exacerbation of ulcerative colitis following...

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Exacerbation of ulcerative colitis following administration of

5-ASA enemas

R-\Rft-\RA A Y<.'l·~u BSc PH\I Rcim:s; s ~ iCLEon MD. FRCSC. ZA~I: COHEN MD. FRCSC

ABSTRACT: A 33-year-old female with a 15 year history of ulcerative coliris presented with worsening dia rrhea followi ng colectomy an d ileorectal a nastom osis six months previously. Fo llowing ad ministration ofS-A SA enemas (Salofalk). the patient developed abdominal cramps. na usea and vomiting. and se vere dia rrhea resulting in hypotcnsion. Sym ptoms a b a ted quickly whe n the 5 -ASA e nema:, were d iscontinued. Although diarrhea and abdominal cramps have been described previously as side effects of oral sulfasalazine. o ral 5-A SA and sulfasalazine enemas, this is che first report of these symptom s occu rring follm,..ing adm inistration of 5-ASA enemas. Can J Gastroenterol 1989;3(2):50-52

K ey W ords: 5-A minosalicylic acid (5-ASAJ. Dnig induced colitis

L'exacerbatio n d e la colite ulce r eu se suite a l 'administration d e lavem e nts au 5-ASA

R ESUME: U ne patience agee de 33 ans et attemte de colice ulcercuse d e p u is 15 annees a souffer c de diarrhec aggravee a pres une colectom ie e t une an ascom ose tlco-rcccale cffcccuees six mois plus tot. Suite a l'injecrion de lavemencs d e 5-ASA (Salofalk; lnce rfa lk ), elle a ere prise de c rampes abdomi nales, de nau sees et d e vomisscments e t d'u ne diarrhee severe res ultan t e n une hy po ce n sion . Les sympcomcs one rapid emcn r d im in uc aprcs l'arre tdes lave mencs de 5-ASA. Bien quc la diarrhcc cc lcs crampcs abdominales aienc ere d ecrites aupara vant comme appartcnan t aux cffcrs secondaires de la sulfasalazine e t du 5-ASA pris par voie buccale. cc aux lavcmcnrs de sulfasalazine. ce rapport est le p rem ier q ui re lie les sympromcs a ux lavements de 5-ASA.

Du'"'"' 11/ (,;,,w1,tl \ur~,·r~ ,.m.I D.:p,nrm.:111.- ,,t <;urgn_\ m1tl f>han:1,1c~ Tcmmcn G.:ner,d Hm1111a/ ,rnd l lnr1\."r,u, of Tornnro. Tc,nmw Onwno

Com:.,J,,111,len.:e 111d r,·/m1m Dr R S :VkL.:oJ 1i1rnnro C,,'11c?rul Ho~/>ital. 2C(l Eli~aberh Srreer ,·11 <l -2-11. li1rn1110. 0111,mu \,{';t, .:?C-1 Tdcphon,· r 'i/\)1 '>..)'i • ./l}'i]

R.:L·cll',d /or />11b/in111un Ma, h. NH.q 4«:.:/•t.:d Oc10/>.:r {. /Q8,...;

50

S l LI ·\~Al ·\/INL 1, t\l'- ll-HC f I\ l: agcnr tn the mnnagcmeni of ulccr

auvc col1t1s. There 1s accumulating elm 1cal evidence chat the saltcylace moiew 5-amano,,nl1cvlic acid ( 5-ASA ). I'> thl' active component while ,;ulfop\ ndmc> acts as a cnrnN molecule.' 11-11 In th,: cohm. th1: Jia:<, honJ whKh Join-, Lhe

two m1,l..:culc-, 1s .:lt:.1vcJ. rdcasing 5-ASA which acts locally w dc::crea::,e inflammation lJnfortunatclv. the U'.->C ol sulfasala:inc may be limited due co mt0lcrancc or allergic reactions. lt 1s estimated chat up re, 20'';, ot patients may develop adverse rcacti(111s to sulfasala:me including nausea, vomiring. hcaJ achc. fever, rash, hcpanc and pu lmonmy Jy,;tuncrion. and b lood Jyscra:. i,1s ( 4. 5) Mosu,( rhe::,c renctions ,1ppear to he due to the s u lph,1 moicry (6) Thu:-.. new 5-ASA preparations have rcccndy become avriilablc wh ich mav he colcratcd bv patients who had nd verse rcacuons co :,u lfasala:mc: However, there a rc a few reports of p:rnc:>nts who have expcn enccJ sirmlar reactions whale taking oral 5-ASA (7-9)

