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ORAL MANIFESTATION OFSYSTEMIC DISEASES
ORAL MEDICINE, DIAGNOSIS AND RADIOLOGY
By
Dr. Puneeta Vohra
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CONTENT
SR.NO TOPIC PAGE NO.1. Introdu t!on "#$%. Ga&tro!nte&t!na' D!&order& (#%%". )e*ato'o+! a' D!&order& %"#$%
. Endo r!ne D!&order& $"#1%--. I**uno'o+! a' d!&order& 1% #1 (
. Nutr!t!ona' D!&order& 1/0#1$(/. Rena' D!&order& 1(0#1($. In e t!ou& D!&ea&e 1(/#% -(. Se2ua''y Tran&*!tted D!&ea&e& % #%(010. B!3'!o+ra4hy %(1#"0%
Obstacles are those frightful things you see,
When you take your eyes off your goal.
Introdu t!on
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It is often said that mouth is the mirror of one s o!n health. The
manifestations, !hich occur in oral ca"ity for any systemic disease, are due
to its embryonic origin 1. #entistry is one of se"eral areas of medicine
concerned !ith oral mucosal lesions !hich are many times indicator for underlying systemic illness to make a sus$ected diagnosis. % number of
these may de"elo$ because of com$lication of or as $artial manifestation of
underlying systemic disease. These may also occur due to $atient s
concurrent drug thera$y for underlying systemic conditions.
It is no! !idely recogni&ed that certain systemic disease such as diabetes
mellitus any many immune disorders may increase risk for $eriodontal
diseases. The hy$othesis that oral conditions such as $eriodontal infections
may be risk factors or indicators for im$ortant medical outcomes re$resents
a $aradigm shift in thinking about causality and the directionality of oral and
systemic association. This $aradigm shift is enca$sulated by ne! term the
$eriodontal medicine !hich refers to $ers$ecti"e that $eriodontal disease is
interrelated !ith systemic health in im$ortant !ays.
The conce$t that oral infections such as $eriodontitis, caries and candidiasis
can ad"ersely affect systemic health is not ne!. %t the end of last century a
theory of focal infection de"elo$ed, that local 'foci of infection !ere
res$onsible for initiation and $rogression of "arious inflammatory systemic
conditions like arthritis, sub acute bacterial endocarditis, $e$tic ulcers etc. a
significant recent ad"ances in health care has been the mo"ement to!ards a
e"idence based $ractice. The im$ortant as$ect of this is risk assementin"ol"ing classification of indi"idual $robability o ac(uiring disease.
The oral ca"ity might be thought to be the !indo! to the body. Oral lesions
and sym$toms are usually the result of local disease, but can be earliest
indication of, or in some instances may be the $rimary features in, $atients
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!ith systemic disease. Oral manifestations can some times lead to diagnosis
alternati"ely* systemic disease may re(uire oral health care to be modified
for $atients or o$erators safety. Oral ca"ity reflects the state of systemic
health more fre(uently than other $arts of body. E"en in ancient timese+amination of mouth and tongue !as gi"en great im$ortance. The oral
tissues are in direct $hysical continuity !ith rest of body and they are also
related "ia blood, lym$hatics, and ner"e $ath!ay. #entist has an im$ortant
role in $re"enti"e medicine as many systemic diseases ha"e $rimary oral
manifestations.
Indi"iduals in oral medicine $artici$ate in interdisci$linary medical care in
the areas of oral manifestations of systemic disease, oral oncology, $ain,
histo$athology !hich are fre(uently hos$ital based ser"ices.
These oral manifestations must be $ro$erly recogni&ed if the $atient is to
recei"e a$$ro$riate diagnosis and referral for treatment. The lesions of the
oral mucosa, tongue, gingi"a, dentition, $eriodontium, sali"ary glands, facial
skeleton, e+tra oral skin and other related structures are caused by some of
the more common systemic diseases.
-ost of these manifestations are nons$ecific but should alert the dentist to
the $ossibility of concurrent systemic disease or latent systemic disease that
may de"elo$ subse(uently.
O %/ -E#ICINE is the s$ecialty of dentistry that is concerned !ith theoral health care of medically com$romised $atients and !ith the diagnosis
and non surgical management of medically related disorders or conditions
affecting the oral and ma+illofacial region. Oral medicine s$ecialists are
concerned !ith the non surgical medical as$ects of dentistry. These
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s$ecialists are in"ol"ed in the $rimary diagnosis and treatment of oral
diseases that do not res$ond to con"entional dental oroma+illofacial surgical
$rocedures, recognition of the interaction of oral and systematic health
integration of medical and oral health care, management of $harmacothera$eutics necessary for treatment of oral and systemic diseases
and in"estigation of the etiology and treatment of oral diseases through basic
science and clinical research
% disease is an abnormal condition of an organism that im$airs bodily
functions. In human beings, disease is often used more broadly to refer to
any condition that causes discomfort , dysfunction , distress, social $roblems,
and or death to the $erson afflicted, or similar $roblems for those in contact
!ith the $erson. In this broader sense, it sometimes includes in3uries,
disabilities , disorders, syndromes , infections , isolated sym$toms , de"iant
beha"iors , and aty$ical "ariations of structure and function, !hile in other
conte+ts and for other $ur$oses these may be considered distinguishable
categories
% systemic disease is one that affects a number of organs and tissues, or
affects the body as a !hole although most medical conditions !ill e"entually
in"ol"e multi$le organs in ad"anced stage
Oral lesions and sym$toms are usually the result of local disease, but can be
the indication of, or in some instances may be main features in, $atients !ithsystemic disease .Oral manifestation can some time lead to diagnosis.
%lternati"ely, systemic diseases may re(uire oral health care to be modified
for $atients or o$erators safety, many systemic diseases can $roduce oral
manifestations furthermore, drugs used in treatment of systemic disease can
4
http://en.wikipedia.org/wiki/Pain_and_nociceptionhttp://en.wikipedia.org/wiki/Dysfunctionhttp://en.wikipedia.org/wiki/Injuryhttp://en.wikipedia.org/wiki/Disabilityhttp://en.wikipedia.org/wiki/Syndromehttp://en.wikipedia.org/wiki/Infectionhttp://en.wikipedia.org/wiki/Symptomhttp://en.wikipedia.org/wiki/Behaviorhttp://en.wikipedia.org/wiki/Human_variabilityhttp://en.wikipedia.org/wiki/Organhttp://en.wikipedia.org/wiki/Pain_and_nociceptionhttp://en.wikipedia.org/wiki/Dysfunctionhttp://en.wikipedia.org/wiki/Injuryhttp://en.wikipedia.org/wiki/Disabilityhttp://en.wikipedia.org/wiki/Syndromehttp://en.wikipedia.org/wiki/Infectionhttp://en.wikipedia.org/wiki/Symptomhttp://en.wikipedia.org/wiki/Behaviorhttp://en.wikipedia.org/wiki/Human_variabilityhttp://en.wikipedia.org/wiki/Organ
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some times ha"e effects on mouth or sali"ary glands or dictate modification
of oral health care .5o!e"er in $ractical terms $roblem is not often serious
because routine restorati"e and orthodontic care under local anaesthesia can
be carried out on most $atients !ithout any significant ha&ard .-a3or $roblems are !ith $atients suffering from bleeding disorders , allergies, on
corticosteroids, or cardiac $roblem .Not only systemic disease affect mouth
but, con"ersely , systemic disease can originate from mouth ,usually as
conse(uence of infection e+am$le infecti"e endocarditis
Educational goals and ob3ecti"es of $erforming oral manifestation of
systemic diseases for dentist oral $hysician6
1. The #entist oral $hysician !ill $ro$erly inter"ie! and e+amine the
$atients and accurately identify the oral diseases and risk factors .Ob3ecti"es
!ill be to $erform an a$$ro$riate dietary history focusing on factors that
increase the risk of oral diseases such as tobacco and alcohol use and the
fre(uency of sugar intake $erform an a$$ro$riate oral e+amination that
effecti"ely "isuali&es all intra oral hard and soft tissue, and identifies normal
landmarks. Correctly identify common oral abnormalities including dental
caries, $eriodontal disease, oral infections, and common benign and
malignant oral lesions. 7enerate an a$$ro$riate differential diagnosis for
common abnormal oral findings and a$$ro$riately document oral findings
and diagnoses.
2. #entist oral $hysician !ill understand the im$ortance of $re"enti"e care
in the maintenance of oral health and !ill be able to counsel $atients and
families a$$ro$riately regarding a$$ro$riate diet for all age grou$
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a$$ro$riate inter"als for dental care and selection of an a$$ro$riate dental
$rofessional. It !ill be a link bet!een oral and systemic disease.
). #entist oral $hysician !ill understand normal anatomy and function of
the oral ca"ity. 5e !ill correctly identify normal anatomy and describe the
function of the muscles, sali"ary glands, teeth, and tem$oromandibular 3oint,
describe common de"elo$mental abnormalities of the oral ca"ity and their
im$act on function.
0. #entist oral $hysician !ill learn the e$idemiology and $atho$hysiology of
oral diseases, and ho! oral $roblems affect $atients ability to li"e !ith other chronic illnesses, he !ill be able to describe the relationshi$s bet!een oral
diseases and systemic diseases, including the oral manifestations of tobacco
use 9either smoked or che!ed:, systemic medications, alcohol use,
autoimmune disease, and immune deficiency, and associations !ith
cardio"ascular disease, $regnancy, and diabetes mellitus.
4. #entist oral $hysician !ill understand common $oints of intersection
bet!een medical and dental care, and the $hysician s role in those situations.
;nderstand the risks and indications for tem$orary cessation of
anticoagulation thera$y in $re$aration for dental surgery. 5e !ill understand
ho! screening for oral disease in $rimary care can identify $atients in need
of treatment and $re"enti"e inter"entions and ho! this can yield to
im$ro"ed outcomes identify screening methods that can be used by a $rimary care $hysician to detect oral $roblems, describe ho! screening can
yield im$ro"ed outcomes and create and sustain effecti"e thera$eutic
relationshi$s.
