Role of Corticosteroids in Oral Lesions

Masoumeh Mehdipour
1
and Ali Taghavi Zenouz
1
[1]
Oral and Maxillofacial Medicine Department, Tariz !acult" of Dentistr", Tariz #niversit" of Medical $ciences,
%ran
1. Introduction
&lucocorticoids 'ere first introduced in the 1()*s and have ecome a 'idel" prescried class of drugs+
,orticosteroids are a class of chemicals that includes steroid hormones naturall" produced in the adrenal cortex of
verterates and analogues of these hormones that are s"nthesized in laoratories+ ,orticosteroids are involved in a
'ide range of ph"siologic processes, including stress response, immune response, and regulation of inflammation,
caroh"drate metaolism, protein cataolism, lood electrol"te levels, and ehavior+ The" are some of the most
common drugs for management of patients undergoing stressful situations such as surger" and dentstr" -&ison
.**)/+
%t has thus ecome common for standard textoo0s in dentistr" to recommend the administration of oral or
intravenous steroids in the management of oral lesions+
$teroids have different effects on different tissues, 'hich are dose dependent+ The reason for varied effect of steroids
lies in its mechanism of action -&rover .**1/+
&lucocorticoids have potent anti2inflammator" actions, including the reduction in the numer and function of
various immune cells, such as T and 3 l"mphoc"tes, monoc"tes, neutrophils,and eosinophils, at sites of
inflammation+ &lucocorticoids decrease the production of c"to0ines,chemo0ines, and eicosanoids and enhances the
production of macrophage migration inhiitor" factor -&ison .**)/+
,orticosteroid drugs are 'idel" used in oral medicine such as in vesiculoullous diseases, orofacial granulomatosis,
temporal arteritis and other oral mucosal disorders+ Topical corticosteroids should e considered the treatment of
choice unless the disease is ver" extensive+ $"stemic therap" is reserved for those 'ith severe, refractor" disease+
2. Mucosal ulceration and inflammation
2.1. Recurrent Aphthous Stomatitis
4ecurrent Aphthous $tomatitis -4A$/ are among the most common oral lesions in the general population, 'ith a
fre5uenc" of 67.68 and three month recurrence rates as high as 6*8+ Aphthous ulcers are often 5uite painful9 ma"
lead to difficult" in spea0ing, eating, and s'allo'ing9 and ma" negativel" affect patients: 5ualit" of life -$hip 1((;/+
4A$ is classified as minor, ma<or, and herpetiform+ Minor 4A$ involves the presence of one to five ulcers at a time,
'ith each ulcer less than 1 cm in diameter+
Ma<or aphthae are a cause of significant d"sphagia and often result in extensive scarring+ %n herpetiform 4A# there
are 1*71** ulcers at a time, ulcer size is usuall" 17= cm, and the ulcers form clustersthat coalesce into 'idespread
areas of ulceration lasting 171* da"s -4ees, >oo 1((;/+
The use of topical and s"stemic steroids in an attempt to manage apthous stomatitis is ased on the presumption that
the aphthae are the result of a noninfectious inflammator" process+ ,orticosteroids ma" act directl" on T
l"mphoc"tes or alter the response of effect or cells to precipitants of immunopathogenesis -?incent 1((./+
2.1.1. Topical corticosteroids
Topical corticosteroid use in patients 'ith 4A$ is intended to limit the inflammator" process associated 'ith the
formation of aphthae+
There are t'o doule2lind, placeo2controlled trials have evaluated the efficac" of topical corticosteroids for 4A$
-Merchant 1(1@9 Thompson 1(@(/+ The patients enrolled in one trial had minor 4A$+ ,lassification of ulcers 'as
not availale for the other trial+ 3oth trials assessed patients for immuno 2competence through laorator" studies+
One trial excluded other medications used in 4A$ -Thompson 1(@(/+ %n oth trials there 'ere significant reductions,
compared 'ith placeo, in ulcer duration and pain severit" and no changes in the fre5uenc" of 4A$ in patients 'ho
applied etamethasone gel or eclomethasone aerosol spra" to ulcers four times dail" for six da"s to four 'ee0s
-?incent 1((.9 Thompson 1(@(/+
T'o non2placeo controlled trials found no significant differences et'een triamcinolone ointment or
etamethasone talets and adhesive vehicles and Oraase in the fre5uenc" and duration of severe 4A$+ $u<ective
improvement tended to e greater 'ith corticosteroids than 'ith adhesive vehicle -Oraase/, although the difference
'as not statisticall" significant -MacAhee 1(;@/+ A single lind, placeo2controlled trial involving fluocinonide
ointment 'as performed in patients 'ith minor and ma<or 4A$+ !luocinonide ointment significantl" reduced ulcer
duration, ut ulcer fre5uenc" and su<ective improvement 'ere the same as for adhesive vehicle -Oraase/+ %n the
latter three trials, stud" design, ulcer severit", and vehicle activit" ma" have contriuted to findings inconsistent 'ith
those in the doulelind, placeo2controlled studies -Aimlott 1(@=/+
The drugs most commonl" adopted for local oral application in 4A$ are h"drocortisone hemisuccinate -as pellets of
.+ 6 mg/ and triamcinolone acetonide -in an adhesive paste containing *+ 18 of the steroid/+ There is little ris0 of
adrenal suppression provided that the recommended dose -fourtimes dail"/ is adhered to -!ield .**=/+
%n severe 4A$ ma" e necessar" to use a more potent steroid preparation+ Bigh potenc" topical steroid preparation
such as fluocinonide, etamethasone or cloetasol placed directl" on the lesions shortens healing time and reduces
the size of lesion+ The gel can e carefull" applied directl" to the lesion after meals and at edtime .2= times a da"
or mixed 'ith an adhesive such as oraase prior to application+ 4ecentl", Co Muzio et al+ treated oral aphthous
lesions " appl"ing cloetasol propionate 'ith a ioadhesive s"stem, 'hich resulted insurprisingl" good outcomes
-Co Muzio .**1/+
Carger lesions can e treated " placing a gauge sponge containing the topical steroid on the ulcer and leaving it in
place for 162=* min to allo' for longer contact of the medication+ #lcerations located in the areas that ma0e them
difficult to see or reach can e controlled " topical dexamethasone elixir, *+ 6 mg D 6 ml held over the area or
applied 'ith a saturated gauge pad to the ulcers, four times per da" for 16 min -Co Muzio .**1/ and etamethasone
sodium phosphate rinse -dissolve *+ 6 mg in 6 mC of 'ater and rinse for .7= min/, steroid aerosol -e+ g+
eclometasone diproprionate, 1** lgDpuff/, or a high2potenc" topical corticosteroid, such as cloetasol *+ *68 in
oraase or fluocinonide *+ *68 in oraase -Eatah .**)/+
2.1.2. Systemic corticosteroids
Ma<or apthous ulcers often re5uire s"stemic treatment as an initial approach+ Therap" 'ith prednisone )* mgDda" for
one 'ee0 is usuall" ade5uate to control the presenting outrea0+ $"stemicall", oral prednisone is most commonl"
emplo"ed+ $"stemic prednisone therap" should e started at 1+ * mgD0g a da" as a single dose in patients 'ith severe
4A$ and should e tapered after 12. 'ee0s+ %ntralesional steroids can e used to treat large indolent ma<or 4A$
lesions -!ield .**=/+
2.2. Behcets disease
3ehcet:s disease is a multis"stem, chronic relapsing inflammator" disease of un0no'n cause, 'hich is characterized
" recurrent oral -aphthous/ ulcers,genital ulcers, uveitis and s0in lesions+ There ma"e a variet" of other
manifestations including <oint,central nervous s"stem, vascular and intestinal lesions of variale severit" -Cai 1((6/+
Aatients 'ith 3ehcet:s disease usuall" have repeated exacerations and remission of their clinical s"mptoms,and in
these individuals treatment is essentiall" s"mptomatic+ The choice of therap" depends on 'hether the clinical
manifestations of the disease are local or s"stemic+
Cocal treatment 'ith corticosteroids often controls oral and genital ulcers, and immunosuppressive therap" is
reserved for severe cases of mucocutaneous involvement -Fazici 1((1/+
%mmunosuppressive therap" is the mainsta" of treatment for 3ehcet:s disease+ $uccessful treatment consists of anti2
inflammator" agents that modif" neutrophil activit"+ %n the acute phase, prednisone, at doses of )*2;* mgDda", ma"
e helpful, used alone or in comination 'ith other immunosuppressive agents -4eich 1((@/+
$"stemic corticosteroids continue to e used extensivel",and ma" e administered as intravenous pulse therap"+
2.!. Oral Lichen "lanus #OL"$
Cichen Alanus -CA/ is an uni5ue inflammator" disorder that affects the s0in, mucous memranes,nails and hair 'as
first descried and named " Grasmus >ilson in 1@;( -Oztas .**=/+ The pathogenesis of CA is not entirel"
understood+ %t is a disorder of altered cell mediated immunit" 'ith exogenous antigens targeting the epidermis+
?arious medical therapies are used for the treatment of Ahototherap" has een used in the treatment of CA for man"
"ears+ The therapeutic properties of corticosteroids 'ere first demonstrated " Gd'ard Hendall and Ahilip Bench in
1()@ -Bench 1()(/+
,orticosteroids ma" e applied topicall" as ointments, pastes, lozenges or mouth'ashes or through an inhaler 'ith a
special adapter+
The est treatment for OCA includes the use of high2potenc" topical corticosteroids -$etterfield .***, 3ruce .**1/+
%t has een reported that topical corticosteroids, 'hich have fe'er side effects, are e5uall" or even more effective
than s"stemic corticosteroids -Codi .**6/+
2.!.1. Topical corticosteroids
Topical corticosteroids are the main sta" in treating mild to moderatel" s"mptomatic lesions+ The" are 'idel" used
in the treatment of OCA to reduce pain and inflammation+ Options -presented in terms of decreasing potenc"/
include *+ *68 cloetasol proprionate gel, *+ 12*+ *68 etamethasone valerate gel, *+ *68 fluocinonide gel, *+ *68
