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Morbus Hailey-Hailey, Mint Kontakt Szenzibilizáció Köbner Tünete

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Morbus Hailey-Hailey, Mint Kontakt Szenzibilizáció Köbner Tünete Pónyai Katinka 4/26/10 18:00 Page 1 BÔRGYÓGYÁSZATI ÉS VENEROLÓGIAI SZEMLE 86. ÉVF. 2. 46–50. Semmelweis Egyetem Budapest, Bôr-Nemikórtani és Bôronkológiai Klinika (igazgató: Kárpáti Sarolta dr., egyetemi tanár)*, Állami Egészségügyi Központ, Bôrgyógyászati Osztály (osztályvezetô: Vajda Adrienne dr.)**, Magyar Psoriasis Alapítvány (elnök: Mikes György)*** Morbus Hailey-Hailey, mint kontakt szenzibilizáció Köbner tünete Hailey-Hailey as Köbner symptom of contact sensibilisation PÓNYAI KATINKA DR.*, BALÓ-BANGA J. MÁTYÁS DR.**, PÓNYAI GYÖRGYI DR.*, HÁRSING JUDIT DR.*, SILLÓ PÁLMA DR.*, HOLLÓ PÉTER DR.*, BERECZ MARGIT DR.***, MARSCHALKÓ MÁRTA DR.*, TEMESVÁRI ERZSÉBET DR.* ÖSSZEFOGLALÁS SUMMARY A Hailey-Hailey betegség (familiaris benignus pemphi- Morbus Hailey-Hailey (chronic benign familial gus) ritka, változó expresszivitású betegség, amelynek pemphigus) is a rare genodermatosis with different hátterében az ATP2C1 gén haploinsufficienciája áll. A fo- expressivity, caused by the haploinsufficiency of ATP2C1. lyamat a traumának kitett területeken jelentkezik, de köb- It develops typically at sites of trauma but can be nerezhetô kontakt szenzibilizáció útján is. A betegség köbnerised by contact sensibility also. Therapies of the hosszú távú tünetmentesítése nem megoldott. condition are only ablative and have many side effects A szerzôk három beteg esetét mutatják be, ahol az egyik with high recurrence rates. leggyakoribb kontaktallergén, a nikkel mellett HgCl2 és We present the case of three patient with Hailey-Hailey perubalzsam érzékenység, ill. cutan infectiok is szerepel- disease where the provoking factors were contact nek a kiváltó tényezôk között. Tartós tünetmentességet sensibilisation (with agents as: nickel, HgCl2 and balsam mindhárom betegnél szigorú nikkel diétával tudtunk elérni. of Peru) along with cutaneous infections. Nickel and A táplálkozás során elfogyasztott nikkel egyrészt az iz- balsam free diet resulted complete recovery and no zadással és vizelettel eliminálódik, másrészt maga az izza- relapses for a long term period. dás korróziós hatása szabad nikkel ionok felszabadulásá- Based on our patient’s long term symptom free period hoz vezet, további percutan szenzibilizációhoz vezetve. we can assume that in case of proved nickel and balsam Betegeink tartós tünetmentessége alapján a nikkel diéta – of Peru sensibilisation, diet is a useful adjuvant treatment igazolt szenzibilizációnál – hasznos kiegészítô terápiának for Hailey-Hailey disease, replacing traditional local or bizonyult, mely a számos mellékhatással járó lokális vagy parenteral treatment with numerous side effects. parenteralis kezeléseket kiválthatja. Kulcsszavak: Key words: Hailey-Hailey - anogenital dermatitis - Hailey-Hailey - anogenital dermatitis - kontakt szenzibilizáció contact sensibilisation A familiaris benignus krónikus pemphigust (Morbus Hai- desmosomális komponensekben. Mindez a keratinocyta ley-Hailey – MHH) elsônek 1939-ben a Hailey testvérek terminális differenciációjához, abnormális adhéziós pro- (William Howard és