Increased Incidence of Cutaneous Vasculitic Ulcers : 30-year Results from a Population-based Retrospective Study

Ac aDV Ac aDV Ad ances in de ma ology and ene eology Ac a De ma o-Vene eologica SHORT COMMUNICATION Ac a De m Vene eol 2017; 97: 653–654 This is an open access a icle unde he CC BY-NC license. www.medicaljou nals.se/ac a Jou nal Compila ion © 2017 Ac a De ma o-Vene eologica. doi: 10.2340/00015555-2608 653 Foo and leg ulce s a e a common diso de . I has been es ima ed ha 0.12–1.1% o he popula ion ha e ulce a- ion o his kind (1). Vasculi ic ulce s ha e been epo ed o accoun o 5–15% o all leg ulce s (2–4). The diag- nosis o asculi ic ulce is a challenge, howe e , as he diagnos ic his ological ea u es a e de ec able only in ecen skin lesions no olde han 48 h (5). Cu aneous small essel asculi is gene ally a ec s blood essels in he supe icial de mis. Vasculi is o he medium o la ge essels occu s deepe in he de mis o e en in subcu aneous issue (6). Thus, a skin biopsy om an adequa e dep h is c ucial o he co ec diagnosis o asculi ic ulce . In addi ion o a his ological assessmen o he skin sample, he accu a e diagnosis o asculi ic skin ulce equi es he exclusion o sys emic asculi is (5, 7, 8). Vasculi ic ulce s a e ypically pain ul and o en equi e a long pe iod o ea men . The ulce may heal and he pa ien may eco e in a ew weeks. Howe e , in he mos di icul cases he ulce a ion may con inue o yea s and se e al elapses may occu (9, 10). Since he e a e only limi ed da a on he epidemiology o cu aneous as- culi ic ulce s, his s udy e alua ed he incidence o his disease in Pi kanmaa Coun y, Finland, o e he pe iod 1980–2010. PATIENTS AND METHODS This e ospec i e s udy was based on a coho o pa ien s aged a leas 17 yea s who we e ea ed o cu aneous asculi ic ulce s a he Depa men o De ma ology, Tampe e Uni e si y Hospi al, in 1980–2010. They we e all li ing in Pi kanmaa Coun y a he ime. The ea men o de ma ological pa ien s om he coun y has been cen alized in he Uni e si y Hospi al. Popula ion da a o Pi kanmaa Coun y we e ob ained om he Finnish Popula ion Regis e Cen e. The o al popula ion aged a leas 17 yea s in he dis ic se ed by Tampe e Uni e si y Hospi al was 316,505 in 1980 and 395,300 in 2010. Pa ien da a we e e ie ed om he Tampe e Uni e si y Hospi- al pa ien da a sys em using In e na ional Classi ica ion o Disease (ICD) codes. The case his o ies o a o al o 1,327 pa ien s we e e alua ed. Pa ien s wi h cu aneous symp oms associa ed wi h sys- emic asculi is we e excluded. Da a om his ological and di ec immuno luo escence examina ions o he pa ien ’s skin biopsy we e eco ded, as s a ed in he de ma opa hologis ’s epo . The e- sul s o assays o an ineu ophil cy oplasmic an ibodies (ANCA), c yoglobulins and phospholipid an ibodies we e eco ded. Ulce was de ined as asculi ic ulce i he de ma opa hologis had s a- ed ha his ological c i e ia o cu aneous asculi ic ulce we e ul illed, o i was s a ed in he case his o y ha he diagnosis o asculi ic ulce had been made based on ypical clinical indings. App o al om he e hics commi ee was no conside ed obliga o y, because he s udy was based on case eco ds, and due pe mission was ob ained o eading hese. The da a we e analysed s a is ically using STATA 13.1 and SPSS so wa e (SPSS 19.0 Inc. Chigaco, IL, USA). Annual incidences o asculi ic ulce s we e calcula ed using Poisson eg ession analysis (11). Incidence a e a ios wi h 95% con idence in e als (CI) we e calcula ed o assess annual a ia ions in he incidence o asculi ic ulce s. RESULTS A o al o 191 pa ien s (age ange 18–95 yea s, median age 66 (SD 17.1) yea s, 73 men) p esen ing o he i s ime and ecei ing ea men o cu aneous asculi ic ulce a he Depa men o De ma ology om Janua y 1980 o Decembe 