Pemfigus Vulgaris Adera

7/21/2019 Pemfigus Vulgaris Adera

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(http://emedicine.medscape.com/article/1064187-overview#showall)

PEP!"$% '$*"%

Author: Bassam Zeina, MD, PhD; Chief Editor: Dirk M Elston, MD more...

Updated: Jun !, !"#

P*+,"+E E%%E,"%

Pemphi$us %ul$aris is an autoimmune, intraepithelial, &listerin$ disease affe'tin$ the skin

and mu'ous mem&ranes. (t is mediated &) 'ir'ulatin$ autoanti&odies dire'ted a$ainst

keratino')te 'ell surfa'es. A potentiall) life*threatenin$ disease, it has a mortalit) rate of

appro+imatel) *-./

%ins and smptoms

Mucous membranes

Mu'ous mem&ranes of the oral 'a%it) are in%ol%ed in almost all patients 0ith

pemphi$us %ul$aris

Patients ma) ha%e ill*defined, irre$ularl) shaped, $in$i%al, &u''al, or palatine

erosions, 0hi'h are painful and slo0 to heal

(nta't &ullae are rare in the mouth

Erosions ma) &e seen on an) part of the oral 'a%it), and the) ma) spread to in%ol%e

the lar)n+, 0ith su&se1uent hoarseness

(n 2u%enile pemphi$us %ul$aris, stomatitis is the presentin$ 'omplaint in more than

"- of 'ases

3ther mu'osal surfa'es ma) &e in%ol%ed, in'ludin$ the 'on2un'ti%a,!/esopha$us

4'auses od)nopha$ia and5or d)spha$ia6,7/ la&ia, %a$ina, 'er%i+, %ul%a,#/penis, urethra, nasal

mu'osa, and anus

Skin

Primar) lesion of pemphi$us %ul$aris is a fla''id &lister filled 0ith 'lear fluid that

arises on health) skin or on an er)thematous &ase

Blisters are fra$ile and ma) rupture, produ'in$ painful erosions 4the most 'ommon

skin presentation6

Nails


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A'ute or 'hroni' paron)'hia, su&un$ual hematomas, and nail d)strophies affe'tin$ one or

se%eral fin$ers or toes ha%e &een reported 0ith pemphi$us %ul$aris., 8/

Vegetating pemphigus vulgaris

9esions in skin folds readil) form %e$etatin$ $ranulations. (n some patients, erosions tend to

de%elop e+'essi%e $ranulation tissue and 'rustin$; these indi%iduals displa) more %e$etatin$

lesions.

eeClini'al Presentationfor more detail.

ianosis

9a&orator) studies in'lude the follo0in$:

istopatholo$): Demonstrates an intradermal &lister; the earliest 'han$es 'onsist of

inter'ellular edema 0ith loss of inter'ellular atta'hments in the &asal la)er

Dire't immunofluores'en'e 4D(


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"mae lirar

Earl), small &lister filled 0ith 'lear fluid arises on health)

skin.

2+3*$

Pemphi$us is deri%ed from the reek 0ordpemphixmeanin$ &u&&le or &lister. Pemphi$us

des'ri&es a $roup of 'hroni' &ullous diseases, ori$inall) named &) @i'hman in =?. he

term pemphi$us on'e in'luded most &ullous eruptions of the skin, &ut dia$nosti' tests ha%e

impro%ed, and &ullous diseases ha%e &een re'lassified.

he term pemphi$us refers to a $roup of autoimmune &listerin$ diseases of the skin and

mu'ous mem&ranes 'hara'teried histolo$i'all) &) intraepidermal &lister and

immunopatholo$i'all) &) the findin$ of in %i%o &ound and 'ir'ulatin$ immuno$lo&ulin

4($6 anti&od) dire'ted a$ainst the 'ell surfa'e of keratino')tes. he 7 primar) su&sets of

pemphi$us in'lude pemphi$us %ul$aris,pemphi$us folia'eus, andparaneoplasti' pemphi$us.

>/ Ea'h t)pe of pemphi$us has distin't 'lini'al and immunopatholo$i' features. Pemphi$us

%ul$aris a''ounts for appro+imatel) ="- of pemphi$us 'ases.

