Non-microbial etiology: foreign body reaction maintaining post-treatment apical periodontitis

21 Pages·2004·1.88 MB·English

EndodonticTopics2003,6,114–134 CopyrightrBlackwellMunksgaard
PrintedinDenmark.Allrightsreserved
ENDODONTICTOPICS2003
Non-microbial etiology: foreign
body reaction maintaining post-
treatment apical periodontitis
P.N. RAMACHANDRAN NAIR
Thepolymerasechainreaction(PCR)isaneleganttechnologyforfaithfullyreplicatingandamplifyingthemaster
moleculeoflife,butavalidscientificprocedureremainsessentialwithoutwhichtheresultingdatahaveonlyvery
limitedvalue.Thepresenceofmicrobialinfectioninthecomplexapicalrootcanalsystemisthemajorcauseofpost-
treatment apical periodontitis in well-treated teeth. However, in rare cases, non-microbial etiological factors,
locatedbeyondtherootcanalsystem(withintheinflamedperiapicaltissues),canmaintainthediseaseinroot-filled
teeth. These factors include foreign body reaction to exogenous materials or endogenous cholesterol crystals,
a cystic condition of the lesion and extraradicular actinomycotic infections. This article addresses foreign body
reactionattheperiapex,asapathobiologicalfactor thatmaintainspost-treatmentapicalperiodontitis.
Apicalperiodontitisisessentiallyadiseaseofrootcanal because of the complexity of the root canal system
infection (1–3).Therational treatmentofthedisease, formed by a main and several accessory canals, their
therefore, has been by elimination or a substantial apical ramifications and anastomoses (15, 16) that
reductionof theinfectiousagentsfrom the root canal cannotbeinstrumented,cleaned,medicatedandfilled
and the exclusion of further pulp–canal infection by with existing instruments, materials and techniques.
root filling. When the root canal treatment is carried Further, there are extraradicular etiological factors –
out properly, healing of the periapical lesion usually located beyond the root canals, within the inflamed
followswithboneregeneration,whichischaracterized periapical tissue – that can interfere with post-
by a gradual reduction of the radiolucency on follow- treatmenthealingofapicalperiodontitis.
up radiographs (4–13). Nevertheless, due to several The etiology of post-treatment apical periodontitis,
reasons, complete healing or reduction of the apical persisting as asymptomatic radiolucencies in well-
radiolucencydoes notoccur inallroot-filledteeth.In treated teeth, has been ill characterized. Early investi-
certain cases, apical periodontitis still persists post- gations of periapical biopsies (17–21) have been
treatment, a condition commonly referred to as limitedbytheuseofunsuitablespecimens,inappropri-
‘endodontic failures’. It is widely acknowledged that atemethodsandcriteria ofanalysisthatfailed toyield
such post-treatment apical periodontitis occurs when relevant etiological information. Examples of proce-
rootcanaltreatmenthasnotadequatelycontrolledand dural limitations include: light microscopy without
eliminatedtheinfection.Problems,mostlyoftechnical correlativeelectronmicroscopicanalysis,evaluationof
nature,thatleadtopost-treatmentapicalperiodontitis randomratherthanserialsections,paraffinembedding
include:inadequateasepticcontrol, poor access cavity rather thanresin embeddingofspecimensandassign-
design, missed canals, inadequate instrumentation, ment of overly broad criteria such as ‘bacteria and/or
debridement and leaking temporary or permanent debris’,whichcanencompassmanypotentialetiologi-
fillings(14).Evenwhenthehigheststandardsandthe cal agents. During the 1990s, a series of carefully
moststringentproceduresarefollowed,apicalperiod- conducted investigations, which have taken into
ontitismaystillpersistasasymptomaticradiolucencies, account appropriate case selection and methods, have
114
Non-microbial etiology:foreignbodyreaction
shownthattherearefourbiologicalfactorsthatleadto surgery and the sampling procedures. Tissue samples
asymptomatic post-treatment apical periodontitis. thus contaminated with intraradicular microbes can
Theseareasfollows: givepositiveresultsforthepresenceofanextraradicular
(i) intraradicularinfectionpersistingintheapicalroot infection. This may explain the renewed reporting of
canalsystem(22); various microbes in the inflamed periapical tissue of
(ii) extraradicular infection, mostly in the form of asymptomaticpost-treatmentlesionsbyculture(36,37)
periapicalactinomycosis(23–26); and molecular techniques (38, 39) in spite of careful
(iii) foreignbodyreactiontoextrudedrootcanalfilling asepticsurgicalandsamplingprocedures.
