DOI: 10.14260/jemds/2015/1597

CASE REPORT

HAILEY- HAILEY DISEASE: 2 CASE REPORTS

Nilofar Diwan1, Nidhi Jivani2, Pragya Nair3

HOWTOCITETHISARTICLE:

NilofarDiwan, NidhiJivani, Pragya Nair.“Hailey- Hailey Disease -2 Case Reports”.JournalofEvolutionofMedicalandDentalSciences2015;Vol.4,Issue63,August 06;Page:11083-11089,DOI:10.14260/jemds/2015/1597

ABSTRACT:Hailey-HaileydiseaseisanautosomaldominantacantholyticdisorderrelativelyuncommoninIndia.Itischaracterizedbypainful,pruritic,foulsmellingvesiclesandbullouslesionswitherosionsinintertriginousareassuchastheneck,axillae,inframammaryareasandgroin.ThedefectinATPC2geneleadstocalciumchanneldysfunctionwhichresultsindefectinepidermis. Fungal infection, intertrigo, psoriasis,extramammary Paget's disease, acanthosisnigricans, pemphigus vegetans and Darier's disease are some of the dermatosis from which it needs to be differentiated.Histopathology has a key role in diagnosis of Hailey-Hailey diseasewithcharacteristic‘dilapidatedbrickwall'appearance. Hailey-Hailey disease can be easily misdiagnosed by general physicians due to lack of knowledge of this uncommon disease as it resembles dermatosis involving intertriginous areas. Due to its relapsing and remitting course there is a need to have effective treatment options. Two cases of Hailey-Hailey disease are presented here.

KEYWORDS:Hailey-Haileydisease,Dilapidatedbrickwall,Intertriginousareas.

KEYMESSAGES:Physiciansmustkeepthisdiseaseasadifferentialdiagnosisinresistantintertriginousdermatosisespeciallywhenthereisapositivefamilyhistory.

INTRODUCTION:Hailey-Haileydisease(HHD)isarareautosomaldominantacantholyticdisorderwhichrecurswithremittingandrelapsingepisodes.[1]ThedefectinATPC2geneleadstocalciumchanneldysfunctionwhichresultsindefectinepidermis.Itischaracterizedbypainful,pruritic,foulsmellingvesiclesandbullouslesionswitherosionsinintertriginousareas.Lesionsgetaggravatedbyfriction,ultravioletradiation,warmth,moistureandsuperficialbacterial,viralorfungalinfections.[2]HistopathologyhasakeyroleindiagnosisofHailey-Haileydisease.Topicalmodalitiesoftreatmentareantibiotics,steroids,tacalcitolanothervitaminD3derivativeandtacrolimuswhilesystemictreatmentincludesantibiotics,steroids,cyclosporine,dapsone,methotrexateandthalidomide.TwocasesofHailey-Haileydiseaseispresentedherewithcharacteristichistopathologicalfeaturestohighlighttheimportanceofearlydiagnosis.

CASEHISTORY: Case 1: A41year’soldmarriedIndianfemalepresentedwithlesionsunderbreastsandingroinssince3yearsassociatedwithitching.H/ofluidfilledlesionspriortopresentinglesionswerepresent.Manytypesoftreatmentintheformoftopicalandsystemicdrugsweretakenwithnoimprovement.Similartypeofcomplaintsinfatherwaspresent.H/osummeraggravationwaspresent.Onexaminationmultiplediscretehyperpigmentedpapulesoverbilateralinframammaryregionsandgroins[Figure-1ab].Nomucosalinvolvementornailchangespresent.

Fig.1a: Multiplediscretehyperpigmentedpapulesoverbilateralinframammaryregion.


Fig.1b:Multiplediscretehyperpigmentedpapulesoverbilateralgroins.

Biopsytakenfromthelesionovergroinshowedthinnedoutepidermiswithpresenceofsuprabasalvesiclescontainingkeratinocyteandinflammatoryinfiltrateofneutrophilsandlymphocytes.Thevilli(Elongatedpapilli)arelinedbysinglelayerbasalcells,protrudingupgradeintovesicles.Anarrowlayerofepidermalcellsproliferatingdownwardintodermisisseen.Upperdermisshowsmononuclearcellinflammatoryinfiltrate.ChangesweresuggestiveofHailey-Haileydisease.

Immunofluorescencetest,duetounavailability,wasnotdoneinoursetup.Patientwastreatedwithoraldoxycyclineandtopicalclobetasolpropionate0.05%creamfor15days. Lesionsresolved,patientwasthengivenbetamethasonevalerateandtacrolimus0.1%ointmenttobecontinued.

Case 2: Afemale,65yearspresentedwithmultipleeruptionsoverflexuralareasofthebody,sincealmost35to40yearswithitchingandburningsensation.H/orecurrentrelapsesinsummer,withwinterremissionswaspresent.Nospecificfamilyhistorywasnoted.O/Emultiplepapularlesionsformingplaqueswithmacerationandmalodorousodourinaxilla,groins,submammaryregions,neckandflexorsofelbowandkneejoints[Figure-2ab].

Fig. 2a: Multiple papular lesions forming plaques with maceration in groins.

Fig. 2b:Multiplepapularlesionsformingplaqueswithmacerationinaxilla.

Atfewplaceslesionswereverrucous.Patientwasobesewithnootherco-morbidcondition.Noorogenitalinvolvementornailchanges.Histopathologicalexaminationshowedsuprabasalseparationproducinglacunae(Bullae).Villicharacterizedbyelongatedpapillaelinedbysinglelayerofbasalcellsseenprotrudingupwardinthebulla.Manycellsofthedetachedstratummalphighiishowslossofintercellularbridgesleadingtoacantholysis.Despiteacantholysisthecellsinthelacuaehavefewintactintercellularbridgesgivingadilapidatedbrickwallappearance.Theacantholyticcellshavehomogenisedcytoplasm,hyperkeratosisandhypogranulosis.Dermisshowsmildchronicinflammation.