P,!P!5%"5

Pemphi$us %ul$aris is an autoimmune, intraepithelial, &listerin$ disease affe'tin$ the skin

and mu'ous mem&ranes and is mediated &) 'ir'ulatin$ autoanti&odies dire'ted a$ainst

keratino')te 'ell surfa'es. (n ?8#, autoanti&odies a$ainst keratino')te surfa'es 0ere

des'ri&ed in patients 0ith pemphi$us. Clini'al and e+perimental o&ser%ations indi'ate that

the 'ir'ulatin$ autoanti&odies are patho$eni'. An immuno$eneti' predisposition is 0ell

esta&lished.

Blisters in pemphi$us %ul$aris are asso'iated 0ith the &indin$ of ($ autoanti&odies to

keratino')te 'ell surfa'e mole'ules. hese inter'ellular or pemphi$us %ul$aris anti&odies &indto keratino')te desmosomes and to desmosome*free areas of the keratino')te 'ell mem&rane.
http://emedicine.medscape.com/article/1064019-overviewhttp://emedicine.medscape.com/article/1064452-overviewhttp://emedicine.medscape.com/article/1064452-overviewhttp://refimgshow%281%29/http://emedicine.medscape.com/article/1064019-overviewhttp://emedicine.medscape.com/article/1064452-overview


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he &indin$ of autoanti&odies results in a loss of 'ell*to*'ell adhesion, a pro'ess termed

a'anthol)sis. he anti&od) alone is 'apa&le of 'ausin$ &listerin$ 0ithout 'omplement or

inflammator) 'ells.

Pemphis vlaris antien

(nter'ellular adhesion in the epidermis in%ol%es se%eral keratino')te 'ell surfa'e mole'ules.

Pemphi$us anti&od) &inds to keratino')te 'ell surfa'e the mole'ules desmo$lein and

desmo$lein 7. he &indin$ of anti&od) to desmo$lein ma) ha%e a dire't effe't on

desmosomal adherens or ma) tri$$er a 'ellular pro'ess that results in a'anthol)sis.

Anti&odies spe'ifi' for nondesmosomal anti$ens also ha%e &een des'ri&ed in the sera of

patients 0ith pemphi$us %ul$aris; ho0e%er, the role of these anti$ens in the patho$enesis of

pemphi$us %ul$aris is not kno0n.

ntiodies

Patients 0ith the mu'o'utaneous form of pemphi$us %ul$aris ha%e patho$eni'

antidesmo$lein and antidesmo$lein 7 autoanti&odies. Patients 0ith the mu'osal form of

pemphi$us %ul$aris ha%e onl) antidesmo$lein 7 autoanti&odies. Patients 0ith a'ti%e disease

ha%e 'ir'ulatin$ and tissue*&ound autoanti&odies of &oth the immuno$lo&ulin 4($6 and

immuno$lo&ulin # 4($#6 su&'lasses.?, "/

More than >"- of the patients 0ith a'ti%e disease produ'e autoanti&odies to the desmosomal

protein desmo$lein. Disease a'ti%it) 'orrelates 0ith anti&od) titers in most patients./ (n

patients 0ith pemphi$us %ul$aris, the presen'e of antidesmo$lein autoanti&odies, as

determined &) en)me*linked immunosor&ent assa) 4E9(A6, is more 'losel) 'orrelated 0ith

the 'ourse of the disease 'ompared 0ith antidesmo$lein 7 autoanti&odies. 9a'k of in %i%o

anti&od) &indin$ 4re%ersion to a ne$ati%e result on dire't immunofluores'en'e6 is the &est

indi'ator of remission and 'an help predi't a la'k of flarin$ 0hen therap) is tapered.

+omplement

Pemphi$us anti&od) fi+es 'omponents of 'omplement to the surfa'e of epidermal 'ells.

Anti&od) &indin$ ma) a'ti%ate 'omplement 0ith the release of inflammator) mediators and

re'ruitment of a'ti%ated 'ells. 'ells are 'learl) re1uired for the produ'tion of the

autoanti&odies, &ut their role in the patho$enesis of pemphi$us %ul$aris remains poorl)

understood. (nterleukin ! is the main a'ti%ator of l)mpho')tes, and in'reased solu&le

re'eptors ha%e &een dete'ted in patients 0ith a'ti%e pemphi$us %ul$aris.


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*E$E+5

$nited %tates

Pemphi$us %ul$aris is un'ommon, and the e+a't in'iden'e and pre%alen'e depends on the

population studied.

"nternational

Pemphi$us %ul$aris has &een reported to o''ur 0orld0ide. Pemphi$us %ul$aris in'iden'e

%aries from ".*7.! 'ases per "",""" population. Pemphi$us %ul$aris in'iden'e is in'reased

in patients of Ashkenai Je0ish des'ent and those of Mediterranean ori$in.


