Prevalence, Spectrum and Clinical Implications of Malignancies in Patients with Bullous Pemphigoid
DOI:
https://doi.org/10.2340/actadv.v103.3979Keywords:
bullous dermatoses, malignant melanoma, mortality rate, bullous pemphigoidAbstract
Current research on the malignancy rate and spectrum of malignancies in patients with bullous pemphigoid is contradictory. The aims of this study were to determine the prevalence and spectrum of malignancy in patients with bullous pemphigoid and to compare demographic, clinical, therapeutic and outcome data between bullous pemphigoid patients with and without malignancy. This retrospective cohort study enrolled 335 patients (194 women and 141 men; mean age at diagnosis of bullous pemphigoid 77.5 ± 12 years) followed up at an Israeli tertiary centre between January 2009 and December 2019: 107 (32%) had malignancy and 228 (68%) did not. Malignancy occurred before and after bullous pemphigoid diagnosis in 82 (77%) and 25 (23%) patients, respectively. Bullous pemphigoid patients with cancer were older (p = 0.02) and had a higher mortality rate (p < 0.0001) than those without malignancy. The 2 groups did not differ in terms of sex, comorbidities, or clinical characteristics. Those who developed malignancy before bullous pemphigoid were younger than those who developed malignancy after bullous pemphigoid (mean age 69.3 vs 82.4 years, p < 0.0001). Overall malignancy rates did not differ between patients with bullous pemphigoid and the general population; therefore, comprehensive malignancy workup may be unnecessary. However, patients with bullous pemphigoid had a greater risk of melanoma (10.7% vs 4.3%, p = 0.0005); therefore, routine skin screening may be recommended.
Downloads
References
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
Wertenteil S, Garg A, Strunk A, Alloo A. Prevalence estimates for pemphigoid in the United States: a sex-adjusted and age-adjusted population analysis. J Am Acad Dermatol 2019; 80: 655-659.
https://doi.org/10.1016/j.jaad.2018.08.030 DOI: https://doi.org/10.1016/j.jaad.2018.08.030
Miyamoto D, Santi CG, Aoki V, Maruta CW. Bullous pemphigoid. An Bras Dermatol 2019; 94: 133-146.
https://doi.org/10.1590/abd1806-4841.20199007 DOI: https://doi.org/10.1590/abd1806-4841.20199007
Colbert RL, Allen DM, Eastwood D, Fairley JA. Mortality rate of bullous pemphigoid in a US medical center. J Invest Dermatol 2004; 122: 1091-1095.
https://doi.org/10.1111/j.0022-202X.2004.22504.x DOI: https://doi.org/10.1111/j.0022-202X.2004.22504.x
Daniel BS, Murrell DF. Review of autoimmune blistering diseases: the pemphigoid diseases. J Eur Acad Dermatol Venereol 2019; 33: 1685-1694.
https://doi.org/10.1111/jdv.15679 DOI: https://doi.org/10.1111/jdv.15679
Bernard P, Antonicelli F. Bullous pemphigoid: a review of its diagnosis, associations and treatment. Am J Clin Dermatol 2017; 18: 513-528.
https://doi.org/10.1007/s40257-017-0264-2 DOI: https://doi.org/10.1007/s40257-017-0264-2
Saschenbrecker S, Karl I, Komorowski L, Probst C, Dähnrich C, Fechner K, et al. Serological diagnosis of autoimmune bullous skin diseases. Front Immunol 2019; 10: 1974.
https://doi.org/10.3389/fimmu.2019.01974 DOI: https://doi.org/10.3389/fimmu.2019.01974
Egami S, Yamagami J, Amagai M. Autoimmune bullous skin diseases, pemphigus and pemphigoid. J Allergy Clin Immunol 2020; 145: 1031-1047.
https://doi.org/10.1016/j.jaci.2020.02.013 DOI: https://doi.org/10.1016/j.jaci.2020.02.013
Ungprasert P, Wijarnpreecha K, Thongprayoon C. Risk of venous thromboembolism in patients with bullous pemphigoid: a systematic review and meta-analysis. Indian J Dermatol Venereol Leprol 2018; 84: 22-26.
https://doi.org/10.4103/ijdvl.IJDVL_827_16 DOI: https://doi.org/10.4103/ijdvl.IJDVL_827_16
Pourali SP, Gutierrez Y, Kohn AH, Rajkumar JR, Jones ME, Ortiz I, et al. Bullous dermatoses and depression: a systematic review. JAMA Dermatol 2021; 157: 1487-1495.
https://doi.org/10.1001/jamadermatol.2021.4055 DOI: https://doi.org/10.1001/jamadermatol.2021.4055
Phan K, Goyal S, Murrell DF. Association between bullous pemphigoid and psoriasis: systematic review and meta-analysis of case-control studies. Australas J Dermatol 2019; 60: 23-28.
