce of cel�ac d�sease were performed �EmA a�d �TG� �� IgA class, or IgG class �� �he case of IgA def�c�e�cy. The ch�ldre� with atopic dermatitis underwent tests for the presence of food allergy �v�a ���erv�ew, �o�al IgE, spec�f�c IgE�.

All �he ch�ldre� had upper GI �rac� e�doscopy perfor-med, a�d 4 of �hem �� add���o� �o �ha�, colo�oscopy. H�s�o-log�cal evalua��o� of all �he b�op�a�es was performed by �he same h�s�opa�holog�s�. A� �he ��me of �he ��ves��ga��o�s 4 ch�ldre� were par�ak��g �� a low glu�e� a�d m�lk-free d�e�.

RESULTS

The �u�r���o�al co�d���o� was �ormal �� 18 �60%� of �he s�u-d�ed ch�ldre�; 5 �17%� d�splayed mal�u�r���o� a�d 7 �23%� were overwe�gh�. Chro��c abdom��al pa�� was observed �� 24 �80%� pa��e��s a�d was mos� freque��ly loca�ed ���ra-abdom��ally. Impa�rme�� �� per�s�al��c reflexes was �o�ed �� 29 �97%� of �he au��s��c ch�ldre� d�ag�osed �� our hosp��al - �� 17 �57%� cases �� �ook �he form of d�arrhea a�d 20 �67%� suffered from co�s��pa��o�; some had al�er�a���g bou�s of d�arrhea a�d co�s��pa��o�. Vom����g a�d/or regurg��a��o�

were repor�ed by 10 �33%� pare��s of �he ch�ldre�. �leed��g ep�sodes from �he gas�ro���es���al sys�em were repor�ed by pare��s �� 6 �20%� cases: 2 from �he upper a�d �he rema-����g 4 from �he lower GI �rac� ��o�e of �he ch�ldre� was brough� �o hosp��al as a� emerge�cy�. I� 23 �77%� cases occurred sudde� �rr��ab�l��y ep�sodes, �� 19 �63%� ea���g d�sorders, a�d �� 12 �40%� cases ch�ldre� refused �o ea� for several days. Moreover, 4 ch�ldre� had prev�ously u�der-go�e surg�cal procedures affec���g �he al�me��ary �rac�: 2 had had a surg�cal a���-reflux procedure, 1 a procedure due �o H�rschspru�g’s d�sease, a�d 1 ow��g �o a relapse of �he rectal mucosa.

The med�cal h�s�or�es of 14 �47%� ch�ldre� revealed symp�oms of a�op�c derma����s, a� �he ��me of �he s�udy �h�s was observed �� 11 �37%� pa��e��s. F�ve ch�ldre� ma��fe-s�ed eleva�ed co�ce��ra��o�s of �o�al serum IgE �121 – 2000 IU/ml� a�d 4 �he prese�ce of spec�f�c IgE a���bod�es ��� 2 cases aga��s� cow’s m�lk pro�e��, 2 aga��s� soya pro�e�� a�d 1 aga��s� egg pro�e���. The prese�ce of au�o-�mmu-�olog�cal d�sorders was �o�ed �� �he fam�ly h�s�or�es of 7 patients.

I� was o�ly �� o�e case �ha� a� �mmu�olog�cal �es� for cel�ac d�sease showed eleva�ed �TG levels w��h �ega-��ve e�domys�al a���bod�es a�d a� ab�ormal h�s�olog�cal picture of the duodenal mucosa (chronic duodenitis with a modera�e degree of lymphocy��c a�d plasma��c ��flam-ma�ory ��f�l�ra��o� �� lam��a propr�a, accompa��ed by �ormal arch��ec�o��cs of ���es���al v�ll� a�d Marsh’s ��dex a� 12/100�.

As ma�y as 10 �33%� pa��e��s �� �ur� were fou�d �o have IgA def�c�e�cy. I� �o ch�ld d�d we f��d a pa�holog�cal co�d���o� of �he l�ver or pa�creas.

