Refractory Periodontitis Associated With Abnormal Polymorphonuclear Leucocyte Phagocytosis

8/14/2019 Refractory Periodontitis Associated With Abnormal Polymorphonuclear Leucocyte Phagocytosis

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14 Magnusson and Lindhe

loss of 2.46 mm (range: 1.56 to 3.90 mm),indicating that in some patients a considerableloss of attac hment is neede d to determin e pro-gression o f disease with a high level of probability.

Magnusson et aP also investigated the repro-ducibility of attac hment level measurement s us-ing the Florida Probe. With the use of fixedreference points on custom-made acrylic stents,a high level of agreement was achieved forattachment level measurements made by differ-ent e xaminers (mean SD = +_0.28 mm) or by asingle examiner during different visits (meanSD = +-0.33 mm). The highest agr eem ent be-tween attachment level measurements wasachieved when the measurements were per-formed at the same visit, even though the mea-surements were perf orm ed by two different exam-iners. It is significant that by using the tolerancemet hod, Magnusso n et al 5 established that theFlorida Probe was more sensitive in detecting atrue attachment loss than was the standardperiodontal probe. For the 10 subjects, the SDvaried from +-0.25 to 0.33 mm, with an averageof +_0.28 mm. With the standard manual probe,Haffajee et al 4 rep ort ed an average of -+0.82 mm,with a range of -+0.52 to 1.30 mm. Using threeSD as a threshold for attachment loss, the aver-age threshold in the Magnusson study5 would be0.84 ram, c omp are d with 2.46 mm tor Haffaj ee 4et al. Thus, it seems that progressive periodontaldisease could be detected earlier by the constant-force electronic probe.

Several reports indicate that measurements ofdee per pockets are difficult. 6+ In the study byHaffa jee et al 4 subjects were classified as havin gadvanced periodontal disease; the Magnussonstudy5 dealt with subjects havi ng minimal-to-earlydisease. However, when the Florida Probe wasused in subjects with severe periodontal disease,the SD was fou nd to be of the same ma gnit ude orlower in that gro up of subjects. Yang et al 1studied different probing designs to investigatethe reproducibility of the Florida Probe. Themaxim um prob ing error was found to be approxi-mately +_0.3 mm, which is considerably smallerthan that found in most previous studies. Theerrors associated with the periodonta l c onditionand probing effect were also estimated. Thevariance components obtained here can be usedfor determining the sample size in controlledclinical studies.

Jeffc oat et a111 have desi gned an electronicperiodontal probe that can automatically detectthe cemento-enameljunction. TheJeffcoat probeprovided highly reproducible measurements in10 human subjects with attachment loss rangingbetween 0.5 and 7.5 mm who were measured 10times f or 2 weeks. ~2 Th e overall me an SD of therepeated measurements was + 0.17 ram.

Two other electronic probes, the TorontoProb e 13 and the Flori da Disk Pr obe 14 have bee ndesigned to measure changes in attachm ent levelusing the occlusal surface or the incisal edge as areference point. The Toronto Probe works onconstant air pressure and measures attachmentlevel from the occlusal surface. In a study ofduplicate measurements in nine subjects, it wasfound that 82% of the measurements were within1 mm difference. The SD for all teeth was +_0.46.The Florida Disk Probe was used independentlyby Low et aP 4 and Os bor n et a115 to assessreproducibility of repeated measurements. Bothstudies resulted in highly reproducible measure-ments with low standard deviations betweenreplicate measure ments (mean SD = +0.26and +0.18 mm respectively). This probe doesnot require a prefabricated stent.

Gerlach et a116 descri bed repeatability of con-trolled pressure relative attachment level mea-surements collected in a multicenter clinical trialsetting. Relative attachment level measurementswere recorded for 213 patients by five differentexaminers at three study centers. For each pa-tient, measurements were recorded from fourperiodontally involved posterior teeth. Duplicateattachment level measurements were collectedat baseline, and after 3 and 6 months from eachselected site. A total of 2,453 duplicate measure-ments were collected during the study. Of these,215 (8.8%) pairs diff ered by mor e tha n 1.0 mm.Overall, the mea n SD of replicate meas ureme ntswas -+0.29 mm. The repeatability shown in thisstudy supports use of controlled pressure prob-ing to evaluate changes in periodontitis in multi-center studies.Electronic probes seem to be superior tomanual probes. In the studies described previ-ously, the range of overall SD for repeatedmeas urem ents of individual sites in differentsubjects was +_0.17 to +_0.32 ram. Regarding theability to detect significant attachment levelchanges, this is an improvement over earlierfindings.