2010 we e iden i ied. A skin biopsy o his ological examina ion had been ob ained om 143 o he 191 pa ien s (74.9%) and om 162 (84.8%) o analysis by di ec immuno luo escence assay (DIF). Al oge he , 126 pa ien s (66.0%) had his ologically con- i med leukocy oclas ic asculi is (G oup 1, Table I) and he emaining 65 pa ien s had been diagnosed on clinical indings wi hou his ological con i ma ion (G oup 2). DIF was diagnos ic in 86 o 191 pa ien s (45.0%). The incidence o asculi ic ulce s in hese g oups was asses- sed sepa a ely. Nine een pa ien s es ed posi i e o pe inuclea an i- neu ophil cy oplasmic an ibodies (P-ANCA) and 2 o cy oplasmic an i-neu ophil cy oplasmic an ibodies (C-ANCA), all wi hou any speci ic de ini ion. The i - es we e low in all he pa ien s who es ed posi i e o c yoglobulins (n = 2) o phospholipid an ibodies (n = 8) and he clinical signi icance o hese emained unce ain. The incidence o leukocy oclas ic asculi ic ulce s among all he pa ien s in 2010 was 45.5/10 6 pe son yea s Inc eased Incidence o Cu aneous Vasculi ic Ulce s: 30-yea Resul s om a Popula ion-based Re ospec i e S udy Teija KIMPIMÄKI 1 , Rii a HUOTARI-ORAVA 2 , Jaakko ANTONEN 3 and Annikki VAALASTI 1 1 Depa men o De ma ology and Alle gology, Tampe e Uni e si y Hospi al, PO Box 2000, FIN-33521 Tampe e, 2 Uni e si y o Tampe e and Fimlab Labo a o ies, and ³Depa men o In e nal Medicine, Tampe e Uni e si y Hospi al, Tampe e, Finland. E-mail: [email p o ec ed] Accep ed Jan 12, 2017; Epub ahead o p in Jan 17, 2017 Table I. His opa hological indings in 191 pa ien s wi h cu aneous asculi ic ulce s All pa ien s (n = 191) G oup 1 (n = 126) G oup 2 (n = 65) His ology (n = 143) Vasculi is 97 97 0 Nega i e 46 27 19 No a ailable 48 2 46 Immuno luo escence (n = 162) Posi i e 86 86 0 Nega i e 76 27 49 No a ailable 29 13 16 G oup 1: Pa ien s wi h his ologically con i med leukocy oclas ic asculi is. G oup 2: Pa ien s whose diagnosis was based on clinical indings only. Ac aDV Ac aDV Ad ances in de ma ology and ene eology Ac a De ma o-Vene eologica Sho communica ion654 www.medicaljou nals.se/ac a (30.4/10 6 pe son yea s o G oup 1 and 39.5/10 6 pe son yea s o G oup 2). The incidence o cu aneous ascu- li ic ulce s inc eased o e he pe iod 1980–2010. The incidence a e a io (IRR) was 1.07 (95% CI 1.05–1.09, p < 0.001) among all he pa ien s. In G oup 1 he IRR was 1.06 (95% CI 1.04–1.09, p < 0.001), and in G oup 2 IRR was 1.09 (95% CI 1.06–1.13). The mean age o he o al popula ion had inc eased om 44.8 yea s in 1980–1990 o 47.6 yea s in 2001– 2010, bu ha o he asculi ic ulce pa ien s was signi- ican ly highe (mean 66.1 yea s; CI 62.8–69.4 yea s) in 2001–2010 han in ei he 1980–1990 (mean 50.7 yea s; CI 42.3–59.2 yea s) o 1991–2000 (mean 62.3 yea s; CI 58.7–65.8 yea s; p < 0.001). DISCUSSION This epo shows ha he annual incidence o cu aneous leukocy oclas ic asculi ic ulce s among he adul po- pula ion o Pi kanmaa Coun y, Finland, in 2010 was 45.5/10 6 . The IRR was 1.07 o e he pe iod 1980–2010, ep esen ing a 7% annual inc ease in he incidence o asculi ic ulce s. The incidence o his ologically con i - med leukocy oclas ic asculi is was simila ly inc eased (IRR 1.06) eaching a le el o 30.4/10 6 . Ou inding o an inc ease in he incidence o cu aneous asculi is is suppo ed by he ecen obse a ion o a compa able incidence a e o biopsy-p o en cu aneous small essel asculi is o 21/10 6 pe son yea s in a e ospec i e popu- la ion-based s udy pe o med in Minneso a, USA (12). We also ound ha he mean age o pa ien s diagnosed as ha ing asculi ic ulce s inc eased mo e s eeply o e he in e al 1980–2010 han did he mean age o he o al popula ion conce ned (15.4 yea s s. 2.8 yea s). Ageing o he popula ion may, howe e , somewha explain he