cloetasol ointment or cream and *+ 18 triamcinolone acetonide ointment -Cevin .**./+
Triamcinolone acetonide is commonl" used either in oraase or lozenge -Thongprasom 1((., Zegarelli 1(;(/+ A
numer of investigations have determined the efficac" of triamcinolone acetonide *+ 18 suspension in the treatment
of OCA+ This drug is availale over the counter and is useful in the treatment of OCA -4ai"i .**=/+
An a5ueous suspension of triamcinolone acetonide *+ 18 'as used as an oral rinse in the treatment of ); patients
'ith s"mptomatic oral lichen planus -?incent 1((*/+ This method proved to e effective, resulting in Icomplete
relief I in .1 patients+ Although these results most li0el" refer to improvement in patientsJ s"mptoms,no specific
information is provided regarding the clinical improvement 'ith this therap"+
3etamethasone valerate, an even more potent anti2inflammator" agent, produced dramatic results in a numer of
controlled studies in patients 'ith oral lichen planus+ %n a doule2lind stud", ,a'son treated =* patients 'ith
s"mptomatic oral lichen planus 'ith etamethasone -*+1 mg/ pellets+ %n @ patients, all lesions virtuall" disappeared
'ithin 1 month, and during the same period, .* of =* patients sho'ed sustantial improvement+ Onl" t'o patients
failed to respond to this therap" -,a'son 1(;@/+
$imilarl", T"ldesle" and Barding sho'ed etamethasone valerate aerosol fitted 'ith a special intraoral adaptor 'as
an excellent treatment in the ma<orit" of .= patients tested in a doule2lind stud" -T"ldesle" 1(11/+ &reenspan et al+
confirmed the efficac" of oth etamethasone valerate aerosol and pellets in a doule2lind stud", noting
improvement in 11 of 1( patients -&reenspan 1(1@/+
Bigh2potenc" steroid mouth'ashes such as disodium etamethasone phosphate or cloetasol propionate, can e
used in 'idespread oral CA ut these ma" cause a significative s"stemic asorption leading to a pituitar"2 adrenal
axis suppression -&onzalez2Moles .**./+
!luocinolone is another steroid, 'hich has een used for treatment of OCA+ ,ompared 'ith the placeo, this drug
has een found to e more effective -?oute 1((=/+
4ecentl", fluticasone propionate spra" has een used effectivel" in the short2term management of s"mptomatic OCA,
ut 1*8 of the patients did not tolerate such treatment for more than = 'ee0s -Begart" .**./+ The more potent
fluorinated steroids can e ver" effective and include fluocinonide *+ *68 -$ilverman 1((19 Cozada 1(@*/ and
fluocinolone acetonide *+ 18+ -Thongprasom 1((./ !luocinonide *+ *68 and fluocinolone acetonide *+ 18 have
een found to e effective in the treatment of severe oral CA that has failed to respond to other medications
-Thongprasom 1((.9 ?oute 1((=/+
A stud" evaluated fluocinolone acetonide *+ 18 in three groupsK solution -!A$/, Oraase -!AO/, and oth+ The est
results achieved 'ith !AO -complete remission of 11+ =8 of patients/+ This stud" had a long2term follo'2up,
'ithout having a control group -Thongprasom .**=/+
A stud" confirmed the efficac" of topical fluocinolone acetonide gel *+ *.6 8, along 'ith the topical antimicroial
drug chlorhexidine, in treatment of erosive OCA -Thongprasom .**=/+
Another stud" sho'ed no difference et'een the fluticasone propionate -!A/ spra" and etamethasone sodium
phosphate -3$A/ mouth rinse+ 3ut !A 'as found to e more acceptale to patients than 3$A, ecause of the
convenience of the spra" form -Begart" .**./+
The application of fluocinonide ointment -*+ *68/ compounded 'ith oraase ; times per da" or cloetasol
propionate ointment -*+ *68/ 'ith oraase = times per da" can control erosive lichen planus effectivel" in most
patients -Gd'ards .**./+
!luocinolone acetonide *+ 18 in oraase has een sho'n to e more effective than a similar triamcinolone acetonide
*+ 18 preparation 'ith no serious side effects -Thongprasom 1((./+
,loetasol propionate in a5ueous solution, ointment,or oraase has also een sho'n to e effective in OCA+
,loetasol can e more effective than fluocinonide in improving lesions and the long2term use of cloetasol -;
months/ ma" help to control the disease,offering sustantial disease2free periods in ;68 of the patients after ;
months of follo'2up -,arone1(((/+
,loetasol propionate, a ver" potent corticosteroid in the Miller and Munro classification, 'as used in a )8 h"drox"
eth"lcellulose ioadhesive gel -,arone1((1/+ ,loetasol propionate *+ *68 ointment has een sho'n to heal OCA,
ut this stud" had a small sample group,'ithout an" control group or follo'2up -4oed2Aetersen 1((./+ Among the
three preparations of cloetasol propionate *+ *68 -ointment, Oraase, and the adhesive denture paste/ the est
results have een achieved 'ith cloetasol propionate in an adhesive denture paste -Co Muzio .**1/+
Although there are some reports of s"stemic asorption and adrenal suppression from super2potent topical steroids
in the treatment of chronic s0in disordersL adrenal suppression has not een found in long2term oral application of
topical corticosteroids such as fluocinonide *+ *68, fluocinolone acetonide *+ 18, and cloetasol *+ *68
-,arone1(((/+
Acute pseudomemranous candidiasis is the onl" common side effect from topical corticosteroid therap"
-Thongprasom 1((./+ This can e prevented 'ith antifungal -miconazole gel/ alone or 'ith chlorhexidine
mouth'ashes -,arone1(((/+
2.!.2. Intralesional corticosteroids
%ntralesional in<ection of corticosteroid for recalcitrant or extensive lesions involves the sucutaneous in<ection of *+
.7*+ ) mC of a 1* mgDmC solution of triamcinolone acetonide " means of a 1+ *2mC .= or .6 gauge tuerculin
s"ringe -Gd'ards .**./+
%ntralesional in<ections of h"drocortisone, dexamethasone, triamcinolone acetonide and meth"lprednisolone have
een used in the treatment of OCA -Zegarelli 1(@*/+ Bo'ever, the in<ections can e painful, are not invarial"
effective, and have a localized effect such as mucosal atroph"+ Three to four or t'ice 'ee0l" treatments of
intralesional triamcinolone acetonide in doses of *+ 671 ml of a 12mgDml suspension seem to e a practical
supplement for the treatment of erosions -Gd'ards .**./+
Zegarelli comined the use of topical and 'ee0l" intralesional corticosteroids in seven patients+ After = 'ee0s, five
patients 'ere graded as having 1**8 clinical improvement+ !urthermore,in most cases, a remission of several
months 'as noted9 recurrences 'ere milder than the original disease state and 'ere managed 'ith topical agents
alone -Zegarelli 1(@=/+ %t is unclear 'h" the response to topical corticosteroid therap" is so variale+
#ndoutedl",the fre5uenc" of application of topical corticosteroids ma0es compliance difficult ecause optimal
effects are not achieved unless the" are applied et'een five and ten times dail" -Zegarelli 1(@*/+
2.!.!. Systemic corticosteroids
$"stemic corticosteroids are reserved for recalcitrant erosive or er"thematous CA 'here topical approaches have
failed+ $"stemic prednisolone is the drug of choice, ut should e used at the lo'est possile dosage for the shortest
duration -)*2@* mg for 621 da"s/ -Gisen .**6/+
$"stemic prednisone can e used to control the ulcers and er"thema in OCA+ $"stemic corticosteroids ma" e
indicated in patients 'hose condition is unresponsive to topical steroids or in patients 'ith mucocutaneous disease
and in high doses -1+ 62. mgD0gDdail"/, ut adverse effects are possile even 'ith short courses -Zegarelli 1(@*9
,hainani2>u .**1/+
The oral dose of prednisone for a 1*20g adult ranges from 1*7.* mgDda" for moderatel" severe cases to as high as
=6 mgDda" -*+ 6 mgD0g dail"/ for severe cases -Zegarelli 1(@=/+ Arednisone should e ta0en as a single morning dose
to reduce the potential for insomnia and should e ta0en 'ith food to avoid nausea and peptic ulceration+ $ignificant
response should e oserved 'ithin one to . 'ee0s+
>hen s"stemic corticosteroids are prescried for periods of longer than . 'ee0s, the dosage of steroid must e
graduall" tapered to avoid precipitating an adrenal crisis+ Tapering can e accomplished " decreasing the dail" dose
of prednisone " 6 mg per 'ee0 -Gd'ards .**./+
$ome studies have compared the efficac" of corticosteroids 'ith some other drugs+ !or example %n a doule2lind
randomized controlled stud", compared the efficac" of topical zinc sulfate in comination 'ith *+ *68 fluocinolone
ointment in the treatment of OCA after . 'ee0s of treatment, 'as founded that topical zinc sulfate in comination
'ith *+ *68 fluocinolone ointment reduced the severit" erosive OCA etter than *+ *68 fluocinolone separatel"
-Mehdipour M Taghavi .*1*/+
2.%. &rythema Multiforme #&M$
Gr"thema Multiforme is a s0in condition considered to e h"persensitivit" reaction to infections or drugs+ %t consists
of a pol"morphous eruption of macules, papules, and characteristic Ntarget: lesions that are s"mmetricall" distriuted
'ith a propensit" for the distal extremities+ There is minimal mucosal involvement+ Berpes simplex virus -B$?/ is
the most commonl" identified etiolog" of this h"persensitivit" reaction, accounting for more than 6* percent of
cases+ Although GM 'as first clinicall" recognized in the earl" 1(th centur" and referred to " a variet" of names, it
'as not until 1@;* that !erdin and von Bera termed the disease OGr"thema Multiforme -!orman .**./+
Gr"thema multiforme -GM/ 'as once thought to e the earl" presentation of a continuum of diseases related to
$tevens2Pohnson s"ndrome -$P$/, 'ith toxic epidermal necrol"sis -TGE/ elieved to e a distinct entit"+ %t is no'
generall" accepted that a separation exists et'een GM and $P$+ ,urrentl", t'o different classifications existK first,
an er"thema multiforme spectrum -minor and ma<or/ and second, an $P$ and TGE spectrum -Camoreux .**;9