E�doscop�c exam��a��o�s of �he upper GI �rac� revealed macroscop�c cha�ges �� �he form of mucosal redde���g �� �he lower esophagus of 4 �13%� ch�ldre�, LA eros�o� �ype A �7-8 mm� �� 1 ch�ld, ��flamma��o� w��h�� �he lowes� �h�rd of �he esophagus w��h �he prese�ce of �umerous “scu�es” �� ye� a�o�her ch�ld; �� 1 pa��e�� ��compe�e�ce of �he card�ac or�f�ce was observed. However, w��h �he excep��o� of �wo cases where eos��oph�l ��f�l�ra��o� was de�ec�ed, �he ou�co-mes of h�s�olog�cal �es�s of �ake� b�op�a�es were �ormal.

Four 4 �13%� ch�ldre� w��h a co�f�rmed Hel�cobac�er �ylor� ��fec��o� exh�b��ed �odules of �he mucous memb-ra�e �� �he a��rum of �he s�omach. I� 2 pa��e��s �rregular mucosal redde���g was d�scovered �� �he same area; ye� a�o�her pa��e�� d�splayed h�s�opa�holog�cal fea�ures of chro��c superf�c�al ��flamma��o�. I� �o�e of �he s�ud�ed ch�ldre� d�d macroscop�c exam��a��o� of �he desce�d��g duode�um reveal a�y cha�ges. However, �� 21 �70%� cases m�croscop�c h�s�opa�holog�cal cha�ges were fou�d �� �he form of chronic inflammation of the mucous membrane. Th�s �umber ��cludes 12 �40%� cases of m�ld eos��oph�l�c ��f�l�ra��o� �Grade 0 accord��g �o �he scale of Wh����g�o��, 2 cases of lymphocy��c a�d plasma��c ��f�l�ra��o�, a�d 1 of eos��oph�l�c duode����s �Wh����g�o� Grade III� w��h �o fea�ures of v�llous a�rophy.

�l�gh� d�sorders �� �he arch��ec�o��cs of �he v�ll�, �� �he form of �he�r bases be��g w�der were observed �� 3 pa��e��s. Chronic inflammation of the mucous membrane with an

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��creased �umber of ���raep��hel�al lymphocy�es was recog���ed �� b�op�a�es of 5 �17%� ch�ldre�. Two pa��e��s prese��ed 40/100 e��erocy�es w��h �ormal arch��ec�o��cs of �he v�ll� a�d he�gh�s of �he cryp�s �Marsh I�; 4 ch�ldre� w��h pa�� �� �he hypogas�r�um, 2 of whom w��h bleed��g u�de-rwe�� colo�oscopy. I� a macroscop�c assessme�� 1 pa��e�� d�splayed decreased vascular mark��gs; h�s�olog�cally, however, m�ld col���s chro��ca ��de�erm��a�a was recog��-zed in all of the children.

DISCUSSION

Gas�ro���es���al compla���s co�s���u�e o�e of �he mos� commo� co�d���o�s of �he developme��al per�od of , so called, a heal�hy ch�ld. Abdom��al pa�� �s a��ually repor�ed eve� by 44% of ch�ldre�; o� a weekly bas�s �� �s a prob-lem of 17% [10]. Arou�d 50% of �he �umber compla��ed about a chronic character of the ailment. Chronic functional abdom��al pa�� �s �o�ed �� 20-25%. Accord��g �o Campo e� al. 80% of �he developme��al age pa��e��s w��h chro��c fu�-c��o�al abdom��al pa�� are fou�d �o have �euro��c d�sorders, whereas 43% suffer from depress�o� [11].