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*ace

Pemphi$us %ul$aris affe'ts persons of all ra'es. he pre%alen'e of pemphi$us %ul$aris is hi$h

in re$ions 0here the Je0ish population is predominant. #/


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nonsteroidal anti*inflammator) dru$s 4HA(Ds6, and other thiol*'ontainin$ 'ompounds.

Fifampin, emotional stress, thermal &urns, ultra%iolet ra)s, and infe'tions 4e$,

'o+sa'kie%irus, erpes%iridae famil)6 ha%e also &een reported as tri$$ers for pemphi$us

%ul$aris.!"/

P!5%"+

Mu'ous mem&ranes t)pi'all) are affe'ted first in pemphi$us %ul$aris. Mu'osal lesions ma)

pre'ede 'utaneous lesions &) 0eeks or months. Patients 0ith mu'osal lesions ma) present to

dentists, oral sur$eons, or $)ne'olo$ists.!, !!/

Mu'ous mem&ranes

o (nta't &ullae are rare in the mouth. More 'ommonl), patients ha%e ill*defined,

irre$ularl) shaped, $in$i%al, &u''al, or palatine erosions, 0hi'h are painful and slo0 to

heal. he erosions e+tend peripherall) 0ith sheddin$ of the epithelium.

o he mu'ous mem&ranes most often affe'ted in pemphi$us %ul$aris are those

of the oral 'a%it), 0hi'h is in%ol%ed in almost all patients 0ith pemphi$us %ul$aris and

sometimes is the onl) area in%ol%ed. Erosions ma) &e seen on an) part of the oral 'a%it).

Erosions 'an &e s'attered and often are e+tensi%e. Erosions ma) spread to in%ol%e the

lar)n+, 0ith su&se1uent hoarseness. he patient often is una&le to eat or drink ade1uatel)

&e'ause the erosions are so un'omforta&le.

o (n 2u%enile pemphi$us %ul$aris, stomatitis is the presentin$ 'omplaint in more

than "- of the 'ases.

o 3ther mu'osal surfa'es ma) &e in%ol%ed, in'ludin$ the 'on2un'ti%a,

!/esopha$us 4'auses od)nopha$ia and5or d)spha$ia6, 7/ la&ia, %a$ina, 'er%i+, %ul%a,#/penis,

urethra, nasal mu'osa, and anus.

kino he primar) lesion of pemphi$us %ul$aris is a fla''id &lister filled 0ith 'lear

fluid that arises on health) skin or on an er)thematous &ase, as sho0n in the ima$es


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&elo0. Earl), small &lister filled 0ith 'lear fluid arises on

health) skin.


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Hails: A'ute or 'hroni' paron)'hia, su&un$ual hematomas, and nail d)strophies

affe'tin$ one or se%eral fin$ers or toes ha%e &een reported 0ith pemphi$us %ul$aris. ,

8/ Patients 0ith paron)'hial pemphi$us usuall) also ha%e oral in%ol%ement.

Pemphi$us in pre$nan'): Pemphi$us %ul$aris o''urrin$ in pre$nan') is rare. @hen

present, maternal autoanti&odies ma) 'ross the pla'enta, resultin$ in neonatal pemphi$us.

Heonatal pemphi$us is transient and impro%es 0ith 'learan'e of maternal autoanti&odies.

!7/ reatment of pemphi$us %ul$aris in pre$nan') is 0ith oral 'orti'osteroids; ho0e%er,

prednisone and its meta&olites 'ross the pla'enta and ha%e &een asso'iated 0ith lo0 &irth

0ei$ht, prematurit), infe'tion, and adrenal insuffi'ien').

Hikolsk) si$n: (n patients 0ith a'ti%e &listerin$, firm slidin$ pressure 0ith a fin$er

separates normal*appearin$ epidermis, produ'in$ an erosion. his si$n is not spe'ifi' for

pemphi$us %ul$aris and is found in other a'ti%e &listerin$ diseases.

As&oe*ansen si$n: 9ateral pressure on the ed$e of a &lister ma) spread the &lister

into 'lini'all) unaffe'ted skin.