Hugh Edward) írták le. teinek produkciójához, csökkent sejt-sejt adhézióhoz és A betegség hátterében az ATP2C1 gén haploinsufficien- acantholysishez vezet. A pumpa gyakorlatilag az összes ciája áll. Az ún. MHH régió a 3q21-24 kromoszóma terü- szövetben megtalálható, de megfelelô kompenzáló me- leten helyezkedik el, mutációja a Golgi asszociált kal- chanizmus nélkül egyedül a keratinocytában van jelen (7, cium-magnézium pumpa, a Ca2+/Mg2+ ATP-áz (hSPCA1) 9, 13, 15). diszfunkcióját okozza. A következményes intracellularis Az irodalom szerint a kor, recidíva arány, súlyosság kalcium szint csökkenés, posttranslációs modifikációkat vagy progresszió tekintetében nincs összefüggés a geneti- okoz a Golgiban a membrán asszociált és az epidermalis kai háttér, az egyes mutációk típusa és a klinikum között. sejt adhézióban szerepet játszó proteinekben, így pl. a Mindez azt sugallja, hogy a genetikai modifikációk vala- 46 Pónyai Katinka 4/26/10 18:00 Page 2 mint a környezeti faktorok nagy szerepet játszanak a be- botulinum toxin A. Photodynamiás terápia mellett nem tegség kialakulásában (15). észleltek megfelelô javulást, és a folyamat fájdalmassága Külsô tényezôk, pl. UV fény, közvetlenül csökkentik az miatt a compliance sem megfelelô. Sebészi beavatkozás- hSPCA1 expressziót: IL-1, 6, 8, TNF alfa közvetítésével ként dermabrasio, CO2- vagy Erbium:YAG lézeres keze- az ATP2CA1 mRNS downregulációjával. A gén haploin- lés, skingrafting alkalmazásáról közöltek kedvezô tapasz- sufficienciája miatt ennek köszönhetô, hogy egyes külsô talatokat (7, 10, 12, 14). hatások, pl. dörzsölés, izzadás, vagy fény hatására jelent- A betegség kezelése, hosszú távú tünetmentesítése je- keznek elôször a tünetek, viszonylag késôn, a 3. 4. évti- lenleg nem megoldott: hónapokig, vagy akár évekig tartó zedben (9, 15). remisszió után hirtelen, rohamokban jelentkezô exacerba- Elsô tünetként a predilekciós területeken (nyak, axilla, tio alakul ki (15). A Köbner jelenség miatt, nem specifi- inguina, perineum) viszketés kíséretében laza falú bul- kus inger hatására (cutan infectio, trauma, UV expozíció, lák, vagy vesiculák alakulnak ki a reakciómentes bôrön. izzadás, dörzsölés) specifikus bôrjelenség, MHH alakul ki A gyors erodálódás miatt macerált, vagy pörkkel fedett (2, 7, 8, 18, 19). A fentiek mellett – ugyancsak Köbner ha- erosiok alakulnak ki. A vaskos pörkképzôdés impetigo tásra – a kontakt szenzibilizáció szintén kiválthatja a tüne- klinikai képére emlékeztethet. A léziók nedvedzenek, teket, amely MHH-ban a csökkent barrier funkciónak kö- odorosusak, fájdalmas fissurákkal tarkítottak. Esetenként szönhetôen a kezelés során alkalmazott lokális szerekre is aktív gyulladásos udvarral körülvett, száraz, varral fedett kialakul, terápia rezisztenciához, vagy progresszióhoz ve- circiner, bizarr alakú plakkok dominálják a klinikai ké- zetve (1, 2, 7, 8, 9, 18, 19). pet (7, 8, 9). A kontakt szenzibilizáció ismert köbnerezô szerepe el- A betegség expressziója változó, az enyhe ekzemától, a lenére – amely egyéb autoimmun hólyagos bôrbetegsé- kiterjedt, törzsre lokalizálódó, hypertrophiás, odorosus geknél is ismert (formaldehid, methilchlor isothiazolino- plakkokkal és fájdalmas fissurákkal tarkított forma is ne, fahéj aldehid, fahéj alkohol expozíció kiváltotta bullo- megjelenhet. Az