Over �he las� years researchers have focused o� a grea-�er ��c�de�ce of GI �rac� pa�holog�es �� ch�ldre� w��h deve-lopme��al problems, ma��ly from �he group of Au��s��c �pec�rum D�sorders �A�Ds�, compared �o �he popula��o� of heal�hy ch�ldre�. �ome au��s��c ch�ldre� may d�splay fea�ures of hyperac��v��y, co�ce��ra��o� d�ff�cul�y, affec-��ve d�sorders, sleep��g d�sorders ��clud��g ��gh���me awa-ke���g, sudde� �rr��ab�l��y ep�sodes, a�x�e�y, aggress�o�, a�orex�c reac��o�s a�d, f��ally, ea���g d�sorders wh�ch are commo�ly bu� erro�eously �rea�ed as a compo�e�� of au��s��c sy�drome. Accord��g �o �he already co�duc�ed observa��o�s a�d s�ud�es all �hese d�sorders may mask �he discomfort of an autistic child. Because of disturbances a�d d�ff�cul��es �� verbal commu��ca��o� w��h �h�s �ype of pa��e��, gas�ro���es���al symp�oms ca� rema�� u�recog-���ed a�d may, �� �ur�, exacerba�e behav�oral d�sorders. The vas� major��y of �he pa��e��s �80%� suffer from chro��c abdom��al pa��. O�ly a few of �hem are able �o repor� �he compla��� spo��a�eously, �� mos� cases �he ��forma��o� �s ga��ed by �he pare��s whe� observ��g �he ch�ld.

I� our s�udy ea���g d�sorders were repor�ed by 63% of �he pare��s; 1/3 of �he pa��e��s refused �o �ake food over several days. The l��era�ure sugges�s �ha� feed��g problems co�cer� as ma�y as 46–89 % fam�l�es w��h au��s��c ch�l-dre�. A �umber of reaso�s have bee� sugges�ed for �he prevale�ce of �u�r���o�al problems �� pa��e��s w��h A�D. Whe� we �h��k abou� fear of �ovel�y, se�sory �mpa�rme��s or co�ce��ra��o� o� de�a�l, we ca��o� forge� abou� b�olog�-cal food ���olera�ce [12,13]. I� mos� cases pa��e��s selec� food o� �he�r ow�, wh�ch may resul� �� co�d���o�s of def�-c�e�cy. Desp��e poss�ble d�ff�cul��es, phys�cal developme�� of most studied children was normal and malnutrition was observed less freque��ly �ha� a �e�de�cy for overwe�gh� or obes��y.

�roblems of �he d�ges��ve sys�em were demo�s�ra�ed by all �he s�ud�ed ch�ldre� a�d were �he ��d�ca��o� �ha� �he �es�s should be performed. Almos� all �he ch�ldre� �96%� were fou�d �o suffer from �mpa�red per�s�al��c reflexes, a

d�sorder ma��fes�ed by regurg��a��o�/vom����g, d�arrhea, co�s��pa��o�, or �hese symp�oms occurr��g al�er�a�ely. I� 1/3 of �he pa��e��s d�sorders had �he form of regurg��a��o� a�d vom����g, sugges���g gas�ro-esophageal reflux. ���ce the patients could not co-operate the incidence of these co�d���o�s was �o� assessed by mea�s of pH-me�ry. E�do-scop�c exam��a��o�s, �� �ur�, revealed macroE�do-scop�c fea�u-res of esophag���s �� 6 �20%� ch�ldre�. H�s�olog�cal �es�s d�d �o� co�f�rm �h�s pa�hology; however, med�cal h�s�or�es show �ha� 2 �7%� ch�ldre� had u�dergo�e a� a���reflux pro-cedure �� �he�r ��fa�cy, a�d �� �he�r cases e�doscopy d�d �o� reveal a�y cha�ges. I� s�ud�es by o�her au�hors gas�ro-esophageal reflux was de�ec�ed more freque��ly �Howard e� al� [3]. Macroscop�c cha�ges of �he gas�r�c mucosa were d�scovered �� 6 �20%� ch�ldre�; �� 4 of �hese cases Hel�co-bac�er �ylor� ��fec��o� was recog���ed �wh�ch correspo�ds w��h �he popula��o� freque�cy� a�d �� a fur�her 2 we o�ly observed �rregular mucosal redde���g of �he a��rum �1 of �hese pa��e��s: prese����g s��gle pe�ech�ae, chro��c super-f�c�al gas�r���s was h�s�olog�cally recog���ed�.

