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CAse report

Acute generalized exanthematous pustulosis associated with spider bite*

Laura de Mattos Milman1 GianaPaulaMüller1

PauloRicardoMartinsSouza1,2 AlineBarcellosGrill1

Deise Louise Bohn Rhoden1 CarlosAugustoMello-da-Silva2

GersonVettorato1

s

Received on 16.09.2014.ApprovedbytheAdvisoryBoardandacceptedforpublicationon05.01.2015.* WorkperformedatDermatologyServiceofHospitalComplexofSantaCasadeMisericórdiadePortoAlegre. Financial Support: None. ConflictofInterest:None.

1 ComplexoHospitalardaSantaCasadeMisericórdiadePortoAlegre–PortoAlegre(RS),Brazil.2 PontifíciaUniversidadeCatólicadoRioGrandedoSul(PUC-RS)–PortoAlegre(RS),Brazil.

©2016byAnaisBrasileirosdeDermatologia

DOI: http://dx.doi.org/10.1590/abd1806-4841.20164045

Abstract:Acutegeneralizedexanthematouspustulosis(AGEP)isanacutefebrilerash,usuallyinducedbydrugs,whichre-centlyhasbeenlinkedtospiderbite.Wereportacaseofamalepatient,48yearsold,withanerythematousrashaccompaniedbyfeverandsmallnon-follicularpustules.Hereportedpreviouspaininthebuttockwiththeonsetofanecroticplaque.ThelesionwascompatiblewithspiderbiteofthegenusLoxosceles.AccordingtotheEuroSCARgroupinstrument,thepatientscored+10indicatingdefinitediagnosisofAGEP.AsthepatienthadacompatiblelesionandhadnoothertriggersofAGEP,inanLoxoscelesendemicarea,theAGEPwouldbeassociatedwithspiderbite,asdescribedinotherpublications.Keywords:Acutegeneralizedexanthematouspustulosis;Arachnidvectors;Spidervenoms

INTRODUCTIONAcutegeneralizedexanthematouspustulosis(AGEP)isan

acute febrilerash,characterizedbynumeroussmallnon-follicularand sterile pustules on erythematous base.1-3

Over90%ofthecasesareinducedbydrugs.Occasionally,AGEPiscausedbyinfectionsandexposuretomercuryandrarelyitmaybetheconsequenceofaspiderbite,asinthecasereported.4,5

CASE REPORT

Male patient, 48 years old, from themetropolitan area ofPortoAlegre(RS),soughtmedicalattentionduetodisseminateder-ythematous lesions and fever for the past four days.

Hereportedaspiderbite in therightbuttockregion.Thespider was not found and the patient reported pain in the area while sleeping in his beach house. In 48 hours a violaceous spot appeared on the site.

On the third day he presented an erythematous eruption accompaniedbyseveraldisseminatedsmallnon-follicularpustules,feverover38ºCandpruritus(Figure1).

Thegluteallesionevolved,infourdays,withtheonsetofanecroticplaque,dryandwelldelimited.Theedemaanderythemaadjacenttothelesionincreased(Figure2).Thepatientdenieduseofpainkillersorotherdrugs.Sinceinfectionwassuspected,cephalexinwas prescribed.

He presented leukocytosis (27,260 leukocytes, with pre-dominanceofneutrophils)andincreasedtransaminases(ALT268;AST56),GGT(366)andbilirubin(TB2.5, IB1.7,DB0.8).AsviralserologywasnegativeandthediagnosiswasAGEP,treatmentwasbegunwithprednisone(80mg/day).

Theclinicalpictureprogressedwithdiffusedesquamationandperiorbitaledema(Figure3),aswellasofhandsandfeet.Onpalmsandplants,therewastheonsetofblisterswithlaterdesqua-

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mation. There was clinical and laboratorial improvement, whichprompted gradual decrease of prednisone until its suspension. The buttocklesionevolvedwithdetachmentofthenecroticplaqueandlocal ulcer.

Histopathology showed pustular dermatitis with neutro-philic vasculitis, focally purpuric, discrete edema in the dermalpapillaeandabsenceofleukocytoclasia(Figures4and5).