!rench .**@/+
$P$ and its more severe progression, TGE, are oth rare mucocutaneous diseases that can e life2threatening and
almost al'a"s caused " drugs -)(/+ $P$ 'as first descried in 1(.. " t'o ph"sicians, $tevens and Pohnson, 'ho
descried a s0in eruption similar to GM that also included purulent con<unctivitis, stomatitis,, and fever -!orman
.**./+
Management of er"thema multiforme involves determining the etiolog" 'hen possile+ The first step is to treat the
suspected infectious disease or to discontinue the causal drug+
2.%.1. Topical steroid therapy
Mild cases of Gr"thema Multiforme do not re5uire treatment+ Oral topical steroids ma" e used to provide s"mptom
relief -$hin .**1/+
Cozada2Eur and Zhong Buang reported that an adhesive paste -Oraase/ form of cloetasol propionate, the most
potent topical corticosteroidis a safe and efficacious alternative to s"stemic therap" in erosive oral lesions -Cozada2
Eur ! 1(()/+
Mouth'ashes of cloetasol propionate in a5ueous solution ma" offer an alternative topical approach to this patient
population+ The mouth'ash solution provides read" access to all lesional areas, and there is excellent control over
the contact time et'een drug and lesion -Pacoson 1(@;/+
2.%.2. Systemic steroid therapy
The role of s"stemic corticosteroids in Gr"thema Multiforme Ma<or -GMM/ and $P$ is controversial+ There is no
literature to date ased on a large, prospective, randomized, or doule2lind stud" evaluating use of s"stemic
corticosteroids in GMMD$P$+
Moderate to severe oral Gr"thema Multiforme ma" e treated 'ith a short course of s"stemic glucocorticosteroid in
patients 'ithout significant contraindications to their use+ Arednisone ma" e used in patients 'ith man" lesions at
dosages of )* to @* mg per da" for one to t'o 'ee0s then tapered rapidl" -Camoreux .**;/+ There have een no
controlled studies of prednisone:s effectiveness, and its use in patients 'ith herpes2associated Gr"thema Multiforme
ma" lo'er the patient:s resistance to B$? and promote recurrent B$? infection follo'ed " recurrent Gr"thema
Multiforme -?olchec0 .**)/+
The dosing and route of administration that provides the most enefit for GMM and $P$ patients is in 5uestion+
Garl" therap" 'ith s"stemic prednisone -*+ 6 to 1+ *mgD0gDda"/ or pulse meth"lprednisolone -1mgD0gDda" for =
da"s/ has een sho'n to e effective -$cull" .**@/+ One author suggests tapering the oral prednisolone over 1 to 1*
da"s, 'hile Aatterson et al+ suggests a high dose of corticosteroids for GMM patients follo'ed " a four2'ee0
tapering course -,hrousos .**)/+ $till another suggests a olus infusion for = to 1 da"s of coricosteroids, 'hich
sho'ed no relapses after treatment 'as discontinued -Ha0ourou1((1/+ %ntravenous -%?/ pulsed dose
meth"lprednisolone -= consecutive dail" infusions of .*7=*mgD0g to a maximum of 6** mg given over . to = hours/
has also een reported, 'ith the suggestion that this approach is superior to oral prednisone ecause the greatest
enefit is seen 'hen treatment is administered as earl" as possile in the progression of the cutaneous insult
-Martinez .***/+
Hardaun and Pon0man recentl" proposed dexamethasone pulse therap" -1+ 6mgD0g %? over =* to ;* minutes on =
consecutive da"s/ to avoid long2term use of s"stemic corticosteroids -Hardaun .**1/+ The authors descried the
pleomorphic effects of dexamethasone on the immune s"stem, including inhiition of epidermal apoptosis "
several mechanisms+ These mechanisms include suppression of various c"to0ines, such as TE!2alpha9 inhiition of
interferon2gamma2induced apoptosis9 and inhiition of !as2mediated 0eratinoc"te apoptosis -Feung .**6/+
>hen treating TGE, it is generall" agreed that after 'idespread sloughing occurs, an" ris0 of infection out'eighs
the potential enefits of s"stemic corticosteroid therap" ->olverton .**1/+
4ecurrent Gr"thema Multiforme often is secondar" to B$?21 and 2. reactivation, although the B$? ma" e
clinicall" silent -Buff 1((./+
2.'. "emphi(us
Aemphigus refers to a group of rare chronic mucocutaneous diseases characterized " painful lesions caused "
intraepidermal anthol"tic structures in the s0in and mucous memrane -$irois .***/+
Oral mucosal lesions in Aemphigus are common -6*821*8/ and predominantl" appear as uccal erosions in the
occlusal line, 'hich is most exposed to trauma and also on the palate, gingival and tongue -$irois .***/+
The exact nature of the disease remains un0no'n+ Aemphigus is characterized " intra2epithelial ulla formation,
due to autoantiodies directed against proteins of the desmosome2tonofilament complex et'een 0eratinoc"tes
-$irois .***/+
Aemphigus vulgaris -A?/ has a high moridit" and mortalit" rate 'ithout treatment+ 3ecause of the rarit" of the
disease, there is not "et a standard treatment regimen -,otell .***/+
The aim of treatment in pemphigus vulgaris is the same as in other autoimmune ullous diseases, 'hich is to
decrease lister formation, promote healing of listers and erosions, and determine the minimal dose of medication
necessar" to control the disease process -Hnudson .*1*/+
#ntil no', treatment consists mostl" of the use of corticosteroid and immunosuppressive drugs+ The use of
corticosteroids in the 1(6*s had reduced mortalit" from ;*8 to (*8 to aout =*8+ The current mortalit" 'as aout
;+ .8 -range * to 1*8/ and did not sho' further significant reduction -3"str"n 1((;/+
The treatment depends on the prognostic elements of the condition, such as the extent of the lesions and antiod"
levels+ Treatment is administered in . phasesK a loading phase, to control the disease, and a maintenance phase,
'hich is further divided into consolidation and treatment tapering+ The asic treatment for pemphigus consists of
either local or s"stemic corticosteroid therap" -!ellner .**1/+
2.'.1. Topical corticosteroids
Cocal corticosteroid therap" is used in cases 'here the A? is not extensive and lesions are limited to the oral cavit"+
,orticosteroids can e prescried in the form of a paste, an ointment or a mouth'ash administered as monotherap"
or as ad<unctive therap" 'ith a s"stemic treatment -!ellner 9 4uocco .**1/+
%n patients 'ith no progressing oral lesions, moderate to high potenc" topical corticosteroids are recommended,
applied .2= times a da", such as *+ *68 fluocinolone acetonide or *+ *68 cloetasol propionate -Bashimoto 9
Ara<apati .**@/+
Dumas et al+ descried 1 pemphigus patients, = of 'hom 'ere treated 'ith cloetasol propionate *+ *68 cream as
monotherap" for their mild A?+ A? 'as defined as OmildQ if fe'er than 1* ne' ullae appeared per 'ee0 and if the
circulating pemphigus antiod" titer 'as 1K=.*+ The cream 'as applied t'ice a da" for at least 16 da"s, and then
tapered+ Cesions 'ere controlled in onl" 1 of the = A? patients -Dumas 1(((/+
2.'.2. Systemic corticosteroid therapy
%n patients 'ith severe disease and spreading of the lesions to s0in surfaces, s"stemic corticosteroids are the
treatment of choice -Hnudson .*1*/+
The dosing schedule of s"stemic corticosteroids in pemphigus is largel" empirical -4atnam 1((*/+ Arednisolone 'as
the first drug used to treat this disease and almost in all situations, is the first line of treatment -,amisa 1((@/+
The starting dose is high9 a total oral dose of 1**7.** mg Arednison is administered dail" until susidence of
clinical signs+ This dose can graduall" e decreased to a maintenance level of )* to 6* mg dail"+ Topical application
of corticoids is effective if small, isolated areas of the oral mucosa are involved+ The acute phase of pemphigus is
associated 'ith changes in gastric mucosa and this condition is further aggravated " ingestion of corticosteroids
-!assmann .**=/+
,orticosteroids ta0en " mouth have man" long2term harmful effects, including adrenal atroph", anormal
sensitivit" to infection, high lood pressure, h"pertrigl"ceridemia, h"pergl"cemia, cortisone m"opath", erosive
duodenitis and stress fracture, as in the case presented here+ To minimize iatrogenic effects, Cever and $chaumurg
recommended a treatment called the Ohigh Cever schemeQ 'ith ver" high loading doses -1**7116 mg ta0en t'ice
dail" for 671* 'ee0s/, follo'ed " the Olo' Cever scheme,Q 'hich includes a rapid reduction in dosage over a fe'
'ee0s, 'ith a maintenance dose of )* mg ever" . da"s accompanied " local ad<uvant treatment -Cever 1(@)/+
The 3ritish Association of Dermatologists recommends patients 'ith mild disease to receive an initial prednisolone
dose of )*2;* mg dail" and in more severe cases, ;*21** mg dail"+ %f there is no response 'ithin a 'ee0,the dose is
increased " 6*21**8 until disease control+ There is no unitized handling considering the tapering of
corticosteroids+ A .68 dose reduction ma" e performed i'ee0l" 'ith slo'er decrease after a dose of .* mgDda"
has een reached -Barman .**=/+
T'o prospective controlled trials explored the effect of i+ v+ corticosteroid pulses in addition to oral prednisolone ut
did not oserve statistical differences et'een treatment groups -!emiano .**.9+ Mentin0 .**;/+
%n one controlled trial, patients randomized to treatment 'ith either lo'2dose oral prednisolone -)62;*mgDda"/ or
high2dose oral prednisolone -1.*216*mgDda"/ sho'ed no significant difference in the time to achieve remission and
in relapse rates at 6 "ears -4atnam 1((*/+
A nonrandomized retrospective controlled trial of 11 pemphigus patients assigned participants to cohorts receiving
prednisone 1 mgD0gDda" or . mgD0gDda"+ Eo statistical difference 'as oserved et'een cohorts in terms of response
to treatment9 ho'ever, there 'as a significantl" higher fre5uenc" of adverse events, particularl" infection, in the .
