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Neurological Cancer is a Risk Factor for Bullous Pemphigoid: 11-Year Population-Based Cohort Study

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Abstract

Background

There is evidence suggesting an association between bullous pemphigoid (BP) and a range of neurological diseases. Whether neurological cancer is a risk factor for BP remains unknown.

Objective

The aim of the study was to investigate the risk of subsequent BP among patients with neurological cancer.

Methods

This nationwide population-based cohort study was based on data obtained from the Taiwan National Health Insurance Research Database between 2000 and 2012. A total of 8313 patients with neurological cancer and 33,252 age-, sex-, and index-date-matched controls were recruited. The hazard ratio (HR) for subsequent BP in patients with neurological cancer was analyzed using a Cox model and Fine-Gray competing risk model, with mortality as the competing event.

Results

The incidence rates of BP per 100,000 person-years were 37.2 for patients with neurological cancer and 6.8 for controls. The crude incidence rate ratio was 5.49 (95% confidence interval [CI] 2.18–13.30). The mean time to occurrence of BP was 4.48 ± 3.40 years for patients with neurological cancer. Neurological cancer (HR 9.65, 95% CI 3.76–24.77 for the Cox model; HR 2.41, 95% CI 1.14–5.14 for the competing risk model), age per year (HR 1.10, 95% CI 1.05–1.15 for the Cox model; HR 1.06, 95% CI 1.02–1.09 for the competing risk model), and dementia (HR 6.31, 95% CI 2.49–15.99 for the Cox model; HR 7.50, 95% CI 2.84–19.85 for the competing risk model) significantly increased the risk of BP.

Conclusions

Neurological cancer increased the risk for subsequent BP by 2.4-fold, with a relatively short gap of 4.5 years.

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References

  1. Schmidt E, Zillikens D. Pemphigoid diseases. Lancet. 2013;381(9863):320–32.

    PubMed  Google Scholar 

  2. Marazza G, Pham HC, Scharer L, Pedrazzetti PP, Hunziker T, Trueb RM, Hohl D, Itin P, Lautenschlager S, Naldi L, et al. Incidence of bullous pemphigoid and pemphigus in Switzerland: a 2-year prospective study. Br J Dermatol. 2009;161(4):861–8.

    PubMed  CAS  Google Scholar 

  3. 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. J Am Acad Dermatol. 1999;41(2 Pt 1):266–8.

    PubMed  CAS  Google Scholar 

  4. Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJ, West J. Bullous pemphigoid and pemphigus vulgaris—incidence and mortality in the UK: population based cohort study. BMJ. 2008;337:a180.

    PubMed  CAS  Google Scholar 

  5. Brick KE, Weaver CH, Lohse CM, Pittelkow MR, Lehman JS, Camilleri MJ, Al-Hashimi M, Wieland CN. Incidence of bullous pemphigoid and mortality of patients with bullous pemphigoid in Olmsted County, Minnesota, 1960 through 2009. J Am Acad Dermatol. 2014;71(1):92–9.

    PubMed  PubMed Central  Google Scholar 

  6. Hubner F, Recke A, Zillikens D, Linder R, Schmidt E. Prevalence and age distribution of pemphigus and pemphigoid diseases in Germany. J Investig Dermatol. 2016;136(12):2495–8.

    PubMed  Google Scholar 

  7. Joly P, Baricault S, Sparsa A, Bernard P, Bedane C, Duvert-Lehembre S, Courville P, Bravard P, Remond B, Doffoel-Hantz V, et al. Incidence and mortality of bullous pemphigoid in France. J Investig Dermatol. 2012;132(8):1998–2004.

    PubMed  CAS  Google Scholar 

  8. Thorslund K, Seifert O, Nilzen K, Gronhagen C. Incidence of bullous pemphigoid in Sweden 2005–2012: a nationwide population-based cohort study of 3761 patients. Arch Dermatol Res. 2017;309(9):721–7.

    PubMed  PubMed Central  CAS  Google Scholar 

  9. Goletz S, Zillikens D, Schmidt E. Structural proteins of the dermal-epidermal junction targeted by autoantibodies in pemphigoid diseases. Exp Dermatol. 2017;26(12):1154–62.

    PubMed  CAS  Google Scholar 

  10. Stanley JR. Cell adhesion molecules as targets of autoantibodies in pemphigus and pemphigoid, bullous diseases due to defective epidermal cell adhesion. Adv Immunol. 1993;53:291–325.

