GASTRIC INVOLVEMENT Histological abnormalities of the stomach consist of s bm cosal collagen !e"osition an!

! re"lacement of smooth m scle #ith fibro s tiss e$ These "athologic changes are less mar%e! than those of the eso"hag s or small intestine$ S&m"toms an! signs The stomach is not s all& the "rimar& so rce of s&m"toms in gastrointestinal s&stemic sclerosis 'SSc() b t it ma& contrib te to eso"hageal s&m"toms #hen em"t&ing is !ela&e! *+,-$ Rarel&) se.ere in.ol.ement of the stomach res lts in gastro"aresis #ith intractable .omiting) #hich ma& ca se #eight loss an! n tritional !eficiencies$ The s&m"toms are intermittent) #ith remissions lasting se.eral months$ Massi.e ""er gastrointestinal blee!ing secon!ar& to m cosal telangiectasia 'as "art of the CREST s&n!rome( can also occ r *+/-$ Gastric antral .eno s ectasia 'GAVE( is an increasingl& recogni0e! com"lication of SSc *12-$ It is best !iagnose! b& gastrosco"&$ Clinical s s"icion sho l! be high) "artic larl& in "atients #ith ne3"laine! iron !eficienc& anemia$ Treatment is s ccessf l sing laser "hotocoag lation *14- or Argon "lasma coag lation *15-) altho gh treatments ma& ha.e to be re"eate!$ There is increasing recognition of this com"lication in both ma6or s bsets of SSc) an! in !iff se c taneo s SSc '!cSSc( im"ro.ement can occ r in association #ith stabili0ation or resol tion of s%in sclerosis$ 'See 78ncommon ca ses of ""er gastrointestinal blee!ing in a! lts7$( 9iagnosis The most sensiti.e metho! of !etecting gastric in.ol.ement is .ia ra!ion cli!e gastric em"t&ing *+1-$ In a!!ition) a bari m meal ma& re.eal a !ilate! atonic stomach) an! en!osco"& ma& sho# a lac% of "eristalsis$ 'See 7Gastro"aresis: Etiolog&) clinical manifestations) an! !iagnosis7$( SMALL INTESTINAL INVOLVEMENT Abnormal small bo#el f nction has been re"orte! in 52 to ;2 "ercent of "atients #ith s&stemic sclerosis 'SSc() an! more than one< half ha.e a histologic abnormalit& at "ostmortem *4=-$ >atho"h&siolog& The res lts of st !ies on the small intestine "oint to#ar! an n!erl&ing ne rom sc lar !isor!er similar to that in the eso"hag s: ?Recor!ings of ! o!enal m&oelectric acti.it& in "atients #ith SSc ha.e re.eale! normal basal slo# #a.e an! s"i%e "otential acti.it& *1+-$ Ho#e.er) the res"onse to mechanical an! h moral stim li in this st !& #as abnormal$ The ma6orit& of "atients sho#e! an abnormall& lo# s"i%e res"onse to !istension) #hile a smaller gro " e3hibite! a !iminishe! res"onse to e3ogeno s "entagastrin an! secretin$ These res lts s ggest a !efect in the intrinsic cholinergic "ath#a& that me!iates the s"i%e res"onse to !istension$ The gro " that faile! to res"on! to h moral stim li ha! longer !isease ! ration an! "robabl& more se.ere !isease$ These fin!ings #ere s ""orte! b& another st !&) #hich fo n! abnormal motor acti.it& as meas re! b& intral minal "ress re *11-$ ?Another re"ort fo n! that "ro3imal small bo#el "ostcibal motilit& #as s all& re! ce! in s&m"tomatic "atients an! that a minorit& of "atients ha! ncoor!inate! fasting or "ostcibal h&"ermotilit& s ggesti.e of a ne ro"ath& *1@-$ These res lts s ""ort the h&"othesis that both ne ro"athic an! m&o"athic stages occ r in the small bo#el of "atients #ith SSc$

>atholog& Light microsco"& re.eals fe# cl es to the e.ol tion of the "atholog& of small intestinal in.ol.ement in SSc$ Villo s str ct re is normal) b t there ma& be collagen !e"osition aro n! Ar nnerBs glan!s) lea!ing to "eriglan! lar sclerosis$ This feat re is sai! to be "athognomonic of intestinal SSc an! ma& occ r in the absence of ra!iologic changes *4@-$ 8nfort natel&) this fin!ing is of limite! clinical .al e since small intestinal bio"sies rarel& incl !e the s bm cosal la&er$ C ll thic%ness bio"sies ma& re.eal a mar%e! increase in s bm cosal an! serosal collagen an! elastin as #ell as atro"h& of the smooth m scle la&ers$ Electron microsco"& has sho#n re! ce! n mbers of smooth m scle cells in the e3ternal m scle la&ers an! a mar%e! "a cit& of 6 nctional com"le3es bet#een m scle cells *1;-$ In a!!ition) #e ha.e fo n! e.i!ence of "erine ronal collagen c ffing) ne ronal !egeneration in the absence of collagen c ffing) an! "eri.asc lar fibrosis$ Malabsor"tion A""ro3imatel& 42 to +2 "ercent of "atients #ith SSc ha.e e.i!ence of malabsor"tion$ Intestinal stasis #ith o.ergro#th of bacteria is consi!ere! to be the ma6or ca se of this com"lication$ One st !