A patient w11h ulccrauve colitts whl, Jcv,:lclpcJ advc:r,c: rcacuon" lO .,uJfasala:i rw and 5-ASA. hrnh or.1l ly (A~acol,

~onv1ch EalOn) and recrnlly (Salofalk. lncerfalk I is reported

CASE PRESENTATION A 3 3-year-old female was ad m ined to

the Toronrc, General Hospital m Ocwber 1987 with a LS year history of ulcermive colins In L972. the patient rre:;enced with diarrhea, nausea and vomiting m::tl:w,t' ,md weighr loss. Banum enema and s1gmoidoscopy were b0th normal S1x mo11Lh:, larcr the paciem presented complain ing of approximately LO bloody howcl movements per day Sigmo1dosco py and banum enema were consistent with panukeranvc coitus. The patient wa, ,carted on sulfasala:ine 1 g!da~ Within rwo days. nausca and concinunu ... vomiting developc..'d and diarrhe:1 worsened The symptom:-. re· -,nlved w1rhm ht1ur:,0f discnnunumg rhc sulfasala2inc. The patient wa-. then successfully created w1th prednisonc..• and rem;imcd symptom-free for five..· vcan,

F01lowmg the pancm's firsc prcgnancv m Marc h 1977. the disease activm m crea::.e<l and predmsonc was restarted . An attempt was made t0 re-mrroducc sulfasala2ine bu 1 again extreme nausea and vnm1tmg precluded m, use From L977 until 1981. the disease fluctuaced but the patient was never completely weU despite sceroid therapy. The paocnt was rechallcnged with sulfasala:ine 250 mg/day 111 1979 and enceric coated sulfasalazine in 1981. On both occasion:-. similar severe symptoms developed which necc%itated admission co hosp1tal and rc:-... olved once the sulfasalazme was discontinued . As well, che patient became inmlcrant of prednisone, developing headaches and severe depression.

Because of the drug intolcr;mces. the patient was started on azathioprine 100 mg/day in 1983. Complete rembs1on was achieved and the pallcnt was weaned off all prednisone m 1984. The panent remained on a:ath1opnne, symptom-free. uncil 1987 when liver cn::ymes were noted to bl' elevated and surgery wa:,, aJv1sl'd During chi-, time..' . Ill 1985, the patient was :,,tarted on Asacol hut developed the same sympwms of vomHing. ~evere diarrhea and abdominal cramps within 4 co 6 h of caking one 400 mg cablec. A second attempt two weeks lacer caused the same adverse reaction

C ·\ :O.: 1 GA'-1 Rnl ,-.:Tl ROL \ ',,, I :,..Jt, ! A l'RII llJ~N

In January 1987. because there was rel;Hive spanng of the rectum, the pauent underwent an abdominal colecmmy and ileorectal anastomosis. lnmally. the patient did well with approximately cwo co four bowel movements pcr day Hl,w· ever, in September 1987 the patient complained of :m increased nu m her ~1f bowel movemenrs ranging from five co lo per day. Sigmoidoscopic examination revealed moderate inflammanon of the rectum and sht' was started on betamcthasone enemas ( Becncso l; Glaxo) and diphenoxylatc ( Lamoni. G .D Searle) . The parienc dc..·veloped headaches which were atcributed co the bctamcchasonc and abdominal bloating which rcsnlved once che diphenox) late was scopped The c..harrhea continued and rhe patient compla111ed of nausea. m:1la1se and weight los:-. and. therefore, was admitted to hospital.

On admission to hosp1tal. the pauent wa;, modc..•racely dehydrarcJ hut phvs1-cal examination was otherwise normal The patient was rehydrated and kept ml bv mouth WhL·n frx,d wa::. re111rrodu.:ed. she was havmg six to eight bowcl movements per d ~iy. Lt was dec,Jcd co try 5-ASA enemas since the patient wa, incolcrant of all other med1cac1on

The pauent received a 4 g . oO m L 5-ASA enema 1Salofalk) at 10:00 At 12:00 she..' hegan co feel nauseated. At 14:00 she hegan t(1 vomit and have cc..,nrinuous e:-..plosivc. watery diarrhea resulting Ill a fall in blood pre:.sure from 100/60 co 85/60 mm Hg and a tadwcardia of 100/min The patient\\ as resuscitated w1th 1 L of normal saline over L h and then Ringers lactate w1th potassium chloride 20 mEq/L ar 125 mUh. By 19:00 the Jiarrhea anJ vom1tmg had abated . No m<,re enemas were given . 1'n, days lmcr the patienr was fully recnver<.!d and was discharged hnme Because of the persistent symptoms anJ her intolerance co medication. proctecromy and che pelvic pouch procedure were earned out in November 1987.

