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The Correlation Between Vitamin B12 Deficiency and Recurrent Aphthous Stomatitis

Andri Changat 0 0!0"!01#

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2012 ,R($AC(

Firstly, I want to thanks to God, because only by Gods help I can finish this paper which discuss about THE CO EC, E!"TIO# $ET%EE# &IT"'I# $() *EFICIE#C+ "#*

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This paper was 3ade to finish the E#G!I.H 4 sub5ect in Faculty of 'edicine, Trisakti ,ni6ersity2 This paper is a re6iew about 6ita3in b() deficiency in 7eneral, and factor which can lead to recurrent aphthous sto3atitis and also how 6ita3in b() deficiency is related to recurrent aphthous sto3atitis2 Hopefully this paper can be useful for whoe6er read this paper, especially to 3edical students2 $esides that, I also accepted all critics and su77estions for the paper so it will be better in the future2 In the case I would say thanks to 8esus Christ, and to * 2 dr72 9artika %, '2-d2 as a lecturer, for all the 7uides and the contributions while preparin7 the paper and also to 3y parents, 3y sister, and for e6eryone who ha6e support 3e so I could finally co3plete this paper2

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ecurrent aphthous sto3atitis / ".0, co33only known as canker sores, has been reported as recurrent oral ulcers, recurrent aphthous ulcers, or si3ple or co3ple@ aphthosis2 One of its 6ariants is the 3ost painful condition of the oral 3ucosa2 ecurrent aphthous sto3atitis has been the sub5ect of acti6e in6esti7ation alon7 3ultiple lines of research, includin7 epide3iolo7y, i33unolo7y, clinical correlations, and therapy2 The natural history of indi6idual lesions of ". is i3portant, because it is the bench 3ark a7ainst which treat3ent benefits are 3easured2 The lesions of recurrent aphthous sto3atitis are not caused by a sin7le factor but occur in an en6iron3ent that is per3issi6e for de6elop3ent of lesions2 These factors include trau3a, s3okin7, stress, hor3onal state, fa3ily history, food hypersensiti6ity and infectious or i33unolo7ic factors2 The clinician should consider these ele3ents of a 3ultifactorial process leadin7 to the de6elop3ent of lesions of aphthous sto3atitis2 The association of lesions of recurrent aphthous sto3atitis with he3atinic deficiencies and 7astrointestinal diseases pro6ides an opportunity to identify a Acorrectable cause,A which, with appropriate treat3ent, can result in a re3ission or substantial lessenin7 of disease acti6ity2 %(-.)RDS / Recurrent aphthous stomatitis0 stress0 hematinic deficiency


&ita3in $() bears the i3portant task of blood for3ation2 It can be absorbed for nor3al functionin7 only in the presence of the intrinsic factor, a 3ucoprotein found in the sto3ach and intestines2 &ita3in $() was ori7inally isolated fro3 ani3al li6er early in (?;>, and was used to treat pernicious ane3ia2 !ater, researchers used fer3entation to isolate lar7e Buantities of &ita3in $() in solution with bacteria /strepto3yces 7riseus0, which techniBue is still widely used in the phar3aceutical field2 The full che3ical na3e of &ita3in $() is Cyanocobala3in2 &ita3in $(), also known as Cobala3in, can be used to cure pernicious ane3ia and is often called the AantiCpernicious ane3ia factor2A The structural presence of phosphorous and cobalt in its 3olecules 7i6es it a reddish hue, 3akin7 it the only crystalline red 6ita3in and earnin7 it the nickna3e, Athe ed &ita3in2A The only 6ita3in to contain all the co33on 3inerals, &ita3in $() co3es in 3any for3s, such as $()a, $()b, and $()c2 It usually consists of a cobalt 3olecule bound to a C# 7roup and an OH or #O) 7roup2 ecurrent "phthous .to3atitis / ".0 often is caused by 3icronutrient i3balance in the body2 The authors conducted a study to deter3ine if there is a relationship between 6ita3in b() deficiency with recurrent aphthous sto3atitis2 The purpose of writin7 this paper is to e@plain the relationship of aphthous sto3atitis with 6ita3in $() deficiency2 .o hopefully this paper will be useful to help dentists and other health practitioner in perfor3in7 his duties well, especially if found patients who were sufferin7 fro3 aphthous sto3atitis2