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/ast but not the least effecti"ely communicate the im$ortance of oral health
in the conte+t of total health.
GASTROINTESTINAL DISORDERS
DISEASES OF THE UPPER DIGESTIVE TRACTGastro esophageal Refux Disease
Hiatal Hernia
DISEASES OF THE LOWER DIGESTIVE TRACT
Disorders o the Stomach
Disorders o the Intestines
=
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DISEASES OF THE HEPATOBILIARY SYSTEM Jaundice
Alcoholic Hepatitis
Drug-Induced Hepatotoxicity
Li er !irrhosisGASTROINTESTINAL SYNDROMES
"ating Disorders# Anorexia and $ulimia
Gardner%s Syndrome
&lummer-'inson Syndrome
&eut(-Jeghers Syndrome
!o)den%s Syndrome
INTROD5CTION To $ro"ide safe and a$$ro$riate dental care, dentists are ty$ically concerned
!ith the $ro$er diagnosis of oral manifestations of gastrointestinal disorders,
homeostasis, risk of infection, drug actions and interactions, the $atient s
ability to !ithstand the stress and trauma of dental $rocedures, and $ro$er
medical referral 9!hen necessary:.
The digesti"e system is com$osed of the eso$hagus, stomach, small
intestine, and large intestine. Each of these com$onents $erforms s$ecific
functions as ingested substances mo"e through the different anatomic areas.
%dditionally, the e+ocrine functions of the $ancreas, li"er, and gall bladder
combine to com$lete the assimilation of dietary calories and nutrients.
>oth dentists and gastroenterologists ha"e their $rimary focus !ithin thealimentary canal. The common embryogenesis of the oral ca"ity and
gastrointestinal tract is occasionally reinforced for the clinician !hen he or
she finds heteroto$ic gastric mucosal cysts in the oral mucous membranes or
on the tongue 2,) . 5o!e"er, in addition to these relati"ely rare anomalies, the
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$aths of gastroenterologists and dentists cross (uite fre(uently in clinical
$ractice.
The oral ca"ity is the $ortal of entry to the 7I tract. /ined by stratifieds(uamous e$ithelium, the tissues of the mouth are often in"ol"ed !hen
indi"iduals ha"e conditions affecting the 7I system. These may be immune
mediated or chemically mediated $rocesses. There is hy$ersensiti"ity to
gluten, a constituent of !heat and other cereals not uncommon in some
ethnic grou$s such as celtic descendants, though not al!ays recogni&ed if
not se"ere.
GASTRTOESOP)AGAL RE6L57 DISEASE
7astroeso$hageal reflu+ disease 97E #: is one of the most commonly
occurring diseases affecting the u$$er gastrointestinal tract. The incidence of
7E # is increasing in the de"elo$ed $o$ulation e+$erience heartburn daily.
@ym$toms can range from mild to se"ere. There is no difference bet!een the
$ercentage of men and the $ercentage of !omen that are affected by 7E #.
7E # is a disease !hich has a significant effect on one s acti"ities of daily
li"ing as !ell as an economic effect on indi"iduals and society. #uring
gastroeso$hageal reflu+, gastric contents 9chyme: $assi"ely mo"e u$ from
the stomach into the eso$hagus.While this can occur normally, it may be
attributed to 7E # if it is associated !ith sym$toms. 7E # is often
considered a syndrome because it can $resent !ith a !ide "ariety of
sym$toms. Aatients may e+$erience mild sym$toms !ith an eso$hagus that
a$$ears to be clinically normal or they may ha"e se"ere sym$toms !ith
surface abnormalities that can be detected !ith an endosco$e. % $resum$ti"e
diagnosis of 7E # may be made for any sym$tomatic condition that is the
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result of gastric contents mo"ing into the eso$hagus. unctional bo!el
disease is a syndrome !ith similar sym$toms and may mimic 7E #* it is
often misdiagnosed as 7E #. 5eartburn is the cardinal sym$tom of 7E #
and is defined as a sensation of burning or heat that s$reads u$!ard from thee$igastrium to the neck. 0 %lthough sym$toms of 7E # can be (uite "aried,
they are $rimarily sym$toms that are associated !ith the se(uelae of
mucosal in3ury. These resultant in3uries include eso$hagitis, eso$hageal
ulceration, stricture, and dys$lasia. Chest $ain is another im$ortant sym$tom
that is related to disorders of the eso$hagus. Chest $ain can mimic the
sym$toms of an acute cardio"ascular disorder and is often the im$etus for
$atients seeking medical care. #ys$hagia is also a common $resenting
com$laint that may ser"e to $rom$t the dentist to refer the $atient to the
$atient s $hysician. @e"eral studies ha"e sho!n that a number of air!ay
$roblems that !ere $re"iously thought to be idio$athic, such as laryngitis,
chronic cough, hoarseness, and asthma, are in fact the result of
microas$iration of reflu+ate into the air!ay. ),4
>arrett s eso$hagus < is a "ariant of 7E # in !hich normal s(uamous
e$ithelium is re$laced by columnar e$ithelium. 0Aatients !ith this
$henomenon sho! an increased incidence of adenocarcinoma. This
condition may increase the incidence of carcinoma by as much as 1BD. %
$rotecti"e effect for adenocarcinoma may result if Helicobacter pylori is
$resent.
The rela+ation of the lo!er eso$hageal s$hincter for the $ur$ose of relie"ing
$ressure in the stomach 9from gas and the ingestion of food: is called the
bur$F mechanism. This $henomenon is a normal $rocess and occurs only
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!hen a $erson is in an erect $osture* gastric contents are thereby $re"ented
from flo!ing into the eso$hagus and $ossibly being as$irated. The
gastroeso$hageal 3unction, !hich $re"ents the regurgitation 9retrograde or
u$!ard flo!: of gastric contents, is com$osed of an internal lo!er eso$hageal s$hincter. E+ternal $ressure on the 3unction by the dia$hragm
also assists in this function. When this barrier fails, gastric contents may
make their !ay into the eso$hagus and cause sym$toms. The cause of lo!er
eso$hageal s$hincter incom$etence is unkno!n* ho!e"er, it does not a$$ear
to be mechanical. 5iatal hernia !as historically recogni&ed as a cause of
7E #, but there is no correlation bet!een s$hincter $ressure and the
$resence of a hiatal hernia, !hich leads to the !idely acce$ted $osition that
7E # is not caused by hiatal hernia. @urgery, scleroderma, and drugs such
as anticholinergics, cardiac "asoconstrictors, and nicotine can also cause an
incom$etent s$hincter.
Ora' hea'th on&!derat!on
egurgitation of gastric contents 9$5 1 2: reduces the $5 of the oral ca"ity
belo! 4.4* this acidic $5 begins to dissol"e enamel. It is most commonly
seen on the $alatal surfaces. Erosion of the enamel e+$oses the underlying
dentin, !hich is a softer, o$a(ue material. The e+tent of erosion de$ends on
the fre(uency and the (uantity of e+$osure along !ith the duration of
disease. Ne!ly e+$osed dentin is smooth and shiny, !hile dentin from $re"ious e+$osures may be stained.
Erosion differs from dental caries in that it is a hard, dished out area !here
enamel has dissol"ed and the underlying dentin is e+$osed. On the other
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hand, caries re"eals soft, discolored dentin and results from the bacterial
breakdo!n of sugars on the surface of the teeth 9@chroeder, 1??4:. The
$re"alence of caries is not increased in $ersons !ith 7E #, $ossibly
because the acidic en"ironment interferes !ith the formation of the dental biofilm. 7ood dental care and control of acid hel$s decrease the $re"alence
of erosion. 5o!e"er, once the erosion occurs, it is irre"ersible and can only
be treated !ith surgical restorati"e $rocedures. Therefore, early recognition
and $atient education is the most effecti"e treatment.
@moking cessation !ill increase the $roduction of sali"a and therefore
counteract the sym$toms of 7E #. atty meals slo! do!n gastric em$tying
and $roduce distention and reflu+. %n increase in the fat content of meals
may be an im$ortant factor in e+$laining Aatients !ho ha"e a diagnosis of
7E # may need to be treated in a semisu$ine $osition and $remedicated
!ith 5 2 rece$tor antagonists or antacids.%ny medications that may cause
nausea 9such as narcotic analgesics: should be $rescribed 3udiciously
because of the increased likelihood of regurgitation and $ossibleas$iration.-ild baking soda mouth rinses 9one half teas$oon of sodium
bicarbonate in = ounces of !ater: may be rinsed and e+$ectorated to
minimi&e dysgeusia due to acid reflu+. To$ical fluoride a$$lications "ia a
custom made occlusi"e tray !ill ensure o$timal dental mineali&ation.
Treat*ent
Estrogen $rogesterone combinations used in contrace$ti"es and during
$regnancy also ha"e been sho!n to decrease s$hincter $ressures. Aroton
$um$ inhibitors 9AAIs: such as ome$ra&ole and 9more recently: lanso$ra&ole
ha"e been found to heal erosi"e eso$hagitis more efficaciously than do 52
1)
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rece$tor antagonists. AAIs $ro"ide not only sym$tomatic relief but also
resolution of signs, including those that in"ol"e significant ulcers and or
eso$hageal damage. = @tudies ha"e sho!n that AAI thera$y can $ro"ide
com$lete endosco$ic mucosal healing of eso$hagitis at 8 to = !eeks in
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disease is most common in Western countries and is slightly more $re"alent
among !hite males. The $eak incidence is in the second and third decades of
life, !ith a second $eak occurring in the si+th and se"enth decades.
@ym$toms of Crohn disease include intermittent attacks of diarrhea,consti$ation, abdominal $ain, and fe"er. Aatients may de"elo$ malabsor$tion
and subse(uent malnutrition. issures or fistulas may occur in $ersons !ith
chronic disease.
Crohns disease is a chronic inflammatory bo!el disease of unkno!n
aetiology, affecting mainly the ileum.
