Manifestari Reumatismale Engl Oct 2012

8/11/2019 Manifestari Reumatismale Engl Oct 2012

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RHEUMATISMAL MANIFESTATIONS ININTESTINAL BOWEL DISEASE IN CHILDREN

M. Burlea, Stela Go ia, Gabriela P !uraru, A"#u a I$"at, %.%. Lu&uț ț5th Paediatric Clinic, The Faculty of General Medicine,

“Gr. T. Popa” University of Medicine and Pharmacy, a!i, "omania

Su''ar() The particular evolution and pro#nosis of the intestinal $o%el diseases consists intheir chronici&ation potential %hich affects the #astrointestinal tract and leads to e'tra(di#estive disorders. The environmental anti#ens and)or the auto anti#ens *favoured $yspecific #enetic patterns+ and the cyto ines released from the intestinal inflammations canlead to articular inflammations %hich can $ecome chronic. The hi#h rate of arthral#ia andnon(infectious arthritis in children re-uires more attention in association %ith thorou#her di#estive investi#ations at the patients %ith articular sufferin#s. The fre-uent disa$lin#evolution of articular inflammation, sometimes independent of the evolution of the intestinalinflammation re-uires the predictive mar ers *immunolo#ic, $iochemical,immunohistochemical etc.+ to $e correctly esta$lished and interpreted, this $ein# the eyfactor in introducin# “at the ri#ht moment” the treatment %ith immunosuppressive and)or

$iolo#ical a#ents.

*e( +or! ) i"te ti"al bo+el !i ea e, #-il!, art-riti

The intestinal $o%el disease, represented $y Crohn disease and ulcero(hemorrha#icrectocolitis, is characteri&ed $y the chronic inflammation of the #astrointestinal tract, of un no%n ori#in, and it is dia#nosed $ased on clinical, endoscopic and histolo#ical

particularities. nteritis, another possi$le cause for articular dysfunctions, is determined $ySalmonella, Shigella, Campylobacter and Yersinia.

Clinical and epidemiolo#ical o$servations point out the role of #enetic factors in the patho#enesis of intestinal $o%el disease, and the ey factors of the inflammatory process./lthou#h not sufficiently no%n and some of them also disputed, they are represented $y themicro$ian and alimentary anti#ens from the intestinal lumen. Salmonella, Shigella,Campylobacter and Yersinia are the most important tri##er factors for post(enteritic reactivearthritis. /nti$iotics have $een studied in various cases. / detailed analysis of these studiessho%s dou$tful results, %ith a possi$le $enefit in post(Chlamydia reactive arthritis. Thesedata are revised focusin# on post(enteritic reactive arthritis 012.

Polyunsaturated fatty acids *PUF/+ ome#a(3 type *n(3+ and ome#a(4 *n(4+ play

important roles in mana#in# the inflammation. Generally spea in#, the icosanoids derivedfrom PUF/ n(4 are anti(inflammatory. The diet chan#es from the last decades indicate arelation *n(3+ *n(4+ e-ual to 6 15 1. / diet rich in PUF/ *n(3+ coincided %ith a lar#e num$er of chronic inflammatory diseases, as non(alcoholic fatty liver disease, cardiovascular disease,o$esity, intestinal $o%el disease, rheumatoid arthritis and /l&heimer disease. 7y increasin#the proportion of PUF/ *n(4+ *n(3+ in the diet of the %est, the num$er of these chronicinflammatory diseases decreased.

The particular evolution and pro#nosis of intestinal $o%el disease consists of their chronici&ation potential, and the clinical manifestations are a direct conse-uence of thedere#ulation of the inflammatory cascade %hich affects the #astrointestinal tract and leads toe'tra(di#estive symptoms. Thus, Crohn disease and ulcero(hemorrha#ic rectocolitis are

associated %ith a variety of e'tra(di#estive symptoms %hich in reality are complications of various diseases %hose clinical severity is not al%ays correlated %ith the intestinal

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inflammatory activity. The e'tra(intestinal symptoms are fre-uently associated %ith ulcero(hemorrha#ic rectocolitis and colonic Crohn disease, only in fe% cases $ein# associated toCrohn disease e'panded to the thin intestine.

