10-drug eruptions (final)

7/21/2019 10-Drug Eruptions (Final)

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Drug EruptionsDrug Eruptions

By

Dr. Aryo Sudrajad, SpKK


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Drug eruptions can mimic a wide range ofDrug eruptions can mimic a wide range ofdermatoses and should be considered in any patientdermatoses and should be considered in any patientwho is taking medications and who suddenlywho is taking medications and who suddenlydevelops a symmetric cutaneous eruption.develops a symmetric cutaneous eruption.

occur in approximately 2-5% of inpatients and inoccur in approximately 2-5% of inpatients and ingreater than % of outpatients.greater than % of outpatients.

!ost drug eruptions are mild" self-limited" and!ost drug eruptions are mild" self-limited" andusually resolve after the o#ending agent has beenusually resolve after the o#ending agent has beendiscontinued. $evere and potentially life-threateningdiscontinued. $evere and potentially life-threateningeruptions occur in approximately in hospitaleruptions occur in approximately in hospital

patients.patients. antimicrobial agents" nonsteroidal anti-in&ammatoryantimicrobial agents" nonsteroidal anti-in&ammatory

drugs '($)*Ds+" cytokines" chemotherapeuticdrugs '($)*Ds+" cytokines" chemotherapeuticagents" anticonvulsants" and psychotropic agentsagents" anticonvulsants" and psychotropic agents


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PathophysiologyPathophysiology

Immunologically mediated reactionsImmunologically mediated reactions ,ype * reactions,ype * reactions 'ie" immediate hypersensitivity reactions+ involve'ie" immediate hypersensitivity reactions+ involve

immunoglobulin E '*gE+mediated release of histamine and otherimmunoglobulin E '*gE+mediated release of histamine and othermediators from mast cells and basophils which result in urticaria"mediators from mast cells and basophils which result in urticaria"angioedema" and anaphylaxis.angioedema" and anaphylaxis.

,ype ** reactions,ype ** reactions'ie" cytotoxic hypersensitivity reactions+ involve'ie" cytotoxic hypersensitivity reactions+ involveimmunoglobulin or immunoglobulin ! antibodies bound to cellimmunoglobulin or immunoglobulin ! antibodies bound to cellsurface antigens" with subse/uent complement 0xation. " whichsurface antigens" with subse/uent complement 0xation. " whichresult in hemolysis and purpura .result in hemolysis and purpura .

,ype *** reactions,ype *** reactions'ie" immune-complex reactions+ involve'ie" immune-complex reactions+ involvecirculating antigen-antibody immune complexes that deposit incirculating antigen-antibody immune complexes that deposit inpostcapillary venules" with subse/uent complement 0xation. "postcapillary venules" with subse/uent complement 0xation. "which result in vasculitis" serum sickness" and urticaria.which result in vasculitis" serum sickness" and urticaria.

,ype *1 reactions,ype *1 reactions'ie" delayed hypersensitivity reactions" cell-'ie" delayed hypersensitivity reactions" cell-mediated immunity+ are mediated by , cells rather than bymediated immunity+ are mediated by , cells rather than byantibodies " which result in contact dermatitis" exanthematousantibodies " which result in contact dermatitis" exanthematousreactions" and photoallergic reactions.reactions" and photoallergic reactions.


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PhysicalPhysical

evaluate for certain clinical features that may indicate aevaluate for certain clinical features that may indicate asevere" potentially life-threatening drug reaction $uchsevere" potentially life-threatening drug reaction $uchfeatures include the following4features include the following4

!ucous membrane erosions!ucous membrane erosions listers 'listers herald a severe drug eruption.+listers 'listers herald a severe drug eruption.+ (ikolsky sign 'epidermis sloughs with lateral pressure6(ikolsky sign 'epidermis sloughs with lateral pressure6

indicates serious eruption that may constitute a medicalindicates serious eruption that may constitute a medicalemergency+emergency+

on&uent erythemaon&uent erythema

)ngioedema and tongue swelling)ngioedema and tongue swelling 7alpable purpura7alpable purpura $kin necrosis$kin necrosis 8ymphadenopathy8ymphadenopathy 3igh fever" dyspnea" or hypotension3igh fever" dyspnea" or hypotension


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MorphologyMorphologyexanthematous 'maculopapular+exanthematous 'maculopapular+

-commonest.-commonest.

-erythematous morbilliform-erythematous morbilliformmaculopapular eruption on trunk andmaculopapular eruption on trunk andextremeties that usually fade withextremeties that usually fade withdes/uamation.des/uamation.