C'!n! a' eature&
It $resents ty$ically !ith abdominal $ain, $ersistent diarrhoea !ith $assage
of blood and mucus, anaemia, and !eight loss. 5o!e"er any $art of
gastrointestinal tract can be in"ol"ed including the mouth.
%n oral bio$sy may conform the $resence of lym$hoedema and
granulomas ,blood tests and intestinal radiology, endosco$y, and bio$sy may
be re(uired to e+clude gastrointestinal lesions .
@econdary deficiencies should be corrected, intralesional corticosteroids
may hel$ control oral lesions such as s!elling, but occasionally systemic
sul$hasala&ine or other agents are re(uired.
Intraoral in"ol"ement in Crohn disease occurs in = ?D of $atients and may
$recede intestinal in"ol"ement. With oral in"ol"ement, the likelihood of
e+traintestinal manifestations is greater. E+traintestinal features are also
common in $ersons !ith Crohn disease, and these may manifest
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systemically as arthritis, clubbing of the fingers, sacroilitis, and erythema
nodosum.
Ora' *an! e&tat!on&
Orofacial sym$toms of Crohn disease include 91: #iffuse labial, gingi"al, or
mucosal s!elling* 92:Cobble stoning of the buccal mucosa and gingi"a* 9):
a$hthous ulcers* 90: -ucosal tags* and 94: %ngular cheilitis.8: Noncaseating
granulomas are characteristic of Orofacial Crohn disease. Oral granulomas
may occur !ithout characteristic alimentary in"ol"ement 9orofacial
granulomatoses:. 5o!e"er, the term orofacial granulomatoses encom$assesa "ariety of other disorders, including sarcoidosis, -elkersson osenthal
syndrome, and, rarely, tuberculosis. Whether $atients !ith orofacial
granulomatoses !ill subse(uently de"elo$ intestinal manifestations of Crohn
disease is uncertain, but histologic similarities bet!een the oral lesions and
the intestinal lesions are ob"ious.
/abial s!elling is most often a cosmetic com$laint, but it can be a $ainful
manifestation of the disease. 7ingi"al and mucosal in"ol"ement may cause
difficulty !hile eating. The $attern of s!elling, inflammation, ulcers, and
fissures is similar to that of the lesions occurring in the intestinal tract. %cute
and chronic inflammation, !ith lym$hocytic and giant cell $eri"ascular
infiltrates, and lym$hoid follicles are the most common histologic findings
in oral and 7I Crohn disease. Noncaseating granulomas are $resent in bio$sy sam$les in a number of cases. Increased dental caries and nutritional
deficiencies may be related to decreased sali"a $roduction and
malabsor$tion in the intestinal tract.
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Oral findings as described abo"e !arrant a full systemic e"aluation for
intestinal Crohn disease, including referral for colonosco$y and bio$sy !ith
histo$athologic correlation. Oral in"ol"ement may $recede systemic
manifestations and sym$toms. Negati"e findings on 7I e"aluations should be re$eated in $atients !ith oral sym$toms. The se"erity of oral lesions may
coincide !ith the se"erity of the systemic disease, and it may be used as a
marker for intestinal im$airment 95alme, 1??):.
5LCERATIVE COLITIS
;lcerati"e colitis is an inflammatory condition !ith some similarities toCrohn disease. 5o!e"er, it is restricted to the colon and is limited to the
mucosa and submucosa, s$aring the muscularis. /esions in the colon consist
of areas of hemorrhage and ulcerations along !ith abscesses. @imilar lesions
may manifest in the oral ca"ity as a$hthous ulcerations or su$erficial
hemorrhagic ulcers. ;lcerati"e colitis is characteri&ed by $eriods of
e+acerbation and remission, and, generally, oral lesions coincide !ith
e+acerbations of the colonic disease. @imilar ulcerations may arise on the
buttocks, abdomen, thighs, and face 95andlers, 1???:. %$hthous ulcers or
angular stomatitis occurs in as many as 4 1BD of $atients.
DISEASE O6 )EPATOBILLARY SYSTEM
Chronic li"er disease im$acts many systems of the body. The coagulation
$ath!ay is one such system. The li"er synthesi&es many of the clotting
factors necessary to sto$ bleeding. In addition, "itamin G, a fat soluble
"itamin, re(uires $ro$er li"er function to be ade(uately absorbed from the
intestines. In $atients !ith li"er disease, the resultant im$aired hemostasis
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can be manifested in the mouth as $etechiae or e+cessi"e gingi"al bleeding
!ith minor trauma. This is es$ecially suggesti"e if it occurs in the absence
of inflammation. Therefore, s$ecial care must be taken during any ty$e of
surgery, oral or other!ise* se"ere hemorrhage can ensue as a result of the $aucity of clotting factors.
Ora' *an! e&tat!on
The only manifestation of ad"anced li"er disease "isible in the oral mucosa
is 3aundice, !hich is the yello! $igmentation that results from the de$osition
of bilirubin in the submucosa. Haundice may occur follo!ing disorders in bilirubin metabolism, $roduction, or secretion. 5e$atocellular damage
affects secretion, the rate limiting ste$ in bilirubin metabolism, allo!ing
con3ugated bilirubin to leak out of the cells and into the blood stream. This
!ater soluble substance is loosely albumin bound, and it is de$osited in the
mucus membranes throughout the body. When 3aundice is due to chronic
li"er disease, the yello! color reflects a direct relation to li"er function.
Haundice manifests at serum le"els of bilirubin greater than 2.4 ) mg d/ or
2 ) times baseline. >ecause they are thinner, the mucosae on the soft $alate
and in the sublingual region are often first to re"eal a yello! hue. With time,
the yello! changes can be "isible at any mucosal site.
>ecause of its high rate of $rogression to chronic he$atitis 94BD: and
cirrhosis, he$atitis C is the leading infectious cause of chronic li"er disease!orld!ide. The association bet!een he$atitis C and oral lichen $lanus is
contro"ersial. The link bet!een the t!o conditions is tenuous and not
sufficient to !arrant screening for he$atitis C infection in all $atients !ith
lichen $lanus
1=
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GARDNERS SYNDROME
This genetic syndrome is chracterised by osteomas, fibromas, e$idermoid
cysts includes $oly$osis. 7ardner s syndrome consists of intestinal $oly$osis
9!hich re$resents $remalignant lesions: and multi$le im$acted
su$ernumerary 9e+tra: teeth. This disorder is inherited as an autosomal
dominant trait, and fe! $atients afflicted !ith this syndrome reach the age of
4B years !ithout surgical inter"ention. 14 In a young $atient !ith a family
history of 7ardner s syndrome, dental radiogra$hy 9such as $antomogra$hy:
can $ro"ide the earliest indication of the $resence of this disease $rocess. 1B
PL5MMER#VINSON SYNDROME
Alummer inson syndrome, originally described as hysterical dys$hagia,F
is noted $rimarily in !omen in the fourth and fifth decades of life. The
hallmark of this disorder is dys$hagia resulting from eso$hageal stricture,
causing many $atients to ha"e a fear of choking.48 Aatients may $resent
!ith a lemontinted $allor and !ith dryness of the skin, s$oon sha$ed
fingernails, koilonychia, and s$lenomegaly. The oral manifestations are the
result of an iron deficiency anemia. Oral findings include atro$hic glossitis
!ith erythema or fissuring, angular cheilitis, thinning of the "ermilion
borders of the li$s, and leuko$lakia of the tongue. Ins$ection of the oral
mucous membranes !ill disclose atro$hy and hy$erkeratini&ation.These oral
changes are similar to those encountered in the $haryn+ and eso$hagus.
Carcinoma of the u$$er alimentary tract has been re$orted in 1B to )BD of
$atients. 11Thorough oral, $haryngeal, and eso$hageal e+aminations are
mandatory to ensure that carcinoma is not $resent. %rtificial sali"a may
reduce the sensation 9and thereby, the fear: of choking.
1?
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PE5T9#:EG)ER;S SYNDROME
Aeut& Heghers syndrome is characteri&ed by multi$le intestinal $oly$s
throughout the gastrointestinal tract but $rimarily in the small intestine.
-alignancies in the gastrointestinal tract and else!here in the body ha"e been re$orted in a$$ro+imately 1BD of $atients !ith this syndrome.
Aigmentation 9$resent from birth: of the face, li$s, and oral ca"ity is a
hallmark of this syndrome. 12 Interestingly, the facial $igmentation fades later
in life although the intraoral mucosal $igmentation $ersists. No s$ecific oral
treatment is necessary.
CO8DEN;S SYNDROME
Co!den s syndrome 9multi$le hamartoma and neo$lasia syndrome: is an
autosomal dominant disease characteri&ed chiefly by facial trichilemmomas,
gastrointestinal $oly$s, breast and thyroid neo$lasms, and oral
abnormalities. Co!den s syndrome is considered to be a cutaneous markerof
internal malignancies. 1) Aebbly $a$illoma like lesions and multi$le fibromas
may be found !idely distributed throughout the oral ca"ity. 10
PYOSTOMATITIS VEGETANS
Oral lesions in mouth, related to inflammatory bo!el disease, are termed
$yostomatitis "egetans, include dee$ fissures, $ustules, ulcers, and $a$illary
$ro3ections. The course of these lesions tends to follo! that of bo!el
disease. -ost $atients !ith these lesions ha"e ulcerati"e colitis or Crohns
disease. @ome ha"e li"er disease Oral lesional bio$sy and gastrointestinal
2B
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in"estigation are re(uired. -anagement is !ith sul$hasala&ine or systemic
coricosteroids
Pyostomatitis Vegetans ulcerations on labial mucosa
COLOR PLATE-I
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CRO)N;S DISEASE o33'e &ton!n+o 3u a' *u o&a and u' erat!on&
PE5T9#:EG)ER;S SYNDROME P!+*entat!on 4re&ent on a e and '!4 &!n e 3!rth
)AEMATOLOGICAL DISORDERS
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RED BLOOD CELL DISORDERS&olycythemia
Anemia
WHITE BLOOD CELL DISORDERS
*uantitati e Disorders*ualitati e Leu+ocyte Disorders
Leu+emia
LYMPHOMAHodg+in%s Disease
,on-Hodg+in%s Lymphoma
$ur+itt%s Lymphoma
ral and Dental !onsiderations
MULTIPLE MYELOMA .reatment
ral /ani estations
Dental /anagement
The $rocess of haemato$oiesis is the formation of cellular com$onents of
the blood from a small $o$ulation of $luri$otential stem cells, !hich areformed in embryonic life and $ersists there after through self regeneration.