(27), other foreign materials or endogenous Apartfromtheproblemofpossiblecontaminationof
cholesterolcrystals(28)and the samples with intraradicular microbes and the
(iv) cysticlesions(28). inabilityofthetechniquetodistinguishbetweenviable
It must be emphasized that of all these factors, andnon-viableorganisms,italsodoesnotdifferentiate
persistentinfectioninthecomplexrootcanalsystemis betweenmicrobesinphagocyticcellsfromextracellular
the major cause of post-treatment apical periodontitis microorganisms in periapical tissues. In summary, the
inwell-treatedteeth(22,29–31). problemofhowtosampletheinflamedperiapicaltissue
In a very recent investigation using a molecular and keep it separate from what is on and in the root
genetic technique (32), all the 22 investigated teeth apex is complex. While molecular genetic techniques
with ‘no symptoms’ but unresolved post-treatment offerprecisionandsophistication,theydonotsolvethe
apical radiolucencies revealed bacterial DNA in intrar- primary problem of how to sample accurately the
adicular samples. In this context, the importance of periapicalgranulomawithoutcontamination.
selecting appropriate cases for investigation cannot be Inrarecases,independentofalow-gradepresenceor
overemphasized. As for instance, five of the 22 teeth a total absence of intraradicular microbes, exogenous
‘had temporary (coronal) restorations’, a factor that materials trapped in the periapical area (27, 40),
would allow bacterial re-infection of the canals by endogenouscholesterolcrystalsdepositedinperiapical
possiblecoronalmicroleakage.Apartfromthepossible tissuesandacysticlesioncanperpetuateapicalperiod-
re-infectionand/orcontaminationthatcanoccureven ontitis after root canal treatment. The purpose of this
in teeth with permanent coronal restorations, the articleistoprovideacomprehensivereviewonaforeign
molecular technique does not differentiate between bodyreactionattheperiapexasapathobiologicalfactor
viable and non-viable organisms, but can pick up a thatcanmaintainpost-treatmentapicalperiodontitis.
minuscule amount of bacterial DNA that is amplified
using the polymerase chain reaction (PCR) (33),
resulting in an exponential accumulation of several Exogenous materials causing foreign
millioncopiesoftheoriginalDNAfragments.Thedata body reaction at the periapex
derivedfromthemoleculartechnique(32)requirevery
Root-fillingmaterials,otherendodonticmaterials(27,
careful interpretation in the light of the technique’s
40) and food particles (41) may reach the periapical
many advantages and numerous limitations, so as to
tissues and cause a foreign body reaction that may be
avoid reaching an overestimating conclusion that all
associated with radiolucency remaining asymptomatic
post-treatment apical periodontitis is caused by the
formanyyears(27).
presenceofintraradicularinfection.
Even greater caution is needed to interpret the
published data on the role of non-actinomycotic
Gutta percha
extraradicular infections in apical periodontitis affect-
ing well root-filled teeth. In addition to the possible The most widely used solid root canal filling material
‘extraneous’ sources, contamination of apical tissue is commercially prepared from gutta percha (trans-
samples with microbes from the infected root canal polyisoprene),thecoagulatedexudatefromPlaquium
remainsaconcern.Thisisbecauseinfectiousagentslive guttatreeofAsiaorfromsimilarlatexderivedfromthe
at the apical foramen of teeth affected by the primary Mimisops globsa tree of South America (42). Dental
(34) and post-treatment apical periodontitis (22, 35). guttaperchaconesarecomposedofabout20%ofgutta
Microbesinthatlocationcanbeeasilydislodgedduring percha, 60–75% zinc oxide and varying amounts of
115
Nair
metal sulfates for radioopacity, waxes and coloring macrophages and giant cells. The accumulation of
agents. Based on in vivo implantation experiments in macrophages in conjunction with the fine particles of
animals, gutta percha cones are considered to be gutta percha is significant for the clinically observed
biocompatible and well tolerated by human tissues impairmentinthehealingofapicalperiodontitis,when
(43–45). However, this view has not been consistent teetharerootfilledwithexcessofguttapercha.Piecesof
with the clinical observation that the presence of gutta gutta percha cones in periapical tissue can gradually
perchainexcessisassociatedwithinterruptedordelayed fragment into fine particles that in turn can induce a
healingoftheperiapex(4,6,9,11,27).Ingeneral,bulk typical foreign body reaction (27, 54, 55) and activate
forms of sterile materials with smooth surfaces placed macrophages (56). The latter are known to release a
within bone or soft tissue evoke a fibrous tissue battery of intercellular mediators that include proin-
encapsulation, while particulate materials induce a flammatorycytokinesandmodulatorsthatareinvolved
foreign body and chronic inflammatory reaction (46– inboneresorption(57–60).
