Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2025;15(1):4458 1 Causal Relationship Between Psoriasis and Bullous Pemphigoid: A Mendelian Randomization Analysis Xiaoxue Wang1, Zexin Zhu2 1 Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China 2 Department of Surgical Oncology, The Comprehensive Breast Care Center, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China Key words: Psoriasis, Bullous pemphigoid, Mendelian randomization, Causal relationship Citation: Wang X, Zhu Z. Causal Relationship Between Psoriasis and Bullous Pemphigoid: A Mendelian Randomization Analysis. Dermatol Pract Concept. 2025;15(1):4458. DOI: https://doi.org/10.5826/dpc.1501a4458 Accepted: August 12, 2024; Published: January 2025 Copyright: ©2024 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: This work was supported by the Natural Science Foundation of China (Grant number: 82404921). Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Zexin Zhu, Department of Surgical Oncology, The Comprehensive Breast Care Center, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China. Email: zhuzexinmd@163.com Introduction: Psoriasis and bullous pemphigoid  (BP)  are the two major types of immune- mediated  inflammatory  skin diseases. Studies have reported the  association between psoriasis and BP;  however, no studies have reported whether a causal relationship exists between these two skin diseases. Objectives: In order to explore the causal relationship between psoriasis and BP, we performed a bidirectional two-sample Mendelian randomization (MR) study. Methods: Genome-wide association study (GWAS) data related to psoriasis and BP were collected. The inverse-variance weighted (IVW) method was primarily applied for our MR analysis; MR-Egger, weighted median, simple mode, and weighted mode methods were also used. Heterogeneity, horizontal pleiotropy, and potential outliers were assessed for the MR analysis results. Results: GWAS data for psoriasis (three cohorts) and BP (one cohort) from publicly available trials were selected. Our MR results showed that psoriasis was causally associated with BP, that psoriasis could increase the risk of BP, and that reversed MR showed BP has no causal effect on psoriasis. No heterogeneity or pleiotropy was detected.  Conclusion: These findings provided new evidence of the causal relationship between psoria- sis and BP. Our MR suggested  that psoriasis is potentially causal to BP, which helps us to im- prove the treatment strategy for patients with psoriasis. The mechanism remains open for further investigation. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2025;15(1):4458 Introduction Psoriasis is a common chronic inflammatory skin disease [1], with  a relatively high incidence and prevalence worldwide. Accordingly, psoriasis affects 2%–3% of adults in the USA and Europe, about 125 million people globally [2, 3]. Stud- ies have reported that patients with severe psoriasis have a significantly increased probability of loss of work, more than four times so, which gives rise to a greater impact on qual- ity of life [4]. Pathologically, the development of psoriasis is mainly attributed to immune dysfunction, vascular injury, disturbance of signal transduction pathway, and imbalance of psoriasis-related gene expression. The most common clin- ical characteristic in psoriasis is red or pink plaques covered by silvery scales. Emerging studies have gradually illumi- nated the pathogenesis of psoriasis in the past years. Mean- while, the etiology of psoriasis still remains largely elusive. A specific aspect of psoriasis progression involves substantial psychological disability, with up to 20% of those affected reporting symptoms of depression [5]. Treatment strategies for patients with psoriasis include topical therapies, oral medications, biologic agents, and phototherapy. For patients with severe disease, which cannot be controlled with the fundamental use of topical therapies (e.g. corticosteroids), systemic biologic agents such as adalimumab, ustekinumab, secukinumab, or ixekizumab more