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ad v is ab le t o b ase co n t i n u ed an t i b ac t e r i a l t h e r a p yon microb ia l suscep tib i li ty .

Antimicrobial Approach to theTreatment of Periodontal DiseasesC o n v en t i o n a l p e r i o d o n t a l t h e r ap y , i n c l u d i n g s cal -ing , roo t p lan ing , an d poss ib ly per i odo n ta l su r-gery , is st il l the t hera py o f cho ice and i s verys u cces s fu l p r o v i d ed t h a t t h e p a t i en t ad h e r e s t o ar eg u l a r m a i n t e n an c e s ch ed u l e . H o w ev e r , i n s o m ef o r m s o f d is ea se , an t i m i c r o b i a l t h e r ap y is ap p r o -p r i a t e a s an ad j u n c t t o co n v en t i o n a l t h e r ap y ( f o rreview4a,44). I n p a t i en t s w i t h ad u l t p e r i o d o n t i t i sad m i n i s t r a t i o n o f s y st em ic an t i b i ot i c s w i t h o u tm ech an i ca l t r ea t m en t h a s s h o w n l it tl e p r o m i s e .

Th e use o f sys temic te t r acycl ine in the t r ea t -m e n t o f j u v en i l e p e r i o d o n t i t i s i s w e ll d o cu -m e n t e d an d h as b een p r o v en e f f ec t iv e i n s up -press ing subg ing ival A actinomycetemcomitans. 26 Inp a t i en t s w i th r e f r a c t o r y p e r i o d o n t a l d i s ea s e s u b -g i n g i v a l p l aq u e ex h i b i t s a h i g h p e r cen t ag e o fmicroo rgan ism s wi th r es i s tance , especia l ly agains tt e t racy c l in e . T h e r e f o r e , M ag n u s s o n e t aP 9 s e-lec ted an t ib io t ics , based o n suscep t ib i l i ty tes t ing ,a s an ad j u n c t t o t r ea t p a t i en t s w i t h r e f r ac t o r yp e r i o d o n t a l d i s ea s e . T h e r e s u l t s w e r e co n s i d e r -ab l y b e t t e r t h a n t h o s e o b t a i n ed i n a p l aceb oco n t r o l g r o u p .

Recen t ly , r esearch has focused on local an t ib i -o t ic t h e r ap y t o ach i ev e a h ig h l o ca l d r u g co n cen -t r a t ion a nd to avo id side ef f ec ts obse rved wi thsys temic admin is t r a t ion . Favorab le r esu l t s haveb ee n d es c r i b ed w i t h t h e l o cal d e l i v e r y o f t e t racy -c l i n e ( 2 5 %) i m p r eg n a t e d e t h y l en e v in y l ace t a t efib er s, 45,46t h e ap p l i ca t i o n o f t e t r acy c li n e ( 2 %) i na l ip id gel , 47 and the app l ic a t ion o f me t ron i da-zole (25%) in l ipid gel . 4s

T h e u s e o f l o w er - t h an - n o r m a l d o s es o f t e t racy -c l i n e t o t r ea t p e r i o d o n t a l d i s ea s e h as b een i n ves -t iga ted by Ri fk in e t a l . 49 Th ey showe d tha t thet r ea t m en t w as e f f ec t i v e i n p r ev en t i n g a t t ach m en tloss in adu l t per iodon t i t i s pa t ien ts . Lo w doses o fte t r acycl ine ef f ec t ive ly inh ib i t pa tho log ica l ly ex-cessive collag ena se act ivi ty in gingival t issue. 5

Ging ival Crevicular FluidA n al y si s o f G C F s ho w s a n u m b er o f en zy m es ,m e t ab o l i c b y p r o d u c t s , s e r u m p r o t e i n s , an d o t h e rs u b s t ances r e l a t ed t o t h e i n f l a m m at o r y p r o cess ,t is s ue d eg r ad a t i o n , an d ce l l d ea t h . I d en t i f i ca t i o n

an d q u an t i f i ca t i o n o f t h e s e s u b s t an ces m ay p r o -v i de b e t t e r u n d e r s t a n d i n g o f b o t h t h e d y n a m i c san d m e t ab o l i c s tag es o f t h e p e r i o d o n t a l t is su es.