50).Apartfromtheparticlesize,thechemicalcomposi- Further,commercialguttaperchaconesmaybecome
tionofguttaperchaisalsoofsignificance.Leachingzinc contaminatedwithtissue-irritatingsubstancesthatcan
oxide from gutta percha cones has been shown to be initiate a foreign body reaction at the periapex. In a
cytotoxic in vitro (51, 52), tissue irritating in vivo and follow-upstudyofnineasymptomaticpersistentapical
associatedwithadjacentinflammatoryreaction(53,54). periodontitis lesions that were removed as surgical
Tissueresponsetoguttaperchawasspecificallystudied block biopsies and analyzed by correlative light and
(54) using subcutaneously implanted Teflon cages in transmission electron microscopy, one biopsy (Fig. 3)
which the gutta percha evoked two distinct types of revealedtheinvolvementofcontaminatedguttapercha
tissue reaction. Large pieces of gutta percha were well (27).Theradiographiclesionpersistedasymptomatically
encapsulatedbycollagenandthesurroundingtissuewas and grew in size during a decade of post-treatment
freeofinflammation(Fig.1).Incontrast,fineparticles follow-up.Thelesionwascharacterizedbythepresence
of gutta percha evoked an intense, localized tissue of vast numbers of multinucleate giant cells with
response (Fig. 2), characterized by the presence of birefringent inclusion bodies (Fig. 4). In transmission
Fig.1. Guinea-pigtissuereactiontoguttapercha(GP)by1monthaftersubcutaneousimplantation(a).Largepiecesof
guttaperchaarewellencapsulatedbycollagenfibersthatrunparalleltothesurfaceoftheguttaperchaparticle.The
interfaceoftheguttaperchaparticleandthehosttissue(arrow)ismagnifiedinstagesin(b,c).Thegapbetweenthe
implantandthecollagencapsuleisartifactual.Notethenon-inflamed,healthysoftdelicateconnectivetissue.Original
magnifications:(a)(cid:1)42;(b)(cid:1)80;(c)(cid:1)200.
116
Non-microbial etiology:foreignbodyreaction
Fig.2. Disintegrated gutta percha particles that maintain post-treatment apical periodontitis. As clusters of fine
particles(a,b)theyinduceintensecircumscribedtissuereaction(TR)around.Notethatthefineparticlesofguttapercha
(GPinc,%ind)aresurroundedbynumerousmononuclearcells(MNC).Originalmagnifications:(a)(cid:1)20;(b)(cid:1)80;
(c)(cid:1)750;(d)(cid:1)200.From:NairPNR.Pathobiologyoftheperiapex.In:CohenS,BurnsRC.eds.PathwaysofthePulp,8
edn.StLouis:Mosby,2002.Reproducedwithpermission.
117
Nair
Fig.3. Twolongitudinalradiographs(insetanda)ofaroot-filledandperiapicallyaffectedleftcentralmaxillaryincisor
ofa54-year-oldman.Thefirstradiograph(inset)takenimmediatelyafterrootfillingin1977showsasmallexcessfilling
thatprotrudesintotheperiapex(arrowheadininset).Notetheexcessfillinghasdisappearedintheradiographtaken10
yearslater(arrowheadina)andshortlybeforesurgerywasperformed.Theapicalblock-biopsyremovedbysurgerydoes
notshowanyexcessfillingasisevidentfromthemacrophotographofthedecalcifiedandaxiallysubdividedpieceofthe
biopsy(b).RF,rootfilling;D,dentine;GR,granuloma.Originalmagnification(b)(cid:1)10.From(27).Reproducedwith
permission.
electron microscopy, the birefringent bodies were granuloma (63) and food-induced granuloma (64).