frequently considered [6]. However, given the highly heterogeneous character of psoriasis, biologic therapies are suitable for only a minority of patients. Bullous pemphigoid (BP) is the major type of pemphi- goid, belonging to an autoantibody-mediated blistering skin disease [7]. BP primarily affects the elderly (with an average age of 80 years at presentation), and the death rate is three times higher than that of controls (pemphigus vulgaris), sta- tistically [8]. Tense bullae that appear on erythematous or normal skin are the clinical features of BP [9]. Subepider- mal blisters with inflammation are the histological hallmark of BP, and eosinophils are frequently observed in the blister cavity and at the intact basement membrane zone [9]. Cor- ticosteroids, azathioprine, and plasmapheresis are treatment options for BP [10]. Recently, studies have reported the as- sociation between BP and other diseases. Accordingly, com- pared to matched controls, patients with BP have a threefold increased risk of developing pneumonia and pulmonary em- bolism [8], and between 30% and 50% of BP patients have neurological diseases [11]. As mentioned, psoriasis and BP are common immune- related dermatological diseases, and studies have also re- ported the association of BP with psoriasis [12]. Whether a causal relationship exists between psoriasis and BP remains unclear. Objectives Mendelian randomization (MR) is an emerging method to determine the existence and the strength of the causal rela- tionship between an exposure and an outcome [13]. In MR, researchers need to choose single nucleotide polymorphisms (SNPs) and use them as instrument variables (IVs) [14]. Dif- ferent from a randomized controlled trial, which is typically expensive, time-consuming, and sometimes infeasible, MR relies on observational data [14]. In order to identify any causal influence between psoriasis and BP, we carried out a bidirectional MR analysis. Based on genome-wide associa- tion studies (GWAS), genetic variants related to psoriasis and BP were screened as instrumental variables (IVs). Methods Study Design Figure 1 shows our MR framework. In this study, there were three key assumptions: 1. Relevance Assumption: Single nucleotide polymorphisms (SNPs) that are substantially linked to exposures are used as instrumental variables (IVs). 2. Independence Assumption: These SNPs (IVs) should not show any correlation with the relevant confound- ing factor. 3. Exclusivity Assumption: These SNPs (IVs) should affect outcomes only through their effect on exposure [15, 16]. GWAS Summary Data Source We retrospectively used summary data associated with psori- asis and BP from MRC Integrative Epidemiology Unit Open GWAS database (https://gwas.mrcieu.ac.uk) and FinnGen (https://www.finngen.fi/en/access_results). Accession num- bers ebi-a-GCST90018907 (psoriasis 5,072 cases; 478,102 controls) [17], ukb-b-10537 (psoriasis 5,314 cases; 457,619 controls), finn-b-L12_PSORI_VULG (psoriasis 2,802 cases; 212,242 controls); finn-b-L12_PEMPHIGOID_BULL (BP 219 cases; 218,066 controls) summary data were ac- cessed from IEU Open GWAS project database (https:// gwas.mrcieu.ac.uk). Our study was conducted by secondary analysis of data from other studies. All participants or their family members provided informed written consent in the original studies. Detailed information of data elements for psoriasis and BP was listed in Table 1. Instrumental Variables Selection Related IVs  for MR analysis followed particular principles:  SNPs should be associated with exposures at the locus-wide significance level (P <5e-06 for psoriasis, Original Article | Dermatol Pract Concept. 