--antimicrobials'penicillin"ampicillin+phenantimicrobials'penicillin"ampicillin+phenytoin"gold9.ytoin"gold9.


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:rticaria:rticaria

-2-2ndndmost common.most common.

-type or type ; hypersensetivity-type or type ; hypersensetivity

reaction.reaction.-0rm erythematous oedematous pla/ue-0rm erythematous oedematous pla/ue

with normal overlying epidermis lastingwith normal overlying epidermis lastingless than 2< hrs.less than 2< hrs.

-angioedema may be associated.-angioedema may be associated.

-ampicillin"salicylates"blood-ampicillin"salicylates"bloodproduct"vaccines"radiocontrast agents9product"vaccines"radiocontrast agents9


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:rticaria:rticaria

-,he most important step in the-,he most important step in the

treatment of drug induced urticaria istreatment of drug induced urticaria is

withdrawal of causative agent withwithdrawal of causative agent with

administration of systemicadministration of systemic

antihistamine.antihistamine.


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)ngioedema)ngioedema

-*s transient edema involving deep dermis-*s transient edema involving deep dermisand subcutaneous = submucosal tissuesand subcutaneous = submucosal tissueswhich can a#ect airway" mucosa" andwhich can a#ect airway" mucosa" andbowels.bowels.

-usually a#ect the eyelid "lips" ears-usually a#ect the eyelid "lips" ears"extremities = genetalia."extremities = genetalia.

-)ssociated with urticaria in 5% of cases.-)ssociated with urticaria in 5% of cases.

-,he ma>or drugs involved in angioedema are4-,he ma>or drugs involved in angioedema are4

)E inhibitors " 7enicillin " ($)*D$.)E inhibitors " 7enicillin " ($)*D$.


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)ngioedema)ngioedema

-may be complicated by life--may be complicated by life-

threatening anaphylaxis whichthreatening anaphylaxis which

present with hypotension =present with hypotension =

tachycardia .tachycardia .


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)ngioedema4 Drug ?eactions)ngioedema4 Drug ?eactions

!anagement!anagement

-@ithdrawal of drug-@ithdrawal of drug

-)ntihistamines" corticosteroids-)ntihistamines" corticosteroids

-Epinephrine may be needed if airway-Epinephrine may be needed if airwayis a#ected.is a#ected.

-?eport of AA7 used in refractory case-?eport of AA7 used in refractory case

'to above and *1*g" $)+'to above and *1*g" $)+


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D?E$$ $yndromeD?E$$ $yndrome-Drug ?ash with Eosinophilia and $ystemic $ymptoms-Drug ?ash with Eosinophilia and $ystemic $ymptoms

-Aormerly called 3ypersensitivity $yndrome '3$$+-Aormerly called 3ypersensitivity $yndrome '3$$+

-,ypically presents with rash and fever 'BC%+" classically-,ypically presents with rash and fever 'BC%+" classicallyerythematous papules and pustules associated with facialerythematous papules and pustules associated with facial

oedema .oedema .

-ther severe systemic manifestations such as hepatitis '5%+"-ther severe systemic manifestations such as hepatitis '5%+"arthralgias" lymphadenopathy 'C5%+" interstitial nephritis '%+"arthralgias" lymphadenopathy 'C5%+" interstitial nephritis '%+"or hematologic abnormalities ';%+.or hematologic abnormalities ';%+.

-3ematologic abnormalities include eosinophilia"-3ematologic abnormalities include eosinophilia"thrombocytopenia" neutropenia" and atypical lymphocytosis.thrombocytopenia" neutropenia" and atypical lymphocytosis.

-an a#ect any organ system 'lungs" ($" *" etc.+-an a#ect any organ system 'lungs" ($" *" etc.+

-$kin biopsy is non-speci0c.-$kin biopsy is non-speci0c.


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D?E$$ $yndromeD?E$$ $yndrome--Common causes:Common causes:

- aromatic anticonvulsants- aromatic anticonvulsants

'carbamaepine" phenytoin"'carbamaepine" phenytoin"

phenobarbital" etc.+ and sulfonamides.phenobarbital" etc.+ and sulfonamides.

Other drugs implicated:Other drugs implicated:

-lamotrigine-lamotrigine

-allopurinol-allopurinol-($)*Ds.-($)*Ds.

-!inocycline-!inocycline


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D?E$$ $yndromeD?E$$ $yndrome-:sually occurs 2-F weeks after initiation of the-:sually occurs 2-F weeks after initiation of the

medication" which is later than most drugmedication" which is later than most drug

eruptions.eruptions.

-,reatment is supportive.-,reatment is supportive.