DISCUSSION Desr1te its effectivenc:.s 111 crcaung

acute ulcerau,·c CClUlls. ,1dc: effecrs have been repl,rted in up to 10'~. of patients caking sulfasalnzine 14.5 ). These reacnon.., mav be dose related or idit.1syncratic Tht.·

Exacerbation ot UC w1lh S·ASA enemas

most common, but least severe. adverse reactions include nausea. vomning. anorexia and headache. Heartburn. cp1· gasmc distres..s and diarrhea arc uccasmn· ally seen Although scnous ad\'er-;(' reactions may inv<>lve almost anv nrgan system, chey are rare. They mduJe skin eruption:.. hepatic anJ pulmonary dysfunction and ncurropenia . agrnnulocyms1s and rhrombocyt0penia . a:, well a:,

ocher hemacolog1ca.l abnormaline~. Gen· eralizcd nllcrgic reacnons w1rh fe\'cr. skin rash. archralgias and lymphadcnopnthv have ,ilso been rcpmted (61

Because most oi the side ctfrn,. of ,ulfa:--ala:ine have been attributed to the sulphapvndme m()it.'ry, the new 5-ASA preparation:. hc1,·e heen n t grc..'at \'alue in the managt'menc nf pauencs ,, nh ulccraci,·c coli us \\ ho ar..: inmlcrant ot sulfm,ala:inc Rcccntlv. however. there have been repnn:, dol.."umcnrinl! :-.1Je etfeccs 111 a small percentage of panents taking oral 5-ASA These include chest pam, ra,hc::.. fe,·cr. Ji:zme:,s headache anJ rencard1ns 17-9) In addmon , worsening ,)f diarrhea and abJomm;1l rain i-.. an unusu.11 hut well documented reat·mm co hmh ora l and recral sulfasala:ine and rhc..•se effect:, ha\'C been rcrnrred followmg the oral admmbtrarion ()( 5-ASA 110-161

Two r<.!ports described four pauenti. who Jevcloped an exnccrbauon ot their l1lcerattvc colitis wirh bmh sulfosala:mc .rnd ora l 'i -ASA (Asa..::ol) 115,16). The ,;ymrmm:- mcluJcd nau:,ca. vom1ung. abdominal pain ;mJ severe profuse diarrhea which \\'a:. bloc.idy in one of the four panent::, As well, three o f four patit.·nt~ devdopcJ fever Each of the four patient~ was rechallenged one co three cimes with sulfosala:1nc and one to tW(> times with 5-ASA In all pauents, the timt> to rhc Pnsc..'t nf -.ymptom" was shorter each nme the panc..'nt \\':h rechallengcd wnh ,-ulfa..,ala:1ne or 5-ASA Ln addmon. symptoms ,..enled quickly tollc..,,\·mg withdrawal of the su If asala:me or 5-ASA .

The presenr patient':.. course rl' ... embles the:,c paricnt:;, in that the s\ rnptc,m" were similar; nause.1 . vomiting, ;1hJc.,minal p:11n anJ diarrhea . Svmptoms \\'ec'rc cxpc..·ncnced on oral :-.ulfasala:me anJ 'i-ASA as wdl as 5-ASA t' ncmas. \Vich rc..'ch.,llenge, the ~ymptllnh appeared mc,re qu1cklv -;(, chm ii 1llowing ad mmis-

51

YOL\.1icra/

trat1on of 1hc.: 5-ASA enema, rhc pauen l bc.:carm.' :..ympcomatIC \\'llhm a few hourl>. Followint? withdra\\'al of 1he drug. svmp

tom" quickly rc'>ol\'c.:J . The prc:..ent pam:nr-. cour:..e 1s ,;1milar co chm of a pre

viow,ly reportc ... i p:men t \,\ ho developed nause:.1. vom1cmg and ahdornmal cramps 2 h ahi'r a ,u lfosala::111,: enema ( '>l"lt) mg

in 24(1 ml of water), one-halt an hl,ur lacer warerv stoob de\·clorx·d, whu.:h '5( Km

bc>G1tnl' hlnodv The nau:..eaand cramps lasrcJ 12 h I II )

5-ASA l'nemm, have been well t<>lc.'rated during -,hon term adminisrracu.in for rwo to eight wccb.. as well a:.. long term adm in1strat1on up to l{l month:.. 117.lM. There have heen 1:,<llarcJ reports

ACKN0\\'1.EOGEMENTS: The ,rntho,-.. th.ink John K ~lurdoch Oruc lniorma11,m Sernc,·, T.,r.,nt,, Gent'ral H,,~riraJ. tor hi, as~1stant·t:!.

