Prevalence, Spectrum and Clinical Implications of Malignancies in Patients with Bullous Pemphigoid


  • Sharon Baum Department of Dermatology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel
  • Shani Steinberg Sackler Faculty of Medicine, Tel Aviv University, Israel
  • Ido Tzanani Department of Dermatology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel
  • Aviv Barzilai Department of Dermatology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel; Institute of Pathology, Sheba Medical Center, Tel Hashomer, Israel
  • Anna Lyakhovitsky Department of Dermatology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel



bullous dermatoses, malignant melanoma, mortality rate, bullous pemphigoid


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. 


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Kridin K, Ludwig RJ. The growing incidence of bullous pemphigoid: overview and potential explanations. Front Med (Lausanne) 2018; 5: 220. DOI:

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. DOI:

Miyamoto D, Santi CG, Aoki V, Maruta CW. Bullous pemphigoid. An Bras Dermatol 2019; 94: 133-146. DOI:

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. DOI:

Daniel BS, Murrell DF. Review of autoimmune blistering diseases: the pemphigoid diseases. J Eur Acad Dermatol Venereol 2019; 33: 1685-1694. DOI:

Bernard P, Antonicelli F. Bullous pemphigoid: a review of its diagnosis, associations and treatment. Am J Clin Dermatol 2017; 18: 513-528. DOI:

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. DOI:

Egami S, Yamagami J, Amagai M. Autoimmune bullous skin diseases, pemphigus and pemphigoid. J Allergy Clin Immunol 2020; 145: 1031-1047. DOI:

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. DOI:

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. DOI:

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. DOI:

Hübner F, Langan EA, Recke A. Lichen planus pemphigoides: from lichenoid inflammation to autoantibody-mediated blistering. Front Immunol 2019; 10: 1389. DOI:

Verheyden MJ, Bilgic A, Murrell DF. A systematic review of drug-induced pemphigoid. Acta Derm Venereol 2020; 100: adv00224. DOI:

Li J, Zuo YG, Zheng HY, Qiu-Ning S. Association between bullous pemphigoid and internal diseases. J Dtsch Dermatol Ges 2013; 11: 263-264. DOI:

Pankakoski A, Sintonen H, Ranki A, Kluger N. Comorbidities of bullous pemphigoid in a Finnish cohort. Eur J Dermatol 2018; 28: 157-161. DOI:

Venning VA, Wojnarowska F. The association of bullous pemphigoid and malignant disease: a case control study. Br J Dermatol 1990; 123: 439-445. DOI:

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. DOI:

Cai SC, Allen JC, Lim YL, Tan SH, Tang MB. Association of bullous pemphigoid and malignant neoplasms. JAMA Dermatol 2015; 151: 665-667. DOI:

Lucariello RJ, Villablanca SE, Mascaró JM, Reichel M. Association between bullous pemphigoid and malignancy: a meta-analysis. Australas J Dermatol 2018; 59: 253-260. DOI:

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. DOI:

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. DOI:

Kridin K, Bergman R. Ethnic variations in the epidemiology of bullous pemphigoid in Israel. Int J Dermatol 2018; 57: 34-39. DOI:

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. DOI:

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. DOI:

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. DOI:

Moro F, Fania L, Sinagra JLM, Salemme A, Di Zenzo G. Bullous pemphigoid: trigger and predisposing factors. Biomolecules 2020; 10: E1432. DOI:

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. DOI:

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. DOI:

Choi R, Cowper S, Young M, Leventhal J. Bullous pemphigoid exacerbated by radiation therapy: an atypical presentation. Adv Radiat Oncol 2022; 7: 100794. DOI:

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. DOI:

Hsu DC, Katelaris CH. Long-term management of patients taking immunosuppressive drugs. Aust Prescr 2009; 32: 68-71. DOI:

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. DOI:

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. DOI:

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. DOI:

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. DOI:

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. DOI:

Grilletta EA, Ellis DL. Paraneoplastic bullous pemphigoid presenting with erythema gyratum repens-like figurate erythema. JAAD Case Rep 2021; 12: 37-39. DOI:

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. DOI:



How to Cite

Baum, S., Steinberg, S., Tzanani , I. ., Barzilai , A. ., & Lyakhovitsky , A. (2023). Prevalence, Spectrum and Clinical Implications of Malignancies in Patients with Bullous Pemphigoid. Acta Dermato-Venereologica, 103, adv00888.

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