When stimulated by haemo$oietic gro!th factors such as cytokines, these
$recursors gi"e rise to $rogenitor cells committed to de"elo$ment along
s$ecific $ath!ays.
RED BLOOD CELL DISORDERS
2)
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POLYCYT)EMIA
Aolycythemia may be defined as an abnormal increase in the erythrocyte
count in the $eri$heral blood, usually accom$anied by an increase in
hemoglobin and hematocrit. Aolycythemia is di"ided into absoluteerythrocytosis 9a true increase in red cell mass: and relati"e erythrocytosis
9the red cell mass is normal, but the $lasma "olume is reduced:. elati"e
$olycythemia is caused by the loss of tissue and intra"ascular fluid, !hich
may be the result of such di"erse conditions as diabetic ketoacidosis,
$ostsurgical dehydration, $rolonged "omiting or diarrhea, or ra$id diuresis
secondary to treatment for congesti"e heart failure. In relati"e $olycythemia,
the hemoglobin rarely rises more than 24gmD, and there are no a$$reciable
oral changes.
Three main grou$s of $olycythemia are recogni&ed6 $rimary $roliferati"e
$olycythemia 9$olycythemia rubra "era:, secondary $olycythemia resulting
from changes in erythro$oietin concentration, and a$$arent $olycythemia.
The latter condition lacks a true increase in red cell mass.
POLYCYT)EMIA VERA
Aolycythemia "era 9A : is a myelo$roliferati"e disorder characteri&ed
by e+cessi"e $roliferation of erythroid elements along !ith granulocytic and
megakaryocytic cells* it usually begins after 4B years of age. The etiology of
A is unkno!n* ho!e"er,it is likely a result of ac(uired genetic changes in
the stem cell leading to disturbances of normal cellular gro!th.
Ora' Man! e&tat!on& % $ur$lish red discoloration of the oral mucosa is "isible on the tongue,
cheeks, and li$s. The gingi"ae are red and may bleed s$ontaneously.
Aetechiae and ecchymoses are obser"ed in $atients !ith $latelet
abnormalities. aricosities seen on the "entral surface of tongue, a fre(uent
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normal finding, are e+aggerated in cases of $olycythemia. Taken in $atients
!ith definite cardio"ascular risks 18.
SECONDARY POLYCYT)EMIA
ERYT)ROCYTOSIS@econdary $olycythemia is due to an increase in erythro$oietin $roduction to
com$ensate for hy$o+ia. This reacti"e erythrocytosis leading to disturbances
of normal cellular gro!th.This reacti"e erythrocytosis has been described in
$eo$le !ho li"e at high altitudes !ith lo! atmos$heric $ressure and in
$eo$le !ith chronic $ulmonary disease, congenital heart disease 9right to
left shunt:, and renal disease 9hydrone$hrosis:. Aheochromocytoma and
other endocrine disorders also ha"e been described as $ossible causes of
erythrocytosis.
APPARENT POLYCYT)EMIA
%$$arent $olycythemia, characteri&ed by an increased hemoglobin
concentration and $acked cell "olume but normal >C mass, is caused by a
reduction in $lasma "olume. %$$arent $olycythemia most commonly affects
middle aged obese men !ith hy$ertension and a significant social history of
smoking and high alcohol consum$tion. @ome cases are associated !ith
diuretic thera$y.Treatment is usually geared to!ard the underlying disorder*
ho!e"er, more aggressi"e measures may be taken in $atients !ith definite
cardio"ascular risks. 18
To $re"ent com$lications, it is recommended that the hemoglobin be
reduced belo! 18 g d/ and the hematocrit to belo! 0
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ANEMIA
Introdu t!on
%nemia is defined as an abnormal reduction in number of circulating red
blood cells, the (uantity of hemoglobin and "olume of $acked red cells in
gi"en unit of blood. 2B This reduction in hemoglobin may result from blood
loss, as in common iron deficiency anemia, from increased destruction of red
blood cells, as in the hemolytic anemias, from decreased $roduction of red
cells, as in $ernicious and folic acid deficiency anemias, or from
combinations of these three.When there is a combination of causes, one
mechanism usually $redominates. %nemias also may be classified accordingto their $atho$hysiologic basis6 si&e 9microcytic, normocytic, or
macrocytic:of the red cells or their hemoglobin concentration
hy$ochromic,normochromic. The term hy$erchromicF is seldom used, but
it refers to a macrocytic cell !ith normal hemoglobin concentration that,
because of its large si&e, has an increased hemoglobin content.
7eneral sym$toms of all anemias include $allor of the skin, $al$ebral
con3uncti"a, and nail beds* dys$nea* and easy fatigability. atigue and
decreased resistance to infection are common systemic sym$toms. The nail
beds and oral mucosa e+hibit $allor. This $allor is a common and easily
recogni&able feature of anemia.
Ora' *an! e&tat!on&
-ucosal conditions, such as glossitis, recurrent a$hthae, candidal infections,
and angular stomatitis, may be more common in $atients !ith anemia.
7lossitis may be the first sign of folate or "itamin > 12 deficiency. The tongue
a$$ears reddened, and the $a$illae are atro$hic, $roducing a smooth 9 baldF:
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a$$earance. %ngular stomatitis is commonly caused by a candidal infection,
and it has been linked to iron deficiency. If the anemia $ersists, resistance to
infection may be decreased.The main com$lication for oral health care is
risk from genral anaesthesia.
)AEMOLYTIC ANAEMIA
I Co**on Cau&e& o )e*o'yt! Ane*!a
E+tracor$uscular factors
O"er!helming infections and to+ins
Cardiac "al"ular $rostheses5y$ers$lenism
h factor incom$atibility 9hemolytic disease of ne!born, erythroblastosis
fetalis:
Chronic li"er disease
%utoimmune hemolytic disease 9eg, as in systemic lu$us erythematosus:
Transfusion reactions
II Intra or4u& u'ar de e t&
%bnormal sha$e of the erythrocytes
5ereditary s$herocytosis
5ereditary elli$tocytosis
III Erythro yte en
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Thalassemia
Other hemoglobino$athies =eg, hemoglobin C and :
V Erythro yte de e t& a&&o !ated ?!th other d!&ea&e
olic acid and "itamin > 12 deficiency anemiasANEMIA O8ING TO BLOOD LOSS
IRON DE6ICIENCY ANEMIA
Iron is essential for synthesis of heme $ortion of haemoglobin. Iron
deficiency anaemia is caused by imbalance bet!een iron intake and loss of
inade(uate utili&ation.
Et!o'o+y
Inade(uate intake of iron, malabsor$tion of iron, increased re(uirement of
iron in gro!ing child and $regnancy, chronic blood loss such as menstrual
and meno$ausal bleeding.
C'!n! a' eature&
Iron deficiency anemia 9blood loss anemia, hy$ochromic microcytic anemia:
is the most common of all anemias, affecting a$$ro+imately )BD of the
!orld s $o$ulation and accounting for u$ to 4BB million cases !orld!ide. It
occurs chiefly in !omen in 0 th and 4 th decades of life. Nails become brittle
and flattened and often sho! s$oon sha$e 9koilonychias: 1<
Cau&e&
2=
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Iron deficiency anemia may result from chronic blood loss, such as occurs in
menstrual or meno$ausal bleeding, $arturition, bleeding hemorrhoids, or a
bleeding malignant lesion or ulcer in the gastrointestinal tract. It also may
de"elo$ in $atients from a "ariety of causes that may decrease the rate of absor$tion of iron, such as subtotal or com$lete gastrectomy, or a habit of
clay eating, or as $art of malabsor$tion syndromes. 1=
Ora' *an! e&tat!on&
The ma3or oral sign of iron deficiency anemia is $allor of the mucosa due to
lack of o+ygenated blood in ca$illary bed in lamina $ro$ria and is associated
!ith lo!er le"els of hemoglobin. In addition, the oral e$ithelial cells become
atro$hic, !ith loss of normal keratini&ation. The tongue may become smooth
due to atro$hy of the filiform and fungiform $a$illae, and glossodynia can
be a $resenting or associated sym$tom. In long standing cases, eso$hageal
strictures or !ebs can de"elo$, resulting in dys$hagia. ecent clinical
in"estigation has sho!n lingual signs and sym$toms to be much less
common than !as $re"iously belie"ed of skin e+tending u$ to and beyondmucocutaneous 3unction. ecurrent a$thous ulceration and candidal lesions
can also occur in iron deficiency anaemia.
5istologic e+amination of the tongue mucosa sho!s a reduction in
e$ithelial thickness, !ith a reduction in the number of cells in s$ite of an
increase in the $rogenitor cell layer. The cell si&e is decreased in the
maturation layers 9in males:, and the nucleocyto$lasmic ratio is higher than
normal. /ingual mucosal atro$hy may occur in the absence of other clinical
findings.
COLOR PLATE-II
2?
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IRON DE66ICIENCY ANEMIA =Atro4hy o ton+ue 4a4!''ae )
D!a+no&!&
)B
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#iagnosis is based on a lo!ered hemoglobin in routine blood counts, on a
$eri$heral smear, the cells are microcytic and hy$ochromic.When the
anemia is !ell de"elo$ed, the mean cor$uscular hemoglobin, the mean
cor$uscular hemoglobin concentration, and the mean cor$uscular "olume aredecreased. Whene"er the hemoglobin "alue is less than 11 g d/, it is of
definite clinical significance. The $atient !ith iron defi ciency anemia !ill
ha"e lo! serum iron concentrations and a high serum iron binding ca$acity.