DISCUSSIONThe LoxoscelesgenuscanbefoundalloverBrazil,mainlyin

thestateofParana.Theyaresmallspiders,non-agressive,ofnoctur-nal habits that bite when compressed against the human body.2,6 The diagnosisofloxoscelismisrarelybasedontheidentificationofthespider. Unless the patient captures the spider and brings it over for identification,thediagnosisispresumptive.InBrazil,10,000casesof Loxosceles bites are reported annually.6,7

The bite is painless and causes local edema and erythe-ma.Theremaybeonsetofecchymoticareasmixedwithpaleness,blistersornecrosis.Thelesionispronetoprogressgravitationally,due to the action of hyaluronidase present in the venom.7

Systemic loxoscelism is rare and commonly associated with discreetsymptoms,suchasmalaiseandmyalgia.Theremayalsobemildhemolysisor,rarely,inthemoresevereforms,hemolyticane-mia and acute renal lesion caused by severe hemolysis.5,6

FIgure 1: Erythema and pustules on the abdomen

FIgure 2:Necroticplaqueontherightbuttock,surroundedbyery-thema and non-follicular pustules

FIgure 3:Desquamationofback

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In spite of the uniformity of the initial lesion being not char-acteristic,itsevolutionwithdetachmentofthenecroticplaqueandformation of ulcer is compatible with Loxoscelesspiderbite,especial-ly because it is an endemic area.6,7

Exanthema following spider bite is uncommon. It occurs in 72hoursandischaracterizedasmorbiliformorscarlatiniformrash.8 Palpablepurple,pustularexanthemaandevenamixofthesetwofindingshavebeendescribed.8

Recently,Loxosceles bitehasbeenlinkedtoAGEP.1-5 The trig-geringofAGEPafterspiderbite israre,anditsmechanismisnotwell understood.

InthepathogenesisofAGEP,IL-8(interleukin-8)andGM-CSF (Granulocyte-macrophage colony-stimulating factor) are im-plicated in polymorphonuclear recruiting for the epidermis. IL-8 isproducedbykeratinocytesandT-cells.Thevenomofthisspider

526 Milman LM, Müller GP, Souza PRM, Grill AB, Rhoden DLB, Mello-da-Silva CA, Vettorato G

containssphingomyelinase,whichstimulatestheliberationofcyto-kines,includingagreatamountofIL-8andGM-CSF,whichwouldtriggerAGEP.2

TheclinicalpictureofAGEPischaracterizedbytheabruptonsetoferythemaandedemainintertriginousareasorintheface,with craniocaudal dissemination and the arising of hundreds of small non-follicular and sterile pustules. It may be preceded or ac-companied by high fever and pruritus. Pustules have an average durationofninedays,evolvingwithdesquamation.Multiformer-ythema-type lesions, edemaof face andhands,purpura,vesicles,blistersandinvolvementofmucosaeareadditionalfindings,someof them found in the case described.1,9,10

Histology may reveal spongiosis and subcorneal or in-traepidermalpustules.Thereisedemainthedermalpapillae,whichmayvaryinintensity,neutrophilsandeosinophilsperivascularin-filtrate and, sometimes, leukocytoclastic vasculitis. Theremay befocalnecrosisofkeratinocytes.1,9,10

Inthecomplementaryevaluation,theremaybeleukocyto-sis,withpredominanceofneutrophils andeosinophils, transitoryloss of renal function and increased aminotransferases, findingsthatwouldjustifysomelaboratorialchangesfoundinthecasede-scribed.1

AccordingtoEuroSCARgroup’sscoringsystem(European project dedicated to severe cutaneous adverse reactions),usedintheiden-tificationofAGEPcases,thepatientscored+10,indicatingdefinitediagnosisofAGEP(Table1).9

AsthepatienthadalesioncompatiblewithLoxosceles spi-derbite,withoutpresentingotherknownAGEPtriggersinaregionwherethisspiderisendemic,theconclusionwasthatAGEPwouldbeassociatedwithspiderbite,asdescribedinotherpublications.2,4,5,8

The increase of bilirubins may be attributed to mild hemo-lysis,frequentlyfoundinloxoscelism.6

Thereisareportthathistologicallycharacterizestheexan-themaafterspiderbitenotlinkedtoAGEPasnecrotizingvasculitis,similartotheoneobservedinthebitearea,butwithoutepidermal

FIgure 4: Intraepidermal pustule and mild spongiosis. Discreet ede-ma of dermal papillae and inflammatory perivascular in-filtrate in the derm (hematox-ilin-eosin, 40x to the left and100xtotheright)

FIgure 5: Vessel in thederm with inflammato-ry perivascu-lar infiltrate,p r e d o m i -nantly neu-t r o p h i l i c ,with some lymphocytes ( h e m a t o x -i l i n - e o s i n ,100x)

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How to cite this article:MilmanLM,MüllerGP,SouzaPRM,GrillAB,RhodenDLB,Mello-da-SilvaCA,VettoratoG.Acutegeneralizedexanthematouspustulosisassociatedwithspiderbite.AnBrasDermatol.2016;91(4):524-7.