A n u m b e r o f en zy m es r e fl ec t i n g ti ss u e r em o d -e l i n g o r d e s t r u c t i o n h av e b een s t u d i ed . T h es einclude collagenase, [3-glucuronidase ( [3-G) , aryl-su l f a tase (AS) , and L-aspar ta te amino t r ans ferase(AST).

Vil lela et a151 stud ied colla geno lytic act ivi ty increv icu lar f lu id f rom sub jec ts w i th chron ic adu l tp e r i o d o n t i t i s, l o ca l i zed j u v en i l e p e r i o d o n t i t i s ,g ing iv i t i s , and f rom heal thy con t ro l sub jec ts .Am on g sub jec ts , co l lagenase ac t iv ity increa sedwi th sever i ty o f d i sease . A mo ng s ites, s ign i f ican tco r r e l a t i o n w as f o u n d b e t w een c r ev i cu l a r f l u idac ti v it y an d p o ck e t d ep t h i n ch r o n i c ad u l t p e r i -o d o n t i t i s an d i n l o ca l i zed j u v en i l e p e r i o d o n t i t i s ,but not in gingivit is .

B i r k ed a l - H an s en e t a152 r ep o r t ed t h a t n e i t h e rg ing ival c r ev icu lar f lu id f low nor co l lageno ly t icac ti vi ty a re g o o d i n d i ca t o r s o r p r ed i c t o r s o f b o n eloss . On the o the r ha nd , Ciancio e t a153 sugges tedthat g ing ival c r ev ic u lar f lu id co l lageno ly t ic ac tiv -i ty m ay b e o f d i ag n o s ti c v a l u e i n p e r i o d o n t a ld i s ea s e , h o w ev e r , t h ey d i d n o t m o n i t o r a t t ach -m en t level changes . I t i s c lear tha t fu r th er inves ti -ga t ion i s need ed to es tab l i sh i f co l lagen ase levelscan b e u s ed a s i n d i ca t o r s o f p ro g r e ss i v e p e r i o d o n -tal disease.

Lam ster e t a154 evaluate d crev icu lar f lu id fo rco l l ag en ase , [3-G , an d A ST d u r i n g d ev e l o p m en to f ex p e r i m en t a l g i n gi vi ti s i n h u m an s . T h ey f o u n dt h a t a f t e r 4 w eek s t h e ab s o l u t e am o u n t o f ac t iv eco l l ag en as e h ad i n c r eas ed 5 5 0 % i n i n t e r p r o x i -mal ar eas . For in terp rox imal s i tes the increase in[3-G activi ty was 180% an d for AS 240% . T hus,these enzy me levels cor r e la t ed pos i t ive ly wi thi n c r eas ed g i n g i v a l i n f l am m at i o n , a l t h o u g h i n -creases in speci f ic enzyme levels lagged s l igh t lybe h in d increa ses in g ingival index . Ha rpe r e t a155evalua ted lysosomal [3-G and AS and cy top lasmicl ac t a te d eh y d r o g en a s e ( L D H ) e n zy m e ac ti vi tyan d t h e co m p o s i t i o n o f s u b g in g i va l p l aq u e f l o r ain pat ien ts w i th adu l t p er iodon t i t i s . [ 3 -G levelsco r r e l a t e d s i g n if i can t ly w it h p o p u l a t i o n s o f s p i ro -chetes , P intermedius, Pgingivalis, and to ta l l actose-negat ive b lack-p igment ing Bacteroides (BPB) . LDHact iv i ty showe d a s ign i f ican t pos i t ive co r re la t ionwith levels of B gingivalis and to ta l l ac tose-negat ive BPBs . AS levels cor re la ted s ign i f ican t lywith B gingivalis only . In these s tud ies no a t -


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Current Concepts in Diagnosis and Treatment 17

t e m p t s w e r e m a d e t o c o r r e l a t e i n c r e a s e s i n l ev e lso f t h e s e e n z y m e s t o c h a n g e s i n a t t a c h m e n t .