-!edication should be stopped as soon as the-!edication should be stopped as soon as the

diagnosis is suspected.diagnosis is suspected.

-orticosteroids have been re/uired in some-orticosteroids have been re/uired in some

cases" but their use is controversial.cases" but their use is controversial.


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E!4 ,his includes a spectrum of diseases 'eg" E!E!4 ,his includes a spectrum of diseases 'eg" E!minor" E! ma>or+6 however" many authoritiesminor" E! ma>or+6 however" many authoritiescategorie $G$ and ,E( as E! ma>or andcategorie $G$ and ,E( as E! ma>or anddi#erentiate them by body surface involvementdi#erentiate them by body surface involvement

E! minor - this is a mild disease6 patients areE! minor - this is a mild disease6 patients arehealthy. *t is characteried by target lesionshealthy. *t is characteried by target lesionsdistributed predominantly on the extremities .distributed predominantly on the extremities .!ucous membrane involvement may occur but is!ucous membrane involvement may occur but isnot severe. 7atients with E! minor recover fully"not severe. 7atients with E! minor recover fully"

but relapses are common. !ost cases are due tobut relapses are common. !ost cases are due toinfection with herpes simplex virus" andinfection with herpes simplex virus" andtreatment and prophylaxis with acyclovir istreatment and prophylaxis with acyclovir ishelpful.helpful.


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$G$4 widespread skin involvement" large and atypical$G$4 widespread skin involvement" large and atypicaltargetoid lesions" signi0cant mucous membranetargetoid lesions" signi0cant mucous membraneinvolvement" constitutional symptoms" and sloughing ofinvolvement" constitutional symptoms" and sloughing of% of the skin. $G$ can be caused by drugs and infections% of the skin. $G$ can be caused by drugs and infections'especially those due to'especially those due to Mycoplasma pneumoniaeMycoplasma pneumoniae+.+.

$G$H,E( overlap4 Epidermal detachment involves -;% of$G$H,E( overlap4 Epidermal detachment involves -;% ofbody surface area.body surface area.

,E(4 ,his is a severe skin reaction that involves a prodrome,E(4 ,his is a severe skin reaction that involves a prodromeof painful skin 'not unlike sunburn+ /uickly followed byof painful skin 'not unlike sunburn+ /uickly followed byrapid" widespread" full-thickness skin sloughing. *t typicallyrapid" widespread" full-thickness skin sloughing. *t typicallya#ects ;% or more the total body surface area. $econdarya#ects ;% or more the total body surface area. $econdaryinfection and sepsis are ma>or concerns" and pneumoniainfection and sepsis are ma>or concerns" and pneumonia

may develop from aspiration of sloughed mucosa. !ostmay develop from aspiration of sloughed mucosa. !ostcases are due to drugs. ,he risk of ,E( in 3*1-positivecases are due to drugs. ,he risk of ,E( in 3*1-positivepatients is -fold higher than in the general population.patients is -fold higher than in the general population.


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!anagement!anagement


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Aixed drug eruptionsAixed drug eruptions4 8esions recur in the same area4 8esions recur in the same areawhen the o#ending drug is given . ircular"when the o#ending drug is given . ircular"violaceous" edematous pla/ues that resolve withviolaceous" edematous pla/ues that resolve withmacular hyperpigmentation is characteristic. 8esionsmacular hyperpigmentation is characteristic. 8esionsoccur ; minutes to B hours after drugoccur ; minutes to B hours after drug

administration. the hands" feet" and genitalia are theadministration. the hands" feet" and genitalia are themost common locationsmost common locations 8eukocytoclastic vasculitis8eukocytoclastic vasculitis4 ,his is the most common4 ,his is the most common

severe drug eruption seen in clinical practice . *t issevere drug eruption seen in clinical practice . *t ischaracteried by non blanching erythematouscharacteried by non blanching erythematousmacules /uickly followed by palpable purpura. Aever"macules /uickly followed by palpable purpura. Aever"

myalgias" arthritis" and abdominal pain may bemyalgias" arthritis" and abdominal pain may bepresent. *t typically appears C-2 days after thepresent. *t typically appears C-2 days after theonset of drug therapy" and a laboratory evaluation toonset of drug therapy" and a laboratory evaluation toexclude internal involvement is mandatory.exclude internal involvement is mandatory.


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Aixed Drug EruptionsAixed Drug Eruptions


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3enoch $chonlein 7urpura'8eukocytoclastic vasculitis+


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3enoch $chonlein 7urpura'8eukocytoclastic vasculitis+


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7hotosensitivity7hotosensitivity

-,wo types include phototoxic eruptions and photoallergic-,wo types include phototoxic eruptions and photoallergic

eruptions.eruptions.

