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Case Report

FIXED DRUG ERUPTION


By:
Ricardo Milkowski
Supervisor:
Fitria Salim
Dermatology Departmet
Medical Fac!lty o" Syia# $!ala Ui%ersity
Dr& 'aioel ()idi Geeral *ospital
+ada (ce#
,-./
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INTRODU0TION
Fixed drug eruptions (FDEs) are defined as recurrent lesions at the same skin
or mucosal sites after repeated intake of the causative agent. he international
prevalence is varia!le !ut is likely similar to that in the "nited States. #ost studies
report fixed drug eruptions to !e the second or third most common skin manifestation
of adverse drug events. Fixed drug eruptions have no kno$n racial predilection. %
genetic suscepti!ility to developing a fixed drug eruption $ith an increased incidence
of &'%(B)) is possi!le. *ne large study of +,- patients revealed a male(to(female
ratio of .:... for fixed drug eruptions. Fixed drug eruptions have !een reported in
patients as young as .., years and as old as /0 years. he mean age at presentation is
1-.+ years in males and 1..1 years in females here are many kno$n causes2
including food additives and pharmaceutical excipients. Sulfonamides2 tetracyclines
and 3S%4Ds are fre5uently implicated. herefore2 the list of etiologic drugs varies
from one place to another and from time to time. he pathogenesis of fixed drug
eruption is not $ell understood. %lthough the exact mechanism is unkno$n2 recent
research suggests a cell(mediated process that initiates !oth the active and 5uiescent
lesions. he process may involve an anti!ody(dependent2 cell(mediated cytotoxic
response. 6D/
7
effector8memory cells play an important role in reactivation of
lesions $ith re(exposure to the offending drug. FDEs usually present as itching or
!urning2 $ellcircumscri!ed2 erythematous macules2 patches2 or pla5ues that leave
hyperpigmentation after resolving. 9esicles or !ullae may occasionally !e seen.
"sually asymptomatic. #ay !e pruritic2 painful2 or !urning. :ainful $hen
eroded. *ccur from 1- min to / h after ingestion of drug in previously sensiti;ed
individual. 'esions persist if drug is continued. <esolve days to fe$ $eeks after drug
is discontinued. he characteristic early lesion is a sharply demarcated macule round
or oval in shape2 occurring $ithin hours after ingestion of the offending drug. 4nitially
erythema2 then dusky red to violaceous. #ost commonly2 lesions are solitary and can
spread to !ecome 5uite large2 !ut they may !e multiple $ith random distri!ution=
numerous lesions may simulate E3. 'esions !ecome edematous2 thus forming a
2
pla5ue2 $hich may evolve to !ecome a !ulla and then an erosion. Eroded lesions2
especially on genitals or oral mucosa2 are 5uite painful. %fter healing2 dark !ro$n
$ith violet hue postinflammatory hyperpigmentation. >enital skin is most commonly
involved site2 !ut any site may !e involved= perioral2 perior!ital. *ccur in
con?unctivae2 oropharynx.
:atch testing of the suspected drug to lesional and non(lesional skin has !een helpful
in a fe$ instances. he exact protocol of patch testing has varied. :atch testing and
oral provocation have !een used to identify the suspected agent and check for cross(
sensitivities to medications.

% refractory period has !een reported in fixed drug
eruption= therefore2 a delay !efore and !et$een patch testing and oral provocation is
recommended. *ne study used an /($eek time $indo$ after lesion resolution and
!et$een tests2 $hich yielded positive results.

