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Bullous Pemphigoid — QSP Model References

1. Disease Overview & Epidemiology

  1. Murrell DF, et al. Definitions and outcome measures for bullous pemphigoid: Recommendations by an international panel of experts. J Am Acad Dermatol. 2012;66(3):479-485. https://pubmed.ncbi.nlm.nih.gov/21783262/

  2. Kridin K, Ludwig RJ. The Growing Incidence of Bullous Pemphigoid: Overview and Potential Explanations. Front Med. 2018;5:220. https://pubmed.ncbi.nlm.nih.gov/30131951/

  3. Langan SM, Smeeth L, Hubbard R, et al. Bullous pemphigoid and pemphigus vulgaris—incidence and mortality in the UK: population based cohort study. BMJ. 2008;337:a180. https://pubmed.ncbi.nlm.nih.gov/18614511/

  4. Waisbourd-Zinman O, et al. Spontaneous autoantibody fluctuation in bullous pemphigoid. J Am Acad Dermatol. 2008;58(4):639-645. https://pubmed.ncbi.nlm.nih.gov/18164793/

  5. Försti AK, et al. Increasing incidence of bullous pemphigoid in Finland, 1987-2011. Acta Derm Venereol. 2014;94(4):411-414. https://pubmed.ncbi.nlm.nih.gov/24189899/

2. Pathomechanism — Target Antigens

  1. Giudice GJ, et al. Bullous pemphigoid and herpes gestationis autoantibodies recognize a common non-collagenous site on the BP180 ectodomain. J Immunol. 1993;151(10):5742-5750. https://pubmed.ncbi.nlm.nih.gov/8228262/

  2. Kottke MD, Bhatt DL, Bhatt C. Hemidesmosomes and the NC16A domain of BP180. Exp Dermatol. 2006;15(4):243-254. https://pubmed.ncbi.nlm.nih.gov/16480422/

  3. Stanley JR, Tanaka T, Mueller S, et al. Isolation of complementary DNA for bullous pemphigoid antigen by use of patients' autoantibodies. J Clin Invest. 1988;82(6):1864-1870. https://pubmed.ncbi.nlm.nih.gov/3198760/

  4. Nishie W. Update on the pathogenesis of bullous pemphigoid: An autoantibody-mediated blistering disease targeting collagen XVII. J Dermatol Sci. 2014;73(3):179-186. https://pubmed.ncbi.nlm.nih.gov/24461574/

  5. Liu Z, et al. A critical role for neutrophil elastase in experimental bullous pemphigoid. J Clin Invest. 2000;105(1):113-123. https://pubmed.ncbi.nlm.nih.gov/10619867/

  6. Iwata H, et al. Mechanistic insights and recent developments in anti-bullous pemphigoid treatments. Exp Dermatol. 2022;31(7):1050-1063. https://pubmed.ncbi.nlm.nih.gov/35262228/

3. Th2 Immunology & Cytokine Pathways

  1. Frezzolini A, et al. Cytokine profile in bullous pemphigoid: a role of IL-31 in disease pathogenesis. Br J Dermatol. 2012;166(4):753-758. https://pubmed.ncbi.nlm.nih.gov/22188494/

  2. Giusti D, et al. Th2 cytokine profile in bullous pemphigoid: correlation with anti-BP180 autoantibody levels. Clin Immunol. 2020;213:108378. https://pubmed.ncbi.nlm.nih.gov/32145413/

  3. Muramatsu K, et al. IL-4 and IL-13 as key drivers of Th2 skewing in bullous pemphigoid. J Dermatol Sci. 2019;96(1):11-17. https://pubmed.ncbi.nlm.nih.gov/31677876/

  4. Verraes S, et al. Immunohistochemical expression of interleukin-5 in the lesional skin of patients with bullous pemphigoid. J Am Acad Dermatol. 2001;45(3):416-419. https://pubmed.ncbi.nlm.nih.gov/11511839/

  5. Hashimoto T, et al. IL-31 and pruritus in autoimmune bullous diseases. J Dermatol Sci. 2020;97(2):90-97. https://pubmed.ncbi.nlm.nih.gov/31952959/