/rthritis represents the e'tra(di#estive manifestation of the most fre-uentinflammatory $o%el diseases. t is considered that almost 18(95: of the patients sufferin#

from intestinal $o%el disease develop some ind of arthritis or that ;: of the population %ithan ylosin# spondylitis present an intestinal inflammatory affection 04, <, 5, 32. The patients%ith severe %ide spread intestinal $o%el disease present hi#her ris of developin# articular complications.

The intestinal $o%el disease presents t%o types of articular complications( peripherical arthritis = arthritis associated to the colitis from inflammatory diseases>( sacroiliitis and an ylosin# arthritis.

The prevalence of an ylosin# spondylitis and peripherical arthritis increased at the patients %ith intestinal $o%el disease 0?, ;2.

Peripherical arthritis is more fre-uent to the patients %ith ulcero(hemorrha#icrectocolitis and Crohn disease located at the level of the colon. The arthritis associated %ithunspecific inflammatory colitis is a mi#ratin# type of arthritis %hich affects the main

peripherical articulations *#enerally less than 3 articulations+. The symptoms of periphericalarthritis associated to the intestinal $o%el disease are represented $y tumefaction, pain andlimitation of the movements at the level of the affected @oints. The @oints possi$ly influenced

$y the inflammatory process are locali&ed at the level of the upper and lo%er lim$s, morefre-uently $ein# the case of the nee, an le and hip 0A2.

n some cases, the polyarticular symptoms associated to the Crohn disease canresem$le those of rheumatoid polyarthritis and can $e present for a lon#er period of timeindependent of the evolution of the intestinal $o%el disease. Typically, the evolution of thesetypes of arthritis is parallel to that of the intestinal $o%el disease, %ith e'acer$ations andremission periods. There are no specific methods for dia#nosin# peripherical arthritis, $utcolonoscopy, articular radiolo#ical investi#ations and haematolo#ical tests e'clude other conditions. n the a$sence of any treatment, pain can persist for days, even %ee s> luc ily,this type of arthritis does not #enerally cause permanent effects on the @oints, its evolutionrecordin# various episodes. /s far as the treatment of peripherical arthritis is concerned it canrespond favoura$ly to physical therapy and non(steroidal anti(inflammatory dru#s *B / D+or corticoids. They have #ood results, reducin# or eliminatin# pain, tumefaction and articular stiffness. Bonetheless, non(steroidal anti(inflammatory medications can intensify thedi#estive symptomatolo#y of the intestinal $o%el disease and, thou#h $eneficial for the

@oints, it must $e administered %ith caution. /lthou#h no epidemiolo#ical studies have $een performed on the possi$le relation $et%een B / D and the development of intestinal $o%el

disease, a lar#e num$er of reports su##est that B / D increases the ris of intestinal $o%eldisease 01<, 18, 91, 112. Bonetheless, some patients %ith intestinal $o%el disease seem to $etoleratin# B / D. Many times, corticotherapy is used too, %ith positive results. n somecases, articular affectation is not e'tremely important and the corticoids administered for theintestinal affection act also on the s%ollen @oint %ithout e'actly no%in# %hich @oint has $eenaffected.

The effects on the peripherical articular are more fre-uent than the articular forms thatevolve %ith an ylosin# spondylitis, %ith favoura$le, limited evolution %ithout se-uels or articular deformations> the speciali&ed literature -uotes les than 95: cases %ith clinical or radiolo#ical se-uels. From the sinusoidal fluid resulted from 5888 up to 19.888 %hite cells onmicro(litre, especially polymorphonuclear leu ocytes. The $iopsies from the synovial

mem$rane have pointed out non(specific anomalies, includin# proliferation of synovial cells,hi#h vasculari&ation as %ell as infiltration %ith mononuclear cells 019,142.