:atch testing must !e performed on a
previously involved site= other$ise2 a false(negative result is likely. Some locations
may !e inappropriate for patch testing= thus2 clinical discretion is advised. *nce patch
testing is complete2 oral provocation should follo$2 $ith the least likely culprits and
the negative patch test agents first2 follo$ed !y more likely causes. *ral provocation
is thought to !e the only relia!le $ay to diagnose fixed drug eruption. :atch testing is
particularly efficacious in identifying a putative cause of the reaction $hen
nonsteroidal anti(inflammatory agents are suspected2 !ut patch testing is not helpful
in discerning reactions to anti!iotics and allopurinol
he main goal of treatment is to identify the causative agent and avoid it.
reatment for fixed drug eruptions (FDEs) other$ise is symptomatic. Systemic
antihistamines and topical corticosteroids may !e all that are re5uired. 4n cases in
$hich infection is suspected2 anti!iotics and proper $ound care are advised.
Desensiti;ation to medications has !een reported in the literature2 !ut this should !e
avoided unless no su!stitutes exist.
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0(SE REPORT
4dentity of patient
3ame : #r. S&
Sex : #ale
<egistration num!er : -(/1(.@(,@
%ge : +, years old
Body $eight : ,@ kg
%ddress : 'ampeuneurot
:hone num!er : -/.100)1@01@
&istory
he chief of complaint :
Black rash on the edge red $ith !urning and itchy since 1 days ago in his !ody
&istory of present illness :
*ne year ago he had a red rash in hand first and had another in chest2 inguinal2
perineal2 femoral and pedis since. he rash came after he consumed the drug that he
!ought in pharmacy $hen he $as sick !ut he have forgotten $hat the drug he
consumed. &e came to doctor and he got therapy !ut rash did not disappear and
!ecame !lack. hree days ago he got stomachache and he came to emergency unit in
meuraxa hospital he got therapy $ith mefenamat acid and some drugs he forgot. %fter
three hours in emergency unit he came home. Ahen he $oke up in the morning he
sa$ in his !ody in the old rash !ecome more larger2 !ecame red on the edge and he
felt itchy and like rash like !urning.
&istory of drugs
Drug he consumed are omepra;ole2 sucralfat2 !odrex(paracetamol and kofein)2
entrostop (attapulgite koloidal)2 mefenamat acid2 amoxicillin2 and another drug that
patient forgot
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&istory of past illness
he patient had this symptomps since the age of . year ago2 got dyspepsia2 got some
unkno$n fever2 got headache2 and he denied any history of allergy.
&istory of family disease
3one of her family had this kind of disease.
&istory of social ha!its
patient used to consumed drugs $ithout prescription of doctor.
:hysical Examination
Dermatological findings
at regio toracal2 ante !rachii2 inguinal2 perineal2 femoral2 and pedis.
:atch &iperpigmentation and Eritematous in the edge2 clear !order2 multiple rash2
nummular configuration2 and generalisata distri!ution
Differential diagnosis :
.. Fixed Drug Eruption
). Erythema #ultiforme
1. Erythema annulare centrifugum
6linical Diagnostic :
Fixed Drug Eruption
Supporting examination
.. :atch est
). Skin Biopsy
reatment
a. #edication
( Systemic :
6orticosteroid : #etyl :rednisolon )x/ mg
%ntihistamin : 4nterhistin )x. (ta!)
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( opical :
.. Salicylic acic 1B 7 4nerson oint (t$ice a day2 in rash)
!. 3on #edication
Stop the drugs that can induce fixed drug eruption
Do not consumed drug $ithout any prescription from doctor
Follow !p
1. *cto!er ..
nd
2 )-.)
Dermatologic Status
at regio toracal2 ante !rachii2 inguinal2 perineal2 femoral2 and pedis.
:atch &iperpigmentation and Eritematous in the edge2 clear !order2 multiple rash2
nummular configuration2 and generalisata distri!ution
a. #edication
( Systemic :
6orticosteroid : #etyl :rednisolon )x/ mg
%ntihistamin : 4nterhistin )x. (ta!)
( opical :
.. Salicylic acic 1B 7 4nerson oint (t$ice a day2 in rash)
2. *cto!er .C
th
2 )-.)
Dermatologic Status
at regio toracal2 ante !rachii2 inguinal2 perineal2 femoral2 and pedis.
:atch &iperpigmentation2 clear !order2 multiple rash2 nummular configuration2 and
generalisata distri!ution
(there are no itchy2 !urning and eritematous)
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DIS0USSION
he term fixed drug eruption descri!es the development of one or more
annular or oval erythematous patches as a result of systemic exposure to a drug= these
reactions normally resolve $ith hyperpigmentation and may recur at the same site
$ith reexposure to the drug. <epeated exposure to the offending drug may cause ne$
lesions to develop in addition to Dlighting upD the older hyperpigmented lesions.
3S%4Ds and anti!iotics are the most common drugs causing FDE among many other
etiologies.
Ta)le .&. Some common causes of fixed drug eruption
%6E inhi!itors
%llopurinol
%ntimicro!ials: co(trimoxa;ole2 sulfonamides2 tetracyclines2 cephalosporins2
penicillin2 clindamycin2 trimethoprim2 metronida;ole
Bar!iturates
Ben;odia;epines
6alcium channel !lockers: amlodipine2 diltia;em
6ar!ama;epine
Dextromethorphan
Diltia;em
Flucona;ole
'amotrigine
3S%4Ds2 including aspirin
:aclitaxel
:aracetamol
:henolphthalein
:roton pump inhi!itors: omepra;ole2 lansopra;ole
Euinine
Salicylates
er!inafine
%lthough the exact mechanism is unkno$n2 recent research suggests a cell(
mediated process that initiates !oth the active and 5uiescent lesions. he process may
involve an anti!ody(dependent2 cell(mediated cytotoxic response. 6D/
7
effector8memory cells play an important role in reactivation of lesions $ith re(
exposure to the offending drug.
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he initial eruption is often solitary and fre5uently located on the lip or
genitalia. <arely2 the eruption may !e intraoral. *ther common locations of the initial
lesion are the hip2 lo$er !ack8sacrum2 or proximal extremity. Aith the initial fixed
drug eruption attack2 a delay of up to ) $eeks may occur from the initial exposure to
the drug to the development of the skin lesion.