2025;15(1):4458 3 P <5e-08 for BP). In addition, linkage disequilibrium (LD) coefficient R2 should be less than 0.001, not closely related (clumping window more than 10,000 kb) to ensure exposure instrument independence. We used the F statistic to measure the strength of the IVs; the values of F-statistics were more than 10. MR Analysis Causal relationships between psoriasis and bullous pemphi- goid (BP) were investigated utilizing Mendelian randomiza- tion (MR) and reverse causality analysis (Supplementary Table S1). In the assessment of exposure and outcome, we employed MR with multiple single nucleotide polymorphisms (SNPs) serving as instrumental variables (IVs). Each IV pro- vides an independent estimate of the causal effect, which can be aggregated through a fixed effect, inverse variance-weighted (IVW) meta-analysis. The primary statistical analysis for as- sessing causal effects was performed using the IVW method, complemented by additional approaches such as simple mode, weighted median, weighted mode, and MR-Egger to further validate the results. The MR-Egger method was applied through a straightforward modification of the previously es- tablished weighted linear regression technique. This method was specifically utilized to assess the robustness of the MR findings as a form of validation. [15, 16, 18]. Sensitivity Analysis The heterogeneity of the chosen SNPs was evaluated using Cochran’s Q test; a p-value of more than 0.05 suggested the lack of heterogeneity. The random effects model was used once significant heterogeneity had been identified. We eval- uated the possible bias from horizontal pleiotropy using the weighted median and MR-Egger regression in order to gauge the robustness of the IVW method. The MR-PRESSO (Men- delian Randomization Pleiotropy RESidual Sum and Out- lier) test was used to identify outliers that might have been influenced by horizontal pleiotropy. The causal effect esti- mates for individual variants were displayed using a scatter plot. Thereafter, we carried out a “leave-one-out” to test the robustness of the results [15, 16, 18]. Table 1. GWAS Summary Data Sources Included in the Study. Diseases GWAS ID N of Cases N of Controls Population N of SNPs Psoriasis ebi-a-GCST90018907 5,072 478,102 European 15 Psoriasis ukb-b-10537 5,314 457,619 European 21 Psoriasis finn-b-L12_PSORI_ VULG 2,802 212,242 European 10 Bullous pemphigoid finn-b-L12_ PEMPHIGOID_BULL 219 218,066 European 14 Abbreviations: GWAS: genome-wide association studies; SNPs: single nucleotide polymorphisms. Figure 1. The flowchart adhered to the principles of MR analysis as outlined in this study. 4 Original Article | Dermatol Pract Concept. 2025;15(1):4458 (ebi-a-GCST90018907: Figure 2; ukb-b-10537: Figure 3; finn-b-L12_PSORI_VULG: Table 2). Instead, the reversed MR showed that BP has no causal relationship with the risk of psoriasis (Table 3). Using the MR-Egger, the rela- tionships between psoriasis and BP had the same direction (Figure 4A–C). Sensitivity Analysis According to the analysis of Cochran’s Q test, our IVW-MR analysis results demonstrated no evidence of heterogeneity among the reported results. Furthermore, the MR-Egger regression and MR-PRESSO analysis results provided evi- dence that there exists no significant horizontal pleiotropy in our MR analysis (Table 4).  The symmetric funnel plot (Figure S1) indicated no evidence of horizontal pleiotropy. We also conducted the leave-one-out method to identify and delete abnormal instrumental variables. The results showed the robustness of our results (Figure S2). These results sug- gest that the MR analysis results were relatively stable. Statistical Analysis All data were analyzed by R software (Version 4.3.2), “Two-Sample MR package” (Version 0.5.8). The statistical significance level is P <0.05. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated. Results Instrumental Variables According to the quality control principle as mentioned, SNPs related to psoriasis and BP were adopted as instrumen- tal variables (IVs). Table 1 shows the essential information regarding psoriasis and BP. The SNPs included in the expo- sure data are detailed in Supplementary Table S2. MR Analysis We conducted a two-sample MR analysis between pso- riasis and BP. The IVW MR analysis demonstrated that psoriasis has a causal relationship with the risk of BP Figure 2. Forest Plot of Mendelian Randomization Analysis for Psoriasis (ebi-a-GCST90018907) on BP Risk. Abbreviations: CI: confidence interval; OR: odds ratio. Figure 3. Forest Plot of Mendelian Randomization Analysis for Psoriasis (finn-b-L12_PSORI_VULG) on BP Risk. Abbreviations: CI: confidence interval; OR: odds ratio. Original Article | Dermatol Pract Concept. 