found to be highly electron dense (Fig. 5). Energy- Pulse granuloma has been reported in lungs (65),
dispersive X-ray microanalysis of the inclusion bodies stomach walls and peritoneal cavities (66). Experi-
using scanning transmission electron microscopy mental lesions have been induced in animals by
(STEM) revealed the presence of magnesium and intratracheal,intraperitonialandsubmucousintroduc-
silicon (Fig. 6). These elements are presumably the tion of leguminous seeds (67, 68). Periapical pulse
remnants of talc-contaminated gutta percha that granulomas areassociated with teeth grossly damaged
protruded into the periapex and had been resorbed bycariesandwithahistoryofendodontictherapy(41,
duringthefollow-upperiod. 69). Pulse granuloma is characterized by the presence
of intensely iodine and periodic acid-Schiff positive
hyaline rings/bodies surrounded by giant cells and
Oral pulse granuloma
inflammatorycells(41,68–70).Thecelluloseinplants
Oral pulse granuloma is a distinct histopathological has been suggested to be the granuloma-inducing
entity (61). It denotes a foreign body reaction to agent (67). However, leguminous seeds are the most
particles of vegetable foods, particularly leguminous frequently involved vegetable in such granulomatous
seeds such as peas, beans and lentils (pulses) that get lesions.Thisindicatesthatothercomponentsinpulses,
lodgedintheoraltissues.Thelesionsarealsoreferred suchasantigenicproteinsandmitogenicphytohemag-
toasthegiantcellhyalinangiopathy(61,62),vegetable glutinins, may also be involved in the pathological
118
Non-microbial etiology:foreignbodyreaction
119
Nair
Fig.5. Low-magnificationtransmissionelectronmicrographshowingtheprofilesofseveralgiantcellswithintheapical
periodontitisshowninFigs3and4.Notethepresenceofmanyslit-likeinclusionbodies(BB –BB ),whichcontaina
1 6
highlyelectron-densematerial.Thismaterialmayremainintactwithintheinclusionbodyormaybepushedawayfrom
itsoriginalsite(BB )ormayappeardisintegrated(BB andBB )bythetissueprocessing.NotethelinesofartifactsAL,
2 3 4
whicharecreatedbyportionsoftheelectrondensematerialhavingbeencarriedawaybytheknife-edge,leavingtracts
behind.Originalmagnification (cid:1)1880.From:(27).Reproducedwithpermission.
tissue response (67). The pulse granulomas are endodontic procedures (41). However, the epidemio-
clinically relevant because particles of vegetable foods logical incidence of pulse-induced post-treatment
can reach the periapical tissues via root canals of teeth apicalperiodontitisisunknown,asonlytwosuchcases
exposed to the oral cavity by trauma, caries or havebeenreportedintheliterature(41,70).
3
Fig.4. Abrightfieldphotomicrographofaplasticembeddedsemithin(2mmthick)sectionoftheapicalareashownin
Fig.1b.Notethelargeapicalperiodontitislesion(AP)(a).Thesamefieldwhenviewedinpolarizedlights(b).Notethe
birefringentbodiesdistributedthroughoutthelesion(b).Theapicalforamenismagnifiedin(c)andthedarkarrow-
headedcellsin(c)arefurtherenlargedin(d).Notethebirefringence(BB)emergingfromslit-likeinclusionbodiesin
multinucleated(N)giantcells.B,bone;D,dentin.Originalmagnifications:(a,b) (cid:1)23;(c)(cid:1)66;(d) (cid:1)330.From:
Nair PNR. Pathology of apical periodontitis. In: Ørstavik D, PittFord TR. eds. Essential Endodontology. Oxford:
Blackwell,1998.
120
Non-microbial etiology:foreignbodyreaction
Cellulose granuloma nantly cellulose-containing materials that are used in
endodonticpractice(71–74).Endodonticpaperpoints
Cellulose granuloma is the term used specifically for are utilized for microbial sampling and drying of root
pathological tissue reaction to particles of predomi- canals. Medicated cotton wool has been used in root
121
Nair
canals as well. Particles of these thermo-sterilized these materials might have been co-existing with
materials can easily dislodge or get pushed into the unidentified etiological agents such as the presence of
periapical tissue (74) so as to induce a foreign body intraradicularinfectioninthosecases.