Skin lesions develop over a period of
hours !ut re5uire days to !ecome necrotic. 'esions may persist from days to $eeks
and then fade slo$ly to residual oval hyperpigmented patches.
Su!se5uent reexposure to the medication results in a reactivation of the site2
$ith inflammation occurring $ithin 1- minutes to .@ hours.

he reactivation of old
lesions also may !e associated $ith the development of ne$ lesions at other sites.
he most common clinical manifestation is the pigmenting fixed drug
eruption2 $hich usually manifests as round or oval2 sharply demarcated
erythematous8edematous pla5ues located on the lip2 hip2 sacrum2 or genitalia.hese
erythematous patches or pla5ues gradually fade $ith residual hyperpigmentation (see
images !elo$). he center of the patch may !lister or !ecome necrotic.
From anamnesis and clinical findings and literatures $e diagnose this patient
$ith fixed drug eruption. he drug that induced fixed drug eruption for this patient is
mefenamat acid that he got $hen he got stomachache three days !efore came to
<S"DF%. he drug that induced fixed drug eruption one year ago $as $e difficult to
configured !ecouse patient forgot the drug he consumed that made the first rash.
4n anamnesis patient told there is no ne$ rash. he rash ?ust !ecame larger2
eritematous2 itchy2 and !urning in the same rash. his is the characteristic of fixed
drug eruption. 4n erythema multiforme2 there is no recurrent lession in the same rash.
Erythme multiform is an acute2 self(limited2 and sometimes recurring skin condition
that is considered to !e a type 49 hypersensitivity reaction associated $ith certain
infections2 medications2 and other various triggers. he initial lesion is a dull(red2
purpuric macule or urticarial pla5ue that expands slightly to a maximum of ) cm over
)+(+/ hours. 4n the center2 a small papule2 vesicle2 or !ulla develops2 flattens2 and
then may clear. %n intermediate ring develops and !ecomes raised2 pale2 and
edematous. he periphery gradually changes to !ecome cyanotic or violaceous and
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forms a typical concentric2 GtargetH lesion. Some lesions consist of only ) concentric
rings.
4n erythema annulare centrifugum usually patients present $ith an
asymptomatic or pruritic eruption of varia!le duration. he eruption may !e
associated $ith an underlying disease (eg2 infection2 malignancy2 sarcoidosis2 other
systemic illness) and its accompanying characteristic symptoms (eg2 night s$eats2
fever2 and chills for tu!erculosis or &odgkin lymphoma). :ertinent physical findings
of erythema annulare centrifugum (E%6) are usually limited to the skin2 !ut a full
physical examination should !e conducted to assess for an underlying systemic
process. he eruption !egins as erythematous papules that spread peripherally $hile
clearing centrally. hese lesions enlarge at a rate of approximately )(, mm8d to
produce annular2 arcuate2 figurate2 circinate2 or polycyclic pla5ues2 as sho$n in the
images !elo$. he margin2 $hich is usually indurated2 varies in $idth from +(@ mm2
and2 often2 a trailing scale is present on the inner aspect of the advancing edge. he
diameter of the polycyclic lesions varies from a fe$ to several centimeters.
9esiculation may !e present. he lesions are pink to red $ith central clear areas.
*ccasionally2 residual hyperpigmentation of dull red2 !ro$n2 or violet is present. %
case of E%6 associated $ith hyper!iliru!inemia and ?aundice secondary to
choledocholithiasis has !een reported.
Blood studies are not useful for the diagnosis of fixed drug eruption (FDE)2
although eosinophilia is common $ith drug eruptions. <echallenging the patient to
the suspected offending drug is the only kno$n test to possi!ly discern the causative
agent. :atch testing of the suspected drug to lesional and non(lesional skin has !een
helpful in a fe$ instances. he exact protocol of patch testing has varied.
:atch testing and oral provocation have !een used to identify the suspected
agent and check for cross(sensitivities to medications.

% refractory period has !een
reported in fixed drug eruption= therefore2 a delay !efore and !et$een patch testing
and oral provocation is recommended. *ne study used an /($eek time $indo$ after
lesion resolution and !et$een tests2 $hich yielded positive results.

:atch testing must
!e performed on a previously involved site= other$ise2 a false(negative result is
9
likely.

Some locations may !e inappropriate for patch testing= thus2 clinical discretion
is advised. *nce patch testing is complete2 oral provocation should follo$2 $ith the
least likely culprits and the negative patch test agents first2 follo$ed !y more likely
causes. *ral provocation is thought to !e the only relia!le $ay to diagnose fixed drug
eruption.
:atch testing is particularly efficacious in identifying a putative cause of the
reaction $hen nonsteroidal anti(inflammatory agents are suspected2 !ut patch testing
is not helpful in discerning reactions to anti!iotics and allopurinol.
he main goal of treatment is to identify the causative agent and avoid it.
reatment for fixed drug eruptions (FDEs) other$ise is symptomatic. Systemic
antihistamines and topical corticosteroids may !e all that are re5uired. 4n cases in
$hich infection is suspected2 anti!iotics and proper $ound care are advised.
Desensiti;ation to medications has !een reported in the literature2 !ut this should !e
avoided unless no su!stitutes exist. he prognosis is very good (du!ia ad !onam)2 and
an uneventful recovery should !e expected.
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:icture .. First visite. :atch hiperpigmentation and eritematous in the edge
:icture .. First visite. :atch hyperpigmentation and eritematous in the edge
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:icture 1. Second visite. :atch hyperpigmentation
:icture +. Second visite. :atch hyperpigmentation
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