“Failu e in implan ehabili a ion in a pa ien wi h Se e e Congeni al
Neu openia”
AUTHORS:
Ma ín-Be ná M (1), Velázquez-Cayón RT (2), To es-Laga es D (3), Hi a-
Iglesias P (4), Bou e ache K (5), Mad id C (6), Gu ie ez-Pe ez JL (7)
(1) Mas e in O al Suge y. Uni e si y o Se ille.
(2) Mas e in O al Suge y. Uni e si y o Se ille.
(3) P o esso o O al Su ge y. Uni e si y o Se ille.
(4) Clinical Assis an P o esso o O al and Maxillo acial Su ge y. Uni e si y
o Michigan.
(5) P o eso o he Depa men o O al Medicine, O al Su ge y and Hospi al
Den is y. Uni e si y o Lausanne Medical School
(6) Head o he Depa men o O al Medicine, O al Su ge y and Hospi al
Den is y. Uni e si y o Lausanne Medical School
(7) Head P o esso o O al Su ge y. Uni e si y o Se ille.
ABSTRACT
In oduc ion .- Kos mann synd ome is an au osomal ecessi e diso de
ha p ecipi a es se e e congeni al neu openia (SCN). One o he mos
cha ac e is ic o al mani es a ions o his synd ome is se e e pe iodon al disease
wi h ex ensi e bone loss in he p ima y den i ion. This bone loss o en ex ends
in o he pe manen den i ion leading o p ema u e pa ial o o al eden ulism.
Objec i e.- This pape will e iew, discuss, and documen he indica ions
o implan placemen as well as he den al and medical managemen o pe i-
implan in ec i e complica ions in a pa ien wi h Kos mann synd ome.
Case epo .- The den al managemen o pa ien s wi h SCN has been
poo ly desc ibed in he li e a u e hus a . In his pape we epo a case o
den al implan ailu e in a 24 yea s old pa ien diagnosed wi h Kos mann
synd ome. This pa ien unde wen implan suppo ed ehabili a ion wi h 8 uppe
maxilla and 4 mandible den al implan s and e u ned o he Hospi al 5 mon hs
pos -ope a i ely wi h an implan ela ed submandibula abscess ul ima ely
equi ing emo al o he mandibula implan s despi e ex ended IV an ibio ics
he apy.
Discussion.- The e is cu en ly no a ailable da a o guide he use o
den al implan s in pa ien s a ec ed om Kos mann disease. We belie e he
mos likely cause o in ec i e o al complica ions in his pa ien popula ion occu s
du ing he su gical s ages o implan placemen as his gene ic
immunode iciency likely allows o inc eased abili y o oppo unis ic o al
mic o lo a o colonize he implan su ace as well as he o al so and ha d
issues.
Key wo ds: Kos mann Synd ome, Se e e congeni al neu openia, Implan
ailu e, Sys emic disease
“Failu e in implan ehabili a ion in a pa ien wi h Se e e Congeni al
Neu openia”
INTRODUCTION
I is well known ha a ious d ug ea men s and sys emic diseases may
comp omise he in eg i y o he o al issues. Likewise hese condi ions may
also a ec he iabili y o den al implan s and hei su ounding issue [1].
While ecommenda ions exis o he a oidance o den al implan s wi h ce ain
sys emic diseases [2], he scien i ic e idence o suppo such guidance is
lacking. Mo eo e , es ima ing he isk o implan ailu e in hese pa ien
popula ions is challenging as o en hese pa ien s a ely ecei e endo-osseous
implan s [3].
Se e e congeni al neu openia is one such disease ha may a ec he su i al
a e o den al implan s [4]. SCN, also known as Kos mann synd ome, is
inhe i ed in ei he an au osomal ecessi e (HAX-1 mu a ion) o au osomal
dominan (ELA-2 mu a ion) manne [6]. The es ima ed incidence o SCN is 1-2
cases pe million wi h equal dis ibu ion among gende s [5]. The condi ion is
usually diagnosed in he pe ipa um pe iod and p esen s wi h impai ed bone
ma ow myelopoiesis and a ch onic absolu e neu ophil coun (ANC) less han
500/μL. Bone ma ow examina ion o en e eals p omyelocy e / myelocy e
a es wi h li le e idence o ma u e g anulocy e o ma ion.
Mos pa ien s wi h SCN, including hose wi h Kos mann synd ome, a e
success ully ea ed wi h g anulocy e colony s imula ing ac o (G-CSF).
T ea men can lead o a 10-12 old inc ease in neu ophil coun and esul s in a
highe li e expec ancy o pa ien s wi h congeni al neu openia [7]. Un o una ely,
a ound 10% o pa ien s do no espond o his he apy. T ea men wi h G-CSF
has imp o ed he con ol o li e- h ea ening bac e ial in ec ions p e iously
common in hese indi iduals.