V+TA1+* B212 D($+C+(*C&ita3in $() has 3any i3portant functions in the body2 It works with the folic acid to 3ake our bodyDs 7enetic 3aterial2 It helps keep le6els of the a3ino acid ho3ocysteine in check, which 3ay help decrease heart disease risk, and it is essential to the production of red blood cells, which carry o@y7en throu7h the blood to the bodyDs tissues and has i3portant role in the 3aintenance of the central ner6ous syste3 too2 Source of Vitamin B12 The ter3 A6ita3in $() A is used as a 7eneric descriptor for the co3alamins Ethose corrinoids /cobaltCcontainin7 co3pounds possessin7 the corrin rin70 ha6in7 the biolo7ic acti6ity of the 6ita3in2 .o3e corrinoids that are 7rowth factors for 3icroor7anis3s not only ha6e no 6ita3in $() acti6ity, but 3ay also be antiC3etabolites of the 6ita3in2 "lthou7h it is synthesiFed e@clusi6ely by 3icroor7anis3s, for practical purposes 6ita3in $() is found only in foods of ani3al ori7in, there bein7 no plant sources of this 6ita3in, for e@a3pleG /(0harper

E77s Fortified foods such as soy3ilk 'eat 'ilk and 3ilk products Or7an 3eats /li6er and kidney0

-oultry .hellfish

Causes of Vitamin B12 Deficiency &ita3in $() deficiency can ha6e a nu3ber of possible causes2 Typically it occurs in people whose di7esti6e syste3s do not adeBuately absorb the 6ita3in fro3 the foods they eat2 This can be caused byG

-ernicious ane3ia, a condition in which there is a lack of a protein called intrinsic factor2 The protein, which is 3ade in the sto3ach, is necessary for 6ita3in $() absorption2 "trophic 7astritis, a thinnin7 of the sto3ach linin7 that affects up to 4:H of people a7ed <: and older2

.ur7ery in which part of the sto3ach andIor s3all intestine is re3o6ed2 Conditions affectin7 the s3all intestine, such as CrohnDs disease, celiac disease, bacterial 7rowth, or a parasite2

E@cessi6e alcohol consu3ption2 "utoi33une disorders, such as Gra6esD disease or syste3ic lupus erythe3atosus !on7Cter3 use of acidCreducin7 dru7s2 $abies born to 3others who are 6e7etarians 3ay also be deficient in 6ita3in $()2

&ita3in $() deficiency can also occur in 6e7etarians, because the best food sources of the 6ita3in are ani3al products2 This 3eans that strict 6e7etarians /6e7ans0 are at risk of de6elopin7 $() deficiency2 The s3all a3ounts of the 6ita3in for3ed by bacteria on the surface of fruits 3ay be adeBuate to 3eet reBuire3ents, but preparations of 6ita3in $() 3ade by bacterial fer3entation are a6ailable2 /harper0 Symptoms of Vitamin B12 Deficiency

" deficiency of 6ita3in $() can lead to ane3ia2 " 3ild deficiency 3ay cause only 3ild, if any, sy3pto3s2 $ut as the ane3ia worsens it 3ay causes sy3pto3s such asG

weakness, tiredness or li7htCheadedness rapid heartbeat and breathin7 pale skin sore 3outh andIor ton7ue easy bruisin7 or bleedin7, includin7 bleedin7 7u3s sto3ach upset and wei7ht loss diarrhea or constipation

If the deficiency is not corrected, it can da3a7e the ner6e cells2 If this happens, 6ita3in $() deficiency effects 3ay includeG

tin7lin7 or nu3bness in fin7ers and toes difficulty walkin7 3ood chan7es or depression 3e3ory loss, disorientation, and de3entia