E�doscopy d�d �o� de�ec� macroscop�c cha�ges �� �he duode�um, ye� �� 21 �70%� pa��e��s chro��c ��flamma��o� of �he duode�al mucosa was fou�d �� h�s�olog�cal �es�s. Twelve 12 �40%� ch�ldre� were d�ag�osed w��h chro��c duode����s w��h eos��oph�l ��f�l�ra��o� assessed as Grade 0 accord��g �o �he scale of Wh����g�o�, bu� poss�bly sug-ges���g food allergy. Eos��oph�l�c duode����s was recog��-�ed �� 1 pa��e��. The pare��s of 18 �60%� ch�ldre� reporrecog��-�ed symp�oms of food allergy, a�d 11 �37%� pa��e��s prese��ed fea�ures of a�op�c derma����s whe� �� hosp��al, �� 1 case accompa��ed by polle� allergy. H�gh �o�al serum IgE co�-ce��ra��o�s fou�d �� 5 �17%� ch�ldre� may ��d�ca�e IgE-depe�de�� allergy. Trajkovsk� e� al. has fou�d s�g��f�ca��ly h�gher levels of �o�al IgE, a�d also spec�f�c IgE, IgG a�d IgM a���bod�es �o food a���ge�s �� A�D pa��e��s [14]. �uch a h�gh ��c�de�ce of food allergy may be co��ec�ed w��h �o�al IgA def�c�e�cy: �o�ed �� our s�udy a�d k�ow� �o occur in autistic children much more often than in the rest of the popula��o� [15]. Accord��g �o M��g e� al. �� A�D pa��e��’s food ���olera�ce �s markedly assoc�a�ed w��h gas�ro���es��-�al dysfu�c��o� [16].

Al�hough �hus far �he collec�ed ev�de�ce does �o� a��es� �he co��ec��o� be�wee� au��sm a�d cel�ac d�sease, �� v�ew of ��creas��gly freque�� occurre�ces of ol�gosymp�oma��c, a�yp�cal or la�e�� forms of �he la��er, we co�duc�ed all �he d�ag�os��c �es�s �ecessary for ��s recog����o� bo�h �mmu�o-log�cal a�d h�s�o�mmu�o-log�cal o�es. The prese�ce of a���-�TG IgA a���bod�es was o�ly �o�ed �� o�e g�rl w��h �ormal arch�-�ec�o��cs of ���es���al v�ll� a�d sl�gh�ly eleva�ed �umber of ���raep��hel�al lymphocy�es. A la�e�� form of cel�ac d�sease ca� be co�s�dered �� her case; co�seque��ly, sys�ema��c observa��o� for �h�s d�sease �s recomme�ded. I�creased �umbers of ���raep��hel�al lymphocy�es �ha� are �o� jo��ed w��h �he �mmu�olog�cal ��d�ca�ors of cel�ac d�sease, a co�-d���o� fou�d �� 16% of �he pa��e��s, may sugges� a d�ffere�� �ype of pa�hology w��h�� �he ���es���es.

D�sorders of �he lower GI �rac� ma��fes�ed by pa�� �� �h�s area or co�s��pa��o� were observed �� 2/3 of �he s�ud�ed group. Ge�erally, co�s��pa��o� �s a commo� problem of �he

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developme��al per�od. The l��era�ure o� au��s��c ch�ldre� sugges�s �ha� �h�s co�d���o� �s fou�d �� abou� 30–40%; �� �he observed group, �hough, �� was �o�ed �� 57% of �he ch�ldre� [9]. Th�s may be affec�ed by appe���e problems, ea���g d�sorders, a�d pa�hology of �he al�me��ary �rac� resul���g from d�sorders �� bo�h �he d�ges��ve a�d �ervous sys�ems. No�e�heless, �� au��s��c ch�ldre� co�s��pa��o� may lead �o a relapse of �he rec�al mucosa more freque��ly �ha� �� �he�r �o�-au��s��c peers [8]. O�e of our pa��e��s was d�ag�osed as hav��g a rec�al prolapse dema�d��g surg�cal ���erve���o�.