Denta' Con&!derat!on&
#ental $atients $resenting !ith sym$toms of anemia or oral signs suggesti"e
of this condition should ha"e a com$lete blood count 9C>C: !ithdifferential. If significantly lo!ered hemoglobin "alues are obtained, the
$atient should be referred to his or her $hysician for a more thorough
medical history, laboratory diagnosis, and treatment. Electi"e oral surgical or
$eriodontal $rocedures should not be $erformed on $atients !ith marked
anemia because of the $otential for increased bleeding and im$aired !ound
healing.When hemoglobin le"els fall belo! 1B g d/, the lo! o+ygen tension
affects the rheologic interactions bet!een the cellular com$onents of blood,
mainly $latelets and endothelium, decreasing their ability to clot effecti"ely.
7eneral anesthesia should not be administered unless the hemoglobin is at
least 1B g d/. The $atient should ne"er be treated !ith iron until the cause of
the microcytic hy$ochromic anemia is found and corrected or until a
thorough search for the cause has $ro"ed fruitless.
Treat*ent
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The diagnosis of iron deficiency anemia is made either by demonstration of
an iron deficient state or by e"aluation of the res$onse to thera$eutic iron
re$lacement. The single most im$ortant as$ect of treatment is identification
of the cause, es$ecially a source of occult blood loss. 1?
PL5MMER VINSON SYNDROME=Pater&on#Bro?n @e''y Syndro*e>
irst described by Alummer and inson, this syndrome is characteri&ed by
dys$hagia and a microcytic hy$ochromic anemia. % smooth and sore tongue,
dry mouth, s$oon sha$ed nails, and angular stomatitis are common findings.
There is atro$hy of the tongue $a$illae, but it is less se"ere than in
$ernicious anemia. There are atro$hic changes in the oral mucosa, the
$haryn+, the u$$er eso$hagus, and the "ul"a. These tissues are dry, inelastic,
and gla&ed in a$$earance. In addition, general sym$toms include
listlessness, $allor, ankle edema, and dys$nea, all related to the anemia.
-any $atients !ith this syndrome are edentulous, ha"ing lost their teeth
early in life. Com$laints of a sore mouth and an inability to !ear dentures
are fre(uent. In addition, $atients !ith Alummer inson syndrome often
com$lain of a s$asm in the throatF or of food sticking in the throat.F The
dys$hagia, !hich re$resents an im$ortant feature of this condition, a$$ears
to be the result of muscular degeneration in the eso$hagus, and stenoses or
!ebs of the eso$hageal mucosa.
The diagnosis of this syndrome can be made on the basis of the history and
hematologic findings. The eso$hageal lesions are demonstrable
radiologically 9barium s!allo!: or by eso$hagosco$y. elati"e degrees of achlorhydria are usually $resent.
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SIC@LE CELL DISEASES
It !as first described by 5errick in 1?1B. In sickle cell disease, an autosomal
recessi"e disorder, an abnormality in the J chain of hemoglobin is $resent in!hich "aline is substituted for the normal glutamic acid residue on si+th
$osition. This relati"ely minor biochemical change results in $rofound
undesirable $hysical characteristics in the hemoglobin. In the $resence of
either a lo!ered blood o+ygen tension or an increased blood $5, the
hemoglobin forms a sickle sha$ed crystal 9a tactoid: !ithin the erythrocyte.
This sickling of the erythrocyte leads to stasis and hemolysis of the red cells,
es$ecially in end ca$illary circulation. The stasis then results in an e"en
lo!er o+ygen tension, an increased $5, and further sickling. The disease is
hereditary and may manifest itself as the sickle cell trait or as sickle cell
anemia. Aatients !ith sickle cell disease or trait are abnormally susce$tible
to infection, $articularly $neumococcal or meningococcal, and
osteomyelitis. @ickling crises can be $reci$itated and $ainful crises caused
by blockage of blood "essels and bone marro! infarcts can affect the 3a!s,
$articularly the mandible. They can cause se"ere $ain and infracted tissues
forms a focus susce$tible to infection. @almonella osteomyelitis is a
recogni&able ha&ard.
Genera' Man! e&tat!on&
It is common in females and mostly clinical sym$toms are e"ident beforeage of )B years. Clinical manifestations begin only after se"eral months as
fetal 5b $rotects against sickling $henomenon. Areci$itating factors are
dehydration, chills and infection but some time the attack occurs
s$ontaneously. There is fatigue, !eakness and shortness of breath. @e"ere
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abdominal $ain, muscle and 3oint $an, at high tem$erature !hich may result
in circulalatory colla$se. There is cardiomegaly, $resence of leg ulcers and
gall stones. -ost of $ersons e+$ire before the age of 0B. @ickle cell anaemia
should be sus$ected in black $atients, $articularly in those of afrocarribeanorigin and in"estigated ,if anaesthesia is antici$ated .if hemoglobin
concentration is less than 1Bgm dl, then $atient is $robably a homo&ygote
!ith sickle cell disease, and hos$itali&ation is necessary for anaesthesia .In
those !ith sickle cell trait the main $recaution is that general anesthesia if
una"oidable should be carried out !ith full o+ygenation .
Ora' *an! e&tat!on&
Other than the 3aundice and $allor of the oral mucosa, $atients often sho!
delayed eru$tion and hy$o$lasia of the dentition secondary to their general
underde"elo$ment. >ecause of the chronic increased erythro$oietic acti"ity
and marro! hy$er$lasia, !hich are attem$ts to com$ensate for the
hemolysis, increased radiolucency resulting from the decreased number of
trabeculae is seen on dental radiogra$hs. This change is noted es$ecially in
the al"eolar bone bet!een the roots of the teeth, !here the trabeculae may
a$$ear as hori&ontal ro!s, creating a ladderlike effect . >y contrast, the
lamina dura a$$ears dense and distinct. In skull films, the di$loe is
thickened, and the trabeculae are coarse and tend to run $er$endicular to the
inner and outer tables, gi"ing a radiogra$hic a$$earance of hair on endF.
The teeth do not $resent undue mobility.%reas of sclerosis or increased
radio$acity re$resent areas of $ast thromboses !ith subse(uent bony
infarction. Aatients !ith sickle cell anemia are $articularly $rone to de"elo$
osteomyelitis, $robably because of hy$o"ascularity of the bone marro!
secondary to thromboses.
)0
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D!a+no&!&
E@5 >/OO# is sealed in a small chamber of microsco$ic slide !ith
metabisulfite 9a reducing agent: for 1 hour and then obser"ed for sickling.
5emoglobin electro$horesis is less e+$ensi"e, more accurate, and moredefiniti"e in the diagnosis of sickle cell disease as it detects hemoglobin
@.1B
Treat*ent
There is no treatment for sickle cell disease other than sym$tomatic
treatment. egular health care and $rom$t antibiotic treatment of infections
are im$ortant. Aainful bone infarcts should be treated !ith N@%I# and fluid
intake should be increased . Aatients !ith sickling disorders are more likely
to ha"e $ain !hich is indistinguishable from toothache K$resumably due to
$ul$al infarcts. Therefore $atients should be treated !ith analgesics in the
first instance unless an ob"ious carious lesion is $resent .%dmission to
hos$ital is re(uired for se"ere $ainful crises not res$onsi"e to analgesics .
T)ALASSAEMIAS=Coo'ey& ane*!a, Med!terranean ane*!a, andErythro3'a&t! ane*!a>
The thalassemias are a grou$ of congenital disorders characteri&ed by a
deficient synthesis of either the L or the J chains of globin in the hemoglobin
molecule. %s a result, the red blood cells are microcytic and hy$ochromic
!ith an aberrant mor$hology. Thalassemias are often considered among the
hy$o$roliferati"e anemias, the hemolytic anemias, and the anemias related
to abnormal hemoglobin. In L thalassemia 9deficient or reduced L chain:
intracellular inclusions, 5ein& bodies are formed by the $reci$itation of the L
chains that accumulate in e+cess follo!ing the im$aired chain $roduction. In
the most se"ere form of this disease, the fetus s red blood cells contain
)4
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hemoglobin com$osed of M chains only. This condition is incom$atible !ith
life, due to the hemoglobin s lack of o+ygen carrying ca$acity. Clinical
signs in L thalassemia de$end on the se"erity of the L chain $roduction
deficiency. J 7lobin synthesis is im$aired in J thalassemia !ith mutationsin the se(uences of the J globin gene, leading to errors in the s$licing of
messenger ribonucleic acid 9m N%:.
Ty$es
%l$ha thalassemia There is reduction or absence of al$ha chain synthesis.
>eta thalassemia There is reduction or absence of beta chains.
5omo&ygous J thalassemia Thalassaemias ma3or or cooley s anemia usually
homo&ygous.
Beta tha'a&&e*!a
5aemolysis is not $rimarily due to lack of beta chains but it is because of
free al$ha chains !hich forms insoluble aggregates that $reci$itate !ith in
>C s and cause damage to cell membrane.
C'!n! a' *an! e&tat!on&
Occurs bet!een age of 8 to 20 month. The skin color becomes ashen gray
due to the combination of $allor, 3aundice, and hemosiderosis. Aatients also
$resent !ith cardiomegaly, he$atomegaly, and s$lenomegaly. J thalassaemia
is a characteri&ed by se"ere hy$ochromic, microcytic anaemia, great
enlargement of li"er and s$leen and skeletal abnormalties due to
e+tramedullary erythro$oiesis. There is failure to thri"e early death if
re$eated transfusion are not gi"en. egular transfusion are life sa"ing and
)8
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$re"ent de"elo$ment of boney deformities but lead to increased de$osition
of iron in tissues. 5aemosiderosis is main cause of com$lications.