REFERENCES Khan AKA. Pms J. Truelove $C An expt'nmc.:n1 to dt'k'rminr.: th..: clCII\','

thernreuuc: moit't\' n t sulfasala:mt' Lancer 1477:1dN2-5

l. Klo1: U, Maier K. Fi-.cha C H,·mkd K Ther:1peum.- cff1c.1cy ol ,-ultasala:mc.: anJ 1ts mccabolue,, m paucnt:o w11h l1lcerat1v<: .:u{m,. and Crohns d1S<:'as,· !'-.. Engl I Med l'-180 :iO > 1499-502

1 Van Hee, PAM, Bakker JH. \';in T.·mgcrer, JHM Effect of ,ulfopvndmc.: 'i-ammo»aliC\ lie acid .ind pl,1eelx, in p.nicnt:- wHh id1oparh1c procm1s: A ,tudv 10 dct<•rmme the ,1u1v,· 1herarr.:ut1c mo1erv oi sulfasala:me Gue 198(.'.2 I :6 32-'>

4 O;,,. l...: .tl.1.1:a:,t\\'OOJ MA, ~cManu~ .1r. Sm:us \V Ad\'erse reac11ons dunng ,ahcyla:o,.ulfapyndme thernpy and 1he relatwn wnh drug mernboli:,m and acet,btor phenorvpe. N Engl J 11.l<!d N7 UH9 ·t'-11 -5

5 T.1ffet SL. Oas KM Su lfasa l:,i=ine aJ, er,e effect:, ,ind dcsens1ti:atiun Dig Dis Sci 19R3:2~:813-42

6 Peppercorn MA Sulfa,,ab:111c pharmacologv, clinical u:,c cox1c1r,. ;md related n,·w drug development Ann

-, .,_

ul Ji::mes:,. heaJ,Khe. nau~ca. consnpmion. tl.itulencc. hurning <'r loca l ;morectal 1rritatinn ,ind a lopecia ( lo,17) Oi 14 patient, \\'irh a h1:..rorv of allcrg1c reacnon-, to ,ulfa:;ala:me or incolcran.::e due ro nau:.ca and vomiting. four I J7<'.,) devclop<'d side effect!'. when givl..'n 5-ASA enema~. Thn•e pam.-nc:. de\'cloped ra:,h anJ lever similar 10 che rcacnon experienced with l>u lfo:;ala:mc while the fourth pattt'nt developed d i::.mes::.. All of these r<'an1nn, uc,: urred \\'1thi11 :i fe\\ hour,

after the tir::.l enema I 21 I. Thi, i:, rhe first report. to rht· author-. k.n,lwledge. t<.l Jocument :..e, ere diarrhea and abJominal pain fo llowmg adminisrrauon c,f S-ASA en<~mas Although the mechant~m for

lntr.:rn Med 141'4. WI 177-8(, 7 L>nnald IP. \\'ill..m'lm SP Thr.: ".iluc ot

5-ammosalicvlic :1c1d m 111flammat.1rv h1>\, cl d1sc,,,.<-. for p.1ucncs mr<'k'r,1111 t>r ;1llcrg1<. to ,t,lfosalazmc P<.)StgraJ Med J l98'i 61 1047-M

s D,·w ~II. Ham<" AD fa·an, BK Rh, .__k, I Ta•.itmcnt ,,f uk<.·r.111, ... colm, w11h or;tl 'i-amint"':'llrn·lic ,1.;1J m rnncnts unable ro 1ake sulfa,...ila:mc L.1n.:c1 19/s};ii ~0 1

4 Habal FM, Greenberg GR. Treatment ot ulceram t' colici,, with ,,ral S-ammv,al.tc,·l1c adJ mdudmg patients w11h advcr~,· rcacm,n:, r~, :,ulfosal.-iz11H· Am J G,h1roentcrol 19'1~.~l 1519

10. \Vt·rlm SL. Grand RJ Bloodv J1.1rrhca: A new complu::attt>n ,,t 5ulfosala;:mc I Pcdratr J<.)7~. 4~ 45l°'· 1