The colo�oscopy performed �� 4 ch�ldre� revealed the presence of non-specific chronic inflammation of the mucous membra�e. Whe� carry��g ou� e�doscop�c exam�-�a��o�s of �he lower d�ges��ve sys�em �� ch�ldre� d�splay-��g developme��al d�sorders, also au��sm, Wakef�eld e� al. recog���ed var�ous ��flamma�ory co�d���o�s referred �o as

enterocolitis autistica �� �early all �he pa��e��s e�rolled ��

�he�r s�udy. The prese�ce of chro��c e��orocol���s �� au��-s��c ch�ldre� �s also ��d�rec�ly proved �� �he observa��o� by A��ho�y e� al., who fou�d ��creased excre��o� of cal-pro�ec��� �� feces [17]. Th�s observa��o� was dema�ded by Fer�ell e� al. – �he use of �wo markers of ��flamma�ory reac��o�s �� �he gu� ��.e. rec�al NO a�d fecal calpro�ec���� were �o� able �o d�sclose a l��k be�wee� A�D a�d ac��ve ���es���al ��flamma��o� [18].

The freque�cy of gas�ro���es���al bleed��g �� au��s��c ch�ldre� seems �o be sl�gh�ly h�gher �ha� �� �he popula��o� a� large. I� our research ep�sodes of bleed��g were observed �� 6 �20%� ch�ldre�, pr�mar�ly from �he lower al�me��ary �rac�. As �he ch�ldre� were �o� hosp��al��ed as a resul�, �he causes rema�� u�k�ow�; whe�her �hey were caused by co�-s��pa��o� or ��flamma��o� requ�res fur�her ��ves��ga��o�.

Hypo�he��cal pa�hoge�es�s of au��sm allows for some o�her fu�c��o�al d�sorders of �he d�ges��ve sys�em: ��crea-sed ���es���al barr�er permeab�l��y, ���es���al dysbac�er�os�s, d�sacchar�de ���olera�ce observed �� 58% au��s��c pa��e��s s�ud�ed by Horwa�h e� al., a�d a role of op�o�d pep��des ob�a��ed from ��comple�ely decomposed pro�e��s �ma��ly gl�admorph��e a�d bov��e caseomorph��e� [4,6,19,20]. Th�s las� hypo�hes�s �s �he reaso� for ���roduc��g el�m��a-��o� d�e�s, ma��ly depr�ved of glu�e� a�d m�lk, af�er wh�ch �� some cases we could observe �mproved commu��ca��o� w��h a ch�ld. K��vsberg e� al. have do�e a s��gle bl��d s�udy of d�e�ary ���erve���o� �� A�D: �hey proved a pos�-��ve effec� of glu�e� a�d case�� free d�e�s �10 pa��e��s, 1 year of observa��o�� [21]. However, �� our s�ud�ed group �he pare��s of 4 �13%� ch�ldre� appl�ed o�ly a low glu�e� a�d m�lk-free d�e�, wh�ch s��ll, �� �he�r op���o�, resul�ed �� �mproved co��ac�. U�for�u�a�ely, up ��ll �ow �here have �o� bee� grea� ra�dom��ed s�ud�es` a�d �he effec��ve�ess of such �rea�me�� �s �o� prove� [22].

What should also be taken into consideration is the �mpac� of �mmu�olog�cal d�sorders o� �he fu�c��o� of �he d�ges��ve sys�em �� au��s��c ch�ldre�. The l��era�ure prov�-des prov�-descr�p��o�s of d�sorders �� cell �mmu���y �depress�o� of CD4 cells, a���-CD2+ a�d �CD20+ T-cells decl��e� a�d humoral �mmu���y ���crease �� INF gamma, IL-1, IL-6,

TNF alfa�. Jyo�ouch� e� al. d�scovered a correla��o� be�wee� pr�mary �mmu�olog�cal d�sorders w��h�� �he ���es���al mucosa of au��s��c pa��e��s a�d gas�ro���es���al symp�oms w��h regard �o au��s��c pa��e��s who d�d �o� repor� such compla���s [23]. The f��d��gs of �he�r research ��d�ca�e also �he prese�ce of �o�-allerg�c hyperse�s���v��y �� �he f�rs� group of pa��e��s [24]. Immu�e aberra��o�s co�s�s�e�� w��h a dysregula�ed �mmu�e respo�se a�d gas�ro���es���al

dysmotility �� A�D pa��e��s could resul� �� m�crob�olog�cal

gu� dysb�os�s [25].