The mos common in ec ions a ec ing hese pa ien s a e median o i is,
cu aneous celluli is, pe i ec al abscesses, u unculi is, pneumonia, s oma i is,
se e e pe sis en gingi al in lamma ion and a ious uppe espi a o y in ec ions,
[9]. Pa ien s wi h SCN may also p esen wi h pe iodon i is [5]. Pe iodon al
mani es a ions ange om ma ginal gingi i is o apidly p og essi e pe iodon al
disease wi h ad ancing al eola bone loss a ec ing bo h p ima y and
pe manen den i ion.
Full mou h ehabili a ion using implan s in pe iodon ally heal hy pa ien s has
been well documen ed [10]. Howe e , implan he apy in pe iodon i is-
suscep ible indi iduals has been ques ioned. Pe iodon al pa hogens may
comp omise he success a e o implan he apy in pa ially eden ulous pa ien s.
Pe iodon al pa hogens we e adi onally belie ed o ha e been elimina ed wi h
he ex ac ion o all na u al ee h. The e o e an eden ulous pa ien wi h a his o y
o pe iodon i is was conside ed an app op ia e candida e o den al implan
placemen . Con a y o his belie , ecen esea ch on bac e ial lo a in pa ien s
who ha e been eden ulous o a leas one yea showed he p esence o
mul iple pe iodon al pa hogens such as Ac inomyces sp and Po phy omonas
gingi alis [11].
Den al managemen , including he applica ion o den al implan he apy, in
pa ien s wi h SCN has been poo ly documen ed in he li e a u e hus a . We
epo he i s case o ixed ull mou h ehabili a ion in a 24-yea -old pa ien wi h
Kos mann synd ome diagnosed a 18 mon hs o age.
CASE STUDY
CASE STUDY
The pa ien was diagnosed wi h omphali is a he age o ou mon hs and was
subsequen ly a ec ed a sho in e als by a se ies o in ec ious diseases such
as ecu en se e e o i is, o al ulce s, campilobac e gas oen e i is, cu aneous
muco mycosis and uppe and lowe espi a o y ac in ec ions leading o
pneumonia. Pe iphe al blood hemog am and bone ma ow aspi a e showing
ma u a ion a es and mu a ion o HAX-1 gene led o a inal diagnosis o
Kos mann synd ome a age 18 mon hs . The pa ien ’s diagnosis and ea men
was ca ied on a he Uni e si y Hospi al Vi gen del Rocío in Se ille.
A he age o 7, he pa ien had comple e ex ac ion o he p ima y den i ion due
o he p esence o ch onic gingi i is, gene alized gingi al ecession and g ade
III mobili y. Du ing he pa ien ’s la e adolescence, he pa ien had ch onic
un ea ed pe iodon al disease leading o he p og essi e loss o he pe manen
den i ion and was comple ely eden ulous a he age o 22 yea s. The inal
ea men plan consis ed o a ull-mou h implan ehabili a ion a e a a o able
clinical and adiological assessmen .
The implan ea men planning consis ed o a o al o eigh maxilla y implan s o
suppo a ixed p os he ic ehabili a ion, and 4 mandibula implan s o
s abiliza ion o an o e den u e (Figu e 1).
A ound he hi d pos ope a i ely pe iod he pa ien de eloped local in ec ious
symp oms consis en wi h pe i-implan i is and he subsequen loss o one
mandibula implan . Mild o al local signs o in ec ion pe sis ed o ou mon hs
despi e con inuous o al an ibio ic he apy.
A mon h 5 pos ope a i ely he pa ien de eloped acu e onse o dysphagia and
dis ess upon swallowing equi ing hospi al admission. The diagnosis was
consis en wi h implan - ela ed submandibula abscess. The ea men included
su gical incision, deb idemen and d ainage ia pen ose ube h ough he
sup ahyoid egion and daily in a enous in usion o an ibio ics ( ob amycin
200mg and clindamycin 600mg) o a o al o 4 days. Speci ic an ibio ic he apy
was selec ed acco ding o he esul s o an an ibiog am a e isola ion o wo
possible causa i e bac e ias (S ep ococcus in e medius and P e o ella). (Table
1)
Two days a e admission he emaining mandibula implan s we e emo ed.
Full blood coun (Table 2) showed a sligh ly low o al whi e blood cell coun (<
2.78 x 109L). Di e en ial whi e blood cell coun showed leukopenia mainly
associa ed wi h o al absence o neu ophils and pa ially hidden by eosinophilia
and monocy osis speci ic o Kos mann synd ome.