$() deficiency in infants, if not detected and treated, can lead to se6ere and per3anent da3a7e to the ner6ous syste32 #ew 3others who follow a 6e7etarian diet should ha6e their babiesD $() le6els checked by a doctor2 Treatment for Vitamin B12 Deficiency &ita3in $() deficiency treat3ent depends on the cause of the deficiency2 If pernicious ane3ia or a proble3 with absorption is the cause, $() replace3ent will be necessary2 'ost often this is 7i6en by in5ectionJ so3e people 3ay be prescribed 6ita3in tablets2

For so3e people, $() supple3entation 3ay be necessary for life2 If a diet lackin7 in ani3al products is the cause, the doctor will reco33end dietary chan7es alon7 with supple3entation of 6ita3in $() by in5ection or tablet2 For 3ost people, treat3ent resol6es the ane3iaJ howe6er, any ner6e da3a7e that has occurred as a result of the deficiency could be per3anent2 ,re4enting Deficiency ,ro3lems 'ost people can pre6ent 6ita3in $() deficiency by consu3in7 enou7h 3eat, poultry, seafood, 3ilk, cheese, and e77s2 If you donDt eat ani3al products or you ha6e a 3edical condition that li3its your absorption of nutrients, e@perts reco33end takin7 a $()Ccontainin7 3ulti6ita3in and eatin7 breakfast cereal fortified with 6ita3in $()2

R(C&RR(*T A,5T5)&S ST)1AT+T+S Bac6ground "phthous sto3atitis, or recurrent aphthous ulcers / ",s0 or canker sores, are a3on7 the 3ost co33on oral 3ucosal lesions physicians and dentists obser6e2 ecurrent aphthous ulcer is a disorder of unknown etiolo7y that can cause clinically si7nificant 3orbidity2 One or se6eral discrete, shallow, painful ulcers are 6isible on the unattached 3ucous 3e3branes2 Indi6idual ulcers typically last >C(: days2 !ar7er ulcers 3ay last se6eral weeks to 3onths and can scar when healin72 "lthou7h the process in idiopathic recurrent aphthous ulcers is usually selfCli3itin7, in so3e indi6iduals, the ulcer acti6ity can be al3ost continuous2 .i3ilar ulcers can be noted in the 7enital re7ion2 $ehKet syndro3e, syste3ic lupus erythe3atosus, and infla33atory bowel disease are syste3ic diseases associated with oral recurrent aphthous ulcers2 ,athophysiology The classic cate7oriFation of recurrent aphthous ulcer is di6ision into 4 clinical for3sG recurrent aphthous ulcer 3inor, recurrent aphthous ulcer 3a5or, and herpetifor3 recurrent

aphthous ulcer2

ecurrent aphthous ulcer affects the followin7 nonkeratiniFed or poorly

keratiniFed surfaces of the oral 3ucosaG

!abial and buccal 3ucosa 'a@illary and 3andibular sulci ,nattached 7in7i6a .oft palate Tonsillar fauces Floor of the 3outh &entral surface of the ton7ue

1! Recurrent aphthous ulcer minor ecurrent aphthous ulcer 3inor is the 3ost co33on for3, accountin7 for L:H of all cases2 *iscrete, painful, shallow, recurrent ulcers s3aller than ( c3 in dia3eter characteriFe this for32 "t any ti3e, one or 3ore ulcers can be present2 !esions heal without scarrin7 within >C(: days2 The periodicity 6aries between indi6iduals, with so3e ha6in7 lon7er ulcerCfree episodes and so3e ne6er bein7 free fro3 ulcers2 2! Recurrent aphthous ulcer ma7or ecurrent aphthous ulcer is for3erly known as periadenitis 3ucosa necrotica recurrens2 This for3 is less co33on than the others and is characteriFed by o6al ulcers 7reater than ( c3 in dia3eter2 In this relati6ely se6ere for3, 3any 3a5or aphthae 3ay be present si3ultaneously2 ,lcers are lar7e and deep, 3ay ha6e irre7ular borders, and 3ay coalesce2 ,pon healin7, which 3ay take as lon7 as = weeks, ulcers can lea6e scarrin7, and se6ere distortion of oral and pharyn7eal 3ucosa 3ay occur2 ! 5erpetiform recurrent aphthous ulcer