A S T i s a n i n t r a c e l l u l a r e n z y m e t h a t i s r e l e a s e dand can be de t ec t ed i n c rev i cu l a r f l u id a s a r e su l to f c e ll dea th . Ch am ber s e t a156 and Pe r ss on e t aP 7h a v e sh o w n t h a t A S T m e a s u r e m e n t s c o r r e l at ew i t h g in g i v al i n f l a m m a t i o n a n d s e e m t o d i f fe r e n -t i a t e s i te s wi th spon tane ous ly occ ur r ing g ing iv i t isin s teady sta tes , f rom si tes wi th ac t ive gingivali n f l a m m a t i o n . I n a l o n g i t u d i n a l s tu d y, C r a w f o r de t a158 show ed tha t e l eva t ed l evel s o f AST ing ing iva l c rev i ce samp le s exh ib i t ed a s t ron g co r re -l a t i o n w i t h l o s s o f a t t a c h m e n t .

P r o s t a g l a n d i n E2 is r e p o r t e d t o b e a p r i n c i p a lb i o c h e m i c a l m e d i a t o r o f p e r i o d o n t a l t is s u e d e -s t r u c t i o n i n h u m a n s . T h e r e is a c l e a r a s s o c i a ti o nb e t w e e n t h e l ev e ls p r e s e n t w i t h in t h e p e r i o d o n -t a l t i s sue s and c rev i cu l a r f l u id and the s t a t e o fpe r iod on ta l hea l t h . 57-61 W hen cons ide r in g g ing i -v it is , a d u l t p e r i o d o n t i t is , a n d j u v e n i l e p e r i o d o n t i -t i s , c rev i cu l a r f l u id l eve l s a re l ow o r nonde t ec t -a b l e in h e a l t h , a n d a r e e l e v a t e d m a r k e d l y w i t hinc rea sed d i sea se seve r i t y . Ex t reme ly h igh l eve l so f p r o s t a g l a n d i n E2 a r e p r e s e n t a t p e r i o d o n t a ls i te s wi th ac t i ve loss o f a t t a chm ent . In s i t e s t ha ta r e i n r e m i s s i o n o r s h o w i n g n o l os s, lo w c o n c e n -t r a t io n s a r e f o u n d . I t c an b e c o n c l u d e d t h a t h i g hl evel s o f p ros t ag l and in Ez cons t i t u t e a s i gn i f i c an tac t i ve d i sea se i nd i ca to r and tha t a d i agnos t i c k i ta s s es s i ng c o n c e n t r a t i o n c o u l d b e a v a l u ab l e t o o l .

A n u m b e r o f s o l ub l e m e d i a t o r s a r e p r o d u c e db y i n f l a m m a t o r y c el ls . T h e i d e n t i f ic a t i o n o f i n t e r -l e u k i n s a n d c y t o k i n e s t h a t c o u l d c o n t r i b u t e t ot i s s u e d e s t r u c t i o n i n p e r i o d o n t a l d i s e a s e h a sinc rea sed i n t e re s t i n c re~icu l a r f l u id l eve l s o fthe se me dia tor s. 62,63

Anti-inflammatory Approach to theTreatmen t of Periodontal DiseasesOve r t he l as t yea r s , cons ide rab l e i n t e re s t ha sb e e n f o c u s e d o n t h e u s e o f n o n s t e r o i d a n t i-i n f l a m m a t o r y d r u g s t o m o d u l a t e t h e h o s t r e-s p o n s e a n d r e s e a r c h h a s s h o w n t h a t s u c h c o m -p o u n d s c a n r e t a r d b o n e l o s s . C o n t r o l l e d s t u d i e sh a v e n o t e d t h is e f f e c t i n a d u l t a n d r e f r a c t o r yp e r i o d o n t a l d i s e as e u s i n g s y s t em i c f l u r b i p r o f e nt h e r a p y a n d i n r a p i d l y p r o g r e s s i v e p e r i o d o n t a ld i s e a s e u s i n g n a p r o x e n o r m e c l o t e n a m a t e s o -di um the rap y. 64-68

