Uğur ÇELİK, Zekayi KUTLUBAY, Cem MAT, Ayşegül SEVİM KEÇİCİ

A survey of bullous diseases in a Turkish university hospital: clinicoepidemiological characteristics and follow-up

Background/aim: Autoimmune bullous diseases, if left untreated, are life-threatening conditions affecting primarily skin and mucous membranes. These blistering disorders are characterized by epidermal or subepidermal detachment. Autoimmunity plays a key role in pathogenesis; therefore, immunosuppressive agents are the treatment of choice. The aim of this study is to document relative frequencies of different autoimmune bullous diseases, patient characteristics, treatment options, and side effects in patients presenting to our bullous skin disease center at İstanbul University, Cerrahpaşa, Cerrahpaşa Medical Faculty. Materials and methods: Medical files were examined retrospectively for all patients with autoimmune bullous diseases who were followed up between 2003 and 2019 at the Bullous Skin Disease Center at İstanbul University, Cerrahpaşa. Results: A total of 346 patient files were examined. Pemphigus vulgaris was the most frequent autoimmune bullous disease, followed by bullous pemphigoid and pemphigus foliaceus, according to our study. There is a general female predominancy for all autoimmune bullous diseases. The most commonly preferred treatment options were high-dose daily corticosteroids. Conclusion: This retrospective study summarizes the patient characteristics, comorbidities, treatment choices, and side effects during 16 years of clinical practice.Key words: Bullous diseases epidemiology, pemphigus vulgaris, bullous pemphigoid

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1. Marazza G, Pham HC, Schärer L, Pedrazzetti PP, Hunziker T et al. Incidence of bullous pemphigoid and pemphigus in Switzerland: a 2-year prospective study. British Journal of Dermatology 2009; 161 (3): 861-868. doi: 10.1111/j.1365- 2133.2009.09300.x
2. V’Lckova-Laskoska MT, Laskoski DS, Kamberova S, Biljanovska NC, Volckova N. Epidemiology of pemphigus in Macedonia: a 15-year retrospective study (1990–2004). International Journal of Dermatology 2007; 46 (3): 253-258. doi:10.1111/j.1365-4632.2006.03010.x
3. Baican A, Baican C, Chiriac G, Chiriac MT, Macovei V et al. Pemphigus vulgaris is the most common autoimmune bullous disease in Northwestern Romania. International Journal of Dermatology 2010; 49 (7): 768-774. doi:10.1111/j.1365- 4632.2009.04345.x
4. Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJ et al. Bullous pemphigoid and pemphigus vulgaris--incidence and mortality in the UK: population based cohort study. British Medical Journal 2008; 337 (7662) : a180. doi:10.1136/bmj.a180
5. Chams-Davatchi C, Valikhani M, Daneshpazhooh M, Esmaili N, Balighi K et al. Pemphigus: analysis of 1,209 cases. International Journal of Dermatology 2005; 44 (6): 470-476. doi:10.1111/j.1365-4632.2004.02501.x
6. Nanda A, Dvorak R, Al-Saeed K, Al-Sabah H, Alsaleh QA. Spectrum of autoimmune bullous diseases in Kuwait. International Journal of Dermatology 2004; 43 (12): 876-881. doi:10.1111/j.1365-4632.2004.02292.x
7. Försti AK, Jokelainen J, Timonen M, Tasanen K. Increasing incidence of bullous pemphigoid in Northern Finland: a retrospective database study in Oulu University Hospital. British Journal of Dermatology 2014; 171 (5): 1223-1226. doi:10.1111/ bjd.13189
8. Daneshpazhooh M, Chams-Davatchi C, Payandemehr P, Nassiri S, Valikhani M et al. Spectrum of autoimmune bullous diseases in Iran: a 10-year review. International Journal of Dermatology 2012; 51 (1): 35-41. doi:10.1111/j.1365- 4632.2011.04946.x
9. Jin P, Shao C, Ye G. Chronic bullous dermatoses in China. International Journal of Dermatology 1993; 32 (2): 89-92. doi:10.1111/j.1365-4362.1993.tb01441.x
10. Adam BA. Bullous diseases in Malaysia: epidemiology and natural history. International Journal of Dermatology 1992; 31 (1): 42-45. doi:10.1111/j.1365-4362.1992.tb03519.x
11. Uzun S, Durdu M, Akman A, Gunasti S, Uslular C et al. Pemphigus in the Mediterranean region of Turkey: a study of 148 cases. International Journal of Dermatology 2006; 45 (5): 523-528. doi:10.1111/j.1365-4632.2004.02533.x
