Risk of Serious Infections in Patients with Bullous Pemphigoid: A Population-based Cohort Study
DOI:
https://doi.org/10.2340/actadv.v103.5329Keywords:
Bullous pemphigoid, Cohort Studies, Infections, Pneumonia, Sepsis, Vesiculobullous skin diseaseAbstract
Patients with bullous pemphigoid are susceptible to serious infections, which are the leading cause of death in these patients. The aims of this population-based cohort study were to investigate the incidence and spectrum of serious infections in patients with bullous pemphigoid and to identify associated risk factors. The outcome measure was any infection requiring hospitalization. Hazard ratios with 95% confidence intervals were estimated using subdistribution hazard models. In total, 12,300 patients with bullous pemphigoid and 49,200 matched controls were identified through the National Health Insurance Research Database in Taiwan. Within 2 years of bullous pemphigoid diagnosis, 5,006 (40.7%) patients developed serious infections, with an incidence of 385.5/1,000 person-years. Patients with bullous pemphigoid were twice as likely to develop serious infections as controls (adjusted hazard ratio, 2.01; 95% confidence interval 1.92–2.10). Systemic corticosteroid use was the strongest risk factor, resulting in a 2-fold increase in the risk for serious infections. Other independent risk factors were advanced age, female sex, low income, and certain comorbidities. In conclusion, this study demonstrated an increased risk of serious infections following a diagnosis of bullous pemphigoid. Prophylaxis of serious infections through active intervention with the risk factors may be essential in reducing the morbidity and mortality associated with bullous pemphigoid.
Downloads
References
Persson MSM, Harman KE, Vinogradova Y, Langan SM, Hippisley-Cox J, Thomas KS, et al. Incidence, prevalence and mortality of bullous pemphigoid in England 1998-2017: a population-based cohort study. Br J Dermatol 2021; 184: 68-77.
https://doi.org/10.1111/bjd.19022 DOI: https://doi.org/10.1111/bjd.19022
Kridin K, Ludwig RJ. The growing incidence of bullous pemphigoid: overview and potential explanations. Front Med (Lausanne) 2018; 5: 220.
https://doi.org/10.3389/fmed.2018.00220 DOI: https://doi.org/10.3389/fmed.2018.00220
Kridin K, Schwartz N, Cohen AD, Zelber-Sagi S. Mortality in bullous pemphigoid: a systematic review and meta-analysis of standardized mortality ratios. J Dermatol 2018; 45: 1094-1100.
https://doi.org/10.1111/1346-8138.14503 DOI: https://doi.org/10.1111/1346-8138.14503
Kridin K, Shihade W, Bergman R. Mortality in patients with bullous pemphigoid: a retrospective cohort study, systematic review and meta-analysis. Acta Derm Venereol 2019; 99: 72-77.
https://doi.org/10.2340/00015555-2930 DOI: https://doi.org/10.2340/00015555-2930
Liu YD, Wang YH, Ye YC, Zhao WL, Li L. Prognostic factors for mortality in patients with bullous pemphigoid: a meta-analysis. Arch Dermatol Res 2017; 309: 335-347.
https://doi.org/10.1007/s00403-017-1736-1 DOI: https://doi.org/10.1007/s00403-017-1736-1
Rzany B, Partscht K, Jung M, Kippes W, Mecking D, Baima B, et al. Risk factors for lethal outcome in patients with bullous pemphigoid: low serum albumin level, high dosage of glucocorticosteroids, and old age. Arch Dermatol 2002; 138: 903-908.
https://doi.org/10.1001/archderm.138.7.903 DOI: https://doi.org/10.1001/archderm.138.7.903
Phoon YW, Fook-Chong SM, Koh HY, Thirumoorthy T, Pang SM, Lee HY. Infectious complications in bullous pemphigoid: an analysis of risk factors. J Am Acad Dermatol 2015; 72: 834-839.
https://doi.org/10.1016/j.jaad.2015.01.029 DOI: https://doi.org/10.1016/j.jaad.2015.01.029
Chen J, Mao X, Zhao W, Zhang B, Chen X, Yu C, et al. Assessment of the characteristics and associated factors of infectious complications in bullous pemphigoid. Front Immunol 2020; 11: 1607.