B e c a u s e o f t h e c o n c e r n o f si d e e f f e ct s w i t h t h euse o f sys t emic t he rapy 69 o f t he se d rugs , t he

c o n c e p t o f lo c al t h e r a p y h a s b e e n a p p r o a c h e d . 7I n a 6 - m o n t h c o n t r o l l e d s tu d y, t h e e f f e c t o n b o n eh e i g h t w a s e v a l u a t e d f o r t h r e e d i f f e r e n t r e g i -m e n s : k e t o r o l a c r i n s e ( 0 . 1% ) w i t h p l a c e b o c a p-su l e twice da i l y (BID) ; f l u rb ip ro fen capsu l e (50m g ) w i t h p l a c e b o r i n s e B I D ; o r p l a c e b o c a p s u l ea n d p l a c e b o r i n s e B I D . S i g n i f ic a n t b o n e l o ss w aso b s e r v e d i n t h e p l a c e b o g r o u p b u t n o t i n t h ef l u r b i p r o f e n o r k e t o r o l a c r i n s e g r o u p s . D a t ai n d i c a t e t h a t t o p i c a l a p p l i c a t i o n o f k e t o r o l a c m a yb e b e n e f i c ia l in t h e t r e a t m e n t o f a d u l t p e r i o d o n -ta l d isease .

SmokingS m o k i n g s e e m s t o b e a n i m p o r t a n t r i s k f a c t o r f o rp e r i o d o n t a l d i s e as e s a n d f o r t h e r e f r a c t o r y f o r min pa r t i cu l a r . M agnu sso n e t a171 and McF ar l anee t a172 rep or t ed t ha t i n two g rou ps o f 21 an d 31re f ra c to r y pa t i en t s , 19 and 28 , r e spec t ive ly had ah i s t o r y o f s m o k i n g . S m o k i n g h a s a ls o b e e n c o n -s i d e r e d a m a j o r r is k i n a d u l t c h r o n i c p e r i o d o n t a ld i sea se . 7~-7~ Sm oki ng ha s a nega t ive im pac t onh e a l i n g a f t e r b o t h n o n s u r g i c a l a n d s u r g ic a l p e r i -odo n ta l t he rapy . 79,s I t ha s a l so be en sugge s t edt h a t s m o k i n g is a s s o ci a t e d w i th i n c r e a s e d r i sk o fs u b g i n g i v a l i n f e c t i o n a n d t h a t s m o k i n g m a ym o d u l a t e t h e p e r i o d o n t a l f l o ra , s l

Immunizat ionE x p e r i m e n t s u s i n g v a c c i n a t i o n a g a i n s t s p e c i f i cp e r i o d o n ta l p a t h o g e n s h a ve b e e n p e r f o r m e d b ys e v e r a l r e s e a r c h g r o u p s w i t h t h e m a i n g o a l o fe l i m i n a t i n g e x i s t i n g p a t h o g e n s a n d p r e v e n t i n gs u b s e q u e n t c o l o n i z a t i o n a n d g r o w t h . M c A r t h u re t a l s2 d e s c r i b e d t h e m o d u l a t i o n o f c o l o n i z a t i o nb y b l a c k - p i g m e n t e d b a c t e r i a in s q u i r r e l m o n k e y sb y i m m u n i z a t i o n w i th P gingivalis. E b e r s o l e e ta l a3 r ep or t ed t ha t P gingivalis i m m u n i z a t i o n s i g -n i f ic a n t ly r e d u c e d t h e e m e r g e n c e o f t h is s p e ci e sd u r i n g d i s e a s e p r o g r e s s i o n i n l i g a t u r e - i n d u c e dd i sea se i n Macacafascicularis. H o w e v e r , i m m u n i -za t i on wi th P intermedia h a d m i n i m a l e f f ec t o nt h e s u b g i n g i v a l p l a q u e i n t h is p r i m a t e . P e r s s o n e ta l s4 r e p o r t e d t h a t a n t i b o d y t i t e r a n d m a x i m u mp e r c e n t a g e o f P gingivalis in M fascicularis w e r ei n v e r se l y c o r r e l a t e d , i n d i c a t i n g t h a t a h u m o r a li m m u n e r e s p o n s e m a y b e e ff e ct iv e i n r e d u c i n g Pgingivalis o v e r g r o w t h . A l t h o u g h t h e s e a n i m a le x p e r i m e n t s l o o k p r o m i s i n g , i t i s n o t r e a s o n a b l e