11 Schwart: AG, T.1rgcn SR, S.ix,,n A. Wemstcin WM Sulfosala:me induced cxacerhauon ol ulcerau,·e coliri, N Engl J ~frd 1%2. 10(l.4{'9-12

11. AJler RD. Sulfa~ala:mc-mduced exacerbation of ulcr.: rmi\c ct,liti, N Engl JMeJ 19~2 . 307 315

I ,. Ruppm H Dom:-chke S Acute ulc<·rari,·e colm,. a ran~ comJ'.'lica11on 01 sulfasala:me cherapy Heraw1,?a,rro· ,•nrcrok>JatY 19R4, 1 I 192-1

1-f Rmg FA , Hcrshfidd NB. Machin CiA. Scort RB Sulfas,lla:mc-mduceJ coJiu,., comJ'.'licating idiopa1h1c ulccrauve colirn,. Can Med r\ssc,cJ 1984; 1>1.43-5

I 'i Au,.,rm CA C.inn PA.)l,ne.., TH.

,Lilfos.,la:me induced col1ti1, i:, unproven. ll 1s presumed m he ,rn allergic pht~n<Hn· t•non ~ Tht: fa<."11hac 11 occur:, qu ickly tolh,\\'tng ingt•,-1ion of suli,1sala:in<' or

'i-ASA anJ with decrca:..cd 11me inter· val tnllo\\ in!.! n.•ch.,llcnl-(l' 1, ,upporr1vc cv1Jence <'f rh1s mechan1,m ( 221.

In c0ndu,-ion. although 5-ASA ,.., u::.u;1llv well colcr,m:d by mo,.,1 pa11cnh, e,·t'n h\ cho:se who have expcm:nccd ,.,iJc dlc.:crs from sulfosa lazinc. it appears that , li:1rrht>:1 and .1 hdomi n;-il pmn ;i,.,,..n,i:1rcd

\\ 1th -.ullasala:me are due rt, the 5-ASA mo1ery Thu:., patients who have experienced 1he,;l' wmptom,.. will l1kel) be

intolerant ol oral anJ rectal 5-ASA prcpar.ui,m,

Holdswnrrh CD Exa,<·rhauon ol d1arrhr.:,1 and ram m rant·nts 1rea1t:d w1rh 5-amm,"alic~ lie a.:1d t,>r uker;111,·,· coitus. Lm,c1 L9b4:1:•>l7-:->

I(', Chakmhor1y TK Bhatia () , Ht'.tding RC. h,rd Ml Salicvlarc mduceJ r.:xaccrbmmn t>f ulcr.:ram:r.: Ct>lm~ Gut I<}K7 ,28 o I , 'i

1, Hon<le~cn S. Ra~mus~n S:-S:. Ra,k-Mad~t·n 1. er al 1-Am1m,salrcvlic ,1etd m thr.: lrt·atmenc ot mtl,1mmatt>rv howd J1~C,1'l." Aua :-.1<:d 'GmJ 19H,,!21 227-42

I h . Gu.irnw J Ch,u:moff M . B,•rk T fri,·dm.rn LS 1-Amintb,1l1cyl1L acid 111 r,·iracrorv J,,ral ulccr;Hl\'l' coliti<;. Long-term rr.:,ult, Am I Ci,blr<>enrcrol Jl.)~7;H2 732 7

I i.J. Bun<lc:.en ::,, ::-:..:d,-cn OH . J,tcoh~en 0. t·1 al. 'i-A mm<•,a lu:vlic ;1nd ,·nema~ m pa11ems w1ch act1vr.: ulc,·rn11v..- coliri~. Scand J G.Nrncnterol 19!-4 . 19 I.)() 7-~2

2(1 Kum· PK . Raman KRK. Hawken K. B(lrrmvman JA Harr lo~, and "i-aminclsal1cvlic aod enr.:m;l~ Ann lntt'rn Med 1982.97 7f.1 6

21 Camr1cn l\ 1 Lmdfranch, CiA Brign,,la C. et al 'l-Ammosalic"lic ;1c1d as rectal ,·ncma in ulcernu,·e .:oliu~ r:irient~ un'lhl ... 11, rakt• ,.,If",:.:-. b!m,·· L:incrr 19H4;i;403

22 Cann PA The mc1dt.:n<.e ;111J mechanics of d1;1rrhea \t 1th '>-ASA In 5 ASA Thr.: State oi rht· Arc T.,r,mro MES Medical f:ducanon Sr.:rv1ces. l':187:4 1 5

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