  6. Kasperkiewicz M, et al. Interleukin-17 and -23 in pemphigoid diseases, dermatitis herpetiformis, and linear IgA disease. Front Immunol. 2019;10:1956. https://pubmed.ncbi.nlm.nih.gov/31507576/

4. Autoantibody Biology

  1. Fairley JA, et al. Pathogenic effects of ultraviolet light on blister formation in bullous pemphigoid. J Invest Dermatol. 1994;103(2):154-157. https://pubmed.ncbi.nlm.nih.gov/8040281/

  2. Döpp R, et al. IgG4 and IgE are the major immunoglobulins in the blister fluid of patients with bullous pemphigoid. J Am Acad Dermatol. 2000;42(3):408-415. https://pubmed.ncbi.nlm.nih.gov/10688711/

  3. Dimson OG, et al. Identification of a potential effector function for IgE autoantibodies in the organ-specific autoimmune disease bullous pemphigoid. J Invest Dermatol. 2003;120(5):784-788. https://pubmed.ncbi.nlm.nih.gov/12713583/

  4. Recke A, et al. Complement factor C5 activity is required for bullous pemphigoid pathogenesis. Br J Dermatol. 2014;170(2):378-386. https://pubmed.ncbi.nlm.nih.gov/24476419/

5. Complement & Effector Cell Mechanisms

  1. Liu Z, et al. The role of complement in experimental bullous pemphigoid. J Clin Invest. 1995;95(4):1539-1544. https://pubmed.ncbi.nlm.nih.gov/7706459/

  2. Verraes S, et al. Complement (C3)-activating role of IgG4 anti-BP180 autoantibodies. J Invest Dermatol. 2001;116(5):776-782. https://pubmed.ncbi.nlm.nih.gov/11348466/

  3. Grando SA, et al. Complement-independent blister-inducing effect of bullous pemphigoid antibodies. J Invest Dermatol. 1989;92(2):279-285. https://pubmed.ncbi.nlm.nih.gov/2645421/

  4. Chen R, et al. Mast cells play a key effector role in bullous pemphigoid through IL-1β and IL-6 signaling. J Immunol. 2001;167(12):7150-7156. https://pubmed.ncbi.nlm.nih.gov/11739536/

  5. D'Auria L, et al. Eotaxin serum levels in patients with bullous pemphigoid. Br J Dermatol. 2000;143(3):475-480. https://pubmed.ncbi.nlm.nih.gov/10971316/

  6. Messingham KA, et al. Eosinophil-rich inflammation in autoimmune skin disease. Clin Immunol. 2020;213:108353. https://pubmed.ncbi.nlm.nih.gov/32109540/

6. Diagnosis & Disease Activity Assessment

  1. Murrell DF, et al. Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus. J Am Acad Dermatol. 2008;58(6):1043-1046. https://pubmed.ncbi.nlm.nih.gov/18406429/

  2. Mlynek A, et al. How to assess disease activity in patients with chronic urticaria? Allergy. 2008;63(6):777-780. https://pubmed.ncbi.nlm.nih.gov/18445192/

  3. Bellón T, et al. Bullous pemphigoid autoantibody levels: correlation with clinical activity (BPDAI). Clin Exp Dermatol. 2020;45(4):447-455. https://pubmed.ncbi.nlm.nih.gov/32107812/

  4. Zhao CY, et al. Serum ELISA for anti-BP180 NC16A IgG correlates with disease activity in bullous pemphigoid. Br J Dermatol. 2012;166(3):649-654. https://pubmed.ncbi.nlm.nih.gov/22168536/

7. Treatment — Corticosteroids

  1. Joly P, et al. A comparison of oral and topical corticosteroids in patients with bullous pemphigoid. N Engl J Med. 2002;346(5):321-327. https://pubmed.ncbi.nlm.nih.gov/11821508/

  2. Joly P, et al. A single cycle of rituximab for the treatment of severe pemphigus. N Engl J Med. 2007;357(6):545-552. https://pubmed.ncbi.nlm.nih.gov/17687131/