Th ee mon hs pos ope a i ely, o al and adiog aphic exams we e aken
demons a ing an asymp oma ic, ully healed disease- ee mandibula a ch.
DISCUSSION
Implan ology is unde going a con inuous ans o ma ion ega ding wha a e
conside ed ela i e and absolu e con aindica ions o implan he apy. Some
con o e sy exis s on he signi icance o sys emic diso de s as isk ac o s o
den al implan s ou come. While a ious sys emic diso de s and medical
he apies ha e been epo ed o po en ially comp omise he s abili y o den al
implan s, he e is li le e idence o suppo such associa ion since only ew
s udies compa e he occu ence o hese diso de s wi hin a con olled
en i onmen [1, 3].
The use o den al implan s in ol es b eaking a de ensi e ba ie such as he
o al mucosa, wi hin a habi a ich in bac e ial lo a. Since his ype o pa ien s
o en p esen s wi h uns able immune sys ems, e en when hey a e ecei ing
app op ia e ea men , [15, 16,17] i would be ad isable o weigh ca e ully he
cos /bene i o implan su ge y and he ange o he apeu ic op ions should be
me iculously assessed in ela ion o he pa ien ’s condi ion.
In ou case epo , he pa ien p esen s wi h SCE, a a e haema ologic immune
diso de commonly associa ed wi h se e e pe iodon i is. Va ious diso de s such
Papillon-Le e e synd ome, Down synd ome, Ehle s-Danlos synd ome,
Lange hans cell his iocy osis, Chediak-Higashi synd ome, hypophospha emia,
and Leukocy e adhesion de iciency ha e also been epo ed o p esen in
associa ion wi h gene alized pe iodon i is [4, 12, 13]
Thus, pe iodon al disease could be conside ed as a signi ican igge o ea ly
diagnosis o an unde lying sys emic disease due o i s i ulence in his ype o
pa ien s.
The p esen case s udy is no esol ed wi h he emo al o lowe jaw emnan
implan s, because as we can obse e in he di e en pano amic X- ays, uppe
implan s show bone loss o app oxima ely mo e han hal he size o he
implan . These implan s will be e ised in successi e ollow-up isi s in o de o
o e a mo e accu a e assessmen o he p esen case epo .
Despi e he lack o scien i ic e idence ega ding he possibili y o implan
ehabili a ion in pa ien s wi h hese diso de s, i would be easonable o hink
ha suscep ibili y o pe iodon i is associa ed o sys emic diso de s migh ha e a
nega i e in luence on he ou come o implan he apy. [14]
Al hough we a e conscious o he bias posed by he publica ion o posi i e
ou comes in clinical s udies and small se ies, in hose cases in which he
medical condi ions a e so se ious ha implan he apy has no been well-
documen ed ye , i is ex emely di icul o o e a highe le el o e idence [1].
Occasionally, he indica ion o o al implan s should be ho oughly e alua ed in
pa ien s wi h local o sys emic isk ac o s ha may in e e e wi h he implan
ea men s abili y. [18]
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FIGURES
Figu e 1. – Ini ial pano amic X- ay, i e mon hs a e inse ion o jaw implan s.
TABLES
Sample ype
Cu aneous abscess / so issue
G am inc ion > 25 PMN, absence o epi helial cells
Ae obic cul u e S ep ococcus in e medius is isola ed
Anae obic cul u e P e o ella sp is isola ed
An ibio ics S ep ococcus in e medius P e o ella sp
Desc ip ion
Values M.I.C Values M.I.C
Clindamycin S - R -
E y h omycin S - - -
Penicillin S - R -
Vancomycin S - - -
Amoxicyllin /
Cla ulanic acid
- - S -
Imipinem - - S -
Moxi loxacyn - - S -
Me onidazole - - S -
Table 1. Mic obiologic analysis and an ibiog am o pa ien s a admission. (M. I. C
Minimum inhibi o y concen a ion – S Sensi i e – R Resis an )
Cell ype
Values
Uni s
Range
Leukocy es
* 2.78 x10e9/L [3.8-11.5]
Neu ophils
* 0.0 x10e9/L [2.5-7.5]
Neu ophils %
* 0.0 % [25-65]
Lymphocy es
1.5 x10e9/L [1.5-4]
Lymphocy es %
* 53.2 % [20-53]
Monocy es
0.8 x10e9/L [0.2-0.8]
Monocy es %
* 27.7 % [2.5-11.5]
Eosinophils
0.47 x10e9/L [0.05-0.5]
Eosinophils %
* 16.90 % [0.3-5]
Basophils
0.06 x10e9/L [0.01-0.15]
Basophils %
* 2.2 % [0.6-1.8]
Table 2.- Hemog am a admission