IgA def�c�e�cy has also bee� de�ec�ed: Wakef�eld e� al. observed �� �� 25% of �he�r s�udy subjec�s a�d �� our research �� was prese�� �� almos� o�e �h�rd of �he group. �es�des, o�her au�o-�mmu�olog�cal problems, such as �he prese�ce of a���bod�es aga��s� �euro�al cells, �europh�la-me��s, �urk��je cells, sero�o��� recep�ors, a�d e�do�hel�al cells, may cause damage �o �he bra�� a�d ���es���es, bo�h d�rec�ly a�d as a resul� of sys�em�c d�sorders. Wha� �s also �ake� ���o accou�� �� A�D �s �he dysfu�c��o� of �he gu�-bra�� ax�s [17,26-29]. �erhaps �� au��s��c ch�ldre�, d�sorders of �he �mmu�olog�cal e��ology may ��flue�ce �he fu�c��o� of �he gu�-bra�� ax�s; �h�s prog�os��ca��o� �s ope� �o fur�her research. Add���o�ally, accord��g �o Val�ce���–McDermo�� e� al a� assoc�a��o� be�wee� ch�ldre� w��h A�Ds a�d la�-guage regress�o�, a fam�ly h�s�ory of au�o�mmu�e d�sease a�d gas�ro���es���al symp�oms was observed [30,31].

The prese�ce of au�o-a���bod�es aga��s� sero�o��� recep�ors d�scovered �� au��s��c ch�ldre� �s a par��cularly ���eres���g phe�ome�o�, �he more so as sero�o��� �s o�e of �he �ra�sm���ers commo� �o �he ce��ral �ervous sys�em, e��er�c �ervous sys�em, e�docr��e sys�em a�d �mmu�e sys�em. �ero�o��� plays a� �mpor�a�� role �� med�a���g v�sceral se�sa��o� a�d homeos�as�s �� �he processes of se�-sa��o�, mo�or ac��v��y a�d excre�ory fu�c��o�. The roles of sero�o��� recep�ors �ypes 3 a�d 4 �5HT3 a�d 5HT4� prese��

�� v�sceral �euro�s, are also esse���al [32]. �ero�o��� co�-s���u�es �he ma�� �ra�sm���er of �he se�sa��o� of pa��, also v�sceral pa��, a�d sero�o�erg�c drugs may be appl�ed �� �he �rea�me�� of �rr��able bowel sy�drome.

M��g e� al. �� �he�r a�alys�s group of 160 pa��e��s w��h A�D fou�d s�ro�g assoc�a��o�s be�wee� gas�ro���es���al dysfu�c��o� a�d food ���olera�ce; sleep d�sorders a�d gas�ro���es���al dysfu�c��o�, a�d sleep d�sorders a�d mood d�sorder. Regard��g �he�r a�d our resul�s �here �s a ques��o� - �f o�e co�curre�� d�sorder may be respo�s�ble for �he o�her or do �hey s�em from a commo� pa�hology? [16].

There �s a co�se�sus repor� o� evalua��o�, d�ag�os�s a�d �rea�me�� of gas�ro���es���al d�sorders �� ��d�v�duals w��h A�Ds, a�d up ��ll �ow, s�a�dard of care �� �he d�ag-�os��c workup a�d �rea�me�� of gas�ro���es���al co�cer�s should be g�ve� as for pa��e��s w��hou� A�Ds [31].

CONCLUSIONS

1. H�gher ��c�de�ce of gas�ro���es���al pa�holog�es �� au��s��c ch�ldre� may ��flue�ce d�sorders of behav�oral pa��er�s. 2. Au��s��c ch�ldre� should also be looked af�er by a gas�roe-��erolog�s�.

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Source of Funding: This research was supported by funds from the State Committee for Scientific Research, Warsaw,

Poland; No 2P05E 084 27

Conflict of Interest: There is no potential conflict of interest, real or perceived

Adres do korespondencji:

Klinika Pediatrii i Neurologii Wieku Rozwojowego, Górnośląskie Centrum Zdrowia Dziecka Śląski Uniwersytet Medyczny ul. Medyków 16, 40-752 Katowice

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