expresszivitás és a genetikai háttér között sus pemphigoid; 1-3 dichlorpropene, benzoin tinctura, pe- összefüggést eddig nem igazoltak (7, 9). sticide, chromium sulphat expozíció kiváltotta pemphigus A léziók jellemzôen mindig ugyanazon a helyen jelent- vulgaris) – az epicutan tesztelést MHH esetén kevés klini- keznek. Az intertriginosus terültek (axilla, nyak, periana- kai esetben közölték (1, 8, 16, 18, 19). lis régió vagy lágyék) sokkal gyakrabban érintettek, rit- Az epicutan tesztelést a szakirodalom csak súlyos klini- kábban a fejbôr, a könyök, a térdhajlat vagy a törzs is. kai indikáció esetén javasolja, tekintettel a teszt során po- Nôkben az elváltozások gyulladásra hajlamosabbak, de a tenciálisan kialakuló súlyos akut exacerbatiora: a pozitív gyógyulás mindkét nemnél heggel, gyakran hiperpigmen- reakciókban típusos MHH tünet alakul ki, mind klinikai- tációval történik. A minimális klinikai formákat gyakran lag mind szövettanilag mutatva a betegség jellemzôit. A kíséri, de csupán egyetlen tünetként is jelen lehet az ún. kórkép allergológiai tesztelése során a tesztsor felragasz- longitudinalis paronychia, a körmök hosszanti irányú fe- tása kiváltotta irritáció nem specifikus Köbnerként is fel- hér csíkozottsága (7, 11). léphet. Ennek megfelelôen a lelet relevanciájának megíté- A betegségre fôként a bôr érintettsége jellemzô, de ext- lése csak megfelelô szakmai gyakorlattal lehetséges, az ir- racutan manifesztációt ( Burge , 1992) is közöltek, a nyál- ritatív reakciók kizárása, ill. egyéb relevancia megítélése kahártya érintettség azonban nagyon ritka (conjunctiva, szempontjából (1, 2, 8, 16). oralis-, oesophagealis mucosa, vulva). Egy esetben beszá- Kontaktérzékenység igazolása esetén a kiváltó anyag moltak disszeminált léziókhoz társultan kialakuló akut eliminációja szükséges. Amennyiben csak és kizárólag májelégtelenségrôl is (9, 13, 15, 17). percutan expozíció történik a kérdéses anyaggal, a követ- A szövettani képre intraepidermalis acantholysis jellem- kezetes elimináció megoldható, és tartós tünetmentesség- zô: a suprabasalis keratinocyták adhéziója megszûnik, de hez vezet. Azonban egyes allergének – így a nikkel és a a statum basale intakt. Az érintetlen stratum basale kerati- perubalzsam is – nemcsak bôrön keresztül, hanem oráli- nocytái „omladozó téglafalként” („dilapidated brick san is felvételre kerülnek, és eliminációjukhoz alimentáris wall”) határolják az intraepidermalis rést a dermisben. Jel- megszorításokra is szükség van. lemzô az enyhe dyskeratosis, ill. a superficialis dermisben Az alább bemutatott három betegünknél a kontakt szen- a perivascularis kereksejtes infiltráció (7). Elektronmik- zibilizáció következtében kialakuló, és szigorú eliminá- roszkóppal jól láthatóak a desmosomáktól visszahúzódó cióra szûnô tünetekre kívánjuk felhívni a figyelmet. perinuclearis keratin filamentum agregatumok (9). A terápiában fôként a tüneti kezelés dominál. Elsôsor- Esetismertetés ban a másodlagos bakteriális felülfertôzôdés megoldása szükséges. Antibiotikum választásnál javasolt a staphylo- 1. beteg: A 38 éves nôbeteg 2008 augusztusában jelentkezett klinikánk gen törzsek elleni kezelés. Terápiarezisztens esetekben lo- STD ambulanciáján, irritatív dermatitis beküldô diagnózissal.
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