2025;15(1):4458 5 is reported that psoriasis leads to an increased risk of the pathosis of other organ systems, for example, cardiovas- cular disease, psoriatic arthritis, obesity, diabetes mellitus, nonalcoholic fatty liver disease, and inflammatory bowel disease, compared with that of the general population [27]. Bullous pemphigoid is characterized by local inflamma- tion and dermal-epidermal separation and belongs to autoantibody-mediated blistering skin disease, with no ap- proved targeted therapy [28]. Immunoprecipitation with BP sera of extracts of cultured keratinocytes identified two hemides- mosomal proteins—BP180 (180 kDa) and BP230 (230 kDa) [29, 30]—both of which have been identified as target an- tigens in BP. Pathologically, BP180 leads to the release of IL-6 and IL-8 [31]. As mentioned, psoriasis and BP are both skin diseases seen in clinical practice. Our MR study results suggest psoriasis itself might cause BP. Previous case-control studies showed similar results [12, 32]. According to a large- scale population-based cohort study, patients with psoriasis were statistically independently associated with a threefold Discussion Our results revealed psoriasis itself is an independent causal factor of BP. In addition, the sensitivity analysis supported the validity of the results. In contrast, our reverse MR analysis showed that BP was not significantly associated with psoria- sis progression. Psoriasis is recognized as a systemic autoim- mune disorder, with its etiology attributed to a combination of environmental factors, immune dysregulation, and genetic predisposition. [19]. The pathogenesis progression of psori- asis has gradually been expounded: extracellular cytokine pathways and intracellular signaling molecules take part in the progression of psoriasis, collectively [20]. Extracellu- lar cytokine pathways mainly included the tumor necrosis factor (TNF)/ interleukin (IL)-23/IL-17 pathways [21-23]; intracellular signaling pathways of transmission mainly included the nuclear factor kappa B (NF-κB) [24], Janus kinase/signal transducer and activator (JAK-STAT) [25], and mitogen-activated protein kinases (MAPK) pathway [26]. It Table 2. Causal Association of Psoriasis (ukb-b-10537) on BP. Methods OR 95% CI P-Value Inverse-variance weighted 1.201E+07 9.066-1.590e+13 0.023 MR-Egger 1.239E+03 1.200e-5-1.281e+11 0.459 Weighted median 1.757E+04 3.269e-4-9.445e+11 0.282 Simple mode 1.340E+22 8.637-2.070e+43 0.055 Weighted mode 4.542E+03 0.001-1.824e+11 0.358 Abbreviations: BP: bullous pemphigoid; CI: confidence interval; MR: Mendelian randomization; OR: odds ratio. Table 3. Reverse Causality Between BP and Psoriasis. BP Psoriasis ID Methods P-Value BP ebi-a-GCST90018907 Inverse-variance weighted 0.181 MR-Egger 0.722 Weighted median 0.765 Simple mode 0.776 Weighted mode 0.891 BP ukb-b-10537 Inverse variance weighted 0.870 MR-Egger 0.631 Weighted median 0.117 Simple mode 0.126 Weighted mode 0.149 BP finn-b-L12_PSORI_VULG Inverse variance weighted 0.319 MR-Egger 0.917 Weighted median 0.902 Simple mode 0.746 Weighted mode 0.756 Abbreviations: BP: bullous pemphigoid; MR: Mendelian randomization. 6 Original Article | Dermatol Pract Concept. 2025;15(1):4458 inhibitors (e.g., secukinumab or ustekinumab), could con- tribute to autoimmune processes and may also be a cause of BP development [12, 35]. As mentioned, specific autoanti- bodies have been identified in BP (BP180, BP230). Although these autoantibodies rarely exist in psoriasis, there may be other autoantibodies stimulated by T cell dysregulation in psoriasis patients. A common characteristic of psoriasis and BP is the disruption of the basement membrane integrity [33]. Our MR analysis indicated that, for psoriasis patients, we should work on preventing BP development early and carefully formulate clinical strategies. Usually, MR analysis