(Fig-3a-10X,3b-40x)ChangesweresuggestiveofHailey-Haileydisease.Patientwasgivenoraldapsone(100mg)daily,oralantibiotics,antifungaltopreventsecondaryfungalinfectionandtopicalsteroids.Afteramonthoffollowupwhenlesionsresolved,topicalsteroidwasreplacedbytacrolimus(0.03%).

Fig.3a:Suprabasalseparationproducinglacunae(bullae).Lossofintercellularbridgesleadingtoacantholysiswithfewintactintercellularbridgesgivingadeliapidatedbrickwallappearance.10X (HEstain)

Fig. 3b:Lossofintercellularbridgesleadingtoacantholysiswithfewintactintercellularbridgesgivingadelapidatedbrickwallappearance. 40X(H&Estain)

DISCUSSION:Hailey-HaileydiseasealsoknownasfamilialbenignchronicpemphigusisarelativelyuncommondiseaseinIndia.Familyhistoryisobtainedinabouttwo-thirdsofthepatients.Incidenceis1in50,000andappearsinthethirddecadeoflife.[3,4]Itisrarelyfoundgenodermatosishavinganautosomaldominantmodeofinheritance.[5]Itwasfirstdescribedin1939bydermatologistbrothersHaileyandHailey.[6]HHDoccursduetodefectinCa2+/Mn2+-ATPaseprotein1(hSPCA1)duetomutationinATP2C.[7]resultinginlackofCa2+signaling,irregularsortingandglycosylationofdesmosomalproteinsinkeratinocyteswhichleadstoepidermaldefects.Lesionscommonlyoccursoverintertriginousareassuchastheneck,axillae,inframammaryareasandgroin.Generalizedordisseminatedformsareobservedbutareextremelyrare,usuallyinducedbysuperficialbacterialskininfection.[8]orevenrarelydrugs.[9]

Lesionsareinitiallyflaccidvesiclesandpapuleswitherythematousbasewhichmayturnintomaceratedorcrustederosions,havetendencytospreadperipherallyandturnintochronic,moist,painful,malodorousvegetationswithpainfulfissures.Theyleavebehindpostinflammatoryhyperpigmentationwithoutscarring.Althoughmucosalinvolvementisnotcommon,oral,esophageal,vulvar.[10]andconjunctivalinvolvementcanoccur.[11]Longitudinalwhitelinesonthefingernailsandfinepalmerpitsareobserved.Atypicalvariantsarehyperkeratotic,verrucous,lichenified,papular,papulovesicularandvesiculopustularforms.Aggravatingfactorsaretrauma,heat,sweating,UVlight,andinfectionscausedbyscabies,bacteria,herpesvirusandyeasts.

Ithastendencyofremissionandexacerbations.RareconsequenceofHHDissquamous-cellcarcinoma.[12]ThedifferentialdiagnosesofHailey-Haileydiseaseincludedfungalinfection,intertrigo,psoriasis,extramammaryPaget'sdisease,acanthosisnigricans,pemphigusvegetansandDarier'sdisease.Histopathologyofearlylesionsshowslacunaeformedbysuprabasilarcleftingwithacantholyticcellseithersinglyorinclumpsliningtheclefts.Thelacunaeprogresstobroad,acantholyticvesiclesandbullae.Intercellularoedemaleadstopartialacantholysisandgivesrisetoareaswithcharacteristicdilapidatedbrickwall'appearance.Acantholytic,dyskeratoticcellsarefoundwithintheepidermis.[13]

Bothofourpatientswerefemale.Suchfemalepredominancehasalsobeenobservedbyotherstudiesalso.[14]Familyhistorywaspositiveincase-1butseverityofdiseasewasmoreincase-2withearlyageofonset.Itshowedthatgeneticinheritanceisnotassociatedwithseverity.Case2presentedwithverrucouslesionsatplaceswhichisanunusualmorphology.

TopicaltacrolimusisfoundtobeeffectiveinHHD.[15]TheinhibitoryeffectofcalcitriolonTcellsandoninflammatorymediatorshasaroleandfoundtobetopicallyeffective.PatientswithaxillaryHailey-HaileydiseasearetreatedwithbotulinumtoxintypeAshowedgoodresponse.[16]Othertopicalmodalitiesaretopicalantibiotics,topicalsteroids,tacalcitolanothervitaminD3derivativeandcyclosporine.Systemictreatmentincludesantibiotics,steroids,cyclosporine,dapsone,methotrexateandthalidomide.Insurgicalmodalitiesdermabrasionorlaserabrasionareeffectivewithlongpostoperativecare.Wideexcisionandgraftingcanalsobeused.

Thefrequencyofexacerbationsmaybedecreasedbywearinglightweightclothingandavoidingactivitiesthatresultinsweatingorskinfriction.DuetoitsrelapsingandremittingcoursethereisaneedtohaveeffectivetreatmentoptionsinfuturetoimprovequalityoflifeofthepatientwithHailey-Haileydisease.Moreover,Hailey-Haileydiseaseisunderestimated.Physiciansmustkeepthisdiseaseasadifferentialdiagnosisinresistantintertriginousdermatosisespeciallywhenthereisapositivefamilyhistory.

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J of Evolution of Med and Dent Sci/ eISSN- 2278-4802, pISSN- 2278-4748/ Vol. 4/ Issue 63/ Aug 06, 2015 Page 1