reaction at the periapex. Therefore, extreme caution
should be exercised during clinical manipulation of Endogenous substances and foreign
endodonticpaperpoints(72).Thepresenceofcellulose body reaction
fibers in periapical biopsies with a history of previous
Tissue-irritating endogenous substances are mainly of
endodontictreatmenthasbeenreported(71–73).The
crystallinefineparticularnature.Bothendogenousand
overallincidenceofcellulose-inducedprimaryorpost-
exogenous crystals induce a pathological tissue re-
treatmentapicalperiodontitisisunknown.Thismaybe
sponse by triggering the cytokine-network-mediated
partly due to the inconspicuous nature of cellulose
inflammation, hard-tissue resorption and soft-tissue
material in periapical biopsies and the difficulty in
damage. Endogenous crystalline substances that have
identifying them without the application of special
beenshowntocausepathogenictissuereactioninclude
stains or micro techniques. In two histopathological
monosodium urate (gout), calcium phosphate dihy-
investigations in which 13 biopsies of post-treatment
drate (pseudogout), basic calcium phosphate (hydro-
apicalperiodontitiswereexamined,alldisplayedmate-
xylapatite) and cholesterol. Although the presence of
rial consistent with cellulose fibers (71, 72). The
cholesterolcrystalsinapicalperiodontitishaslongbeen
endodontic paper points and cotton wool consist of
observedtobeacommonhistopathologicalfeature,its
cellulose, which is neither digested by humans nor
etiologicalsignificancetopost-treatmentapicalperiod-
degraded by the body cells. They remain in tissues for
ontitishasnotyetbeenfullyappreciated.
long periods of time (73) and evoke a foreign body
reaction around them. The particles, when viewed in
Biology of cholesterol
polarized light, reveal birefringence due to the regular
structuralarrangementofthemoleculeswithincellulose Cholesterol (75) is a lipid of the steroid family that is
(71). Paper points infected with intraradicular micro- presentinallanimaltissues.Thenameisderivedfrom
organismscanprojectthroughtheapicalforameninto Chole-stereos meaning ‘bile-solid’ because of its occur-
theperiapicaltissue(Fig.7)andallowabiofilmtogrow renceingallstones.Cholesterolwasthefirststeroidto
aroundthepaperpoint(Fig.7c,d).Thiswillsustainand have its structure elucidated. It has the characteristic
intensifypost-treatmentapicalperiodontitis. core of the ‘cyclopentanoperhydrophenanthrene’ ring
(Fig. 8). Cholesterol is an important component of
animal cell membranes and is a determinant of
Other foreign materials
membrane properties. It is abundant in ‘membrane-
Amalgam,endodonticsealercementsandcalciumsalts rich’ tissues (myelin) and cells (secretory cells) and is
derived from periapically extruded calcium hydroxide the precursor of bile acids, provitamin D3 and several
{Ca(OH)2} also occur in periapical tissues. In a hormones(76).
histological and X-ray microanalytical investigation of
29apicalbiopsies,31%ofthespecimenswerefoundto
Cholesterol in health
contain materials compatible with amalgam and
endodontic sealer components (40). However, an Cholesterol is essential to life and most of the body
etiological significance of these materials has not been cholesterol is produced in the liver. The entire body
conclusively shown by experiments. It is possible that requirementofcholesterolcanbemetbyendogenous
3
Fig.6. High-magnificationtransmissionelectronmicrograph(c)oftheintactbirefringentbodylabeledBB inFig.5.
1
Notethedistinctdelimitingmembranearoundthebirefringentbody(BB).Energy-dispersiveX-raymicroanalysisofthe
electrondensematerialcarriedoutinscanningtransmissionelectronmicroscope(STEM:carriedoutatthepointwhere
thetwohairlinesperpendiculartoeachothercrossintheleftinset)revealedthepresenceofsilicon(Si),magnesium(Mg)
andlead(Pb)in(a),whereasanothersiteintheneighboringcytoplasmofthesamegiantcell(arrowheadintheright
inset)doesnotshowthepresenceofSiandMg(b).Leadanduranium(U)areusedforsectioncontrasting,andemission
incopper(Cu)isfromthesection-supportinggridmadeofcopper.Originalmagnification (cid:1)11000;insets (cid:1)3300.
From(27).Reproducedwithpermission.
122
Non-microbial etiology:foreignbodyreaction
Fig.7. Amassivepaper-pointgranulomaaffectingaroot-canal-treatedhumantooth(a).Thedemarcatedareain(b)is
magnifiedin(c)andthatinthesameisfurthermagnifiedin(d).Notethetipofthepaperpoint(FB)projectingintothe
apicalperiodontitislesionandthebacterialplaque(BP)adheringtothesurfaceofthepaperpoint.RT,roottip;EP,
epithelium; PC, plant cell. Original magnifications: (a)(cid:1)20; (b)(cid:1)40; (c)(cid:1)60; (d)(cid:1)150. From: Nair PNR.
Pathobiology of the periapex. In: Cohen S, Burns RC. eds. Pathways of the Pulp, 8th edn. St Louis: Mosby, 2002.
Reproducedwithpermission.
123