chooses an exposure and an out- come. In our research, we chose three cohorts for psoriasis increased risk of BP [12]. In addition, a systematic review and meta-analysis showed a significantly higher rate of pso- riasis in patients with BP compared to controls [33]. The literature has also reported the co-occurrence of these two diseases [34]. To date, few studies have reported the potential mecha- nisms leading to the association between psoriasis and BP. Phototherapy is a prevalent treatment for patients with pso- riasis that may lead to autoantibody formation due to the change of the antigenicity of the basement membrane [12]. Utilization of immunosuppressants, such as biologic agents, is another explanation for how psoriasis could increase the risk of BP. The use of biologic agents, for instance, TNF-α Table 4. Sensitivity Analysis of Our MR Analysis. Psoriasis ID Q P-value for Cochran Q test Egger-intercept P-value for MR-Egger intercept P-value for MR-PRESSO Global test ebi-a-GCST90018907 16.227 0.181 -0.020 0.738 0.226 ukb-b-10537 18.495 0.489 0.051 0.148 0.417 finn-b-L12_PSORI_VULG 14.829 0.095 -0.112 0.279 0.160 Abbreviations: MR: Mendelian randomization; MR-PRESSO: Mendelian randomization pleiotropy residual sum and outlier. A B C MR Test MR Test 1.0 0.75 0.25 0.00 -0.25 -0.50 0.005 0.010 0.015 0.020 0.50 0.25 0.00 -0.25 0.3 0.6 0.9 0.5 0.0 0.5 SN P ef fe ct o n Bu llo us P em ph ig oi d || id :fi nn -b -L 12 _P EM PH IG O lD _B U LL SN P ef fe ct o n Bu llo us P em ph ig oi d || id :fi nn -b -L 12 _P EM PH IG O lD _B U LL SN P ef fe ct o n Bu llo us P em ph ig oi d || id :fi nn -b -L 12 _P EM PH IG O lD _B U LL 1.0 Inverse variance weighted MR Egger Simple mode Weighted median Weighted mode Inverse variance weighted MR Egger Simple mode Weighted median Weighted mode Inverse variance weighted MR Egger Simple mode Weighted median Weighted mode SNP e�ect on Psoriasis vulgaris || id:ebi-a-GCST90018907 SNP e�ect on Non-cancer illness code, self-reported: psoriasis || id:ukb-b-10537 SNP e�ect on Psoriasis vulgaris || id:finn-b-L12_PSORI_VULG MR Test Figure 4. Scatter Plots showing Significant Causal Effects among Three Psoriasis Cohorts and BP, respectively: (A) ebi-a-GCST90018907, (B) ukb-b-10537, (C) finn-b-L12_PSORI_VULG. Original Article | Dermatol Pract Concept. 2025;15(1):4458 7 Transduct Target Ther. 2023;8(1):1-38. DOI: 10.1038/s41392-023 -01655-6. PMID: 38008779. 2. Iversen L, Daudén E, Segaert S, et al. Reformulations of well- known active ingredients in the topical treatment of psoriasis vulgaris can improve clinical outcomes for patients. J Eur Acad Dermatol Venereol. 2017;31(8):1271-1284. DOI: 10.1111/jdv .14277. PMID: 28419600. 3. Krajina I, Stupin A, Šola M, Mihalj M. Oxidative stress induced by high salt diet—possible implications for development and clinical manifestation of cutaneous inflammation and endothelial dysfunc- tion in psoriasis vulgaris. Antioxidants (Basel). 2022;11(7):1269. DOI: 10.3390/antiox11071269. PMID: 35883760. 4. Meyer N, Paul C, Feneron D, et al. Psoriasis: an epidemiological evaluation of disease burden in 590 patients. J Eur Acad Derma- tol Venereol. 2010;24(9):1075-1082. DOI: 10.1111/j.1468-3083 .2010.03600.x. PMID: 20236205. 5. Sahi FM, Masood A, Danawar NA, Mekaiel A, Malik BH. Associa- tion between psoriasis and depression: a traditional review. Cureus. 2020;12(8):e9708. DOI: 10.7759/cureus.9708. PMID: 32944430. 6. Hoffman MB, Hill D, Feldman SR. Current challenges and emerging drug delivery strategies for the treatment of psoriasis. Expert Opin Drug Deliv. 2016;13(10):1461-1473. DOI: 10.1080 /17425247.2016.1188801. PMID: 27164301. 7. Hammers CM, Stanley JR. Mechanisms of disease: pemphigus and bullous pemphigoid. Annu Rev Pathol. 2016;11(1):175-197. DOI: 10.1146/annurev-pathol-012615-044313. PMID: 26907530. 8. Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJP, West J. Bullous pemphigoid and pemphigus vulgaris—incidence and mortality in the UK: population-based cohort study. BMJ. 2008;337:a180. DOI: 10.1136/bmj.a180. PMID: 18614511. 