https://doi.org/10.3389/fimmu.2020.01607 DOI: https://doi.org/10.3389/fimmu.2020.01607
Cai SC, Allen JC, Lim YL, Chua SH, Tan SH, Tang MB. Mortality of bullous pemphigoid in Singapore: risk factors and causes of death in 359 patients seen at the National Skin Centre. Br J Dermatol 2014; 170: 1319-1326.
https://doi.org/10.1111/bjd.12806 DOI: https://doi.org/10.1111/bjd.12806
Joly P, Benichou J, Lok C, Hellot MF, Saiag P, Tancrede-Bohin E, et al. Prediction of survival for patients with bullous pemphigoid: a prospective study. Arch Dermatol 2005; 141: 691-698.
https://doi.org/10.1001/archderm.141.6.691 DOI: https://doi.org/10.1001/archderm.141.6.691
Roujeau J-C, Lok C, Bastuji-Garin S, Mhalla S, Enginger V, Bernard P. High risk of death in elderly patients with extensive bullous pemphigoid. Arch Dermatol 1998; 134: 465-469.
https://doi.org/10.1001/archderm.134.4.465 DOI: https://doi.org/10.1001/archderm.134.4.465
Cortés B, Marazza G, Naldi L, Combescure C, Borradori L. Mortality of bullous pemphigoid in Switzerland: a prospective study. Br J Dermatol 2011; 165: 368-374.
https://doi.org/10.1111/j.1365-2133.2011.10413.x DOI: https://doi.org/10.1111/j.1365-2133.2011.10413.x
Lehman JS, Khunger M, Lohse CM. Infection in autoimmune bullous diseases: a retrospective comparative study. J Dermatol 2013; 40: 613-619.
https://doi.org/10.1111/1346-8138.12175 DOI: https://doi.org/10.1111/1346-8138.12175
Langan SM, Hubbard R, Fleming K, West J. A population-based study of acute medical conditions associated with bullous pemphigoid. Br J Dermatol 2009; 161: 1149-1152.
https://doi.org/10.1111/j.1365-2133.2009.09350.x DOI: https://doi.org/10.1111/j.1365-2133.2009.09350.x
Hsieh CY, Su CC, Shao SC, Sung SF, Lin SJ, Kao Yang Y-H, et al. Taiwan's National Health Insurance Research Database: past and future. Clin Epidemiol 2019; 11: 349-358.
https://doi.org/10.2147/CLEP.S196293 DOI: https://doi.org/10.2147/CLEP.S196293
Wu CY, Wu CY, Lin YH, Chang YT. Statins did not reduce the mortality risk in patients with bullous pemphigoid: a population-based cohort study. Dermatol Sin 2021; 39: 153-154.
https://doi.org/10.4103/ds.ds_14_21 DOI: https://doi.org/10.4103/ds.ds_14_21
Wu CY, Wu CY, Li CP, Lin YH, Chang YT. Association of immunosuppressants with mortality of patients with bullous pemphigoid: a nationwide population-based cohort study. Dermatology 2022; 238: 378-385.
https://doi.org/10.1159/000516632 DOI: https://doi.org/10.1159/000516632
Wu CY, Wu CY, Li CP, Chou YJ, Lin YH, Chang YT. Association between dipeptidyl peptidase-4 inhibitors and risk of bullous pemphigoid in patients with type 2 diabetes: a population-based cohort study. Diabetes Res Clin Pract 2021; 171: 108546.
https://doi.org/10.1016/j.diabres.2020.108546 DOI: https://doi.org/10.1016/j.diabres.2020.108546
Dai YX, Tai YH, Chen CC, Chang YT, Chen TJ, Chen MH. Bidirectional association between alopecia areata and major depressive disorder among probands and unaffected siblings: a nationwide population-based study. J Am Acad Dermatol 2020; 82: 1131-1137.
https://doi.org/10.1016/j.jaad.2019.11.064 DOI: https://doi.org/10.1016/j.jaad.2019.11.064
Dai YX, Tai YH, Chang YT, Chen TJ, Chen MH. Increased risk of alopecia areata among patients with endometriosis: a longitudinal study in Taiwan. Dermatol Sin 2021; 39: 41-44.