Ora' *an! e&tat!on&
>ima+illary $rotrusion and other occlusal abnormalities are fre(uent in
thalassemia ma3or cases.#ental and facial abnormalities include $oor
s$acing of teeth, a marked o$ened bite, $rominent malar bones, and a saddle
nose. In addition, the $neumati&ation of the ma+illary sinuses is delayed.%s
a result of these skeletal changes, the u$$er li$ is retracted, gi"ing the child a
chi$munk facies.F The radiogra$hic changes seen in the 3a!s include
generali&ed rarefaction of the al"eolar bone, thinning of cortical bone,
enlarged marro! s$aces, and coarse trabeculae, !hich are similar to the
changes obser"ed in sickle cell disease $atients. In the $arietal bones, the
thin corte+ co"ering the coarse "ertical trabeculae and the enlarged di$lo
$roduce a hair on endF $icture. Cranial ner"e $alsies ha"e been described in
thalassemia due to the e+tramedullary hemato$oiesis resulting in $ressure
on the ner"es. In J thalassemia ma3or, there is no correlation bet!een thechronologic, skeletal, and dental de"elo$mental age. The skeletal retardation
increases !ith age due to hy$o+ia from se"ere anemia, endocrine
hy$ofunction secondary to iron de$osition, or the to+ic action of iron
en&yme systems leading to tissue in3ury. The dentin and enamel are
indicators of iron de$osition, and deciduous and $ermanent teeth of $atients
!ith thalassemia contain u$ to fi"e times the iron concentration measured in
normal $atients. The high concentration of iron e+$lains the discoloration of
teeth in $atients !ith J thalassemia ma3or.
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D!a+no&!&
5emolytic anemia !ith hy$ochromic microcytic red blood cells that "ary in
si&e and sha$e is characteristic of thalassemia ma3or. The hemoglobin
electro$horesis sho!s increased amounts of fetal hemoglobin and "ariableamounts of normal adult hemoglobin. In $atients homo&ygous for J
thalassemia, there is no detectable hemoglobin %. Arenatal diagnosis of
thalassemia is facilitated by deo+yribonucleic acid 9#N%: analysis of
amniotic fluid cells, and it $lays an im$ortant role in genetic counseling.
Treat*ent
Aatients !ith mild thalassemia 9L trait or J minor: are clinically normal and
re(uire no treatment. In other cases, the $atient s sur"i"al de$ends on blood
transfusions. Are"ention of a hemoglobin concentration decrease to under 1B
g d/ im$ro"es the chances of normal de"elo$ment and sur"i"al into
adulthood. This hy$ertransfusion treatment results in iron o"erload !ith
hemosiderosis and iron de$osition in all body tissues.
Denta' Mana+e*ent
%s in any $atient !ith a chronic anemia, $oor healing may ensue after
surgical dental $rocedures. The $ossibility al!ays e+ists of e+acerbating the
sym$toms of cerebral or cardiac hy$o+ia if substantial bleeding occurs in a
$atient !ho is already anemic. @urgery has been used successfully to treat
the facial deformities.
ANEMIA O8ING TO DECREASED PROD5CTION O6 RED CELLSMEGALOBLASTIC ANEMIA
The term megaloblastic anemiaF is used to describe a grou$ of disorders
characteri&ed by a distinct mor$hologic $attern in hema$oietic cells. These
cells ha"e small immature nuclei and large mature cyto$lasms.
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-icrosco$ically, this nuclear cyto$lasmic asynchrony is described as
megaloblastic.F This grou$ of disorders chiefly affects cells !ith ra$id
turno"er. The most common form of "itamin > 12 deficiency is $ernicious
anemia it is also called as $rimary anemia, addisons anemia or biermer sanemia, !hich is due to atro$hy of the gastric mucosa resulting in a lack of
intrinsic factor secretion. Intrinsic factor acts by binding to the "itamin > 12
molecule, forming a com$le+ that crosses the ileal mucosa and $rotects the
"itamin from $roteolysis. The disease can be the result of an autoimmune
reaction to either the gastric $arietal cells or intrinsic factor and is often seen
in connection !ith other autoimmune diseases such as 7ra"es disease.
Ora' Man! e&tat!on&
7lossitis and glossodynia are the classic oral sym$toms of $ernicious
anemia. The tongue is beefy redFand inflamed,!ith small erythematous
areas on the ti$ and margins. There is a loss of filiform $a$illae, and, in
ad"anced disease, the $a$illary atro$hy in"ol"es the entire tongue surface
together !ith a loss of the normal muscle tone also called as hunters
glosstis.The erythematous macular lesions also can in"ol"e the buccal and
labial mucosa. 21 Aatients may com$lain of dys$hagia and taste aberrations.
#iscomfort described by denture !earers !ho ha"e $ernicious anemia is
$robably due to the !eakened mucosal tissues. %lthough the burning
mouthF sensation diagnosed in $ernicious anemia can be due to a
neuro$athy, other causes of oral burning, including candidiasis, should be
considered.
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Color plate-III
S*a'' ero&!on& on 3u a' *u o&a
due to !tB1% de ! !en y
PERNICIO5S ANEMIAAtro4hy o 4a4!''ae and 'o3u'at!on& on ton+ue
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SIDEROPENIC ANEMIA
It is certain $athological condition in !hich iron gets accumulated in
mitochondria and a$$ears as a ring of granules round the nucleus. These are
called as ring sideroblast and chracterised cell of sidero$enic anemia !hich
is either hereditary or ac(uired.
APLASTIC ANEMIA
It is rare disorder chracterised by $eri$heral blood $ancyto$enia 9anemia,
leuco$enia, thrombocyto$enia: associated !ith bone marro! su$$ression
anconis anemia is an inherited anemia that manifests in early childhood.
chracterised by $ancyto$enia, bone marro! hy$o$lasia, and congenital
anomalies. The management is to sto$ any drugs that may be res$onsible
and to gi"e antibiotic and transfusions.
Ora' Man! e&tat!on&
Oral mucosa sho!s $allor. In some cases s$ontaneous hemorrhage may
occur from gingi"a. Aetechiae are often $resent on soft $alate and in se"ere
cases submucosal ecchymosis. /arge ragged ulcers co"ered by gray or black
necrotic membrane may be $resent, !hich are the result of generali&ed lack
of resistance to infection and trauma.
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)e*ato'o+! a' !nd!n+&
>C count is remarkably diminished as lo! as 1 million cells mm ).
W>C and $latelet count is as lo! as 2BBB mm ) . >leeding time is $rolonged
clotting time is normal. %nemia is normocytic !ith some degeree of
macrocytosis.
Denta' *ana+e*ent
7ingi"al bleeding can be reduced by antithrombolytic agent such as
aminoca$roic acid and transe+emi+ acid 2Bmg kg I# 20 hrs before the $rocedure and continued for three days.
8)ITE BLOOD CELL DISORDERS
The three ty$es of granulocytes are neutro$hils, eosino$hils, and
baso$hils.Neutro$hils are the most dominant of all circulating $hagocytes
/ym$hocytes are the $rimary cells in"ol"ed in immunity. They a$$ear tooriginate from $luri$otential stem cells in the bone marro! and migrate to
other lym$hoid tissues, including lym$h nodes, s$leen, thymus, and mucosal
surfaces of the gastrointestinal tract. There are t!o ty$es of lym$hocytes
thymus de$endent T lym$hocytes and non thymus de$endent >
lym$hocytes.Aeri$heral blood contains a$$ro+imately 0,BBB to 11,BBB
W>Cs $er cubic millimeter 0 /eukocytes $rotect against foreign in"aders
such as fungi, bacteria, "iruses, and $arasites.
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LE5@EMIA
/eukemia, originally described by ircho! in 1=Cs of the bone marro!. This neo$lastic $rocess
is characteri&ed by differentiation and $roliferation of malignantlytransformed hemato$oietic stem cells, leading to su$$ression of normal
cells. The malignant cells re$lace and turn off the normal marro! elements,
causing anemia, thrombocyto$enia, and a deficiency of normally functioning
leukocytes. In time, the leukemic cells infiltrate other body organs,
destroying normal tissue.
%ny of the !hite blood cells may be in"ol"ed by this disorder and for this
reason disease is often classified as6
1./ym$hoid 9lym$hoblastic,lym$hocytic: leukemia in"ol"ing the
lym$hocytic series.
2.-yeloid9myelogenous:leukemia in"ol"ing $rogenitor cell that gi"es rise
to terminally differentiated cells of myeloid series 9erythrocyte,granulocyte,
monocyte and $latelets:
The classification may be modified to indicate the course of disease by
a$$lication of terms acute, sub acute, and chronic.
Et!o'o+y
irus E$stein >arr "irus, her$es like "irus and 5T/ 9human T cell
leukemic "irus: ha"e been considered to be the etiological agents
res$onsible for leukemia. adiation and atomic energy o"er the dose of 1BBrads, it is kno!n to significantly increase the risk of leukemia. /eukemia
among radiologists and Ha$anese e+$osed to the atomic blast are more, as
com$ared to other $o$ulation. Chronic e+$osure to aniline dyes, ben&ene
and $henylbuta&one ha"e been recogni&ed to be associated !ith
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leukemia.;sually in these $atients $ancyto$enia due to marro! hy$er$lasia
occurs $rior to leukemia. Aatient treated !ith anticancer drug like mel$halan
and chlorambucil ha"e an increased risk of de"elo$ing leukemia, usually of
acute myelocytic "ariety. Aresence of certain genetic and chromosomalfactors like a $hiladel$hia chromosome is found in about 14 $ercent of
cases of acute lym$hocytic leukemia.
AC5TE LE5@EMIA
%cute leukemia is a disorder in !hich there is a failure of maturation of
leukocytes. %s a result there is an accumulation of immature cells !ithin the
bone marro! and later in the blood. It is the most common ty$e of leukemia,
e+ce$t in children 9in !hom acute lym$hoblastic leukemia is more
common:.
Patho4hy&!o'o+y
There is a block in differentiation of leukemic and stem cells and leukemic
blasts ha"e $rolonged. Thus accumulation of leukemic blast in acute
leukemia results $rimarily from failure of maturation into functional stage.
%s leukemic blast accumulates in the marro!, they su$$ress the normal
hemato$oietic stem cells.
C'!n! a' eature&
It is more common in children and young adults bet!een the age of 14 and
)? years. -ales are affected more commonly than females !ith a ratio of
)62. There is abru$t stormy onset !ith $yre+ia and enlargement of s$leen.