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18 M a g n u s s o n a n d L i n d h e

t o a s s u m e t h a t i m m u n i z a t i o n i n h u m a n s w i l l b euse d in the for e se e ab le fu tur e .

R e f e r e n c e s

1. Gibbs CH, Hir schfeld JG, Lee JG, et al. Description andclinical evaluation of a new computerized periodontalpr ob e- -t he Florida Pro be.J Clin Periodonto11988; 15:137-144.

2. Magnusson I, Fuller ~%', Heins PJ, et al. Correlationbetween electronic and visual readings of pocket de pthwith a newly developed constant force probe. J ClinPeriodontol 1988;15:180-184.

3. Goodson JM, Kondo n N. Periodontal pocket dep thmeasure ments by fiber optic technology. J Clin Dent1988;1:35-38.

4. Haffajee AD, Socransky SS, Goodson JM. Com paris on ofdifferent data analysis for detecting changes in attach-me nt level. J Clin Pe rio don tol 1983; 10:298-310.

5. Magnusson I, Clark WB, Marks RG, et al. Attachmentlevel measurements with a constant force electronicprobe. J Clin Periodontol 1988;15:185-188.

6. Glavind L, L6e H. Errors in the clinical assessment ofperio donta l destruc tion..[ Peri odon t Res 1967;9:180-184.

7. L6e H, Aner ud A, Boysen H, et al. The natural h istory ofperiodontal disease in man. J Periodontol 1978;49:607-620.

8. Van der Velden U. Probing torce and the relationship ofthe pro be tip to the p eriod onta l tissues. J Clin Periodo n-to11979;6:106-114.

9. Goods onJM, Tan ner ACR, Haffajee AD, et al. Patterns ofprogression and regression of advanced destructive peri-odonta l dis eas e.J Clin Periodonto11982;9:472-481.

10. Yang MCK, Marks RG, Magnusso n I, et al. Reproduci bil-ity of an electronic probe in relative attachment levelmeasurements.J Clin Periodonto11992;19:541-548.

11. Jeffc oat MK, Williams RC, Hohna n BL, et al. Dete ction o factive alveolar bone destruction in human periodontaldisease by analysis of radiopha rmac eutica l uptake af ter asingle injection of 99m-Tc-methylene diphosphonate.J Periodontol Res 1986;21:677-684.

12. Jeffc oat MK, Jeffc oat RL, Captain K, et al. Attac hmen tlevel probing with automated CEJ detection: Clinicaltrial s.J Dent Res 1989;68:236 (A440).

13. Bir ek P, McCull oeh CAG, Hardy V. Gingival at tac hmen tlevel measurements with an automated periodontalprobe. J Clin Pe rio don tol 1987; 14:472-477.

14. Low SB, Taylor M, Marks RG, et al. Measuring attach-ment level with an electronic disk probe. J Dent Res1989;68:359 A.

15. Osborn J, Stolten bergJ , Huso B, et al. Comparison ofmea sure men t variability using a stand ard and co nstantforc e pr obe. J Periodonto11990;61:497-503.

16. Gerlach RW, Mere dith MP, Cavana ughJn PE Repeatabil-ity of controlled pressure periodontal attachment mea-sure ment s in a multi-c enter setting. J Dent Res 1995;74:128A.

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Refractory Periodontitis Associated With Abnormal Polymorphonuclear Leucocyte Phagocytosis