&) for e3am"le) "erforme! 6e6 nal as"irates in 52 nselecte! "atients #ith SScD bacterial o.ergro#th) !efine! as E42; organismsFmL) #as "resent in one<thir! *1=-$ The ma6orit& of "atients #ith bacterial o.ergro#th ha! small bo#el in.ol.ement an! steatorrheaD b& com"arison) "atients #ith normal bacterial co nts ha! normal intestinal f nction$ Ho# bacteria im"air n trient !igestion or cell lar trans"ort in "atients #ith malabsor"tion is still "oorl& n!erstoo! *1=<1/-$ One "ro"ose! mechanism is that bacteria !econ6 gate an! !eh&!ro3&late con6 gate! bile salts) thereb& re! cing fat em lsification an! micelle formation *+5)@2-$ A!!itional "ossibilities incl !e .asc lo"ath&) l&m"hatic obstr ction) #all fibrosis) im"aire! motilit&) an! "ancreatic !&sf nction *@4<@+-$ Ho#e.er) a"art from minimal inflammator& cell infiltrates) .illo s mor"holog& a""ears normal *@5)@1-$ C rthermore) no !efect in intestinal "ermeabilit& #as fo n! in one re"ort as estimate! b& the oral a!ministration of cellobiose 'a !isacchari!e( an! mannitol 'a "ol&h&!ric alcohol( *@5-$ Clinical manifestations The ma6or manifestations of small intestinal in.ol.ement are ! e to re! ce! "eristalsis #ith res lting stasis an! intestinal !ilatation *@@-$ This res lts in ab!ominal !istension an! "ain arising from !ilate! bo#el loo"s$ Aacterial o.ergro#th s bseG entl& emerges ! e to intestinal stasis an! "ooling$ As fat malabsor"tion ens es) the "atientBs s&m"toms ma& change from !istension) "ain) bloating) an! consti"ation to !iarrhea) steatorrhea) an! #eight loss$ A rare com"lication is intestinal "se !o<obstr ction) res lting in rec rrent obstr cti.e s&m"toms *1;)@;-$ Affecte! "atients t&"icall& com"lain of an alteration in bo#el habit #ith !iarrhea) consti"ation) or both 'intermittentl&( 'see 7Chronic intestinal "se !o< obstr ction7($ In com"arison) "ersistent !iarrhea an! steatorrhea are most li%el& ! e to fat malabsor"tion$ Other rare com"lications are small bo#el "erforation) "ne matosis c&stoi!es intestinalis) an! small bo#el .ol. l s *@=<;2-$ 'See 7Treatment of gastrointestinal !isease in s&stemic sclerosis 'sclero!erma(7$(

9etection of bacterial o.ergro#th The gol! stan!ar! for the !etection of bacterial o.ergro#th is small bo#el as"iration$ It is not i!eal) ho#e.er) since it is in.asi.e an! ma& nee! to be re"eate! ! e to bacteria regro#th$ A& com"arison) the gl cose h&!rogen breath test is a nonin.asi.e e3amination) altho gh false negati.e res lts ma& occ r #hen the "re!ominant organisms "ro! ce CO5$ A st !& com"are! a "eren!osco"ic metho! of small bo#el as"iration sing a sterile !o ble<l men t be #ith the gl cose h&!rogen breath test *@1-$ Of the 54 "atients st !ie!) onl& one ha! a false negati.e gl cose h&!rogen breath test for bacterial o.ergro#th$ There #ere no false "ositi.es$ He recommen! initial screening #ith a gl cose h&!rogen breath test$ 'See 7Clinical manifestations an! !iagnosis of small intestinal bacterial o.ergro#th7) section on BLact loseB$( He "erform as"iration in "atients #ho ha.e !e.elo"e! resistance to rotating antibiotics) as manifeste! b& !iarrhea that is !iffic lt to control #ith em"irical antibiotics$ 'See 7Treatment of gastrointestinal !isease in s&stemic sclerosis 'sclero!erma(7) section on BMalabsor"tionB$( Ra!iogra"hic fin!ings Ra!iological e3amination sing bari m remains the most sensiti.e an! s"ecific techniG e a.ailable for the !iagnosis of small bo#el !isease in SSc *;4-$ S "erior .is ali0ation of 6e6 nal an! ileal loo"s "l s e.al ation of small bo#el transit time can be achie.e! sing small bo#el follo# thro gh #ith int bation of the ! o!en m an! instillation of contrast !irectl& into the small intestine$ Alternati.el&) a small bo#el enema ma& be "erforme!