@ym$toms usually result from bone marro! su$$ression and infiltration of other organs and tissues by leukemic cells. Weakness, fe"er, headache,
generali&ed s!elling of lym$h nodes, $etechiae or hemorrhage in skin and
mucous membrane are seen. There is $ain in bones and tenderness, resulting
from marro! e+$ansion, !ith infiltration of sub$eriosteum.Central ner"ous
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manifestations such as headache, "omiting, ner"e $alsies resulting from
meningeal s$read is more common in children than in adults, and more
common in %// than %-/. The clinical features are due to anemia and
thrombocyto$enia "i&. $allor, dys$nea, fatigue, $etechiae, ecchymosis,e$ista+is and melena. 5e$atos$lenomegaly is $resent in later stages.
There is an increased susce$tibility to infection. Cer"ical lym$hadeno$athy,
secondary to $haryngeal se$sis is seen. Intracranial and subarachnoid
hemorrhage may result from thrombocyto$enia and leukostasis
9intra"ascular clum$ing of leukemic blasts in the small blood "essels of
brain:.There is recurrent infection of lungs, urinary tract skin, mouth, rectum
and u$$er res$iratory tract, !hich may result in fe"er. /ocali&ed tumors
consisting of leukemic cells called h'oro*a& , surface of !hich turn green
!hen e+$osed to light because of the $resence of myelo$erodio+ase.
Ora' *an! e&tat!on&
The submental, cer"ical and $re and $ostauricular lym$h nodes may be
enlarged and tender. Aaresthesia of lo!er li$ and chin may be $resent. There
may be toothache due to leukemic cell infiltration of dental $ul$. The oral
mucous membrane sho!s $allor, ulceration !ith necrosis, $etechiae,
ecchymosis and bleeding tendency. There may be massi"e necrosis of
lingual mucosa !ith sloughing. 7ingi"a sho!s hy$ertro$hy and cyanotic
discoloration. The hy$ertro$hy may be due to leukemic cell infiltration
!ithin gingi"a or due to local irritants. The gingi"a a$$ears boggy,
edematous and dee$ red bleeds easily due to ulceration of sulcus e$itheliumand necrosis of underlying tissue. -obility of $ermanent teeth may be
$resent. Oral infections 9candidal, "iral and bacterial: are serious and
$otentially fatal com$lication in leukemic $atients.
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COLOR PLATE -IV
A ute Leu ae*!a,G!n+! a' En'ar+e*ent and 5' erat!on&
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)e*ato'o+! a' !nd!n+&
The total W>C count may "ary from a "ery lo! count less than 1 + 1B 8 $er
cu mm to as high as 4BBB + 1B 8 $er cu mm or more. The $eri$heral smear
sho!s significant number of immature granulocytes or lym$hatic $recursorsor e"en stem cells. >one marro! is hy$ercellular !ith re$lacement of
normal marro! elements by leukemic blast cells in "arying degree.
There is an associated normochromic anemia, thrombocyto$enia and
decrease in normally functioning neutro$hils.
Mana+e*ent
irst $hase is $hase of induction, $ateint is treated using combination of
"incristine 91.0 mg m 2 e"ery !eek of 1 month:, / as$araginase 98BB units m 2
bi!eekly for 1 month: and $rednisone 90B mg m 2 orally daily for 1month:.
%s the leukemic cells regress, regro!th of normal cells occurs and the
$atient goes ra$idly into remission. Ahase of consolidation in this, drugs
used include daunorubicin, merca$to$urine, cytarabine, and methotre+ate
!ith intra thecal thera$y using the last t!o drugs, together !ith irradiation
of the cranium to eradicate the disease from central ner"ous
system. adiation reduces the risk of rela$se in central ner"ous system !hen
gi"en !ith methotre+ate. Ahase of maintenance, in this $hase, $atient
recei"es a re$eating cycle of abo"e drugs until t!o or three years ha"e been
com$leted. %llogenic bone marro! trans$lantation from 5/% identical t!in
is done. %blati"e thera$y has been utili&ed to eradicate the $atientPs residual
leukemic cells and normal cells !ith intensi"e irradiation and chemothera$y.%fter this reconstruction of the hemo$oietic tissue is done !ith $recursor
cells from the donor. %cute non lym$hoblastic leukemia is treated !ith
daunorubicin, cytarabine and 8 thioguanine. %ll these drugs are "ery to+ic to
the normal as !ell as leukemic cells and therefore, treatment is gi"en in
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$ulses to reduce to+icity. Catabolic $roducts of leukemic cells $roduce uric
acid and cause hy$eruricemia, !hich is $re"ented by allo$urinol. In
su$$orti"e thera$y transfusion of red cells and $latelets may be re(uired in
cases of se"ere anemia and thrombocyto$enia.Combination of higher antibiotics like aminoglycosides !ith ce$halos$orin, allo$urinol, before
starting anti leukemic agents are gi"en to $re"ent hy$eruricemia. To$ical
treatment to sto$ gingi"al bleeding includes remo"ing ob"ious local irritants
and direct $ressure. ;se of absorbable gelatin or collagen s$onge to$ical
thrombin is hel$ful. The management of oral ulcers includes to$ical
antibacterials !ith $o"idone iodine solution, chlorhe+idine rinses or
tetracycline rinses. Asychological su$$ort is "ery im$ortant as delusion and
hallucinations are not uncommon during $eriods of se"ere bone marro!
failure.
C)RONIC LE5@EMIA
Chronic leukemias are characteri&ed by the $resence of large leukemic cells
and differentiated W>Cs in the bone marro!, $eri$heral blood and other
tissues. It has a $rolonged clinical course e"en !ithout thera$y.
C)RONIC MYELOID LE5@EMIA
Patho4hy&!o'o+y
It is associated !ith the $resence of a distincti"e chromosomal abnormality,
i.e. Ahiladel$hia chromosome.
C'!n! a' eature&
The disease occurs chiefly bet!een the age of )4 to 8B years. The disease
may be disco"ered during routine e+amination, !hen s$lenomegaly or an
ele"ated count is noted. There may be slo!ly ad"ancing anemia !ith loss of
!eight, $rominence of abdomen and disscomfort in the left u$$er (uadrant
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due to s$lenomegaly. %ttacks of acute left u$$er abdominal $ain may
de"elo$ due to infarction of s$leen. %nemia causes !eakness, fatigue and
dys$nea on e+ertion. %s the disease $rogress thrombocyto$enia can cause
$etechiae, ecchymosis as !ell as hemorrrhage from the skin and mucousmembrane. /i"er may be enlarged but lym$h nodes are normal.
)e*ato'o+! a' !nd!n+
E+amination of blood sho!s a normocytic and normochromic anemia.
W>C count is considerably increased and may be bet!een 4B + 1B 8 to
4BB Q 1B8 cells $er cu mm. Aeri$heral smear sho!s mature leukocytes but,
fe! immature forms may also be $resent. The $latelet count is often high
initially but !ith treatment, it comes do!n.
Mana+e*ent
The treatment of choice is chemothera$y using the drug busul$han gi"en
orally in a dose of 0 mg daily or in large doses of 4B 1BB mg s$aced 2 to )
!eeks a$art. The treatment is continued for 12 to 1= !eeks and should be
discontinued !hen W>C count is bet!een 1B + 1B 8 and 2B + 1B 8 $er cu mm,
other !ise busul$han may cause a$lasia of the bone marro!.% combination
chemothera$y using a small dose of busul$han 2 mg daily along !ith
merca$to$urine 4Bmg daily or thioguanine =B mg daily. adiothera$y and
s$lenectomy are other treatment of choice.
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C)RONIC LYMP)ATIC LE5@EMIA
Chronic /ym$hatic /eukemia is a slo!ly $rogressing malignancy in"ol"ing
lym$hocytes.
Patho4hy&!o'o+y
It is characteri&ed by the accumulation of long li"ed, non functional >
lym$hocytes.
C'!n! a' eature&
It occurs more fre(uently in males and ma3ority of the $atients are o"er 04
years, the onset is "ery insidious. Tiredness and ill health are common,
although some $atients are sym$tom free and the disorder is foundincidentally. >one marro! infiltration causes anemia and thrombocyto$enia
and results in $allor, !eakness, dys$nea and $ur$ura. There is a moderate
enlargement of lym$h nodes !hich are firm, rubbery and discrete. /i"er and
s$leen are usually enlarged and $al$able. There is an increased susce$tibility
to infection as the leukemic > cells are non functional. /eukemic infiltration
results in skin nodules, intestinal malabsor$tion, $ulmonary obstruction or
com$ression of the central or $eri$heral ner"ous system. The most common
grou$s of lym$h nodes in"ol"ed are cer"ical, a+illary and inguinal grou$.
C'!n! a' &ta+!n+
@tage % /ym$hocytosis is less than three areas of lym$hoid enlargement, no
anemia or thrombocyto$enia.
@tage > -ore than three areas of lym$hoid enlargement, no anemia or
thrombocyto$enia.
@tage C %nemia or thrombocyto$enia, regardless of number of area of
lym$hoid enlargement.
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Ora' *an! e&tat!on&
The most common oral finding is hy$ertro$hy of gingi"a. There may be
ulceration !ith necrosis and gangrenous degeneration, a dark bro!n e+udate
and foul fetor oris are $resent. Tongue is fre(uently s!ollen and dark.egional lym$hadeno$athy is seen. a$id loosening of teeth due to necrosis
of $eriodontal ligament has been re$orted. #estruction of al"eolar bone also
occurs in some cases.
)e*ato'o+! a' !nd!n+&
Aeri$heral blood smear sho!s mild anemia and a large number of small
lym$hocytes. /ym$hoblasts are rare but increase in the terminal stages of
disease. W>C count may increase u$ to 1BBB + 1B 8 $er cu mm.