mgD0gDda" cohort+ Despite the retrospective, nonrandomized nature of the stud", the results indicate that higher
doses of corticosteroid are no more effective than lo'er doses, and are associated 'ith higher rates of complications+
Overall, the limited evidence indicates that lo'er steroid dose regimens -R1 mgD0gDda"/ have e5uivalent efficac" in
controlling disease as higher dose regimens, and ma" have decreased associated moridit" -!ernandes .**1/+
Another nonrandomized, controlled trial of .* A? patients studied participants receiving either a 1.6 mgDda"
tapering schedule of prednisone or a 6* mgDda" tapering schedule of prednisone plus intravenous etamethasone .*
mgDda"+ %n this stud", the cohort receiving the pulse therap" 'as found to have faster clinical resolution of
s"mptoms, 'ith statisticall" significant difference -!emiano .**./+
Aulse corticosteroid usuall" seems to result onl" in short2term relief from the disease and most li0el" needs
continued administration of oral corticosteroids -!unauchi 1((1/+
>erth has compared these t'o therapeutic protocols+ %t 'as onl" a retrospective stud" that included t'o
heterogeneous groups of patients 'ith completel" different therapeutic regimens for each patient+ %t included nine
patients 'ho had received pulse therap" and six patients 'ho had received conventional treatment+ $ome received
onl" one course of pulse therap", 'hile others received t'o courses+ This stud" sho'ed the superiorit" of pulse
therap" over conventional treatment ->erth 1((;/+
2.'.!. Intralesional corticosteroid therapy
%ntralesional corticosteroid therap" accelerates the scarring process of a lesion or is used to treat persistent lesions+
This treatment, 'hich gives inconsistent results, involves sulesional in<ections given ever" 1 to 16 da"s9 treatment
is stopped after = in<ections if there is no improvement+ $carring is accompanied " cutaneous or mucosal atroph"
the ma<or dra'ac0 of this treatment -!ellner 9 4uocco .**1/+ %f the patient has extraoral lesions or if the oral
damage is extensive, s"stemic corticosteroid therap" is initiated immediatel"+ The initial dose depends on the
chronicit" of the lesions and the severit" of the disease+ A dail" application of prednisone *+ 67. mgD0g is
recommended -!ellner 9Toth .**1/+ Depending on the response, the dose is graduall" decreased to the minimum
therapeutic dose, ta0en once a da" in the morning to minimize side effects+
The lac0 of randomized controlled trials precludes an" conclusions as to 'hether these protocols are superior to
those using higher loading doses+ An ad<uvant drug is prescried for most patients 'ith severe A?, 'ith the
o<ectives of reducing the cortisone dose and ensuring stale remission+ Bo'ever, the use of ad<uvant therap"
remains controversial -Mutasim .**)/+
2.). Mucous Mem*rane "emphi(oid #MM"$
Mucous Memrane Aemphigoid -MMA/ or ,icatricial pemphigoid is a rare autoimmune listering disorder that
affects the mucous memranes and s0in+ %t 'as first descried " Thost in 1(11 -Thost 1(11/+
This disease is extremel" difficult to treat despite the use of aggressive comination immunosuppressive regimens+
,icatricial pemphigoid 'ith multiple mucosal site involvement has the 'orst prognosis due to its high resistance to
medical therap" resulting in loss of function through scarring -Tht Fu .**1/+
During the past 6* "ears, the mainsta" of treatment for MMA has een s"stemic glucocorticoids+ Bo'ever, the high
doses needed to otain clinical response are generall" poorl" tolerated, especiall" in "oung patients, and are
associated 'ith man" adverse effects -3orradori .**)/+
2.).1. Topical steroid therapy
Mild localized lesions usuall" respond to topical steroids, including triamcinolone, fluocinonide and cloetasol
propionate+ Aatients 'ith mild oral disease should e treated 'ith topical and intralesional steroids+
Des5uamative gingivitis can often e managed 'ith topical steroids in soft dental splint that covers the gingiva,
although the clinician using topical steroids over large areas of mucosa must closel" monitor the patient for side
effects such as candidiasis and effects of s"stemic asorption -4eich 1((@/+
Cozada 2Eur and Zhong Buang treated patients 'ith severe erosive disease, using cloetasol propionate mixed in an
adhesive paste+ The" reported a complete response in ;.+ 68 of the series -16 patients/, an excellent response in .(+
18 -1 patients/, and a failed response in @+ =8 -. patients/+ The" concluded that their treatment 'as efficacious and
safe -Cozada2Eur 1((1/+
%n lo' ris0 patients 'ith lesions confined to the oral mucosa andDor s0in, topical corticosteroids are advised, such as
*+ 18 triamcinolone acetonide, *+ *68 fluocinoloneacetonide, or *+ *68 cloetasol propionate in oraase, applied =2
) times a da" during (2.) 'ee0s+ %n patients 'ith isolated erosions, intralesional corticosteroid in<ections
-triamcinolone in 621* mgDml solution/ can e used+ %n su<ects presenting gingival lesions in the form of
des5uamative gingivitis, *+ *68 cloetasol propionate is recommended, 'ith n"statin 1**,*** %# to avoid
candidiasis overinfection -3agan .**6, $cull" .**@/+ >hen MMA affects the palate, esophagus or nasal mucosa,
eclomethasone dipropionate or udesonide -6*2.** Sg/ can e prescried -3agan .**6/+
2.).2. Systemic steroid therapy
MMA can e rapidl" progressive, and s"stemic steroids have een used as initial treatment for patients 'ith
extensive oral ulceration or as additional treatment on patients 'ho did not respond to topical steroids+ $"stemic
corticosteroids such as prednisolone at 12 . mgD0gDda" are the first2line medications in ,A ecause of their potent
anti2inflammator" and immunosuppressive effects -Mondino 1(@1/+
The serum autoantiod" titers remain ver" high after the disappearance of clinical lesions+ Therefore the enefit of
steroids in enign mucous memrane pemphigoid might e due to anti2inflammator" actions, including lo'ered
enz"me release,reduced cell migration and decreased lea0age of humoral factors -Hnudson .*1*/+
%n high ris0 patients 'ith multiple oral lesions, rapidl" progressing spread of the disease to other mucosal
memranes such as the e"es, genital, esophagus or nasophar"ngeal zone, or recurrent lesions, the administration of
prednisone 12. mgD0gDda", 'ith gradual dose reduction, and immune suppressors such as c"clophosphamide -*+ 62.