+$%E%

he 'ause of pemphi$us %ul$aris remains unkno0n; ho0e%er, se%eral potentiall) rele%ant

fa'tors ha%e &een identified.

eneti' fa'tors: Predisposition to pemphi$us is linked to $eneti' fa'tors.!#/Certain

ma2or histo'ompati&ilit) 'omple+ 4MC6 'lass (( mole'ules, in parti'ular alleles of human

leuko')te anti$en DF# 4DFB"#"!6 and human leuko')te anti$en DF08 4DKB""76,

are 'ommon in patients 0ith pemphi$us %ul$aris.!, !8, !=, !>, !?, 7"/

A$e: Peak a$e of onset is from "*8" )ears. (nfants 0ith neonatal pemphi$us remit

0ith 'learan'e of maternal autoanti&odies. he disease ma) de%elop in 'hildren or in older

persons. Disease asso'iation: Pemphi$us o''urs in patients 0ith other autoimmune diseases,

parti'ularl) m)asthenia $ra%isand th)moma.7/ A stud) of " patients 0ith pemphi$us

found # patients 0ith autoimmune th)roid disease and 7 patients 0ith rheumatoid arthritis.

(n this stud), ho0e%er, autoimmune diseases 0ere no more 'ommon in ?8? first*de$ree

relati%es of patients 0ith pemphi$us than in the $eneral population.7!/
http://emedicine.medscape.com/article/1171206-overviewhttp://emedicine.medscape.com/article/193809-overviewhttp://emedicine.medscape.com/article/1171206-overviewhttp://emedicine.medscape.com/article/193809-overview


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"E*E," "%E%

Bullous Pemphi$oid

Dermatitis erpetiformis

Er)thema Multiforme


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Dire't immunofluores'en'e sho0in$ inter'ellular

immuno$lo&ulin throu$hout the epidermis of a patient 0ith pemphi$us %ul$aris.

kin &iops) spe'imens pla'ed in transport media ma) )ield false*ne$ati%e results;

therefore, fresh tissue is the preferred su&strate for D(< studies.

(n the patients serum, (D(< demonstrates the presen'e of 'ir'ulatin$ ($

autoanti&odies that &ind to epidermis. Cir'ulatin$ inter'ellular anti&odies are dete'ted usin$

(D(< in >"*?"- of patients 0ith pemphi$us %ul$aris. he titer of 'ir'ulatin$ anti&od)

'orrelates 0ith disease 'ourse.77/

!"%,"+ ""%

istopatholo$) demonstrates an intradermal &lister. he earliest 'han$es 'onsist of

inter'ellular edema 0ith loss of inter'ellular atta'hments in the &asal la)er. upra&asal

epidermal 'ells separate from the &asal 'ells to form 'lefts and &listers. Basal 'ells are

separated from one another and stand like a ro0 of tom&stones on the floor of the &lister, &ut

the) remain atta'hed to the &asement mem&rane. Blister 'ells 'ontain some a'anthol)ti' 'ells.

istopatholo$) 'an help differentiate pemphi$us %ul$aris from pemphi$us folia'eous, 0hi'h

demonstrates a more superfi'ial epidermal 'lea%a$e.

an'k preparation is a smear taken from the &ase of a &lister or an oral erosion that 'ontains

a'anthol)ti' 'ells. Blisterin$ is pre'eded &) eosinophili' spon$iosis in some patients. he

superfi'ial dermis has a mild, superfi'ial, mi+ed inflammator) infiltrate, 0hi'h in'ludes some

eosinophils.

E"+ +*E

he aim of treatment in pemphi$us %ul$aris is the same as in other autoimmune &ullous

diseases, 0hi'h is to de'rease &lister formation, promote healin$ of &listers and erosions, and

determine the minimal dose of medi'ation ne'essar) to 'ontrol the disease pro'ess. Hote the

ima$es &elo0. herap) must &e tailored for ea'h patient, takin$ into a''ount pree+istin$ and
http://refimgshow%286%29/


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'oe+istin$ 'onditions. Patients ma) 'ontinue to e+perien'e mild disease a'ti%it) 0hile under

optimal treatment.

Erosions and healin$ areas on the &a'k.

ealin$ areas on the 'hest and a&domen.