This least co33on for3 /<C(:H of cases0 has the s3allest of the aphthae, co33only no lar7er than ( 33 in dia3eter2 The aphthae tend to occur in clusters that 3ay consist of tens or hundreds of 3inute ulcers2 Clusters 3ay be s3all and localiFed, or they 3ay be distributed throu7hout the soft 3ucosa of the oral ca6ity2 Causes "lthou7h the clinical characteristics of recurrent aphthous ulcer are wellCdefined, the precise etiolo7y and the patho7enesis of recurrent aphthous ulcer re3ain unclear2 'any possibilities ha6e been in6esti7ated2 ecurrent aphthous ulcer is a 3ultifactorial condition, and it is likely that i33uneC3ediated destruction of the epitheliu3 is the co33on factor in recurrent aphthous ulcer patho7enesis2 Host risk factors associated with recurrent aphthous ulcer are described below2 1! 8enetics " fa3ily history of recurrent aphthous ulcers is e6ident in so3e patients2 " fa3ilial connection includes a youn7 a7e of onset and sy3pto3s of increased se6erity2 hi7hly correlated in identical twins2M(=N "ssociations between specific H!" haplotypes and recurrent aphthous ulcer ha6e been in6esti7ated2 #o consistent association has been de3onstrated, 3ost likely because of the lack of any i33uno7enetic basis for recurrent aphthous ulcer2 Howe6er, host susceptibility is clearly 6ariable, with a poly7enic inheritance pattern, and penetrance depends on other factors2M(>N 2! 5ematinic deficiency In se6eral studies, he3atinic /iron, folic acid, 6ita3ins $C= and $C()0 deficiencies were twice as co33on in patients with recurrent aphthous ulcers than in control sub5ects2 "s 3any as ):H of patients with recurrent aphthous ulcer had a deficiency2 !ower dietary intake of folate and 6ita3in $C() is 3ore co33on a3on7 persons with aphthous ulcers,M(LN and treat3ent with (::: 3c7Id has shown benefit in indi6iduals re7ardless of seru3 $C () le6els2M(?, ):N " s3all 7roup of adolescents were shown to ha6e reduced incidence and pain fro3 recurrent aphthous sto3atitis when 7i6en )::: 37Id of ascorbic acid2M)(N

ecurrent aphthous ulcer is

.erolo7ic workup is warranted2 He3o7lobin and $C indices are not sufficient in all cases2 ! +mmune dysregulation "t present, no unifyin7 theory of the i33unopatho7enesis of recurrent aphthous ulcer e@ists, but i33une dysre7ulation 3ay play a si7nificant role2 Cytoto@ic action of ly3phocytes and 3onocytes on the oral epitheliu3 see3s to cause the ulceration, but the tri77er re3ains unclear2 ,pon histolo7ic analysis, recurrent aphthous ulcer consists of 3ucosal ulcerations with 3i@ed infla33atory cell infiltrates2 TChelper cells predo3inate in the preulcerati6e and healin7 phases, whereas TCsuppressor cells predo3inate in the ulcerati6e phase2 Other findin7s associated with i33une dysre7ulation include the followin7G

educed response of patientsD ly3phocytes to 3ito7ens Circulatin7 i33une co3ple@es "lterations in the acti6ity of natural killer cells in 6arious sta7es of diseaseM))N Increased adherence of neutrophils educed Buantities and functionality of re7ulatory T cells in lesional tissue Increased e@pression of proCinfla33atory Th( 7enesM)4N elease of tu3or necrosis factorCalpha /T#FCalpha0M);N .i7nificant in6ol6e3ent of 3ast cells in the patho7enesis of recurrent aphthous ulcer educed cellular e@pression of heat shock protein )> and interleukin (: in aphthous lesionsM)<, )=N

Ele6ated le6els of sali6ary and seru3 cortisol, as well as increased an@ietyM)>N Increased TollClike receptor acti6ityM)LN O@idati6e stress /altered le6els and balance of 7lutathione and 3alondialdehyde0M)?N