https://doi.org/10.4103/ds.ds_52_20 DOI: https://doi.org/10.4103/ds.ds_52_20
Robert JG. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16: 1141-1154.
https://doi.org/10.1214/aos/1176350951 DOI: https://doi.org/10.1214/aos/1176350951
Fine JP, Gray RJ. A Proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496-509.
https://doi.org/10.1080/01621459.1999.10474144 DOI: https://doi.org/10.1080/01621459.1999.10474144
Ren Z, Narla S, Hsu DY, Silverberg JI. Association of serious infections with pemphigus and pemphigoid: analysis of the Nationwide Inpatient Sample. J Eur Acad Dermatol Venereol 2018; 32: 1768-1776.
https://doi.org/10.1111/jdv.14961 DOI: https://doi.org/10.1111/jdv.14961
Borradori L, Van Beek N, Feliciani C, Tedbirt B, Antiga E, Bergman R, et al. Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol 2022; 36: 1689-1704.
https://doi.org/10.1111/jdv.18220 DOI: https://doi.org/10.1111/jdv.18220
Venning VA, Taghipour K, Mohd Mustapa MF, Highet AS, Kirtschig G. British Association of Dermatologists' guidelines for the management of bullous pemphigoid 2012. Br J Dermatol 2012; 167: 1200-1214.
https://doi.org/10.1111/bjd.12072 DOI: https://doi.org/10.1111/bjd.12072
Glesby MJ, Hoover DR. Survivor treatment selection bias in observational studies: examples from the AIDS literature. Ann Intern Med 1996; 124: 999-1005.
https://doi.org/10.7326/0003-4819-124-11-199606010-00008 DOI: https://doi.org/10.7326/0003-4819-124-11-199606010-00008
Joly P, Roujeau JC, Benichou J, Picard C, Dreno B, Delaporte E, et al. A comparison of oral and topical corticosteroids in patients with bullous pemphigoid. N Engl J Med 2002; 346: 321-327.
https://doi.org/10.1056/NEJMoa011592 DOI: https://doi.org/10.1056/NEJMoa011592
Widdifield J, Bernatsky S, Paterson JM, Gunraj N, Thorne JC, Pope J, et al. Serious infections in a population-based cohort of 86,039 seniors with rheumatoid arthritis. Arthritis Care Res (Hoboken) 2013; 65: 353-361.
https://doi.org/10.1002/acr.21812 DOI: https://doi.org/10.1002/acr.21812
Schneeweiss S, Setoguchi S, Weinblatt ME, Katz JN, Avorn J, Sax PE, et al. Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis. Arthritis Rheum 2007; 56: 1754-1764.
https://doi.org/10.1002/art.22600 DOI: https://doi.org/10.1002/art.22600
Williams HC, Wojnarowska F, Kirtschig G, Mason J, Godec TR, Schmidt E, et al. Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial. Lancet 2017; 389: 1630-1638.
https://doi.org/10.1016/S0140-6736(17)30560-3 DOI: https://doi.org/10.1016/S0140-6736(17)30560-3
Abdat R, Waldman RA, de Bedout V, Czernik A, McLeod M, King B, et al. Dupilumab as a novel therapy for bullous pemphigoid: a multicenter case series. J Am Acad Dermatol 2020; 83: 46-52.
https://doi.org/10.1016/j.jaad.2020.01.089 DOI: https://doi.org/10.1016/j.jaad.2020.01.089
Balakirski G, Alkhateeb A, Merk HF, Leverkus M, Megahed M. Successful treatment of bullous pemphigoid with omalizumab as corticosteroid-sparing agent: report of two cases and review of literature. J Eur Acad Dermatol Venereol 2016; 30: 1778-1782.
https://doi.org/10.1111/jdv.13758 DOI: https://doi.org/10.1111/jdv.13758
Additional Files
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2023 Tsung-Hsien Chang, Chun-Ying Wu, Yun-Ting Chang, Ying-Syuan Lyu, Chen-Yi Wu
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All digitalized ActaDV contents is available freely online. The Society for Publication of Acta Dermato-Venereologica owns the copyright for all material published until volume 88 (2008) and as from volume 89 (2009) the journal has been published fully Open Access, meaning the authors retain copyright to their work.
Unless otherwise specified, all Open Access articles are published under CC-BY-NC licences, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.