mgD0gDda"/, azathioprine 12. mgD 0gDda", or m"cophenolate mofetil .2.+ 6 gDda" has een descried -3agan .**69
Hnudson .*1*/+
2.+. Bullous "emphi(oid #B"$
3ullous Aemphigoid -3A/ is an autoimmune disease characterized " suepidermal listering, 'hich are often
pruritic -!itzpatric0 .**@/+
3ullous pemphigoid occurs most commonl" in the elderl", 'ith an onset et'een ;6 and 16 "ears of age+ Arognosis
is influenced " age and general condition of the patient, not " extent of disease activit"+
Treatment includes topical and s"stemic corticosteroids, steroid2sparing immunosuppressants, and tetrac"cline in
comination 'ith niacinamide -Pol" .**6/+
2.+.1. Topical steroid therapy
%n a stud" of 1* patients 'ith extensive and generalized 3A, treatment 'ith *+ *68 cloetasol propionate cream
achieved complete healing in all patients 'ithin 11 da"s of treatment+ $even of the 1* patients remained in remission
at the time of reporting -171* months/ ->esterhof 1(@(/+
T'ent" patients 'ith 3A -involvement of less than ;*8 od" surface/ in a second stud" 'ere treated 'ith ver"
potent topical corticosteroidsK in seven patients 3A 'as completel" suppressed and the same numer otained
remission 'ith an 112month follo'2up+ There 'ere mild side2effects of cutaneous infection and s0in atroph"+ The
use of topical corticosteroids has also een reported in a large numer of case reports and smaller series of fe'er
than five patients -Zimmermann 1(((/+
Aotent topical corticosteroids should e considered in patients 'ith limited or moderate disease -Mutasim .**)/+
%n a large randomized controlled trial, initial disease control and 12"ear survival 'ere significantl" etter 'hen
treating extensive 3A 'ith cloetasol propionate cream )* mg dail" compared 'ith oral prednisolone 1mgD0gDda"
'hile in moderate 3A -T 1* listersDda"/ outcomes using cloetasol cream and prednisolone *+ 6mgD0g 'ere similar
-Pol" .**./+
4ecentl", lo'er doses of topical cloetasol propionate -1*2=*g dail"/ 'ere sho'n to have similar short2term efficac"
ut reduced side2effects compared to the high dose topical regimen -)*g dail" cloetasol propionate/ -Pol" .**(/+
2.+.2. Systemic steroid therapy
Bigh2doses of s"stemic corticosteroids are the standard for initial treatment of 3A to gain control over the eruptions,
and prolonged high2doses are often used in severe cases+ Adverse side effects from s"stemic corticosteroids seem to
e the main cause of mortalit" in 3A -Mamela0 .**1/+
4ecommended initial doses of prednisolone are .* mgDda" or *+ = mgD0gDda" in localised or mild disease, )* mgDda"
or *+ ; mgD0gDda" in moderate disease, and 6*21* mg or *+ 1621 mgD0gDda" in severe disease ->o<naro's0a .**./+
%n patients 'ith limited disease, cloetasol propionate cream alone is used9 in patients 'ith moderate disease,
cloetasol propionate cream is comined 'ith dapsone -1+ *21+ 6mgD0gDda"/ and in severe cases, oral prednisolone
-*+ 6mgD0gDda"/ is added+ %nstead of dapsone, dox"c"cline -.**mgDda"/ ma" e given -Hasper0ie'icz .**(/+
2.+.!. Intralesional corticosteroid therapy
%ntralesional triamcinolone acetonide =21* mg per ml can e administered to resistant lesions+ Gxperience in
in<ecting correctl" is necessar" to maximise efficac" and minimise atroph"+ >here pemphigoid does not respond to
steroids, or large maintenance doses are re5uired, other Nsteroid2sparing: agents can e used+ Bo'ever, the evidence
for effectiveness of these drugs is limited and man" have 'orr"ing side effect profiles+ The" should therefore e
used cautiousl" " those 'ith experience in their actions -4eich 1((@/+
2.,. Systemic Lupus &rythematosus
Cupus Gr"thematosus ma" run in one of the t'o 'ell recognized forms+ $"stemic -acute/ or Discoid -chronic/+ 3oth
of them ma" have oral manifestations+ Discoid Cupus Gr"thematosus -DCG/ is a chronic s0in condition of sores 'ith
inflammation and scarring favoring the face, ears and scalp+ %t proal" occurs in geneticall" predisposed
individuals -Hhare .*11/+
$"stemic Cupus Gr"thematosus -$CG/ is a chronic disease characterized " protean manifestations, often 'ith a
'axing and 'aning course+ %n the past, a diagnosis of $CG often implied a decreased life span caused " internal
organ s"stem involvement or the toxic effects of therap", ut recent improvements in care have dramaticall"
enhanced the survival of $CG patients+ Eonetheless, increased mortalit" remains a ma<or concern and current
treatments for $CG remain inade5uate -%ppolito .**@/+
Oral ulcerations of s"stemic lupus er"thematosus are transient, occurring 'ith acute lupus flares+ $"mptomatic
lesions can e treated 'ith high potenc" topical corticoids or intralesional steroid in<ections+ $"stemicall" lo' dose
prednisone 1*2.* mg Dda" or an alternate da" dose of .*2)* mg ma" e needed -Aedersen 1(@) 94eich 1((@/+
4educing corticosteroid use is an important goal in treatment of patients 'ith $CG if it occurs in the context of a
treatment that effectivel" controls disease activit"+ Therefore, for a medical product to e laeled as reducing
corticosteroid usage, it should also demonstrate another clinical enefit, such as reduction in disease activit" as the
primar" endpoint+
The evaluation of efficac" should e ased on the proportion of patients in treatment and control groups that achieve
a reduction in steroid dose to less than or e5ual to 1* mg per da" of prednisone or e5uivalent, 'ith 5uiescent disease
and no flares for at least = consecutive months during a 12"ear clinical trial+ !or a result to e clinicall" meaningful,
the patient population should e on moderate to high doses of steroids at aseline+ Trials should also assess the
occurrence of clinicall" significant steroid toxicities -Ad Boc >or0ing &roup on $teroid2$paring ,riteria in Cupus
.**)/+
%n the localized variet" of Discoid Cupus the lesions tend to e confined to the head and nec0 and in the generalized
variet" the" occur oth aove and elo' the nec0+ The disease ma" occur at an" age9 'ith higher incidence et'een
.* to )* "ears of age+ %t has a prolonged course and can have a considerale effect on 5ualit" of life+ Aotent topical
steroids and antimalarials are the mainsta" of treatment -Hhare .*11/+
Topical steroids are the mainsta" of treatment of DCG+ Aatients usuall" start 'ith a potent topical steroid -e+ g+,
etamethasone or cloetasol/ applied t'ice a da", then s'itch to a lo'er2potenc" steroid as soon as possile+ The
minimal use of steroids reduces the recognized side effects li0e atroph", telengiaectasiae, striae, and purpura+
%ntralesional in<ection of corticosteroids -t"picall", this author uses triamcinolone acetonide = mgDmC/ is useful as
ad<unctive therap" for individual lesions+ Aotential for atroph" relates to the amount of corticosteroid in<ected in an"
area9 therefore, dilute concentrations are preferred+ %n addition, the treating ph"sician must ta0e care to limit the total
dose of the in<ections at an" given officeDclinic visit to avoid s"stemic toxicit" from the steroids9 eg, if a patient is
given 1* mC of triamcinolone = mgDmC, this means that the patient has received a total of =* mg, and toxicit" is the
same as if it had een delivered orall" or " intramuscular in<ection -Aan<'ani .**(/+
Oral steroids ma" e re5uired for the control of s"stemic lupus ut are not generall" eneficial in DCG+ !or patients
'ith progressive or disseminated disease or in those 'ith localized disease that does not respond to topical
measures, the addition of s"stemic agents should e considered+
!. -acial pain
!.1. Bells palsy
%diopathic facial pals", also called 3ell:s pals", is an acute disorder of the facial nerve, 'hich ma" egin 'ith
s"mptoms of pain in the mastoid region and produce full or partial paral"s is of movement of one side of the face
-?alenUa .**1/+
!acial nerve paral"sis ma" e congenital or neoplastic or ma" result from infection, trauma, toxic exposures, or
iatrogenic causes+ %ncreasing evidence suggests that the main cause of 3ell:s pals" is reactivation of latent herpes
simplex virus t"pe 1 in the cranial nerve ganglia+ Bo' the virus damages the facial nerve is uncertain -&ilden .**)/+
Treatment of 3ell pals" should e conservative and guided " the severit" and proale prognosis in each particular
case+ $tudies have sho'n the enefit of high2dose corticosteroids for acute 3ell pals" -$ullivan .**19 GngstrVm
.**@/+
Taverner in 1(6) 'as the first to design a controlled treatment trial of steroids ut unfortunatel" the numer of
patients 'as too small to permit a signifcant statistical evaluation -Taverner 1(6)/+
Attempts to treat 3ell:s pals" 'ith steroids changed in the 1(1*s+ After the initial pulication of Adour et al+ several
series of treatments 'ith prednisone for 3ell:spals" 'ere designed, ut almost all of them 'ere of unsatisfactor"
5ualit" -Adour 1(1./+ Eevertheless, the ma<orit" of authors claimed that the" had sho'n steroids to e enefcial to a
statisticall" signifcant degree+
T'o recent s"stematic revie's concluded that 3ellJs pals" could e effectivel" treated 'ith corticosteroids in the
first seven da"s, providing up to a further 118 of patients 'ith a good outcome in addition to the @*8 that