    PubMed  CAS  Google Scholar 

  11. Brick KE, Weaver CH, Savica R, Lohse CM, Pittelkow MR, Boeve BF, Gibson LE, Camilleri MJ, Wieland CN. A population-based study of the association between bullous pemphigoid and neurologic disorders. J Am Acad Dermatol. 2014;71(6):1191–7.

    PubMed  PubMed Central  Google Scholar 

  12. Forsti AK, Jokelainen J, Ansakorpi H, Seppanen A, Majamaa K, Timonen M, Tasanen K. Psychiatric and neurological disorders are associated with bullous pemphigoid—a nationwide Finnish Care Register study. Sci Rep. 2016;6:37125.

    PubMed  PubMed Central  CAS  Google Scholar 

  13. Forsti AK, Huilaja L, Schmidt E, Tasanen K. Neurological and psychiatric associations in bullous pemphigoid-more than skin deep? Exp Dermatol. 2017;26(12):1228–34.

    PubMed  Google Scholar 

  14. Kibsgaard L, Rasmussen M, Lamberg A, Deleuran M, Olesen AB, Vestergaard C. Increased frequency of multiple sclerosis among patients with bullous pemphigoid: a population-based cohort study on comorbidities anchored around the diagnosis of bullous pemphigoid. Br J Dermatol. 2017;176(6):1486–91.

    PubMed  CAS  Google Scholar 

  15. Papakonstantinou E, Limberg MM, Gehring M, Kotnik N, Kapp A, Gibbs BF, Raap U. Neurological disorders are associated with bullous pemphigoid. J Eur Acad Dermatol Venereol. 2019;33(5):925–9.

    PubMed  CAS  Google Scholar 

  16. Pankakoski A, Sintonen H, Ranki A, Kluger N. Comorbidities of bullous pemphigoid in a Finnish cohort. Eur J Dermatol. 2018;28(2):157–61.

    PubMed  CAS  Google Scholar 

  17. Kokkonen N, Herukka SK, Huilaja L, Kokki M, Koivisto AM, Hartikainen P, Remes AM, Tasanen K. Increased levels of the bullous pemphigoid BP180 autoantibody are associated with more severe dementia in Alzheimer’s disease. J Investig Dermatol. 2017;137(1):71–6.

    PubMed  CAS  Google Scholar 

  18. Li L, Chen J, Wang B, Yao Y, Zuo Y. Sera from patients with bullous pemphigoid (BP) associated with neurological diseases recognized BP antigen 1 in the skin and brain. Br J Dermatol. 2009;160(6):1343–5.

    PubMed  CAS  Google Scholar 

  19. Chen J, Li L, Chen J, Zeng Y, Xu H, Song Y, Wang B. Sera of elderly bullous pemphigoid patients with associated neurological diseases recognize bullous pemphigoid antigens in the human brain. Gerontology. 2011;57(3):211–6.

    PubMed  Google Scholar 

  20. Seppanen A, Suuronen T, Hofmann SC, Majamaa K, Alafuzoff I. Distribution of collagen XVII in the human brain. Brain Res. 2007;1158:50–6.

    PubMed  Google Scholar 

  21. Kunzli K, Favre B, Chofflon M, Borradori L. One gene but different proteins and diseases: the complexity of dystonin and bullous pemphigoid antigen 1. Exp Dermatol. 2016;25(1):10–6.

    PubMed  Google Scholar 

  22. Chen CT, Hu HY, Chang YT, Li CP, Wu CY. Cancer is not a risk factor for bullous pemphigoid: 10-year population-based cohort study. Br J Dermatol. 2019;180(3):553–8.

    PubMed  CAS  Google Scholar 

  23. Dai YX, Wang SC, Chou YJ, Chang YT, Chen TJ, Li CP, Wu CY. Smoking, but not alcohol, is associated with risk of psoriasis in a Taiwanese population-based cohort study. J Am Acad Dermatol. 2019;80(3):727–34.

    PubMed  Google Scholar 

  24. Wu CY, Hu HY, Li CP, Chou YJ, Chang YT. Comorbidity profiles of psoriasis in Taiwan: a latent class analysis. PLoS One. 2018;13(2):e0192537.

    PubMed  PubMed Central  Google Scholar 

  25. Hou YC, Hu HY, Liu IL, Chang YT, Wu CY. The risk of autoimmune connective tissue diseases in patients with atopy: a nationwide population-based cohort study. Allergy Asthma Proc. 2017;38(5):383–9.

    PubMed  Google Scholar 

  26. Lau B, Cole SR, Gange SJ. Competing risk regression models for epidemiologic data. Am J Epidemiol. 2009;170(2):244–56.