12. Bertram F, Bröcker EB, Zillikens D, Schmidt E. Prospective analysis of the incidence of autoimmune bullous disorders in Lower Franconia, Germany. Journal de Deutsche Dermatologische Gesellschaft 2009; 7 (5): 434-440. doi:10.1111/j.1610-0387.2008.06976.x
13. Wong SN, Chua SH. Spectrum of subepidermal immunobullous disorders seen at the National Skin Centre, Singapore: a 2-year review. British Journal of Dermatology 2002; 147 (3): 476-480. doi:10.1046/j.1365-2133.2002.04919.x
14. Tsankov N, Vassileva S, Kamarashev J, Kazandjieva J, Kuzeva V. Epidemiology of pemphigus in Sofia, Bulgaria. A 16-year retrospective study (1980–1995). International Journal of Dermatology 2000; 39 (2): 104-108. doi:10.1046/j.1365- 4362.2000.00864.x
15. Wilson C, Wojnarowska F, Mehra NK, Pasricha JS. Pemphigus in Oxford, UK, and New Delhi, India: a comparative study of disease characteristics and HLA antigens. Dermatology 1994; 189 (Suppl 1): 108-110. doi:10.1159/000246946
16. Hietanen J, Salo OP. Pemphigus: an epidemiological study of patients treated in Finnish hospitals between 1969 and 1978. Acta Dermato-Venereologica 1982; 62 (6): 491-496.
17. Bastuji-Garin S, Souissi R, Blum L, Turki H, Nouira R et al. Comparative epidemiology of pemphigus in Tunisia and France: unusual incidence of pemphigus foliaceus in young Tunisian women. Journal of Investigative Dermatology 1995; 104 (2): 302-305. doi:10.1111/1523-1747.ep12612836
18. Salmanpour R, Shahkar H, Namazi MR, Rahman-Shenas MR. Epidemiology of pemphigus in south-western Iran: a 10- year retrospective study (1991–2000). International Journal of Dermatology 2006; 45 (2): 103-105. doi:10.1111/j.1365- 4632.2004.02374.x
19. Michailidou EZ, Belazi MA, Markopoulos AK, Tsatsos MI, Mourellou ON et al. Epidemiologic survey of pemphigus vulgaris with oral manifestations in northern Greece: retrospective study of 129 patients. International Journal of Dermatology 2007; 46 (4): 356-361. doi:10.1111/j.1365- 4632.2006.03044.x
20. Simon DG, Krutchkoff D, Kaslow RA, Zarbo R. Pemphigus in Hartford County, Connecticut, from 1972 to 1977. Archieves of Dermatology 1980; 116 (9): 1035-1037.
21. Micali G, Musumeci ML, Nasca MR. Epidemiologic analysis and clinical course of 84 consecutive cases of pemphigus in eastern Sicily. International Journal of Dermatology 1998; 37 (3): 197-200. doi:10.1046/j.1365-4362.1998.00428.x
22. Schmidt E, Zillikens D. Diagnosis and treatment of patients with autoimmune bullous disorders in Germany. Dermatologic Clinics 2011; 29 (4): 663-671. doi:10.1016/j.det.2011.06.007
23. Kumar KA. Incidence of pemphigus in Thrissur district, south India. Indian Journal of Dermatology Venereology and Leprology 2008; 74 (4): 349-351. doi:10.4103/0378-6323.42901
24. Seo PG, Choi WW, Chung JH. Pemphigus in Korea: clinical manifestations and treatment protocol. Journal of Dermatology 2003; 30 (11): 782-788. doi:10.1111/j.1346-8138.2003. tb00478.x
25. Amin MN, Islam AZ. Clinical, histologic and immunologic features of pemphigus in Bangladesh. International Journal of Dermatology 2006; 45 (11): 1317-1318. doi:10.1111/j.1365- 4632.2006.02942.x
26. Tallab T, Joharji H, Bahamdan K, Karkashan E, Mourad M et al. The incidence of pemphigus in the southern region of Saudi Arabia. International Journal of Dermatology 2001; 40 (9): 570-572. doi:10.1046/j.1365-4362.2001.01247.x
27. Asilian A, Yoosefi A, Faghini G. Pemphigus vulgaris in Iran: epidemiology and clinical profile. Skinmed 2006; 5 (2): 69-71. doi:10.1111/j.1540-9740.2006.03756.x
28. Seidenbaum M, David M, Sandbank M. The course and prognosis of pemphigus. A review of 115 patients. International Journal of Dermatology 1988; 27 (8): 580-584. doi:10.1111/j.1365-4362.1988.tb02409.x
29. Aboobaker J, Morar N, Ramdial PK, Hammond MG. Pemphigus in South Africa. International Journal of Dermatology 2001; 40 (2): 115-119. doi:10.1046/j.1365-4362.2001.01124.x
30. Golusin Z, Poljacki M, Jovanoviç M, Ethuran V, Stojanoviç S et al. Some epidemiological features of pemphigus chronicus in South Vojvodina: a 12-year retrospective study. International Journal of Dermatology 2005; 44 (9): 792-793. doi:10.1111/ j.1365-4632.2004.02421.x
31. Sustic N, Rucevic I, Barisic-Drusko V. Epidemiology of acquired bullous diseases in Eastern Croatia: a retrospective prewar to postwar study. Acta Dermatovenerologica Croatia 2005; 13 (4): 228-232.