Corti'osteroids ha%e impro%ed o%erall mortalit), &ut no0 mu'h of the mortalit) and

mor&idit) in these patients relates to the ad%erse effe'ts of therap). @hether massi%e doses of

steroids ha%e an) ad%anta$e o%er doses of m$5k$5d is un'lear.7#/

(mmunosuppressi%e dru$s are steroid sparin$ and should &e 'onsidered earl) in the 'ourse of

the disease. Epidermal $ro0th fa'tor ma) speed healin$ of lo'alied lesions.7/ Man)

authorities no0 use ritu+ima&, the anti*CD!" anti&od), as first* or se'ond*line therap).78, 7=, 7>,

7?, #", #/ he antitumor ne'rosis fa'tor dru$s sulfasalaine and pento+if)lline ha%e &een

reported as effe'ti%e ad2un'ti%e treatments, redu'in$ the serum le%el of tumor ne'rosis fa'tor

and resultin$ in rapid 'lini'al impro%ement. #!/ Dapsone has &een su$$ested as a steroid*

sparin$ a$ent in the maintenan'e phase of pemphi$us %ul$aris treatment#7/ ; dapsone has also

&een su$$ested as a first*line a$ent.##/

(ntra%enous immuno$lo&ulin therap) has &een su$$ested as effi'a'ious in pemphi$us

%ul$aris treatment.#, #8, #=, #>/ Ama$ai et al reported on the su''essful use of intra%enous

immuno$lo&ulin in pemphi$us patients 0ho did not full) respond to s)stemi' steroids, #?/ and

Asar'h et al reported its use in pediatri' patients."/

(nfli+ima& has pro%en effe'ti%e in some patients 0ith refra'tor) disease, and photod)nami'

therap) has &een su$$ested as a possi&le ad2un'ti%e treatment for re'al'itrant ul'eration./

+%$,,"%

Mana$ement of patients 0ith pemphi$us %ul$aris re1uires 'oordination of 'are &et0een the

dermatolo$ist and the patients primar) 'are ph)si'ian.
http://refimgshow%285%29/http://refimgshow%284%29/


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An ophthalmolo$ist should e%aluate patients 0ith suspe'ted o'ular in%ol%ement and

those re1uirin$ prolon$ed hi$h*dose steroids.

Patients 0ith oral disease ma) re1uire a dentist and5or an otolar)n$olo$ist for

e%aluation and 'are.

Patients on s)stemi' steroids should maintain ade1uate %itamin D and 'al'ium intake

throu$h diet and supplements. Patients 0ith a histor) of renal 'al'uli should not re'ei%e

'al'ium 'ar&onate.

Patients re'ei%in$ lon$*term s)stemi' 'orti'osteroids should &e e%aluated &) a

rheumatolo$ist 0ithin the first 7" da)s of treatment for osteoporosis risk assessment and

'onsideration of a &isphosphonate for proph)la+is a$ainst osteoporosis.

Diet

Ho dietar) restri'tions are needed, &ut patients 0ith oral disease ma) &enefit from a%oidin$

'ertain foods 4e$, spi') foods, tomatoes, oran$e 2ui'e6 and hard foods that ma) traumatie the

oral epithelium me'hani'all) 4e$, nuts, 'hips, hard %e$eta&les and fruit6.

A'ti%it)

Ad%ise patients to minimie a'ti%ities that traumatie the skin and that ma) pre'ipitate

&listerin$, su'h as 'onta't sports. Hontraumati' e+er'ises, su'h as s0immin$, ma) &e helpful.

Additionall), Dental plates, dental &rid$es, or 'onta't lenses ma) pre'ipitate or e+a'er&ate

mu'osal disease.

E"+," %$*5

he aim of treatment is to redu'e the inflammator) response and autoanti&od) produ'tion.

@hile tar$et*spe'ifi' therap) is not a%aila&le, nonLtar$et*spe'ifi' treatments 'urrentl) are

used. he most 'ommonl) used medi'ations are 'orti'osteroids.

he introdu'tion of 'orti'osteroids has redu'ed mortalit) $reatl), &ut si$nifi'ant mor&idit)

remains. (mmunosuppressants should &e 'onsidered earl) in the 'ourse of disease, as steroid*

sparin$ a$ents. M)'ophenolate mofetil and aathioprine are the usual a$ents 'onsidered as

initial 'hoi'es.!, 7/ 3nl) one pla'e&o*'ontrolled &linded stud) of m)'ophenolate has

demonstrated more rapid impro%ement in the short run &ut no si$nifi'ant steroid*sparin$

effe'ts in the lon$ term.#/ A retrospe'ti%e 'hart re%ie0 has su$$ested a therapeuti' ladder for

patients 0ith pemphi$us %ul$aris, &ut these authors approa'h has not &een %alidated.