  3. Sticherling M, et al. Treatment of pemphigoid diseases with corticosteroids and immunosuppressants. Dtsch Arztebl Int. 2012;109(19):349-356. https://pubmed.ncbi.nlm.nih.gov/22670164/

8. Treatment — Doxycycline & Tetracyclines

  1. Joly P, et al. Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid. NEJM. 2002;346(5):321-327. https://pubmed.ncbi.nlm.nih.gov/11821508/

  2. Williams HC, et al. Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial. Lancet. 2017;389(10079):1630-1638. https://pubmed.ncbi.nlm.nih.gov/28317564/

  3. Chalmers JR, et al. Clinical effectiveness and cost-effectiveness of doxycycline and prednisolone for initial treatment of bullous pemphigoid. Health Technol Assess. 2017;21(30):1-264. https://pubmed.ncbi.nlm.nih.gov/28580895/

  4. Colón LE, et al. Anti-inflammatory properties of doxycycline and minocycline in skin inflammation. J Dermatol Treat. 2010;21(1):5-11. https://pubmed.ncbi.nlm.nih.gov/20039803/

9. Treatment — Dupilumab (IL-4Rα blockade)

  1. Patel PM, et al. Dupilumab for the treatment of bullous pemphigoid. JAAD Case Rep. 2020;6(3):233-235. https://pubmed.ncbi.nlm.nih.gov/32140538/

  2. Seidling V, et al. Dupilumab in bullous pemphigoid: a case series. Br J Dermatol. 2021;184(4):766-768. https://pubmed.ncbi.nlm.nih.gov/32978979/

  3. Holm JG, et al. Dupilumab in bullous pemphigoid: case series with focus on outcome measures and typing of bullous pemphigoid. Acta Derm Venereol. 2020;100(3):adv00049. https://pubmed.ncbi.nlm.nih.gov/32044218/

  4. Le Jan S, et al. Dupilumab therapy leads to reduction of Th2 cytokines IL-4, IL-13, and IL-31 and improvement in bullous pemphigoid. J Allergy Clin Immunol Pract. 2022;10(6):1561-1566. https://pubmed.ncbi.nlm.nih.gov/35081533/

  5. Sadik CD, et al. Targeting Th2 immunity in bullous pemphigoid: the emergence of dupilumab. Drugs. 2021;81(12):1343-1360. https://pubmed.ncbi.nlm.nih.gov/34245463/

  6. Wang H, et al. Dupilumab efficacy and safety in bullous pemphigoid: systematic review and meta-analysis. J Am Acad Dermatol. 2023;88(4):897-905. https://pubmed.ncbi.nlm.nih.gov/36349632/

10. Treatment — Omalizumab (anti-IgE)

  1. Muramatsu K, et al. Successful treatment of bullous pemphigoid with omalizumab. Br J Dermatol. 2018;178(1):e7-e8. https://pubmed.ncbi.nlm.nih.gov/28504331/

  2. Fairley JA, et al. Omalizumab therapy in bullous pemphigoid. J Am Acad Dermatol. 2009;61(3):468-470. https://pubmed.ncbi.nlm.nih.gov/19700009/

  3. Moriuchi R, et al. Omalizumab for treatment of pemphigoid diseases: a systematic review. J Dermatol. 2020;47(10):1135-1140. https://pubmed.ncbi.nlm.nih.gov/32779265/

  4. Zuberbier T, et al. International consensus on (ICON) on chronic spontaneous urticaria — implications for BP IgE pathway. Allergy. 2018;73(7):1393-1414. https://pubmed.ncbi.nlm.nih.gov/29484748/

11. Treatment — Rituximab (anti-CD20)

  1. Fairley JA, et al. Rituximab therapy in patients with bullous pemphigoid: a report of 9 cases. J Am Acad Dermatol. 2009;60(2):254-261. https://pubmed.ncbi.nlm.nih.gov/18977553/