spontaneousl" improve -4amse" .***9 &rogan .**1/+
Other studies have sho'n the enefits of treatment 'ith steroids9 in one, patients 'ith severe facial pals" sho'ed a
significant improvement after treatment 'ithin .) hours -$hafsha0 1(()9>illiamson 1((;/+
%mmunocompetent patients 'ithout specific contraindications are prescried prednisone at 1 mgD0gDd -maximum @*
mg/ for the first 'ee0, 'hich is tapered over the second 'ee0+ Around a fifth of patients 'ill progress from partial
pals", so these patients should also e treated -4amse" .***/+
Bo'ever the $ullivan stud" 'ith )(; participants compared different cominations of prednisolone, ac"clovir and
placeo+ The" found significant enefit from prednisolone ut not ac"clovir -$ullivan .**1/+
Bato assessed the efficac" of valac"clovir 'ith .(; participants divided into t'o groups -valac"clovir 'ith
prednisolone,and placeo'ith prednisolone/ and found significant enefit from valac"clovir -Bato .**1/+
!.2. Ramsay .unt syndrome
4amsa" Bunt s"ndrome -4B$/ is caused " the reactivation of a previous ?aricella zoster virus -?Z?/ infection+
4B$ is a potentiall" serious viral infection that accounts for approximatel" 1.8 of all facial nerve palsies -4oillard
1(@;9 #ri .**=/+
?Z? is also the cause of Oshingles,Q 'hich fre5uentl" presents 'ith a classic painful dermatomal distriution of
vesicles and crusted s0in ulcerations+ %n addition to the alarming facial pals", 4B$ ma" also e characterized "
severe otalgia, sensorineural hearing loss, vertigo, painful s0in vesicles and aguesia in the ipsilateral anterior tongue
-Biroshige .**./+
The treatment of 4amsa" Bunt s"ndrome is not entirel" agreed upon+ Definitive treatment consists of antiviral
therap" and sometimes includes steroids+ Ad<unctive steroid therap" can e helpful in the management of the facial
paral"sis of 4B$ -Hinishi .**1/+
Bo'ever, man" authors caution against implementing steroid therap", especiall" 'ith periocular lesions, as the" fear
dissemination of the ?Z? infection -?an de $teene .**)9 B"vernat 9 Bill .**6/+
The largest retrospective treatment stud" sho'ed a statisticall" significant improvement in patients treated 'ith
ac"clovir and prednisone 'ithin = da"s of onset+ ,omplete recover" occurred in 168 of patients treated 'ithin the
first = da"s, ut in onl" =*8 of those treated after 1 da"s+ This suggests that prompt diagnosis and management
improves outcome in 4amsa" Bunt s"ndrome+ %mportantl", no statisticall" significant outcome differences 'ere
noted et'een patients treated 'ith intravenous or oral ac"clovir -Mura0ami 1((1/+
A large prospective stud" demonstrated that comination therap" 'ith ac"clovir and steroids led to etter recover"
of facial nerve function than steroids alone -Hinishi .**1/+ These findings 'ere confirmed " responses to nerve
excitailit" testing+ Although there are no evidence2ased dosing recommendations, pulished trials t"picall"
administered ac"clovir at @** mg " mouth 6 timesDda" for 121* da"s and prednisone at 1 mgD0gDda" " mouth for 6
da"s follo'ed " a taper -Mura0ami 1((1/+
4B$ ma" present 'ith a spectrum of clinical variations, including facial s'ellings that appear to e of odontogenic
origin+ As a result, dentists ma" e challenged to ma0e the correct diagnosis of 4B$ versus an odontogenic infection
in a timel" manner+ Appropriate supportive and prompt antiviral therap" comined 'ith close follo'2up is
associated 'ith significantl" etter functional recover" and outcomes -Hinishi .**1/+
!.!. "ostherpetic /eural(ia#"./$
Aostherpetic Eeuralgia -ABE/ continues to e a significant clinical prolem, 'ith an average of .68 of patients
developing persistent neuropathic pain after acute herpes zoster -BZ/ -Aavan2Cangston 9 $chmader .**@/+
This condition signals damage to the affected nerve+ Aatients ma" continue experiencing pain and discomfort even
after listers have alread" cleared+ #suall", patients ma" feel a sharp or deep pain along the area 'ere listers first
appeared+ %t is elieved that repetitive painful stimuli that reach the central nervous s"stem might lead to central
sensitization of the nociceptive s"stem, the most important mechanism underl"ing long2lasting chronic pain+
%nterventions that decrease the repetitive painful stimuli and inflammation during the acute phase of BZ ma"
attenuate central sensitization and sustantiall" reduce the incidence of chronic pain -Hell" .**1 9 Pohnson .**./+
Treatment includes corticosteroids, 'hich are used to treat pain, s'elling and effectivel" reduces the ris0 of
recurrence of post2herpetic neuralgia+ $teroids 'ere found to accelerate the resolution of acute neuritis and provide a
clear improvement in 5ualit"2of2life measures in comparison to those patients treated 'ith antivirals alone+ The use
of oral steroids had no effect on the development or duration of postherpetic neuralgia -D'or0in .**1/+
Bistoricall", epidural, intrathecal, and s"mpathetic nerve loc0s have all een used in the treatment of pain caused
" BZ and ABE+ %t 'as accepted " some investigators that nerve loc0s do not provide lasting relief in estalished
ABE, ut in<ection of corticosteroids has een suggested to e of some enefit+
Arednisolone, a corticosteroid, is the most common drug administered in heav" doses to herpes patients+ Moderate
doses of prednisone )* mg dail" for 1* da"s, 'hich is graduall" tailed off over the follo'ing = 'ee0s is an effective
and safe regime 'hich reduces the occurrence of postherpetic neuralgia+
The use of steroids in con<unction 'ith an antiviral for uncomplicated herpes zoster is controversial+ $teroids 'ere
found to accelerate the resolution of acute neuritis and provide a clear improvement in 5ualit"2of2life measures in
comparison to those patients treated 'ith antivirals alone+ The use of oral steroids had no effect on the development
or duration of postherpetic neuralgia+ The optimal duration of steroid therap" is not 0no'n+ %f prescried, it seems
reasonale for steroids to e used concurrentl" 'ith antiviral therap"+ The duration of steroid use should not extend
e"ond the period of antiviral therap"+ $teroids should not e given alone -'ithout antiviral therap"/, o'ing to
concern aout the promotion of viral replication -?an >i<c0 .**;/+
%ntrathecal administration of corticosteroids has also een attempted+ A trial involving a series of ) intrathecal
in<ections of meth"lprednisolone and lidocaine in patients 'ith estalished postherpetic neuralgia demonstrated a
significant and persistent reduction in pain among corticosteroid2treated patients 'hen compared 'ith untreated
patients or those treated 'ith intrathecal lidocaine alone+ Hotani et al+ pulished remar0ale results after the
intrathecal in<ection of meth"lprednisolone in patients 'ith intractale ABE for at least 1 "r, 'hich sho'ed a 6*8
decrease in interleu0in2@ concentrations, and this decrease correlated 'ith the duration of neuralgia and 'ith the
extent of gloal pain relief -Hotani .***/+
The use of oral or epidural corticosteroids in con<unction 'ith antiviral therap" has een found to e eneficial in
treating moderate2to2severe acute zoster, ut to have no effect on the development or duration of postherpetic
neuralgia ->ood1(()9 >hitle" 1((;/+
!.%. Temporomandi*ular 0oint disorders
Temporomandiular <oint -TMP/ disorders are the main cause of chronic facial pain and a ma<or cause of disailit"
-Borten 1(6=/+
$everal decades ago, Toller suggested that intra2articular corticosteroid in<ections 'ere onl" useful in adult patients
'ith TMP disorders9 a single intra2articular in<ection resulted in resolution of TMP pain and other s"mptoms in ;.8
of adult patients, compared to onl" 118 of pediatric patients -Toller 1(11/+
%ntra2articular in<ection of steroids into the temporomandiular <oint -TMP/ space is not a recent su<ect+ Borten in
1(6=, 'as the first 'ho reported this procedure 'hich 'as ased on the 'or0 of Bollander et al+ in 'hich the"
descried the effect of intra2articular in<ection of h"drocortisone in various <oint disorders+ $ince then, a numer of
papers have reported var"ing degrees of success ->ood1(()9 Bollander 1(61/+
A variet" of methods are currentl" used for intra2articular corticosteroid in<ection to the TMP, each 'ith the goal of
minimizing the potential for tissue damage+ %ntra2articular corticosteroid formulations are often diluted 'ith a local
anesthetic prior to in<ection into the TMP -Hopp 1(@19 Alstergren 1((;/+
Eumerous corticosteroid formulations are availale for intra2articular in<ection, ranging from solutions of more
solule agents to suspensions of triamcinolone hexacetonide and other relativel" insolule steroids+ Although the
efficac" of various corticosteroids is presumed to differ, studies of this topic have een limited ->ise .**69&er'in
.**;9 Cavelle .**1/+
Triamcinolone acetonide 'hich has een used for intra2articular in<ection is ver" slo'l" asored from the in<ection
sites+ The dose ranges et'een . to )* mg, depending upon the size of the <oint in<ected -Bollander 1(619