9. Schmidt E, Zillikens D. Pemphigoid diseases. Lancet. 2013; 381(9863):320-332. DOI: 10.1016/S0140-6736(12)61140-4. PMID: 23237497. 10. Kirtschig G, Middleton P, Bennett C, Murrell DF, Wojnarowska F, Khumalo NP. Interventions for bullous pemphigoid. Cochrane Database Syst Rev. 2010;(10):CD002292. DOI: 10.1002 /14651858.CD002292.pub3. PMID: 20927731. 11. Bastuji-Garin S, Joly P, Lemordant P, et al. Risk factors for bullous pemphigoid in the elderly: a prospective case–control study. J Invest Dermatol. 2011;131(3):637-643. DOI: 10.1038 /jid.2010.301. PMID: 20944650. 12. Ho YH, Hu HY, Chang YT, Li CP, Wu CY. Psoriasis is associ- ated with increased risk of bullous pemphigoid: a nationwide population-based cohort study in Taiwan. J Dermatol. 2019;46(7): 604-609. DOI: 10.1111/1346-8138.14902. PMID: 31062428. 13. Mounier N, Kutalik Z. Bias correction for inverse variance weight- ing Mendelian randomization. Genet Epidemiol. 2023;47(4): 314-331. DOI: 10.1002/gepi.22522. PMID: 37036286. 14. Wang K. Interval estimate of causal effect in summary data-based Mendelian randomization in the presence of winner’s curse. Genet Epidemiol. 2024;48(2):74-84. DOI: 10.1002/gepi.22545. PMID: 38282283. 15. Bowden J, Del Greco M F, Minelli C, Davey Smith G, Sheehan N, Thompson J. A framework for the investigation of pleiot- ropy in two-sample summary data Mendelian randomization. Stat Med. 2017;36(11):1783-1802. DOI: 10.1002/sim.7221. PMID: 28114746. 16. Boef AGC, Dekkers OM, le Cessie S. Mendelian randomization studies: a review of the approaches used and the quality of re- porting. Int J Epidemiol. 2015;44(2):496-511. DOI: 10.1093/ije /dyv071. PMID: 25953784. in three different GWAS databases; we analyzed the causal association between the three individual cohorts (exposure) and the BP (outcome). Interestingly, these three cohorts ob- tained similar results, namely that psoriasis has a causal im- pact on BP. These analyses enhance the robustness of our outcomes. Limitations There are several limitations to our  study. First, we were unable to divide the cohorts or perform subgroup analyses due to the original GWAS statistics. Second, our MR analy- sis only included individuals of the European population. As using a single European population in our MR analysis can limit population stratification bias, caution is needed when interpreting these findings and their applicability to different populations. Third, our results indicated that psoriasis has a causal influence on BP. There was no evidence that BP itself was a casual risk to psoriasis, but this does not mean BP had no impact on psoriasis. The fundamental mechanisms and pathways that contribute to the causal relationship between psoriasis and BP require further investigation and clarification. As previously mentioned, MR analysis can be conducted using only summary data, i.e., it is unnecessary to use individual- level data [14]. Inverse-variance weighted two-sample Men- delian randomization (IVW-MR) is the most commonly used approach that utilizes genome-wide association stud- ies (GWAS) summary statistics to infer the existence and the strength of the causal effect between an exposure and an outcome. In addition, two-sample MR methods expect the exposure and the outcome GWAS summary statistics to be obtained from independent samples. Estimates from this method can be biased due to weak instruments and to the winner’s curse, which can change as a function of the over- lap between the exposure and outcome samples. It should be noted that the method we used may bias our results [13, 14]. Conclusion Our MR analysis provides evidence that psoriasis has a causal impact on BP. Our findings indicate that we should pay attention to the possibility of BP development so as to improve treatment strategies for patients with psoriasis. Fur- ther investigations are required to elucidate the underlying mechanisms between the contributing risk factors of psori- asis to BP. References 1. Guo J, Zhang H, Lin W, Lu L, Su J, Chen X. Signal- ing pathways and targeted therapies for psoriasis. Signal 8 Original Article | Dermatol Pract Concept. 