$ 8nfort natel&) collagen !e"osition can occ r before ra!iogra"hic abnormalities become a""arent$ 9ilatation of intestinal loo"s is the most "rominent ra!iogra"hic feat re #hen absence of "eristalsis affects the ! o!en m an! "ro3imal 6e6 n m$ A characteristic sign of small bo#el SSc is a Ihi!e<bo n!J or I#ire<s"ringJ a""earance "ro! ce! b& closel& "ac%e! .al. lae in a !ilate! bo#el 'image 4( *;5-$ This fin!ing is ! e to ne rom sc lar abnormalities an! e3cessi.e collagen !e"osition$ In the later stages of the !isease) "se !o< obstr ction occ rs) an! ! o!enal an! 6e6 nal loo"s become mar%e!l& !ilate! #ith arrest of contrast #ithin the bo#el *;+-$ In "ractice) #e !o not often "erform bari m follo#<thro gh or small bo#el enema$ These tests are c mbersome an! time<cons ming an! ma& gi.e a false negati.e res lt$ The& ma& be a sef l confirmator& test) b t) if "ersistent !iarrhea is "resent #ith a "ositi.e breath test) #e ass me that bacterial o.ergro#th is "resent$ Aari m st !ies #ith small bo#el bio"s& are "erforme! if an alternate !iagnosis) s ch as inflammator& bo#el !isease or celiac !isease) is consi!ere!$ Magnetic resonance imaging 'MRI( has also been se! to assess sclero!erma bo#el in.ol.ement an! is li%el& to be increasingl& se! for assessment of !isease an! e3cl sion of other "athologies *;1-$ COLON AN9 ANORECTAL INVOLVEMENT Colonic !isease occ rs in 42 to @2 "ercent of "atients #ith s&stemic sclerosis 'SSc() #ith the anorect m as the most freG entl&

affecte! area *;@-$ One st !&) for e3am"le) fo n! that the colon is almost as freG entl& in.ol.e! as the eso"hag sD in a!!ition) "atients #ith abnormal eso"hageal manometr& almost al#a&s ha! abnormal anorectal motilit& *;;-$ >atholog& SSc in.ol.ement of the large intestine is similar "athologicall& to that of the small intestine$ Collagen is !e"osite! in the m cosa an! s bm cosa) #hile the m sc laris e3terna n!ergoes atro"h&$ Thinning of the m sc lar #all lea!s to the !e.elo"ment of #i!e<mo the! !i.ertic li on the antimesenteric bor!er that can be !etecte! on bari m enema 'image 5($ >atho"h&siolog& >h&siologic st !ies sho# that the gastrocolic refle3) in #hich ingeste! foo! lea!s to significant s"i%e an! contractile acti.it& in the colon) is absent earl& in the co rse of SSc *@,-$ A!ministration of the anticholinesterase) neostigmine) restores the "ost"ran!ial motilit& res"onse in "atients #ith earl& SSc b t not in those #ith longstan!ing !isease$ 9isor!ere! anorectal f nction is also an earl& fin!ing in SSc an! is a ma6or factor in the !e.elo"ment of fecal incontinence$ Magnetic resonance imaging 'MRI( abnormalities in s ch "atients incl !e for#ar! b c%ling of the anterior rectal #all) air in the ""er "ortion of the anal s"hincter) an! atro"h& of fibrotic a""earing s"hincteric m scle *;=-$ The most common manometric abnormalit& is an absent or !iminishe! rectoanal inhibitor& refle3 *;;-$ The res"onse of the internal anal s"hincter is !iminishe! or absent) an! the res"onse of the e3ternal s"hincter is either normal or increase!$ These changes correlate #ith the re! ction in the am"lit !e of rela3ation of the lo#er eso"hageal s"hincter$ These fin!ings are similar to those seen in Hirschs"r ngBs !isease an! are consistent #ith a ne ronal abnormalit& in the m&enteric "le3 s$ The later stages of the !isease are characteri0e! b& re! ctions in resting "ress res of the internal an! e3ternal s"hincters) in the length of the anal canal) an! in com"liance ! e to collagen !e"osition *;;);,-$ S&m"toms Consti"ation 'less than t#o s"ontaneo s stools "er #ee%( an! fecal incontinence are common "roblems in SSc *+5);/-$ Other) less freG ent s&m"toms of colonic !isease incl !e rectal "rola"se) s"ontaneo s "erforation) an! colonic infarction$ 9iarrhea is s all& a s&m"tom of small bo#el bacterial o.ergro#th