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Advancing Treatment in Bullous Pemphigoid: A Comprehensive Review of Novel Therapeutic Targets and Approaches

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Abstract

Bullous pemphigoid is one of the most common autoimmune bullous diseases occurring primarily in the elderly. Pathogenic autoantibodies against BP180 and BP230 at the dermal–epidermal junction cause subepidermal blisters, erosions, and intense pruritus, all of which adversely affect the patients’ quality of life and may increase their morbidity and mortality. Current systemic treatment options for bullous pemphigoid are limited to corticosteroids and immunosuppressants, which can have substantial side effects on these vulnerable patients that even exceed their therapeutic benefits. Therefore, more precisely, targeting therapies to the pathogenic cells and molecules in bullous pemphigoid is an urgent issue. In this review, we describe the pathophysiology of bullous pemphigoid, focusing on autoantibodies, complements, eosinophils, neutrophils, proteases, and the T helper 2 and 17 axes since they are crucial in promoting proinflammatory environments. We also highlight the emerging therapeutic targets for bullous pemphigoid and their latest discoveries in clinical trials or experimental studies. Further well-designed studies are required to establish the efficacy and safety of these prospective therapeutic options.

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Data Availability

The data used in the current review were obtained from the original articles cited in the references and publicly available information from ClinicalTrials.gov. The datasets used and/or analyzed during the current review are available from the corresponding author (Chun-Bing Chen).

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Acknowledgements

Figures 1 and 2 were created with BioRender.com.

Funding

This work was supported by grants from the National Science and Technology Council, Taiwan (NSTC 109–2320-B-182A-008-MY3, 110–2320-B-182A-014-MY3, 111–2326-B-182A-003-, 111–2314-B-182A-113-MY3, 112-2326-B-182A-003-MY3), and Chang Gung Memorial Hospital (CORPG3L0471, CORPG3L0472, CORPG3M0361, CMRPG3M2221).

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Authors and Affiliations

  1. Department of Medical Education, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Hsuan-Chi Chen

  2. Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Keelung, Linkou, Taipei, Taiwan

    Chuang-Wei Wang, Hua-En Lee, Wen-Hung Chung & Chun-Bing Chen

  3. Cancer Vaccine and Immune Cell Therapy Core Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, Linkou, Taiwan

    Chuang-Wei Wang, Hua-En Lee, Wen-Hung Chung & Chun-Bing Chen

  4. Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung, Taiwan

    Chuang-Wei Wang, Wen-Hung Chung & Chun-Bing Chen

  5. Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China

    Chuang-Wei Wang, Wen-Hung Chung & Chun-Bing Chen

  6. Xiamen Chang Gung Allergology Consortium, Xiamen Chang Gung Hospital, Xiamen, China

    Chuang-Wei Wang, Wen-Hung Chung & Chun-Bing Chen

  7. Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA

    Wu Han Toh

  8. Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Wu Han Toh

  9. Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA

    Wu Han Toh

  10. Department of Biology, Johns Hopkins University, Baltimore, MD, USA

    Wu Han Toh

  11. School of Medicine, National Tsing Hua University, Hsinchu, Taiwan

    Chun-Bing Chen

  12. College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Hua-En Lee, Wen-Hung Chung & Chun-Bing Chen

  13. Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Chun-Bing Chen

  14. Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan

    Wen-Hung Chung & Chun-Bing Chen

  15. Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan

    Wen-Hung Chung

  16. Department of Dermatology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China

    Wen-Hung Chung

  17. Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Wen-Hung Chung

  18. Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan

    Wen-Hung Chung

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  1. Hsuan-Chi Chen
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Contributions

Conceptualization, H-CC, C-BC and W-HC; methodology and resources, H-CC, C-WW, W-HT, H-EL, and C-BC; writing—original draft preparation, H-CC and C-BC; writing—review and editing, H-CC, C-WW, W-HT, H-EL, W-HC, and C-BC; supervision, C-BC and W-HC; submission, H-CC and C-BC. All authors have read and agreed to the published version of the manuscript. Correspondence and reprint requests to C-BC.

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Correspondence to Wen-Hung Chung or Chun-Bing Chen.

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Chen, HC., Wang, CW., Toh, W.H. et al. Advancing Treatment in Bullous Pemphigoid: A Comprehensive Review of Novel Therapeutic Targets and Approaches. Clinic Rev Allerg Immunol 65, 331–353 (2023). https://doi.org/10.1007/s12016-023-08973-1

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