    PubMed  PubMed Central  Google Scholar 

  27. de Glas NA, Kiderlen M, Vandenbroucke JP, de Craen AJ, Portielje JE, van de Velde CJ, Liefers GJ, Bastiaannet E, Le Cessie S. Performing survival analyses in the presence of competing risks: a clinical example in older breast cancer patients. J Natl Cancer Inst. 2016;108(5):djv366.

    PubMed  Google Scholar 

  28. Austin PC, Fine JP. Practical recommendations for reporting Fine-Gray model analyses for competing risk data. Stat Med. 2017;36(27):4391–400.

    PubMed  PubMed Central  Google Scholar 

  29. Messingham KN, Miller AD, Narayanan NS, Connell SJ, Fairley JA. Demographics and autoantibody profiles of pemphigoid patients with underlying neurologic diseases. J Investig Dermatol. 2019;139(9):1860–6.

    PubMed  CAS  Google Scholar 

  30. Chen YJ, Wu CY, Lin MW, Chen TJ, Liao KK, Chen YC, Hwang CY, Chu SY, Chen CC, Lee DD, et al. Comorbidity profiles among patients with bullous pemphigoid: a nationwide population-based study. Br J Dermatol. 2011;165(3):593–9.

    PubMed  CAS  Google Scholar 

  31. Lai YC, Yew YW, Lambert WC. Bullous pemphigoid and its association with neurological diseases: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2016;30(12):2007–15.

    PubMed  CAS  Google Scholar 

  32. Seppanen A, Autio-Harmainen H, Alafuzoff I, Sarkioja T, Veijola J, Hurskainen T, Bruckner-Tuderman L, Tasanen K, Majamaa K. Collagen XVII is expressed in human CNS neurons. Matrix Biol. 2006;25(3):185–8.

    PubMed  Google Scholar 

  33. Laffitte E, Burkhard PR, Fontao L, Jaunin F, Saurat JH, Chofflon M, Borradori L. Bullous pemphigoid antigen 1 isoforms: potential new target autoantigens in multiple sclerosis? Br J Dermatol. 2005;152(3):537–40.

    PubMed  CAS  Google Scholar 

  34. Taghipour K, Chi CC, Bhogal B, Groves RW, Venning V, Wojnarowska F. Immunopathological characteristics of patients with bullous pemphigoid and neurological disease. J Eur Acad Dermatol Venereol. 2014;28(5):569–73.

    PubMed  CAS  Google Scholar 

  35. Seppanen A. Collagen XVII: a shared antigen in neurodermatological interactions? Clin Dev Immunol. 2013;2013:240570.

    PubMed  PubMed Central  Google Scholar 

  36. Messingham KN, Randall G, Fairley J. Exploring mechanisms of IgE-mediated autoimmunity through the lens of bullous pemphigoid. G Ital Dermatol Venereol. 2016;151(2):186–97.

    PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Dermatology, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 11217, Taiwan

    Chen-Yi Wu & Yun-Ting Chang

  2. Department of Public Health, Institute of Public Health, National Yang Ming University, Taipei, Taiwan

    Chen-Yi Wu, Hsiao-Yun Hu & Yiing-Jenq Chou

  3. Department of Dermatology, National Yang-Ming University, Taipei, Taiwan

    Chen-Yi Wu & Yun-Ting Chang

  4. Department of Education and Research, Taipei City Hospital, Taipei, Taiwan

    Hsiao-Yun Hu

  5. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Chung-Pin Li

  6. National Yang-Ming University School of Medicine, Taipei, Taiwan

    Chung-Pin Li

Authors
  1. Chen-Yi Wu
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  2. Hsiao-Yun Hu
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Correspondence to Chen-Yi Wu.

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Funding

This study was supported by Grants from the Ministry of Science and Technology, ROC (MOST 108-2314-B-075-041-MY3) and Taipei Veterans General Hospital (V107C-009).

Conflict of interest

Chen-Yi Wu, Hsiao-Yun Hu, Yiing-Jenq Chou, Chung-Pin Li, and Yun-Ting Chang have no conflicts of interest to declare.

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Wu, CY., Hu, HY., Chou, YJ. et al. Neurological Cancer is a Risk Factor for Bullous Pemphigoid: 11-Year Population-Based Cohort Study. Am J Clin Dermatol 21, 591–597 (2020). https://doi.org/10.1007/s40257-019-00494-y

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  • DOI: https://doi.org/10.1007/s40257-019-00494-y

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