inc eased incidence o asculi ic ulce s du ing he las h ee decades. The e may also be o he ac o s, e.g. medi- ca ion o in ec ions, ha could no be e alua ed eliably in his e ospec i e s udy. The e a e some limi a ions a ached o his wo k. Ce ain clinical da a may be incomple e, as he ma e ial was collec ed e ospec i ely. On he o he hand, he ob- se a ion pe iod was qui e long, as he da a co e ed he in e al om 1980 o 2010. In common wi h i s names and de ini ions, he diagnos ic c i e ia o asculi ic ulce ha e al e ed o e he pe iod 1980–2010, and his may ha e in luenced he incidence a es in he epo s co e- ing he pe iod be o e 1994, pa icula ly hose epo ed be o e 1994, when cu aneous leukocy oclas ic asculi is was de ined as isola ed cu aneous leukocy oclas ic angii- is wi hou sys emic asculi is o glome uloneph i is (13). The e o e, cases o asculi ic ulce wi h sys emic disease may ha e been included in he p e ious epo s conce ning he incidence o cu aneous leukocy oclas ic asculi is be o e 1994, and i s ac ual incidence may ha e been lowe han was epo ed p io o ha da e. The ope a ional en i onmen , ne e heless, emained he same be ween 1980 and 2010, as did he hospi al dis ic ’s e e al policy. In conclusion, hese esul s indica e ha cu aneous asculi ic ulce s a e mo e common in Pi kanmaa Coun y, Finland, nowadays han hey we e p e iously. We sug- ges ha ageing o he popula ion is he main eason o his, bu p ospec i e s udies would be needed in o de o examine he ae iology and pa hogenesis o his disease sys ema ically, wi h he ul ima e objec i e o p e en ing new cases. ACKNOWLEDGEMENTS The au ho s a e g a e ul o Heini Huh ala, MA, o he skil ul s a is ical analyses. The au ho s decla e no con lic s o in e es . REFERENCES 1. G aham ID, Ha ison MB, Nelson EA, Lo ime K, Fishe A. P e- alence o lowe -limb ulce a ion: sys ema ic e iew o p e- alence s udies. Ad Skin Wound Ca e 2003; 16: 305–316. 2. Kö be A, Klode J, Al-Benna S, Wax C, Schadendo D, S ein- s aesse L, e al. E iology o ch onic leg ulce s in 31,619 pa ien s in Ge many analyzed by an expe su ey. J D sch De ma ol Ges 2011; 9: 116–121. 3. Pannie F, Rabe E. Di e en ial diagnosis o leg ulce s. Phle- bology 2013; 28 Suppl 1: 55–60. 4. Bi sch M, Lau sen I, Engel A-M, Ch is iansen M, Olesen La sen S, I e sen L, e al. Epidemiology o ch onic wound pa ien s and ela ion o se um le els o mannan-binding lec in. Ac a De m Vene eol 2009; 89: 607–611. 5. Sais G, Vidalle A, Jucglà A, Se i je O, Condom E, Pey i J. P ognos ic ac o s in leukocy oclas ic asculi is. A ch De - ma ol 1998; 134: 309–315. 6. S one JH, Nousa i HC. “Essen ial” cu aneous asculi is: wha e e y heuma ologis should know abou asculi is o he skin. Cu Opin Rheuma ol 2001; 13: 23–34. 7. Ca lson JA, Ca alie e LF, G an -Kels JM. Cu aneous ascu- li is: diagnosis and managemen . Clin De ma ol 2006; 24: 414–429. 8. Jenne e JC, Falk RJ. Pa hologic classi ica ion o asculi is. Pa hol Case Re 2007; 12: 179–185. 9. Ca lson JA, Ng BT, Chen K-R. Cu aneous asculi is upda e: Diagnos ic c i e ia, classi ica ion, epidemiology, e iology, pa hogenesis, e alua ion and p ognosis. Am J De ma opa hol 2005; 27: 504–528. 10. Ma zano AV, Vezzoli P, Be i E. Skin in ol emen in cu aneous and sys emic asculi is. Au oimm Re 2013; 12: 467–476. 11. Ki kwood BR, S e ne JAC. Poisson eg ession. In: Medical S a is ics, 2nd edn. Ox o d: Blackwell Publishing L d, 2003: p. 249–262. 12. A o a A, We e DA, Gonzalez-San iago TM, Da is MDP, Lohse CM. Incidence o leukocy oclas ic asculi is, 1996 o 2010: a popula ion-based s udy in Olms ed coun y, Minneso a. Mayo Clin P oc 2014. 13. Jenne e JC, Falk RJ, And assy K, Bacon PA, Chu g J, G oss WL, e al. Nomencla u e o sys emic asculi ides. A h i is Rheum 1994; 37: 187–192.