-7hototoxic eruptions-7hototoxic eruptionsare due to absorption of :1 lightare due to absorption of :1 light

'usually :1)+ by the drug" which causes a release of'usually :1)+ by the drug" which causes a release ofenergy and damage to cells. 8ooks like a bad sunburn"energy and damage to cells. 8ooks like a bad sunburn"

which may blister.which may blister.

-7hotoallergic eruptions-7hotoallergic eruptionsare a lymphocyte-mediatedare a lymphocyte-mediated

reaction caused by exposure to :1)" which converts thereaction caused by exposure to :1)" which converts thedrug to an immunologically active compound thatdrug to an immunologically active compound that

activates lymphocytes" causing an ecematous reactionactivates lymphocytes" causing an ecematous reaction

in a photodistributionin a photodistribution..


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-:sually due to topical agents including-:sually due to topical agents including

fragrances and sunscreens.fragrances and sunscreens.

-oth types can be caused by-oth types can be caused byphenothiaines" chlorpromaine" sulfa" andphenothiaines" chlorpromaine" sulfa" and

($)*D$" although phototoxic reactions are($)*D$" although phototoxic reactions are

more common with these agentsmore common with these agents..


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Erythroderma4Erythroderma4,his is widespread in&ammation of,his is widespread in&ammation ofthe skin " and it may result from an underlying skinthe skin " and it may result from an underlying skincondition" drug eruption" internal malignancy" orcondition" drug eruption" internal malignancy" orimmunode0ciency syndrome. 8ymphadenopathy isimmunode0ciency syndrome. 8ymphadenopathy isoften noted" and hepatosplenomegaly" leukocytosis"often noted" and hepatosplenomegaly" leukocytosis"eosinophilia" and anemia may be present.eosinophilia" and anemia may be present.

EErythema nodosumrythema nodosum4 ,his is characteried by4 ,his is characteried bytender" red" subcutaneous nodules that typicallytender" red" subcutaneous nodules that typicallyappear on the anterior aspect of the legs. 8esionsappear on the anterior aspect of the legs. 8esionsdo not suppurate or become ulcerated . *t is ado not suppurate or become ulcerated . *t is areactive process often secondary to infection" but itreactive process often secondary to infection" but itmay be due to medications" especially oralmay be due to medications" especially oralcontraceptives and sulfonamidescontraceptives and sulfonamides


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Eritroderma


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Eritema nodusum


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Eritema nodusum


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)cute generalied)cute generalied

exanthematous pustulosisexanthematous pustulosis

')E7+')E7+-)cute-onset fever and generalied scarlatiniform-)cute-onset fever and generalied scarlatiniformerythema occur with many small" sterile" nonfollicularerythema occur with many small" sterile" nonfollicularpustules.pustules.

-,he clinical presentation is similar to pustular psoriasis"-,he clinical presentation is similar to pustular psoriasis"but )E7 has more marked hyperleukocytosis withbut )E7 has more marked hyperleukocytosis withneutrophilia and eosinophilia.neutrophilia and eosinophilia.

-!ost cases are caused by drugs 'primarily antibiotics+-!ost cases are caused by drugs 'primarily antibiotics+

often in the 0rst few days of administration. ) fewoften in the 0rst few days of administration. ) fewcases are caused by viral infections" mercurycases are caused by viral infections" mercuryexposure" or :1 radiation.exposure" or :1 radiation.

- )E7 resolves spontaneously and rapidly" with fever- )E7 resolves spontaneously and rapidly" with feverand pustules lasting C- days then des/uamationand pustules lasting C- days then des/uamationover a few days.over a few days.


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)cute generalied)cute generalied

exanthematous pustulosisexanthematous pustulosis

')E7+')E7+


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Anticoagulant Skin NecrosisAnticoagulant Skin Necrosis

--) rare I4 J") rare I4 J"some times life-threateningsome times life-threateningreaction by warfarin due to ischemic infarcts byreaction by warfarin due to ischemic infarcts byocclusive thrombi.occlusive thrombi.

-,ypically begin ;-5 days after therapy.-,ypically begin ;-5 days after therapy.

-linically erythematous" painful pla/ues-linically erythematous" painful pla/ues

hemorrhagic blisters and necrotic ulcers.hemorrhagic blisters and necrotic ulcers.-!ost common site 4 breast" thighs and buttocks.-!ost common site 4 breast" thighs and buttocks.

-,hose with hereditary protein de0ciency are at-,hose with hereditary protein de0ciency are athigh risk.high risk.