32. Kyriakis K, Tosca A, Lehou J, Hatzis J, Vareltzidis A et al. A 5-year retrospective study on pemphigus and pemphigoid. Australasian Journal of Dermatology 1989; 30 (1): 33-36. doi:10.1111/j.1440-0960.1989.tb00405.x
33. Naldi L, Bertoni M, Cainelli T. Feasibility of a registry of pemphigus in Italy: 2 years experience. Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED). International Journal of Dermatology 1993; 32 (6): 424-427. doi:10.1111/j.1365-4362.1993.tb02813.x
34. Coronel-Pérez IM, Rodríguez-Rey EM, Pérez-Bernal AM, Camacho FM. Epidemiology of pemphigus in the Hospital Universitario Virgen Macarena, Seville, Spain, 2005- 2006. Actas Dermo-Sifiliograficas 2009; 100 (2): 121-125. doi:10.1016/s0001-7310(09)70229-7
35. Mahé A, Flageul B, Cissé I, et al. Pemphigus in Mali: a study of 30 cases. British Journal of Dermatology 1996; 134 (1): 114- 119.
36. Chiossi MP, Roselino AM. Endemic pemphigus foliaceus (‘‘Fogo selvagem’’): a series from the northeastern region of the state of São Paulo, Brazil, 1973–1998. Revista do Instituto de Medicina Tropical de São Paulo 2001; 43 (2): 59-62. doi:10.1590/s0036-46652001000200001
37. Abrèu-Velez AM, Hashimoto T, Bollag WB, Arroyave St, Abreu-Velez CE et al. A unique form of endemic pemphigus in northern Colombia. Journal of American Academy of Dermatology 2003; 49 (4): 599-608. doi:10.1067/s0190- 9622(03)00851-x
38. Benchikhi H, Ghafour S, Disky A, Bichra L, Nejjam F et al. Pemphigus: analysis of 262 cases. International Journal of Dermatology 2008; 47 (9): 973-975. doi:10.1111/j.1365- 4632.2008.03616.x
39. Ishii N, Maeyama Y, Karashima T, Nakama T, Kusuhara M et al. A clinical study of patients with pemphigus vulgaris and pemphigus foliaceous: an 11-year retrospective study (1996– 2006). Clinical and Experimental Dermatology 2008; 33 (5): 641-643. doi:10.1111/j.1365-2230.2008.02881.x
40. Milinković MV, Janković S, Medenica L, Nikolić M, Reljić V et al. Incidence of autoimmune bullous diseases in Serbia: a 20- year retrospective study. Journal de Deutsche Dermatologische Gesellschaft 2016; 14 (10): 995-1005. doi:10.1111/ddg.13081
41. Goon AT, Tan SH. Comparative study of pemphigus vulgaris and pemphigus foliaceus in Singapore. Australasian Journal of Dermatology 2001; 42 (3): 172-175. doi:10.1046/j.1440- 0960.2001.00509.x
42. Khaled A, Taazayet SB, Ben Alaya N, Souissi A, Zeglaoui F et al. The course and prognosis of pemphigus in 47 Tunisian patients. Journal of European Academy of Dermatology and Venereology 2013; 27 (1): 81-85. doi:10.1111/j.1468- 3083.2011.04362.x
43. Sinha AA, Hoffman MB, Janicke EC. Pemphigus vulgaris: approach to treatment. European Journal of Dermatology 2015; 25 (2): 103-113. doi:10.1684/ejd.2014.2483
44. Sellami KM, Ben Ayed M, Mouquet H, Drouot L, Zitouni M et al. Anti-desmoglein 1 antibodies in Tunisian healthy subjects: arguments for the role of environmental factors in the occurrence of Tunisian pemphigus foliaceus. Clinical and Experimental Immunology 2004; 137 (1): 195-200. doi:10.1111/j.1365-2249.2004.02493.x
45. Bastuji-Garin S, Turki H, Mokhtar I, Nouira R, Fazaa B et al. Possible relation of Tunisian pemphigus with traditional cosmetics: a multicenter case–control study. American Journal of Epidemiology 2002; 155 (3): 249-256. doi:10.1093/ aje/155.3.249
46. Bernard P, Vaillant L, Labeille B, Bedane C, Arbeille B et al. Incidence and distribution of subepidermal auto-immune bullous skin diseases in three French regions. Bullous Diseases French Study Group. Archieves of Dermatology 1995; 131 (1): 48-52.