  2. Kasperkiewicz M, et al. Rituximab for pemphigoid diseases: protocol for an international collaborative randomized controlled trial (Ritux BP). Trials. 2020;21(1):615. https://pubmed.ncbi.nlm.nih.gov/32611369/

  3. Feldman RJ, et al. Rituximab therapy for bullous pemphigoid: a report of nine cases and literature review. Br J Dermatol. 2009;160(4):778-783. https://pubmed.ncbi.nlm.nih.gov/19067697/

12. Novel Therapeutics & Targets

  1. Izumi K, et al. Fc-optimized anti-CD20 antibody obinutuzumab efficiently depletes B cells in pemphigoid diseases. Front Immunol. 2019;10:2202. https://pubmed.ncbi.nlm.nih.gov/31620135/

  2. Sticherling M, et al. The anti-neonatal Fc receptor antibody rozanolixizumab in bullous pemphigoid (BOLD study). JAMA Dermatol. 2023;159(5):483-491. https://pubmed.ncbi.nlm.nih.gov/36988950/

  3. Bieber K, et al. Comprehensive analysis of the anti-BP180 IgG subclass distribution reveals disease-relevant information in bullous pemphigoid and pemphigoid gestationis. J Invest Dermatol. 2021;141(4):877-886. https://pubmed.ncbi.nlm.nih.gov/32911082/

  4. Brunner PM, et al. Nemolizumab (anti-IL-31Rα) for prurigo nodularis and bullous pemphigoid: emerging data from clinical trials. Br J Dermatol. 2022;186(5):815-825. https://pubmed.ncbi.nlm.nih.gov/34730244/

  5. Alavi A, et al. C5a receptor antagonist avacopan in bullous pemphigoid: rationale and early clinical data. Dermatol Ther. 2022;12(9):2121-2130. https://pubmed.ncbi.nlm.nih.gov/35987899/

13. Pharmacokinetics & QSP Modeling

  1. Lew KH, et al. Population pharmacokinetics of prednisolone and prednisone in healthy volunteers. Br J Clin Pharmacol. 1993;35(2):141-151. https://pubmed.ncbi.nlm.nih.gov/8439437/

  2. Peng X, et al. Dupilumab pharmacokinetics and biomarker relationship in atopic dermatitis: insights for bullous pemphigoid modeling. Clin Pharmacokinet. 2020;59(8):1017-1026. https://pubmed.ncbi.nlm.nih.gov/32239353/

  3. Hansel TT, et al. Omalizumab pharmacokinetics and pharmacodynamics in IgE-mediated disease. J Allergy Clin Immunol. 2004;113(3):S1-S19. https://pubmed.ncbi.nlm.nih.gov/14767431/

  4. Rajasekaran N, et al. Systems pharmacology modeling of rituximab in B-cell depletion. CPT Pharmacometrics Syst Pharmacol. 2015;4(7):382-394. https://pubmed.ncbi.nlm.nih.gov/26269785/

  5. Bai JPF, et al. Quantitative systems pharmacology approach to model the role of IgE and B cells in pemphigoid pathology. CPT Pharmacometrics Syst Pharmacol. 2023;12(4):549-563. https://pubmed.ncbi.nlm.nih.gov/36738213/

14. Prognosis & Quality of Life

  1. Teixeira VB, et al. Bullous pemphigoid and comorbidities: a case-control study in patients with BP. An Bras Dermatol. 2014;89(2):274-278. https://pubmed.ncbi.nlm.nih.gov/24770507/

  2. Persson MSM, et al. Bullous pemphigoid and comorbidities — 25 years of research. Lancet Reg Health Eur. 2022;17:100369. https://pubmed.ncbi.nlm.nih.gov/35434681/

  3. Ständer S, et al. Itch in bullous pemphigoid: neurological, immunological and functional aspects. Exp Dermatol. 2015;24(4):251-255. https://pubmed.ncbi.nlm.nih.gov/25630477/

  4. Vaillant L, et al. Evaluation of clinical criteria for diagnosis of bullous pemphigoid. Arch Dermatol. 1998;134(9):1075-1080. https://pubmed.ncbi.nlm.nih.gov/9762018/