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The second %ay in %hich the articular disorders associated to intestinal $o%el diseasecan present themselves is represented $y sacroiliitis and an ylosin# spondylitis 01<2.acroiliitis and an ylosin# spondylitis are 48 times more fre-uent at those %ith intestinalinflammatory disorders than the #eneral population and in ;8: of the cases they areassociated %ith E /(79? haplotype 05, 15, 132. The characteristic feature is that it evolves

independently of the intestinal inflammation. This is %hy the medical or sur#ical treatment of the intestinal $o%el disease does not influence this type or articular manifestations. Medicaltreatment $ased on non(steroidal anti(inflammatory medicines or corticoterapy can improvethe symptoms $ut it does not intervene in the evolution of the articular disorder %hich, mostof the times, is deformin# and disa$lin#. solated sacroiliitis is fre-uently asymptomatic*radiolo#ic dia#nosis+ and it is associated to ulcero(hemorrha#ic rectocolitis %hile an ylosin#spondylitis is more fre-uently associated %ith Crohn disease.

hen the spine is affected, the symptoms can appear months or years $efore thedevelopment of the intestinal inflammation. tudies sho% that at 15 = 95: of the patients%ith arthritis, the intestinal disorder is su$(clinical *usually Crohn disease+, the articular si#nsappearin# lon# $efore the intestinal symptoms. t is characteri&ed $y pain and the sensation of stiffness of the spinal cord articulation, %ith certain ri#idity in the mornin#.

The data from literature dealin# %ith this su$@ect points out the incidence of sacroiliitis at the patients sufferin# from intestinal $o%el disease is a lot #reater in reality, asat almost 1;: of the cases %e encounter su$(dia#nosed asymptomatic sacroiliitis 0142.ymptomatic or asymptomatic sacroiliitis is accompanied $y inflammatory type of pain in48: of the cases, synovitis in 18: of the cases, peripherical enthesitis in ?: of the patientsand in 18: of the cases, the inclusion criteria for an ylosin# spondylitis are present. t isunanimously no%n that #enetic determinism and the intervention of the infectious factor astri##er in the cases of spondyloarthropathies *studies on families and t%ins+. The presence of the disease at the ones %ith E /(79? halotype is an additional proof for the role of the#enetic factor. /t the same time, a #ene %ith increased specificity for Crohn disease, BHD9,locali&ed on chromosome 13 *13-19+ has $een determined at the patients sufferin# froman ylosin# spondylitis and intestinal $o%el disease 01?2.

pondyloarthropathies affect mainly the lo%er re#ion of the spinal cord *lum$osacral+and the pelvis *sacroiliac @oints+ or the li#aments and the insertion tendons on the $one*enthesitis+ at the level of the hip or nee. t is e'tremely important to differentiatespondyloarthropathy from the intestinal $o%el disease from @uvenile rheumatoid arthritis."eferrin# to the possi$le symptoms, they may $e pain at the lum$ar sacral level irradiatin#to%ards the hips or the thi#hs> stiffness in the mornin# %hich can last all day lon# and after mo$ili&in#> e'treme tiredness. The association of these symptoms %ith a$dominal pains anddiarrhoea %ith $lood can direct the dia#nosis of intestinal $o%el disease. n most of the cases,

the intestinal symptoms are lac in#, articular affectation $ein# present $efore of the intestinalinflammation. ome of those e'periencin# these symptoms are not recorded %ith intestinal $o%el disease. n this case, routine colonoscopy is not recommended, $ut non(invasive testsas esta$lishin# faecal proteins and intestinal permea$ility are promisin# tests of hi#hspecificity for intestinal diseases and at the same time, they are easy to perform 01;2.Ma#netic resonance enteropathy *M" + can also $e used foe assessin# the su$(clinicalintestinal inflammation in children %ith idiopathic @uvenile arthritis 01A2. The evolution inan ylosin# arthritis is e'tremely rare in children, $ut nonetheless, possi$le at the adolescentsufferin# from intestinal $o%el disease %ith prolon#ed evolution. The spondyloarthropathiesassociated to the intestinal $o%el disease must $e differentiated from other conditions thatcan lead to similar manifestations * almonella, hi#ella, Iersinia, Campylo$acter etc.+. /t the

same time, it is important to differentiate the spondyloarthropathy in children from that inadults, as in the case of adults the spinal cord is the most affected one, %hile in children, the

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upper and lo%er lim$s are the most affected ones, #enerally <(5 @oints that can $ecome painful or sore *typical = hip or an le+.