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/Fitu+ima& and intra%enous immuno$lo&ulin ha%e also pro%en useful alone or in

'om&ination, and some authorities are no0 usin$ ritu+ima& as first*line therap) for se%ere

disease.8/

A small 'ase 'ontrol trial sho0ed impro%ed la&orator) and 'lini'al out'omes in patients 0ith

pemphi$us %ul$aris treated 0ith a 'om&ination of ')toto+i' a$ents plus intra%enous

immuno$lo&ulin 4(I(6'ompared 0ith those treated 0ith 2ust (I(.=/

C)'lophosphamide is used for refra'tor) disease. he role of &iolo$i' a$ents is &ein$

in%esti$ated. Ea'h of these a$ents should &e pres'ri&ed and monitored &) ph)si'ians familiar

0ith them. @ound 'are for erosions in'ludes dail) $entle 'leanin$, appli'ation of topi'al

a$ents to promote 0ound healin$, and use of nonadhesi%e dressin$s. he $oal of 0ound 'are

is to promote healin$, minimie trauma to the surroundin$ skin, and diminish s'arrin$.

Anti*inflammator) a$ents

+lass %mmar

(nhi&it the inflammator) pro'ess &) inhi&itin$ spe'ifi' ')tokine produ'tion.

Iie0 full dru$ information

Prednisone (eltasone eticorten rasone %terapred)

Ma) de'rease inflammation &) re%ersin$ in'reased 'apillar) permea&ilit) and suppressin$

PMH a'ti%it). ta&ilies l)sosomal mem&ranes and suppresses l)mpho')tes and anti&od)

produ'tion.


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aathioprine meta&olism, &efore startin$ patients on aathioprine.>, ?, 8"/ Also see the 'lini'al

$uideline summar) from the British Asso'iation of Dermatolo$ists, uidelines for

pres'ri&in$ aathioprine in dermatolo$).8/

Iie0 full dru$ information

;athioprine ("mran)

Anta$onies purine meta&olism and inhi&its s)nthesis of DHA, FHA, and proteins. Ma)

de'rease proliferation of immune 'ells, 0hi'h results in lo0er autoimmune a'ti%it). (n

'on2un'tion 0ith prednisone, more effe'ti%e than prednisone alone. Ma) &e an effe'ti%e

monotherap) in mild 'ases, althou$h therapeuti' effe't is dela)ed 7* 0k.

Consider 0ithdra0al if no impro%ement 0ithin 7 mo.

+P"+,"%

e'ondar) infe'tion, 0hi'h ma) &e either s)stemi' or lo'alied to the skin, ma) o''ur

&e'ause of the use of immunosuppressants and the presen'e of multiple erosions. Cutaneous

infe'tion dela)s 0ound healin$ and in'reases the risk of s'arrin$.

9on$*term immunosuppressant therap) ma) result in infe'tions and se'ondar)

mali$nan'ies 4e$, Gaposi sar'oma6, o0in$ to impaired immune sur%eillan'e.

ro0th retardation has &een reported in 'hildren takin$ s)stemi' 'orti'osteroids and

immunosuppressants.

Bone marro0 suppression has &een reported in patients re'ei%in$

immunosuppressants. An in'reased in'iden'e of leukemia and l)mphoma is reported in

patients re'ei%in$ prolon$ed immunosuppression.

(mpaired immune responsi%eness 'aused &) 'orti'osteroids and other

immunosuppressi%e dru$s ma) result in the rapid spread of infe'tion. Corti'osteroids

suppress 'lini'al si$ns of infe'tion and ma) allo0 diseases su'h as septi'emia or tu&er'ulosis

to rea'h an ad%an'ed sta$e &efore dia$nosis.

3steoporosis ma) o''ur follo0in$ the use of s)stemi' 'orti'osteroids.

Adrenal insuffi'ien') has &een reported follo0in$ prolon$ed use of $lu'o'orti'oids.
http://guideline.gov/summary/summary.aspx?doc_id=12327http://guideline.gov/summary/summary.aspx?doc_id=12327http://guideline.gov/summary/summary.aspx?doc_id=12327http://reference.medscape.com/drug/azasan-imuran-azathioprine-343191http://reference.medscape.com/drug/azasan-imuran-azathioprine-343191http://emedicine.medscape.com/article/1083998-overviewhttp://guideline.gov/summary/summary.aspx?doc_id=12327http://guideline.gov/summary/summary.aspx?doc_id=12327http://reference.medscape.com/drug/azasan-imuran-azathioprine-343191http://reference.medscape.com/drug/azasan-imuran-azathioprine-343191http://emedicine.medscape.com/article/1083998-overview


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Pemfigus Vulgaris Adera