$ilermann1(1@/+ %n cases of TMP, the dose is usuall" 1* mg -&ra" 1(()/+ Triamcinolone acetonide is a safe drug,
although anaph"lactic shoc0 follo'ing in<ection of triamcinolone acetonide has een reported+ A repeat in<ection is
occasionall" used ut the third in<ection should e used 'ith caution as the expectation of further improvement
decreases 'ith successive in<ections -Carsson 1(@(/+
%n recent studies of <uvenile idiopathic arthritis, intra2articular corticosteroid -triamcinolone/ in<ections improved or
even completel" eliminated TMP pain in 112@@8 of children for several months -Arashahi .**69 ,ahill .**19
4ingold .**@/+
%n a controlled stud" of adults 'ith TMP arthritis, a single intra2articular in<ection of corticosteroid
-meth"lprednisolone/ diluted 'ith lidocaine significantl" reduced <oint pain and other s"mptoms for )2; 'ee0s+ The
pharmacologic effect of intra2articular meth"lprednisolone lasts =2) 'ee0s, so these findings 'ere consistent 'ith
the expected timeline of corticosteroid effect+ Eo adverse events 'ere reported -Alstergren 1((;/+
Bo'ever, the efficac" ma" var" depending on the specific cause of TMP degeneration+
!.'. Temporal arteritis #TA$
Temporal arteritis -TA/, also 0no'n as cranial arteritis or &iant ,ell Arteritis -&,A/, 'as first clinicall" recognized
in 1@(* 'hen Butchinson descried an @*2"ear2old man 'hose painful inflamed temporal arteries precluded his
'earing a hat -Butchinson 1@(*/+ %n 1(=., Borton et al+ correlated the histopathologic features 'ith the clinical
features and applied the name arteritis temporalis+ Other names include arteritis cranialis, Borton disease,
granulomatous arteritis, and arteritis of the aged -Borton 1(=./+
There is universal agreement that glucocorticosteroids are the mainsta" of treatment for &,A and should e initiated
immediatel" and aggressivel", 'ith the goal of suppressing inflammation and preventing visual loss and ischemic
stro0e -Ba"reh .**=9 4ahman9 Aipitone .**6/+
Oral prednisone is first2line acute therap" for &,A+ Although no consensus exists for initial dose of prednisone, the
vast ma<orit" of patients respond to a dose of 1 mgD0gDd, or et'een )* and ;* mgDd -$alvarani .**.9 >e"and
.**=/+ The dose of prednisone is lo'ered after .7) 'ee0s, and slo'l" tapered over (71. months -,han .**1/+
Bigher doses of @* to 1** mgDd are suggested for patients 'ith visual or neurological s"mptoms of &,A+ %? pulse
meth"lprednisolone has een proposed as an induction therap", particularl" in cases 'here vision is at ris0
-4ahman 9 4ahman .**6/+
%. Medical emer(encies in dental practice
%.1. Adrenal crisis prophyla1is
Aatients 'ith a histor" compatile 'ith adrenal suppression and presenting 'ith features of adrenal crisis should e
treated urgentl"+
Acute adrenal crisis, 'ith insufficienc" of mineralocorticoids and glucocorticoids,is a medical emergenc"+ The
patient presents 'ith adominal pain, 'ea0ness, h"potension, deh"dration, nausea and vomiting+ Caorator"
findings ma" include decreased sodium -h"ponatraemia/, elevated potassium -h"per0alaemia/, decreased lood
glucose -h"pogl"cemia/, acidosis and uraemia+ !e' patients have all these findings, 'ith h"potension and nausea
eing most common+
Aatients 'ith secondar" AddisonJs most t"pical presentation is of h"potension,and h"ponatraemia 'ithout volume
depletion+ Additional s"mptoms ma" include fatigue, 'ea0ness, arthralgia, nausea, and orthostatic dizziness
associated 'ith h"potension+
Aatients ta0ing exogenous glucocorticoids+ Gxogenous glucocorticoids can cause adrenal gland suppression and
resultant atroph"+ >ith atroph" of the adrenal glands there is a decreased glucocorticoid response to stress, and this
ma" precipitate an adrenal crisis -Gd'ards 1((6/+
%.1.1. Mana(ement
i+ %ntravenous fluids, in the form of 68 dextrose in normal saline, should e given to address the volume
depletion that is often present+
ii+ Arimar" adrenal insufficienc"K start on .*7.6 mg h"drocortisone per .) h
iii+ $econdar" adrenal insufficienc"K 167.* mg h"drocortisone per .) h9 if orderline fail in cos"ntropin test
consider 1* mg or stress dose cover onl"
iv+ B"drocortisone should e given intravenousl" initiall"+ %f improvement has occurred 'ithin .) hours,
'hich is common, the h"drocortisone dose can e decreased+ This can e changed to an oral formulation
'henever the patient is stale+ The dose can e decreased " one third to one half the dose dail" until a
maintenance dose of .* mg in the morning and 1* mg in the afternoon or at night is attained+ $ome patients
ma" need onl" a dose of .* mgDda" total -i+e+, .* mg ever" morning, or 16 mg in the morning and 6 mg in
the afternoon or at night/+
v+ A search for the condition that precipitated the crisis, such as infection, should e underta0en+ Treatment of
the underl"ing cause should e instituted+
vi. Aatients 'ill not need mineralocorticoid replacement, ecause the renin2angiotensin2aldosterone axis is
intact -Arlt .**(/+
%.2. Anaphyla1is shoc2
Anaph"laxis is the 5uintessential disease of emergenc" medicine+ The term anaph"laxis literall" meaning Oagainst
protectionQ 'as introduced " 4ichet and Aortier in 1(*. -3ro'n 1((6/+
%t is a potentiall" fatal illness 'ith rapid onset that can affect "oung, health" people+ %t must e diagnosed clinicall",
and is potentiall" curale if treated immediatel" -&olden .**1/+
A s"stematic revie' of the literature has failed to demonstrate the effectiveness of an" of these medications in the
treatment of anaph"laxis -G'an .*1*/+
$teroids are unli0el" to e helpful in the treatment of acute anaph"laxis+ The" have a dela"ed onset of ) to ; hours+
$teroids are thought to pla" a role in preventing reound anaph"laxis9 ho'ever, this has never een proven -4evie'
Anaph"laxis in the emergenc" department .**@/+
As 'ith the antihistamines, despite their man" theoretical enefits on mediator release and tissue responsiveness,
there are no placeo2controlled trials to confirm the effectiveness of steroids in anaph"laxis+
Most clinicians ho'ever give prednisone 1 mgD0g up to 6* mg orall" or h"drocortisone 1+ 62= mgD0g %? particularl"
in patients 'ith air'a" involvement and ronchospasm, ased empiricall" on their important role in asthma -$oar
.**@/+
%t is unclear if steroids prevent a iphasic reaction 'ith recrudescence of s"mptoms follo'ing recover", as
supporting data are unconvincing -Cieerman .**6/+
$teroids are of course fundamental to the management of recurrent idiopathic anaph"laxis -4ing .**.9&reenerger
.**1/+
'. &mer(ency dru(s in (eneral dental practice
'.1. Intracanal corticosteroid in root canal therapy
The application of antiinflammator" agents on exposed pulp tissue in an attempt to prevent or minimize
inflammator" reaction and to favor healing has een investigated for a long time+ ,orticosteroid can e used as a
dressing agent for deep cavities and exposed pulp tissue in order to control the inflammator" pulp response and
reduce postoperative pain+ The therapeutic effect of a corticosteroid agent seems to depend upon its potenc",
concentration and ailit" to diffuse into connective tissue -Bolland 1((19&ordon Marshall .**./+
The results of studies that emplo" corticosteroids as a cavit" liner support that these medications are effective in
reducing or preventing postoperative thermal sensitivit"+ 4esearchers have sho'n that application of corticosteroidD
antiiotic association for short period of time 'as effective to control inflammation in the pulp tissue 'ithout
determining changes in the healing process -$antini 1(@=/+
Triamcinolone acetonide is a potent corticosteroid that could e used effectivel" to eliminate or at least reduce the
severe inflammation that might occur secondar" to endodontic treatment -Eegm .**1/+
'.2. "erioperati3e corticosteroid use in dentoal3eolar sur(ery
$everal authors have examined the effects of corticosteroids for prevention of pain and edema associated 'ith oral
surger"+ Dental surgeons are often advised to use corticosteroids during and after third molar removal and other
dentoalveolar surger" to reduce postsurgical edema+ The most commonl" used forms of corticosteroids in
dentoalveolar surger" include dexamethasone -oral/, dexamethasone sodium phosphate and dexamethasone acetate,
and meth"lprednisolone acetate and meth"l prednisolone sodium succinate+ Dexamethasone has a longer duration of
action than methl"prednisolone and is considered more potent -Alexander .***/+
Meth"lprednisolone has een used in a numer of studies+ Meth"lprednisolone is usuall" administered via the
intramuscular or intravenous route though the possiilit" of topical -intraalveolar/ application has een descried,
'ith a reduction in moridit" and possile side effects+ This drug is five times more potent than cortisol, 'ith scant
associated saline retention and an intermediate duration of action -1.2=; hours/ -MicW2Clorens .**;9 Ceone .**19
?egas23ustamante .**@/+
3ased on the literature revie', interim recommendations for the use of corticosteroids are proposed, including
dosages and regimens that appear rational for oral, intramuscular, or intravenous corticosteroid administration efore