REFERENCES1. Razera F, Olm GS, Bonamigo RR. Neutrophilic dermatoses: part II. An Bras

Dermatol. 2011;86:195-209.2. Makris M, Spanoudaki N, Giannoula F, Chliva C, Antoniadou A, Kalogeromitros D.

Acute generalized exanthematous pustulosis (AGEP) triggered by a spider bite. Allergol Int. 2009;58:301-3.

3. Leclair MA, Maynard B, St-Pierre C. Acute generalized exanthematous pustulosis with severe organ dysfunction. CMAJ. 2009;181:393-6.

4. Davidovici BB, Pavel D, Cagnano E, Rozenman D, Halevy S; EuroSCAR; et al. Acute generalized exanthematous pustulosis following a spider bite: report of 3 cases. J Am Acad Dermatol. 2006;55:525-9.

5. Lane L, McCoppin HH, Dyer J. Acute generalized exanthematous pustulosis and Coombs-positive hemolytic anemia in a child following Loxosceles reclusa envenomation Pediatr Dermatol. 2011;28:685-8.

6. Malaque CM, Santoro ML, Cardoso JL, Conde MR, Novaes CT, Risk JY, et al. Clinical Picture and laboratorial evaluation in human loxoscelism. Toxicon. 2011;58:664-71.

7. Cardoso JLC, França FOS, Wen, FH, Malaque CMS, Haddad V. Animais peçonhentos no Brasil. 2 ed. São Paulo: Editora Sarvier; 2009. p. 182-3.

8. Robb CW, Hayes BB, Boyd AS. Generalized vasculitic exanthema following Loxosceles recluse envenomation. J Cutan Pathol. 2007;34:513-4.

Mailing address:Laura de Mattos MilmanRua Professor Annes Dias, 295Centro Histórico90020-090 - Porto Alegre - RSBrazilE-mail: lmmilman@terra.com.br

9. Fernando SL. Acute generalised exanthematous pustulosis. Australas J Dermatol. 2012;53:87-92.

10. Sidoroff A, Halevy S, Bavinck JN, Vaillant L, Roujeau JC. Acute generalized exanthematous pustulosis (AGEP) - A clinical reaction pattern. J Cutan Pathol. 2001;28:113-9.

necrosis.8 These alterationswerenot found in ourpatient,whoseanatomopathologicalresultswerecompatiblewithAGEP.

TheprognosisofAGEPisgoodwhentriggeredbymedica-tion.1Duetofewreportsofcaseslinkedtospiderbite,itisnotclearif there is alteration of the prognostic.

Otherreportshadtheiretiologicaldiagnosismadedifficultbythesimultaneousandearlyuseofantibiotics.Inthisreport,asthe patient started their use when he already presented lesions with

Table 1: AGEPscoreofpatientdeterminedbytheuseofcriteriafromEuroSCARstudygroup

Criteria Description ScoreMorphology Pustules Typical,non-follicularandsterile +2 Erythema Typical,diffuse +2 Distribution Compatible,trunkandmembers +1 Desquamationpost-pustulation Yes +1 Additionalfindings No Course Mucosal involvement No 0 Acutestart(<10days) Yes 0 Resolution<15days Yes 0 Fever (≥ 38 ºC) Yes +1 Polymorphonuclear(≥7.000) Yes +1 Histopathology Biopsyofskin Intraepidermalpustulewithdermaledema, +2 perivascularneutrophilicinfiltrateTOTAL SCORE +10

Interpretationaccordingtofinalscore:≤0:absenceofAGEP;1-4:possibleAGEP;5-7:probableAGEP;8-12:AGEPascertaindiagnosis

AGEPcharacteristics,theantibioticdidnotseemrelevantintrigger-ing the pathology.

Treatment is symptomatic.1Ashortcourseofsystemiccor-ticoidmaybeconsideredinseverecases,butusuallyitisnotneces-sary,duetotheself-limitingcharacteroflesions.3,10

This report ofAGEP associated with spider bite aims topointouttothisraretriggeringfactorinBrazil,whereincidentsbyLoxoscelesbitesarefrequent.q