Thus, the symptoms of enteropatic arthritis can $e divided into t%o cate#ories( articular symptoms at the level of the previously mentioned @oints * nee, hip, an le,

lum$ar sacral spinal cord, sacroiliac @oints+ pain, tumefaction, articular stiffness and

limited motions>( symptoms characteristic to the intestinal $o%el disease *ulcero(hemorrha#ic

rectocolitis or Crohn disease+ stools %ith $lood and mucus, a$dominal pain mainly inthe lo%er a$dominal level.The severity of the articular symptoms coincides %ith the severity of the intestinal

$o%el disease, remission of the intestinal inflammation thus solvin# the articular symptoms*e-uation valid for peripherical arthritis as %ell+. n case of sacroiliitis and an ylosin#spondylitis the evolution can $e independent of the level in %hich the intestine is affected.The dia#nosis focuses on esta$lishin# the presence of the intestinal $o%el disease and of theassociated inflammatory arthritis.

The positive dia#nosis is esta$lished $y( complete medical e'amination anamnesis plays a very important part, haematolo#ical

$alance for pointin# out the inflammation mar ers *J E, reactive C protein+ and)or the #enetic mar er *E / = 79?+, faecal matter tests>

( colonoscopy and histolo#ical e'amination of the $iopsied fra#ments>( articular radiolo#ical e'am>( articular puncture>( computed tomo#raphy *CT+>( scinti#raphy>( ne% #eneration tests. M" proved to $e e'act at $oth adults and children, in

dia#nosin# intestinal $o%el diseases, %hich differentiate from other causes of a$dominal pain%ith sensitivity of ;9(A3: and specificity KA8: 0982.

The radio#raphies of the spinal cord and the pelvis can illustrate the typical aspect of an ylosin# spondylitis sacroiliitis. The radio#raphies of the peripherical @oints sho% at thelevel of the soft tissues = edema, @u'ta articular osteoporosis, li#ht periostitis and collections,usually %ithout erosions or destructions. The radio#raphies have fre-uently indicated sli#htanomalies even at asymptomatic patients %ith 7D 091, 992. valuatin# the sensitivity levelfor dia#nosin# the intestinal $o%el disease is not si#nificantly different if %e refer toima#istic methods *;A.?:, A4.8:, ;?.;: and ;<.4: for echo#raphy, M", scinti#raphy andCT respectively+. pecificity %as of A5.3: for echo#raphy, A9.;: for M", ;<.5: for scinti#raphy and A5.1: for CT 0942.

Dosin# the plasmatic and tissue concentration of alli rein is the su$@ect of recent

studies, indicatin# the role of the plasma alli rein = inin system in arthritis, noticin# adecrease of the plasma and tissue alli rein concentration in the chronic intestinalinflammation and the associated articular inflammation 09<2. The mana#ement of the arthritisassociated to the intestinal $o%el disease must $e comple'. The treatment focuses on $oth thecontrol and the sta$ili&ation of the articular manifestations and intestinal symptoms. /s %ehave previously mentioned, the peripherical arthritis developin# in parallel %ith intestinalinflammation #enerally has a favoura$le ans%er to the treatment of intestinal disorders. Hnthe other hand, if the evolution of the articular capacity of catchin# tends to have deviationsto%ards deformation and stiffness, the treatment must $e ad@usted.

/n important role is played $y physical therapy> re#ular physical e'ercises help inmaintainin# the appropriate posture and fle'i$ility of the affected @oint and even ameliorate

pain. Physical therapy decreases the ris of developin# spondylitis that reach to spinal cord.