Mana+e*ent
7eneral measure to maintain good health, ade(uate rest, good food and
e+ercise should be ad"ised. In chemothera$y, chlorambucil 8 to 1B mg day
for 10 days !ith break of 10 days and cyclo$hos$hamide 2 to ) mg kg I
for 8 days. Combination thera$y of cyclo$hos$hamide, do+orubicin,
"incristine, and $rednisone ha"e been recommended. adiothera$y !ith "ery
small doses, of only 14B rads o"er a $eriod of fi"e !eeks, is "ery effecti"e
and may induce satisfactory remission. @teroids are gi"en if the bone
marro! is se"erely in"ol"ed initial treatment !ith $rednisone 0B mg daily
and 24 4B mg daily later should be gi"en.
Rad!o+ra4h! eature& o 'eu e*!a
It affects the entire body as it is malignancy of bone marro!. It is $resentedas ill defined $atchy radiolucent area. There is destruction of al"eolar,bone
loss may be in form of trans"erse lines of increased radiolucency or irregular
areas and loss $roduces the so called, moth eaten a$$earance. @clerosis of
bone may be $resented alone or in combination !ith destructi"e lesion. In
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Onion $eel a$$earance there is formation of bone beneath the $eriosteum.
The ne! bone takes the form of a thin !hite line $arallel !ith the shaft of
the bone and sometimes se$arated from it by a thin dark line 9onion $eel
effect:. @kull is rarely in"ol"ed and it may re"eal areas of bonedestruction.The de"elo$ing teeth may be dis$laced from their normal
$osition.There is also genrali&ed loss of lamina dura !ith loosening of teeth.
7enerali&ed bone loss may be seen.
)AIRY LE5@EMIA
It a "ariant of chronic lym$hatic leukemia in !hich there is s$lenomegaly,
se"ere neutro$enia, monocyto$enia and the characteristic a$$earance of
hairy cells in blood and bone marro!. These hairy cells a$$ear to be a cross
bet!een the lym$hocytes and monocytes. It occurs mainly in adults and
sho! male $redilection. -anifestations result from infiltration of bone
marro!, li"er, s$leen. @$lenomegaly is massi"e and he$atomegaly is less
common. 5airy cell can be identified on the $eri$heral smear.
PROLYMP)OCYTIC LE5@EMIA
It is another "ariant of chronic lym$hatic leukemia in !hich there is massi"e
s$lenomegaly !ith little lym$hadeno$athy and a "ery high W>C count.
The characteristic cell is a large lym$hocyte !ith $rominent nucleus.
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ALE5@EMIC LE5@EMIA
It is the sub leukemic form of leukemia in !hich the W>C count of the
$eri$heral blood is normal or e"en subnormal and abnormal or immature
leukocytes may be $resent.Denta' Con&!derat!on&
To$ical treatment to sto$ gingi"al bleeding like remo"al of local irritants,
direct $ressure and use of absorbable gelatin, collagen s$onge, to$ical
thrombin and $lacement of microfibrillar collagen. If these local measures
are not successful $latelet transfusion is gi"en. Alatelet transfusion and
intra"enous combination of antibiotics is re(uired before any dental
treatment.
Ora' 5' er&
Oral mucosal ulcers are common findings in leukemic $atients taking
chemothera$y and are fre(uently caused by the direct effect of
chemothera$eutic drugs on the oral mucosal cells. The ulcers are
characteristically large, irregular, and foul smelling, and are surrounded by
$ale mucosa caused by anemia and a lack of normal inflammatory
res$onse. The most common cause of oral ulcers in leukemic $atients
recei"ing chemothera$y is recurrent 5@ infections. These infections
in"ol"e the intraoral mucosa and the li$s. /esions fre(uently begin !ith the
classic cluster of "esicles ty$ical of recurrent 5@ and (uickly s$read,
causing large ulcer. The management of non 5@ oral ulcers in leukemic
$atients should $re"ent the s$read of locali&ed infection, minimi&e bacteremia, $romote healing, and reduce $ain. The ulcers in hos$itali&ed
leukemic $atients taking chemothera$y may be infected !ith organisms not
commonly associated !ith oral infection, $articularly gram negati"e enteric
bacilli. To$ical antibacterial treatment can be attem$ted !ith $o"idone
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iodine solutions, bacitracin neomycin ointments, or chlorhe+idine
rinses.Gaolin and $ectin $lus di$henhydramine oral rinses can be used to
reduce $ain.
Ora' !n e t!on&
Candidiasis is a common oral fungal infection, but infections !ith other
fungi, such as Histoplasma , Aspergillus , or Ahycomycetes, fungi, also may
begin on the oral tissues.When these lesions are sus$ected, a bio$sy
s$ecimen, a fine needle as$iration, or a cytology smear must be obtained
because a culture alone is not a reliable test for these organisms. #iagnosis
of dental infection, $articularly $eriodontal and $ericoronal infections, is
difficult in neutro$enic leukemic $atients because normal inflammation is
absent.
LE5@OPENIA
Leu o4en!a is deficiency of !hite cells, !hich can be a chancehaemotological finding and may cause no sym$tom until it becomes so
se"ere as to im$air defence against infection.
AGRAN5LOCYTOSIS
It is also called as granulocyto$enia, agranulocytic angina. It is a serious
disease characteri&ed by marked leuko$enia !ith reduction and absence of neutro$hilic leukocytes.
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PRIMARY AGRAN5LOCYOSIS
The etiology of $rimary agranulocytosis is unkno!n. @econdary
agranulocytosis is used !hen cause is recogni&ed. -ild neutro$enia !hen
1BBB mm) to 2BBB mm) neutro$hils are $resent. -oderate neutro$enia !hen
4BB mm) to 1BBB mm) neutro$hils are $resent. Idiosyncrasy or sensiti&ation
to certain drugs like amino$hylline, chlor$roma&ine and $henylbuta&one,
ben&ene, bismuth, chloram$heenicol, sulfonamides and use of cytoto+ic
drugs or antimetabolics, deficiency of "itamin > 12 and folic acid. Certain
infections decrease the number of neutro$hils in circulating blood because of
increased migration of neutro$hils into the tissue, destruction of neutro$hils
or direct effect of microorganism and its to+ins on the bone marro!.
Infection !ith he$atitis % and "aricella &oster "irus infection are commonly
associated !ith neutro$enia. O"er!helming bacterial infection, $articularly
se$ticemia can be accom$lished by neutro$enia because cells are used at
ra$id rate to o"ercome infection. #iseases causing se(uestration of
neutro$hils includes systemic lu$us erythematosus and eityPs syndrome. It
can be associated !ith leukemia, $ancyto$enia and hy$ers$lenism.
5emodialysis $atient e+$erience decrease in neutro$hil o!ing destruction by
com$lement acti"ated by the dialysis membrane. Irradiation can cause
neutro$enia due to direct to+ic effect on di"ision of bone marro! cells.
C'!n! a' eature&
It can occur at any age but it some!hat more common in adults, $articularly
in !oman. It is also common in $rofessional and in hos$ital as they ha"e
easy access of the offending drugs and often use drug sam$le in3udiciously.
@ym$toms may be sudden or gradual. The condition begins !ith sore throat,
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high fe"er and often rigors, !hich may be follo!ed by $rostration. @kin
a$$ears $ale and anemic and in some cases, 3aundiced. There is ra$idly
ad"ancing necrotic ulceration of throat and mouth !ith little e"idence of $us
formation In most of the cases $atient dies !ithin ) to 4 days due to to+emiaand se$ticemia.
Ora' *an! e&tat!on&
The most common sites are gingi"a and $alate, tonsil and $haryn+.
There may be associated $ain, e+cessi"e sali"ation and s$ontaneous oral
hemorrhage. The oral lesions a$$ear as necroti&ing ulcerations of oralmucosa, tonsils and $haryn+. The lesions a$$ear as ragged and necrotic and
are co"ered !ith a gray black membrane. The necrotic tissue is often foul
smelling. On margins of lesion there is lack of inflammation.The disease
s$reads (uickly in gingi"al tissues causing destruction of su$$orting
structures and ine"itable loss of deciduous and $ermanent teeth.
@u$$orting al"eolar bone is ra$idly destroyed, so that teeth are denuded of
bone and are su$$orted only by soft tissues. ery rarely, infection s$reads to
dee$ into the marro! to cause osteomyelitis.
)e*ato'o+! a' !nd!n+&
-a3ority of $atients sho! a leukocyte count belo! 2BBB cells $er cu mm )
and granulocyte count belo! 1BB cells $er cu mm ) . 5emoglobin and $latelet
counts are normal.
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CYCLIC NE5TROPENIA
In y '! neutro4en!a there is fall in the number of circulating neutro$hils at
regular inter"als of ) 0 !eeks. It is therefore necessary to monitor the !hitecell count daily for se"eral !eeks inorder to diagnose the condition. It may
cause oral ulceration and $eriodontal breakdo!n. Etiology is drugs and
chemicals infections and long term e+$osure to radiation. In Oral ca"ity
s$ontaneous hemorrhage may occur from gingi"a. Aetechiae may be seen in
soft $alate.
Treat*ent
The uni"ersally acce$ted treatment for most cases of cyclic neutro$enia is
careful monitoring of the $atient for infection during neutro$enic $eriods
and "igorous early management of infection. In some $atients, use of
corticosteroids, adrenocorticotro$in, or testosterone modulates the shar$
reduction in marro! function.;nfortunately, these drugs are not successful
for all $atients. The use of granulocyte colony stimulating factor 97 C@ :
has been em$loyed to boost neutro$hil le"els. ;nlike !ith congenital
agranulocytosis, 7 C@ thera$y in cyclic neutro$enia is not associated !ith
the de"elo$ment of acute myeloid leukemia or myelody$lasia. 20
Ora' and Denta' Con&!derat!on&
Oral lesions are common in cyclic neutro$enia and may be the ma3or
clinical manifestation of the disease. The t!o most common oral
manifestations are oral mucosal ulcers and $eriodontal disease. The oral
ulcers recur !ith each ne! bout of neutro$enia and resemble the large dee$
scarring ulcers seen in ma3or a$hthous stomatitis. The $eriodontal
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