Increased le6els of autoi33une thyroidCrelated proble3s and antithyroid antibodies, althou7h the si7nificance is unclearM4:N

9! 1icro3ial infection esearchers disa7ree about the role of 3icrobes in the de6elop3ent of recurrent aphthous ulcers2 E3phasis has been on a 3icrobial a7ent as a pri3ary patho7en or an anti7enic sti3ulus2 #u3erous studies ha6e failed to pro6ide stron7 e6idence to support the role of herpes si3ple@ 6irus, hu3an herpes6irus, 6aricellaCFoster 6irus, or cyto3e7alo6irus in the de6elop3ent of aphthous ulcers2M4(, 4)N ecurrent aphthous ulcer for3ation 3ay be a TCcellO3ediated response to anti7ens of Streptococcus sanguis that crossCreact with the 3itochondrial heat shock proteins and induce oral 3ucosa da3a7e2 Helicobacter pylori has been detected in lesional tissue of oral ulcers, but the freBuency of seru3 i33uno7lobulin G antibodies to H pylori is not increased in recurrent aphthous ulcers, and the or7anis3s ha6e ne6er pro6en causati6e2M44, 4;, 4<, 4=, 4>N ,hysical (:amination e7ardless of the clinical for3 of recurrent aphthous ulcer, ulcers are confined to the nonkeratiniFed 3ucosa of the 3outh, sparin7 the dorsu3 of the ton7ue, the attached 7in7i6a, and the hard palate 3ucosae, that are keratiniFed2 "lthou7h patients 3ay ha6e sub3andibular ly3phadenopathy, fe6er is rare2 'ost patients are otherwise well2

ecurrent aphthous ulcer 3inorG

ecurrent aphthous ulcer 3inor is characteriFed by

discrete shallow ulcers s3aller than ( c3 in dia3eter2 The ulcers are co6ered by a yellowC7ray pseudo3e3brane /fibrinous e@udate0 and are surrounded by an erythe3atous halo2

ecurrent aphthous ulcer 3a5orG ecurrent aphthous ulcer 3a5or is characteriFed by o6al ulcers that are lar7er /P( c3 in dia3eter0 and deeper than those obser6ed in recurrent aphthous ulcer 3inor2 The ulcers 3ay coalesce and often ha6e an irre7ular border2


Herpetifor3 recurrent aphthous ulcerG Herpetifor3 recurrent aphthous ulcer is characteriFed by crops of s3aller ulcersJ tens of ulcerations 3ay be present in clusters2 The ulcers can coalesce to produce a widespread area of irre7ular ulceration2

Correlation Between Vitamin B12 Deficiency and Recurrent Stomatitis Aphthous "lthou7h there are no clear detailed info about this infor3ation, but se6eral researches de3onstrate that patients with recurrent aphthous sto3atitis are 3ore likely to ha6e lower dietary intakes of 6ita3in $() and folate2 .o3e studies said that 6ita3in $() also has i3portant role on 3ucose tissue 3aintenance2 "lthou7h there is no clear patophysiolo7y but 6ita3in $() treat3ent, which is si3ple, ine@pensi6e and low risk, see3s to be effecti6e for patients sufferi7 fro3 recurrent aphthous sto3atitis2 (L (?


-oor oral health are co33on, but they can often be pre6ented by practicin7 7ood dental hy7iene, includin7 re7ular brushin7 and flossin72 $acteria that are 3ost co33on for responsible for initiatin7 bactere3iaG Streptococcus viridans 7roup is also i3portant in causin7 people to

suffer fro3 infecti6e endocarditis2 One of the co3plications of infecti6e endocarditis that is i3portant is con7esti6e heart failure and neurolo7ic e6ents which can also influence the pro7nosis of infecti6e endocarditis2 Therefore, people should be 3ore aware about their oral hy7ine so that it does not lead to poor oral health2


(2 'urray 92 obert, et al2 Harpers Illustrated $ioche3istry2 )Lth ed2 ,."G 'cGrawCHill Co3panies, Inc2J )::?J p2;)4C; )2 2

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