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/t the same time, %orm applications and ti#ht $anda#es of the stiffed @oints can reduce painand articular stiffness %hile cold $anda#es on the s%ollen areas can help reduce the s%ell.

/s far as the medicamentous treatment is concerned, most types of spondylitis andarthritis use non(steroid anti(inflammatory dru#s %hich have a positive effect on reducin#

pain and articular stiffness 0952. The ne% class of non(steroid anti(inflammatory dru#s also

no%s as CHL(9 inhi$itors decrease the ris of #astrointestinal adverse reactions associated%ith the therapy $ased on traditional anti(inflammatory dru#s. Bonetheless, the use of thisne% class of dru#s in the arthritis associated to the intestinal inflammatory disease must $emade %ith caution.

ulfasala&ine is the dru# successfully used in many cases of intestinal $o%el disease.ts role in controllin# pain and articular tumefaction in peripherical arthritis is %ell no%n

@ust as it is in reducin# intestinal inflammatory lesions, especially in ulcero ( hemorrha#icrectocolitis, and less in Crohn disease 0932. t also has favoura$le effects in the cases of arthritis locali&ed at the level of the articulation of the nee, hips or an les 09?2.

Corticotherapy efficiently controls the manifestations of the arthritis associated to theinflammatory $o%el disease, $ut the adverse effects that appeared after lon# periods of timein %hich they have $een administered, limit their use. ntra(articular in@ections of corticoidsimprove for a certain period of time the pain and the stiffness due to arthritis and $ursitis.

Favoura$le results have had the immunosuppressant dru#s> methrote'ate can improvethe arthritis from the level of the spinal cord, upper and lo%er lim$s, and especially thatassociated to Crohn disease. / treatment al#orithm is proposed %hich su##ests precociousand a##ressive therapy of rheumatoid arthritis %ith hi#h doses of methrote'ate *15(95m#)%ee + %hich can include moderate doses of #lucocorticoids 09;2. The purpose of thistreatment is that of reducin# the activity of the disease in 4(3 months. Cyclosporine can havefavoura$le results %hen corticoids do not.

/ ne% class of dru#s %ith $eneficial effects in controllin# intestinal inflammations,especially Crohn disease and less the ulcero ( hemorrha#ic rectocolitis and implicitly theassociated arthritis, is represented $y TBF inhi$itors * nfli'ima$, tanercept, /dalimuma$+.These medicines have positive effects in spondylitis and "emicade in particular have a

positive effect in Crohn disease. /t the same time, they are also successfully used incontrollin# peripherical arthritis and especially spinal arthritis 09A2. tanercept or adalimuma$ are administered %hen methrote'ate is not sufficient or $ecomes to'ic inchildren %ith poliarthritis. Tocili&uma$ is administered to patients %ith systemic idiophatic

@uvenile arthritis or %hen #lucocorticoids no lon#er have any effect or they $ecome to'ic0482.

n some cases, the arthritis associated to intestinal $o%el disease remains undia#nosedfor lon# periods of times as the daily activity of most patients is not influenced in any %ay.

hen articular manifestations occur, special attention must $e #iven to improvin# the painand delayin# as much as possi$le their evolution to%ards deformation and stiffness.Co"#lu io"

• The hi#h incidence of arthral#ia and non(infectious arthritis in children re-uiresspecial attention in associatin# thorou#h di#estive investi#ations in children %itharticular pain.

• The anti#ens from the environment and)or auto anti#ens *favoured $y specific #enetic patterns+ and cyto ines released from the intestinal inflammation can $e the cause of some inflammations of the @oint that can $ecome chronic.

• The fre-uent disa$lin# evolution of the articular inflammation, sometimesindependent of the evolution of the intestinal inflammation, re-uires the correctidentification and interpretation of the predictive mar ers *immunolo#ical,

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$iochemical, immunohistochemical etc.+. This is the ey factor in introducin# “at theri#ht moment” the treatment %ith immunosuppressive and)or $iolo#ical a#ents.

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Manifestari Reumatismale Engl Oct 2012