and after extractions and other dentoalveolar surger"+ These largel" empiric recommendations might re5uire
ad<ustment 'hen evidence2ased data ecome availale in future studies
). Ad3erse effects of steroids
,orticosteroids are chemical compounds of hormonal nature derived from cholesterol+ Their iological po'er and
actions depend on their chemical structure+ Due to the remar0ale anti2inflammator" and immunoregulator" effects
of the corticosteroids, the" have een emplo"ed as first step in the management of different diseases, and sometimes
the" are the onl" possile drug to use in dail" medical practice+ Despite their clinical efficac", the" can induce
multiple severe adverse effects+
Adverse effects of corticosteroids ma" e due to local effects on the s0in or mucosa at the site of or to s"stemic
effects follo'ing asorption of the oral drugs+ $"stemic side effects are rarer than local side effects+
).1. Systemic ad3erse effects
$"stemic side effects occur ecause the steroids contained in the corticosteroid ecome asored into the lood
stream and egin to affect other parts of the od", such as the adrenal gland -a gland that produces man" of the
od":s natural steroids/+
$"stemic side effects can include -Cozada2Eur 1((19 3ircher 1((;/K
B"pothalamic2Aituitar"adrenal Axis and $econdar" Adrenal
%nsufficienc"
>eight gain
Osteoporosis
Diaetes
Bigh 3lood Aressure -h"pertension/
As"chological Gffects
%ndigestion or Bearturn
,ushing:s $"ndrome
Moon !ace
3one Damage
Decreased &ro'th in ,hildren
$0in can ecome thin, easil" ruised and slo' to heal
Avascular Eecrosis -a painful one condition/
&laucoma
).2. Local ad3erse effects
>hile topical steroids have tremendous enefit in reducing inflammation, the" also have significant side effects+
Most of these side effects are seen 'ith long2term use, ut some ma" e noticed 'ithin da"s of starting therap"+ The
ris0 of side effects from topical corticosteroids is related to drug potenc", duration of therap", fre5uenc" of
application and anatomical area+ Cocal side effects can include -He".**=9 3aid .**;/K
Tach"ph"laxis
3urning Mouth
B"pogeusia
Oral Bair" Ceu0opla0ia
B"persensitive 4eactions to the Drug
Topical $teroid Allerg"
$0in Atroph"
$triae 2 $tretch Mar0s
Acne formD4osacea li0e eruptions
,andidosis
Dela"ed Bealing
!ine Bair &ro'th
).2.1. Special Considerations
3ecause corticosteroids cause the adrenal glands to slo' or stop the production of cortisol, the" cannot e
discontinued aruptl"+ %t ta0es some time for the adrenal glands to egin producing cortisol again+ &raduall"
tapering the dose of corticosteroids allo's the od" to egin producing its o'n suppl" of cortisol again+
#nderta0e 'eight earing exercise -such as ris0 'al0ing/
$top smo0ing
Avoid excess alcohol inta0e
,ontraindications for acute B$? %nfection
,reams are less effective in the mouth than ointments, and the ointment form is preferred+
+. 4uidelines on the mana(ement of dental patients on corticosteroid therapy in community dental clinics
&eneral dental procedures for patients receiving long2term steroid medication do not 'arrant supplementation 'ith
additional glucocorticoids+
The aims of these guidelines are to assist and support Dentists and Dental therapists 'hen providing dental treatment
to patients 'ho are currentl" receiving, or 'ho have received ,orticosteroid therap" in the past t'elve months+
+.1. -or routine conser3ati3e dentistry or minor oral sur(ery #to include one simple e1traction$ under local
anaesthesia
Although Opinions ,onflict On >hether An" $ignificant $uppression Of Adrenal !unction Occurs %n Aatients
Ta0ing Co' Doses Of $teroids -#nder 1+ 6 Mg Arednisolone/ Availale Gvidence $uggests That $upplementation %s
#nnecessar" !or Cocal Anaesthetic Arocedures+
+.2. -or minor sur(ery under (eneral anesthesia for patients under(oin( (eneral anesthesia for minor sur(ery
1** Mg B"drocortisone %ntramuscularl" $hould 3e Administered And The #sual &lucocorticoid Medications
Maintained+
+.!. -or ma0or sur(ery
1** Mg B"drocortisone Delivered As A 3olus Are2Operativel" !ollo'ed 3" 6* Mg @2Bourl" !or )@ Bours %s
Ade5uate+
+.%. American Society Of Anaesthesiolo(ists #ASA$ "hysical Classification Status
1+ A normal health" patient
.+ A patient 'ith mild s"stemic disease
=+ A patient 'ith severe s"stemic disease
)+ A moriund patient 'ho is not expected to survive 'ithout surger"
6+ A declared rain2dead patient 'hose organs are eing removed for donor purposes+
Aatients 'ith A$A score 1 and . 'ho are currentl" on or 'ho have een on corticosteroids in the last "ear+
Aatients 'ith A$A score = and ) 'ho are currentl" on or 'ho have een on corticosteroids in the last "ear+
An" patient that does not fit the aove criteria or if the clinician is in an" dout then the patient should not e treated
in the primar" care setting and should e referred -&ison .**)/+
Aphthous 5lcers Treatment 6 Mana(ement
AuthorK ,rispian $cull", MD, AhD, MD$, MD$, ,3G, M4,$, !D$4,$, !D$4,A$, !!D4,$%,
!D$4,$G, !4,Aath, !Med$ci, !BGA, !#,C, !$3, D$c, D,hD, DMed-B,/, Dr-B,/ 9 ,hief GditorK
Arlen D Me"ers, MD, M3A more+++
%dentif" and correct predisposing factors for recurrent aphthous stomatitis -4A$/+ Gnsure that patients rush
atraumaticall" -eg, 'ith a small2headed, soft toothrush/ and avoid eating particularl" hard or sharp foods -eg, toast,
potato crisps/ and avoid other trauma to the oral mucosa+
$C$ should e avoided if implicated as a predisposing factor+ An" iron or vitamin deficienc" should e corrected
once the cause of that deficienc" has een estalished+ %f an ovious relationship to certain foods is estalished,
these should e excluded from the diet+ Aatch testing ma" e indicated to reveal allergies+ The occasional patient
'ho relates ulcers to her menstrual c"cle or to use of an oral contraceptive ma" enefit from suppression of
ovulation 'ith a progestogen or a change in the oral contraceptive+
%n most cases, the natural histor" of 4A$ is one of eventual remission+ Bo'ever, for some patients, remission occurs
spontaneousl" several "ears later9 thus, treatment is indicated in these patients if discomfort is significant+ 4elief of
pain and reduction of ulcer duration are the main goals of therap"+ There is a huge range of supposed or possile
remedies availale, ut o<ective evidence sho's the most efficac" from corticosteroids and antimicroials used
topicall"+
[), 6]
?itamin 31. used orall" ma" have some effect
Topical corticosteroids -T,s/ remain the mainsta"s of treatment+ A spectrum of different T,s can e used+
At est, T,s reduce painful s"mptoms ut not the rate of ulcer recurrence+ The commonl" used
preparations are as follo'sK
o B"drocortisone hemisuccinate pellets -,orlan/, .+6 mg used ) times dail"
o Triamcinolone acetonide in carox"meth"l cellulose paste -Adcort"l in oraase ['ithdra'n in
some countries], Henalog/, administered ) times dail"
o 3etamethasone sodium phosphate as a *+62mg talet dissolved in 16 mC of 'ater to ma0e a mouth
rinse, used ) times dail" for ) minutes each time
B"drocortisone and triamcinolone preparations are popular ecause neither causes significant adrenal
suppression9 ho'ever, ulcers still recur+
3etamethasone, fluocinonide, fluocinolone, fluticasone, and cloetasol are more potent and effective than
h"drocortisone and triamcinolone, ut the" carr" the possiilit" of some adrenocortical suppression and a
predisposition to candidiasis+
Topical tetrac"clines ma" reduce the severit" of ulceration, ut the" do not alter the recurrence rate+ A
dox"c"cline capsule of 1** mg in 1* mC of 'ater administered as a mouth rinse for = minutes or
tetrac"cline 6** mg plus nicotinamide 6** mg administered ) times dail" ma" provide relief and reduce
ulcer duration+ Avoid tetrac"clines in children "ounger than 1. "ears 'ho might ingest them and develop
tooth staining+
,hlorhexidine gluconate and ioadhesive -&elclair/ mouth rinses reduce the severit" and pain of ulceration
ut not the fre5uenc"+
Anti2inflammator" agents can help9 a spectrum of topical agents such as enz"damine and amlexanox ma"
help+ 3enz"damine h"drochloride mouth'ash, though no more eneficial than a placeo, can produce
transient pain relief+
%f 4A$ fails to respond to local measures, s"stemic immunomodulators ma" e re5uired+ A 'ide spectrum
of agents has een suggested as eneficial, ut fe' studies have een performed to assess their efficac" -or
their adverse effects are significant/+ Thalidomide 6*21** mg dail" is effective against severe 4A$,
although ulcers tend to recur 'ithin = 'ee0s+ Teratogenicit", neuropath", and other adverse effects dissuade
most ph"sicians from its use+
!e', if an", of the other medications used for 4A$ have undergone serious scientific evaluation+ These
include iologics, transfer factor, gamma2gloulin therap", sodium cromogl"cate lozenges, dapsone,
colchicine, pentoxif"lline, levamisole, colchicine, azathioprine, prednisolone, azelastine, alpha .2interferon,
ciclosporin, degl"cerinated li5uorice, 62aminosalic"lic acid -62A$A/, prostaglandin G. -A&G./, sucralfate,
diclofenac, and aspirin+