https://doi.org/10.1111/ajd.12899 DOI: https://doi.org/10.1111/ajd.12899
Hübner F, Langan EA, Recke A. Lichen planus pemphigoides: from lichenoid inflammation to autoantibody-mediated blistering. Front Immunol 2019; 10: 1389.
https://doi.org/10.3389/fimmu.2019.01389 DOI: https://doi.org/10.3389/fimmu.2019.01389
Verheyden MJ, Bilgic A, Murrell DF. A systematic review of drug-induced pemphigoid. Acta Derm Venereol 2020; 100: adv00224.
https://doi.org/10.2340/00015555-3457 DOI: https://doi.org/10.2340/00015555-3457
Li J, Zuo YG, Zheng HY, Qiu-Ning S. Association between bullous pemphigoid and internal diseases. J Dtsch Dermatol Ges 2013; 11: 263-264.
https://doi.org/10.1111/ddg.12002 DOI: https://doi.org/10.1111/ddg.12002
Pankakoski A, Sintonen H, Ranki A, Kluger N. Comorbidities of bullous pemphigoid in a Finnish cohort. Eur J Dermatol 2018; 28: 157-161.
https://doi.org/10.1684/ejd.2018.3243 DOI: https://doi.org/10.1684/ejd.2018.3243
Venning VA, Wojnarowska F. The association of bullous pemphigoid and malignant disease: a case control study. Br J Dermatol 1990; 123: 439-445.
https://doi.org/10.1111/j.1365-2133.1990.tb01447.x DOI: https://doi.org/10.1111/j.1365-2133.1990.tb01447.x
Atzmony L, Mimouni I, Reiter O, Leshem YA, Taha O, Gdalevich M, et al. Association of bullous pemphigoid with malignancy: a systematic review and meta-analysis. J Am Acad Dermatol 2017; 77: 691-699.
https://doi.org/10.1016/j.jaad.2017.05.006 DOI: https://doi.org/10.1016/j.jaad.2017.05.006
Cai SC, Allen JC, Lim YL, Tan SH, Tang MB. Association of bullous pemphigoid and malignant neoplasms. JAMA Dermatol 2015; 151: 665-667.
https://doi.org/10.1001/jamadermatol.2014.5263 DOI: https://doi.org/10.1001/jamadermatol.2014.5263
Lucariello RJ, Villablanca SE, Mascaró JM, Reichel M. Association between bullous pemphigoid and malignancy: a meta-analysis. Australas J Dermatol 2018; 59: 253-260.
https://doi.org/10.1111/ajd.12764 DOI: https://doi.org/10.1111/ajd.12764
Jackson SR, Koestenbauer J, Carroll AP, Oo TH, Chou S, Indrajit B. Paraneoplastic bullous pemphigoid - a sign of clear cell renal carcinoma. Urol Case Rep 2020; 30: 101119.
https://doi.org/10.1016/j.eucr.2020.101119 DOI: https://doi.org/10.1016/j.eucr.2020.101119
Das A, Das S, Das SK, Basuthakur S. A case of paraneoplastic bullous pemphigoid in association with squamous cell carcinoma of lung. J Postgrad Med 2015; 61: 197-199.
https://doi.org/10.4103/0022-3859.150906 DOI: https://doi.org/10.4103/0022-3859.150906
Kridin K, Bergman R. Ethnic variations in the epidemiology of bullous pemphigoid in Israel. Int J Dermatol 2018; 57: 34-39.
https://doi.org/10.1111/ijd.13813 DOI: https://doi.org/10.1111/ijd.13813
Alpsoy E, Akman-Karakas A, Uzun S. Geographic variations in epidemiology of two autoimmune bullous diseases: pemphigus and bullous pemphigoid. Arch Dermatol Res 2015; 307: 291-298.
https://doi.org/10.1007/s00403-014-1531-1 DOI: https://doi.org/10.1007/s00403-014-1531-1
Iwashita K, Matsuyama T, Akasaka E, Mizutani K, Yamamoto K, Kondoh A, et al. The incidence of internal malignancies in autoimmune bullous diseases. Tokai J Exp Clin Med 2007; 32: 42-47.