2025;15(1):4458 27. Korman NJ. Management of psoriasis as a systemic disease: what is the evidence? Br J Dermatol. 2019;182(4):840-848. DOI: 10.1111/bjd.18245. PMID: 31225638. 28. Vikár S, Szilveszter KP, Koszorú K, Sárdy M, Mócsai A. The Syk inhibitor entospletinib abolishes dermal-epidermal sepa- ration in a fully human ex vivo model of bullous pemphigoid. J Invest Dermatol. 2024;144(8):1733-1742. DOI: 10.1016/j. jid.2024.01.009. PMID: 38296021. 29. Díaz LA, Ratrie H, Saunders WS, et al. Isolation of a human epider- mal cDNA corresponding to the 180-kD autoantigen recognized by bullous pemphigoid and herpes gestationis sera. Immunolo- calization of this protein to the hemidesmosome. J Clin Invest. 1990;86(4):1088-1094. DOI: 10.1172/jci114812. PMID: 1698819. 30. Stanley JR, Hawley-Nelson P, Yuspa SH, Shevach EM, Katz SI. Characterization of bullous pemphigoid antigen: A unique base- ment membrane protein of stratified squamous epithelia. Cell. 1981;24(3):897-903. DOI: 10.1016/0092-8674(81)90115-x. PMID: 7018697. 31. Schmidt EE, Reimer S, Jainta S, et al. Autoantibodies to BP180 associated with bullous pemphigoid release interleukin-6 and interleukin-8 from cultured human keratinocytes. J Invest Dermatol. 2000;115(5):842-848. DOI: 10.1046/j.1523-1747 .2000.00141.x. PMID: 11069622. 32. Kridin K, Bergman R. Association between bullous pemphi- goid and psoriasis: A case-control study. J Am Acad Dermatol. 2017;77(2):370-372. DOI: 10.1016/j.jaad.2017.02.057. PMID: 28711088. 33. Phan K, Goyal S, Murrell DF. Association between bullous pem- phigoid and psoriasis: systematic review and meta-analysis of case-control studies. Australas J Dermatol. 2018;60(1):23-28. DOI: 10.1111/ajd.12899. PMID: 30141189. 34. Su F, Wang T, Qin Q, Xie Z. Upadacitinib for the manage- ment of bullous pemphigoid coexisting with psoriasis vul- garis: a case report and literature review. J Dermatol Treat. 2024;35(1):e2302394. DOI: 10.1080/09546634.2024.2302394. PMID: 38263708. 35. Ho PH, Tsai TF. Development of bullous pemphigoid during secuk- inumab treatment for psoriasis. J Dermatol. 2017;44(9):e220-e221. DOI: 10.1111/1346-8138.13909. PMID: 28543960. 17. Sakaue S, Kanai M, Tanigawa Y, et al. A cross-population atlas of genetic associations for 220 human phenotypes. Nat Genet. 2021;53(10):1415-1424. DOI: 10.1038/s41588-021-00931-x. PMID: 34594039. 18. Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512-525. DOI: 10.1093/ije/dyv080. PMID: 26050253. 19. Armstrong AW, Read C. Pathophysiology, clinical presenta- tion, and treatment of psoriasis. JAMA. 2020;323(19):1945. DOI: 10.1001/jama.2020.4006. PMID: 32427307. 20. Conrad C, Gilliet M. Psoriasis: from pathogenesis to targeted therapies. Clin Rev Allergy Immunol. 2018;54(1):102-113. DOI: 10.1007/s12016-018-8668-1. PMID: 29349534. 21. Teng MWL, Bowman EP, McElwee JJ, et al. IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune - mediated inflammatory diseases. Nat Med. 2015;21(7):719-729. DOI: 10.1038/nm.3895. PMID: 26121196. 22. Martin DA, Towne JE, Kricorian G, et al. The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical find- ings. J Invest Dermatol. 2013;133(1):17-26. DOI: 10.1038/jid .2012.194. PMID: 22673731. 23. Hu P, Wang M, Gao H, et al. The role of helper T cells in psoriasis. Front Immunol. 2021;12:788940. DOI: 10.3389/fimmu.2021 .788940. PMID: 34975883. 24. Zhou X, Chen Y, Cui L, Shi Y, Guo C. Advances in the patho- genesis of psoriasis: from keratinocyte perspective. Cell Death Dis. 2022;13(1):81. DOI: 10.1038/s41419-022-04523-3. PMID: 35075118. 25. Krueger JG, McInnes IB, Blauvelt A. Tyrosine kinase 2 and Janus kinase–signal transducer and activator of transcription signal- ing and inhibition in plaque psoriasis. J Am Acad Dermatol. 2022;86(1):148-157. DOI: 10.1016/j.jaad.2021.06.869. PMID: 34224773. 26. Liang J, Chen P, Li C, et al. IL-22 down-regulates Cx43 expres- sion and decreases gap junctional intercellular communication by activating the JNK pathway in psoriasis. J Invest Derma- tol. 2019;139(2):400-411. DOI: 10.1016/j.jid.2018.07.032. PMID: 30171832.