-3eparin-3eparin

induction of platelte aggregatesinduction of platelte aggregates

thrombosis K skin necrosis both at site ofthrombosis K skin necrosis both at site ofin>ection and at distant sites as well as internalin>ection and at distant sites as well as internalorgans.organs.

-,hrombocytopenia " but other coagulation pro0le-,hrombocytopenia " but other coagulation pro0le

are normal.are normal.


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Anticoagulant Skin NecrosisAnticoagulant Skin Necrosis


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La StudiesLa Studies 3istory and physical examination are often suLcient3istory and physical examination are often suLcient

for diagnosing mild asymptomatic eruptions.for diagnosing mild asymptomatic eruptions. $evere or persistent eruptions may re/uire further$evere or persistent eruptions may re/uire further

diagnostic testing.diagnostic testing. iopsy can be helpful in con0rming the diagnosis of a drugiopsy can be helpful in con0rming the diagnosis of a drug

eruption.eruption. count with di#erential may show leukopenia" count with di#erential may show leukopenia"

thrombocytopenia" and eosinophilia in patients with seriousthrombocytopenia" and eosinophilia in patients with seriousdrug eruptions.drug eruptions.

$erum chemistry studies may be useful. 8iver involvement$erum chemistry studies may be useful. 8iver involvement

leading to death can occur in persons with hypersensitivityleading to death can occur in persons with hypersensitivitysyndromes. $pecial attention should be paid to thesyndromes. $pecial attention should be paid to theelectrolyte balance and renal andHor hepatic function indiceselectrolyte balance and renal andHor hepatic function indicesin patients with severe reactions such as $G$" ,E(" orin patients with severe reactions such as $G$" ,E(" orvasculitisvasculitis


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,reatment4,reatment4

-!reatment o" drug eruptions is generally supporti#e-!reatment o" drug eruptions is generally supporti#eand depend on se#erity$and depend on se#erity$-!here are e issues to e considered in possile drug-!here are e issues to e considered in possile drug

eruptions:eruptions:

-,he assessment of the cutaneous eruption-,he assessment of the cutaneous eruption2-,he probability of a relation between the cutaneous eruption2-,he probability of a relation between the cutaneous eruptionand the drugand the drug;-*f a drug eruption is probable" clinical and laboratory factors;-*f a drug eruption is probable" clinical and laboratory factorsthat might alert the clinician to the potential seriousness ofthat might alert the clinician to the potential seriousness ofthe eruptionthe eruption


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-$ymptomatic treatment primarily is predicated on the-$ymptomatic treatment primarily is predicated on thediscontinuation of the o#ending agent" if possible.discontinuation of the o#ending agent" if possible.

-)ntihistamines help to relieve pruritus and the signs and-)ntihistamines help to relieve pruritus and the signs andsymptoms of urticaria and angioedema.symptoms of urticaria and angioedema.

-,opical and systemic corticosteroids can provide additional-,opical and systemic corticosteroids can provide additionalrelief. ,opical corticosteroids are most bene0cial forrelief. ,opical corticosteroids are most bene0cial forecematous disease" but provide little bene0t in urticaria.ecematous disease" but provide little bene0t in urticaria.

--8ife-threatening reactions such as angioedema and8ife-threatening reactions such as angioedema andanaphylaxisanaphylaxis re/uire prompt treatment with epinephrine"re/uire prompt treatment with epinephrine"antihistamines" andHor systemic corticosteroids.antihistamines" andHor systemic corticosteroids.

-- treatment of $tevens-Gohnson syndrome and toxictreatment of $tevens-Gohnson syndrome and toxicepidermal necrolysisepidermal necrolysis includes &uid replacement" painincludes &uid replacement" paincontrol" and often antibiotics to prevent secondary infection.control" and often antibiotics to prevent secondary infection.

,he role of systemic corticosteroids" intravenous,he role of systemic corticosteroids" intravenousimmunoglobulin" and plasmapheresis in these conditions isimmunoglobulin" and plasmapheresis in these conditions iscontroversial.controversial.


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ont..ont..

-warfarin necrosis-warfarin necrosis treated by itstreated by its

discontinuation parenteral vitamin N"discontinuation parenteral vitamin N"

and monoclonal protein concentrateand monoclonal protein concentrate

..

-Desensitiation-Desensitiationis a reasonableis a reasonable

approach for patients with an allergyapproach for patients with an allergyto penicillins" cephalosporins" orto penicillins" cephalosporins" or

sulfonamides.sulfonamides.


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Thank youThank you

10-drug eruptions (final)

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