Schulze F, Neumann K, Recke A, Zillikens D, Linder R, Schmidt E. Malignancies in pemphigus and pemphigoid diseases. J Invest Dermatol 2015; 135: 1445-1447.
https://doi.org/10.1038/jid.2014.547 DOI: https://doi.org/10.1038/jid.2014.547
Balestri R, Magnano M, La Placa M, Patrizi A, Angileri L, Tengattini V, et al. Malignancies in bullous pemphigoid: a controversial association. J Dermatol 2016; 43: 125-133.
https://doi.org/10.1111/1346-8138.13079 DOI: https://doi.org/10.1111/1346-8138.13079
Moro F, Fania L, Sinagra JLM, Salemme A, Di Zenzo G. Bullous pemphigoid: trigger and predisposing factors. Biomolecules 2020; 10: E1432.
https://doi.org/10.3390/biom10101432 DOI: https://doi.org/10.3390/biom10101432
Wang LL, Patel G, Chiesa-Fuxench ZC, McGettigan S, Schuchter L, Mitchell TC, et al. Timing of onset of adverse cutaneous reactions associated with programmed cell death protein 1 inhibitor therapy. JAMA Dermatol 2018; 154: 1057-1061.
https://doi.org/10.1001/jamadermatol.2018.1912 DOI: https://doi.org/10.1001/jamadermatol.2018.1912
Tanita K, Fujimura T, Kambayashi Y, Tsukada A, Sato Y, Hashimoto A, et al. Intensity-modulated radiotherapy triggers onset of bullous pemphigoid in a patient with advanced melanoma treated with nivolumab. Case Rep Oncol 2018; 11: 114-118.
https://doi.org/10.1159/000487127 DOI: https://doi.org/10.1159/000487127
Choi R, Cowper S, Young M, Leventhal J. Bullous pemphigoid exacerbated by radiation therapy: an atypical presentation. Adv Radiat Oncol 2022; 7: 100794.
https://doi.org/10.1016/j.adro.2021.100794 DOI: https://doi.org/10.1016/j.adro.2021.100794
Kumar N, Chugh H, Tomar R, Tomar V, Singh VK, Chandra R. Exploring the interplay between autoimmunity and cancer to find the target therapeutic hotspots. Artif Cells Nanomed Biotechnol 2018; 46: 658-668.
https://doi.org/10.1080/21691401.2017.1350188 DOI: https://doi.org/10.1080/21691401.2017.1350188
Hsu DC, Katelaris CH. Long-term management of patients taking immunosuppressive drugs. Aust Prescr 2009; 32: 68-71.
https://doi.org/10.18773/austprescr.2009.035 DOI: https://doi.org/10.18773/austprescr.2009.035
Kridin K, Hundt JE, Ludwig RJ, Amber KT, Bitan DT, Cohen AD. Melanoma is associated with an increased risk of bullous pemphigoid: a large population-based longitudinal study. Arch Dermatol Res 2022; 314: 77-83.
https://doi.org/10.1007/s00403-021-02211-4 DOI: https://doi.org/10.1007/s00403-021-02211-4
Hwang BJ, Zhang Y, Brozowski JM, Liu Z, Burette S, Lough K, et al. The dysfunction of BP180/collagen XVII in keratinocytes promotes melanoma progression. Oncogene 2019; 38: 7491-7503.
https://doi.org/10.1038/s41388-019-0961-9 DOI: https://doi.org/10.1038/s41388-019-0961-9
Bateman AC, Turner SJ, Theaker JM, Howell WM. HLA-DQB1*0303 and *0301 alleles influence susceptibility to and prognosis in cutaneous malignant melanoma in the British Caucasian population. Tissue Antigens 1998; 52: 67-73.
https://doi.org/10.1111/j.1399-0039.1998.tb03025.x DOI: https://doi.org/10.1111/j.1399-0039.1998.tb03025.x
Büdinger L, Borradori L, Yee C, Eming R, Ferencik S, Grosse-Wilde H, et al. Identification and characterization of autoreactive T cell responses to bullous pemphigoid antigen 2 in patients and healthy controls. J Clin Invest 1998; 102: 2082-2089.
https://doi.org/10.1172/JCI3335 DOI: https://doi.org/10.1172/JCI3335
Caccavale S. The association of bullous pemphigoid and malignancy: a case control study. G Ital Dermatol Venereol 2015; 150: 764-765.
Gilmour E, Bhushan M, Griffiths CE. Figurate erythema with bullous pemphigoid: a true paraneoplastic phenomenon. Clin Exp Dermatol 1999; 24: 446-448.
https://doi.org/10.1046/j.1365-2230.1999.00528.x DOI: https://doi.org/10.1046/j.1365-2230.1999.00528.x
Grilletta EA, Ellis DL. Paraneoplastic bullous pemphigoid presenting with erythema gyratum repens-like figurate erythema. JAAD Case Rep 2021; 12: 37-39.
https://doi.org/10.1016/j.jdcr.2021.03.043 DOI: https://doi.org/10.1016/j.jdcr.2021.03.043
Shrestha P, George MK, Baidya S, Rai SK. Bullous pemphigoid associated with squamous cell lung carcinoma showing remarkable response to carboplatin-based chemotherapy: a case report. J Med Case Rep 2022; 16: 184.
https://doi.org/10.1186/s13256-022-03323-9 DOI: https://doi.org/10.1186/s13256-022-03323-9
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2023 Sharon Baum, Shani Steinberg, Ido Tzanani , Aviv Barzilai , Anna Lyakhovitsky
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.