47. Jung M, Kippes W, Messer G, Zillikens D, Rzany B. Increased risk of bullous pemphigoid in male and very old patients: a population-based study on incidence. Journal of American Academy of Dermatology 1999; 41 (2 Pt 1): 266-268. doi:10.1016/s0190-9622(99)70061-7
48. Zillikens D, Wever S, Roth A, Weidenthaler-Barth B, Hashimoto T et al. Incidence of autoimmune subepidermal blistering dermatoses in a region of central Germany. Archieves of Dermatology 1995; 131 (8): 957-958. doi:10.1001/ archderm.131.8.957
49. Serwin AB, Musialkowska E, Piascik M. Incidence and mortality of bullous pemphigoid in north-east Poland (Podlaskie Province), 1999-2012: a retrospective bicentric cohort study. International Journal of Dermatology 2014; 53 (10): e432-e437. doi:10.1111/ijd.12492
50. Cozzani E, Parodi A, Rebora A, Delmonte S, Barile M et al. Bullous pemphigoid in Liguria: a 2-year survey. Journal of European Academy of Dermatology and Venereology 2001; 15 (4): 317-319.
51. Gudi VS, White MI, Cruickshank N, Herriot R, Edwards SL et al. Annual incidence and mortality of bullous pemphigoid in the Grampian region of North-east Scotland. British Journal of Dermatology 2005; 153 (2): 424-427. doi:10.1111/j.1365- 2133.2005.06662.x
52. Ong E, Goldacre R, Hoang U, Sinclair R, Goldacre M. Associations between bullous pemphigoid and primary malignant cancers: an English national record linkage study, 1999-2011. Archieves of Dermatological Research 2014; 306 (1): 75-80. doi:10.1007/s00403-013-1399-5
53. Joly P, Baricault S, Sparsa A, Bernard P, Bédane C et al. Incidence and mortality of bullous pemphigoid in France. Journal of Investigative Dermatology 2012; 132 (8): 1998-2004. doi:10.1038/jid.2012.35
54. Brick KE, Weaver CH, Lohse CM, Pittelkow MR, Lehman JS et al. Incidence of bullous pemphigoid and mortality of patients with bullous pemphigoid in Olmsted County, Minnesota, 1960 through 2009. Journal of American Academy of Dermatology 2014; 71 (1): 92-99. doi:10.1016/j.jaad.2014.02.030
55. Banihashemi M, Zabolinejad N, Vahabi S, Razavi HS. Survey of bullous pemphigoid disease in northern Iran. International Journal of Dermatology 2015; 54 (11): 1246-1249. doi:10.1111/ ijd.12619
56. Parker S, Dyson S, Brisman S, Pennie M, Swerlick RA et al. Mortality of bullous pemphigoid: an evaluation of 223 patients and comparison with the mortality in the general population in the United States. Journal of American Academy of Dermatology 2008; 59 (4): 582-588. doi:10.1016/j. jaad.2008.07.022
57. Bastuji-Garin S, Joly P, Lemordant P, Sparsa A, Bedane C, et al. Risk factors for bullous pemphigoid in the elderly: a prospective case-control study. Journal of Investigative Dermatology 2011; 131 (1): 637-643. doi:10.1038/jid.2010.301
58. Cordel N, Chosidow O, Hellot MF, Delaporte E, Lok C et al. Neurological disorders in patients with bullous pemphigoid. Dermatology 2007; 215 (3): 187-191. doi:10.1159/000106574
59. Stinco G, Codutti R, Scarbolo M, Valent F, Patrone P. A retrospective epidemiological study on the association of bullous pemphigoid and neurological diseases. Acta Dermato-Venereologica 2005; 85 (2): 136-139. doi:10.1080/00015550410024481
60. Chuang TY, Korkij W, Soltani K, Clayman J, Cook J. Increased frequency of diabetes mellitus in patients with bullous pemphigoid: a case-control study. Journal of American Academy of Dermatology 1984; 11 (6): 1099-1102. doi:10.1016/ s0190-9622(84)70266-0