Reviews
Vol. 17 No. 3 (2025)
Venous thromboembolism in bullous pemphigoid: current evidence from an updated systematic review
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 29 January 2025
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Various studies have shown that individuals with bullous pemphigoid (BP) are more likely to develop venous thromboembolism (VTE). However, it is important to acknowledge that these studies primarily focused on individuals in Western nations, which restricts their generalization to a wider demographic. The present systematic review aims to assess the cumulative risk of VTE in individuals with BP compared to healthy individuals. PubMed, Cochrane, and Scopus databases were searched for evidence-based research papers on BP and VTE. Eligibility criteria were based on the PICOS criteria (population, intervention, comparison, outcome, and study design). The Newcastle-Ottawa scale assessed methodological quality. After database searches, 115 studies meeting the inclusion criteria were identified. A manual inquiry yielded an additional 11 articles. After removing duplicates (n=54), 72 publications underwent title and abstract evaluation, resulting in the exclusion of 44 manuscripts. Consequently, the remaining full-text articles were thoroughly reviewed, and ultimately, 9 publications were included. The studies were conducted in Denmark, the USA, the UK, Taiwan, and Italy. The findings enhanced the generalizability of the correlation between VTE and BP. Individuals with systemic autoimmune diseases were found to have a 1.5 to 4 times higher likelihood of developing VTE. The analysis revealed that patients with pemphigus face a twofold higher risk of VTE, especially within the first few years after diagnosis. These results may enhance the recognition of pulmonary embolism in BP patients and motivate the prevention of secondary risk markers associated with VTE. Given the morbidity, the VTE risk in BP patients warrants greater attention in public healthcare.
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1. 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;84:22-6. DOI: https://doi.org/10.4103/ijdvl.IJDVL_827_16
2. Moro F, Fania L, Sinagra JLM, et al. Bullous pemphigoid: Trigger and predisposing factors. Biomolecules 2020;10:1432. DOI: https://doi.org/10.3390/biom10101432
3. Kridin K, Shihade W, Bergman R. Mortality in patients with bullous pemphigoid: A retrospective cohort study, systematic review and meta-analysis. Acta Derm Venereol 2018;99:72-7. DOI: https://doi.org/10.2340/00015555-2930
4. Persson MS, Begum N, Grainge MJ, et al. The global incidence of bullous pemphigoid: a systematic review and meta-analysis. Br J Dermatol 2022;186:414-25. DOI: https://doi.org/10.1111/bjd.20743
5. Tamaki H, Khasnis A. Venous thromboembolism in systemic autoimmune diseases: A narrative review with emphasis on primary systemic vasculitides. Vasc Med 2015;20:369-76. DOI: https://doi.org/10.1177/1358863X15573838
6. Hsu CH, Hsu CK. Beyond the Surface: Investigating the Relationship Between Autoimmune Blistering Disorders and Venous Thromboembolism. J Am Heart Assoc 2023;12:e031086. DOI: https://doi.org/10.1161/JAHA.123.031086
7. Langan SM, Hubbard R, Fleming K, West J. A population-based study of acute medical conditions associated with bullous pemphigoid. Br J Dermatol 2009;161:1149-52. DOI: https://doi.org/10.1111/j.1365-2133.2009.09350.x
8. Maqsood MH, Weber BN, Haberman RH, et al. Cardiovascular and Venous Thromboembolic Risk With Janus Kinase Inhibitors in Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-Analysis of Randomized Trials. ACR Open Rheumatol 2022;4:912-22. DOI: https://doi.org/10.1002/acr2.11479
9. Ferranti M, Gobbo G, Cicogna GT, Alaibac M. A monocentric retrospective observational study of comorbidities in patients affected by autoimmune bullous diseases. In Vivo (Brooklyn) 2020;34:2113-8. DOI: https://doi.org/10.21873/invivo.12016
10. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021;372. DOI: https://doi.org/10.1136/bmj.n71
11. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603-5. DOI: https://doi.org/10.1007/s10654-010-9491-z
12. Chen TL, Huang WT, Loh CH, et al. Risk of Incident Venous Thromboembolism Among Patients With Bullous Pemphigoid or Pemphigus Vulgaris: A Nationwide Cohort Study With Meta-Analysis. J Am Heart Assoc 2023;12:e029740. DOI: https://doi.org/10.1161/JAHA.123.029740
13. Schneeweiss MC, Merola JF, Wyss R, et al. Venous Thromboembolism in Patients With Bullous Pemphigoid. JAMA Dermatol 2023;159:750-6. DOI: https://doi.org/10.1001/jamadermatol.2023.1461
14. Chen CL, Wu CY, Lyu YS, et al. Association between bullous pemphigoid and risk of venous thromboembolism: A nationwide population-based cohort study. J Dermatol 2022;49:753-61. DOI: https://doi.org/10.1111/1346-8138.16412
15. Shaheen MS, Silverberg JI. Association of inflammatory skin diseases with venous thromboembolism in US adults. Arch Dermatol Res 2021;313:281-9. DOI: https://doi.org/10.1007/s00403-020-02099-6
16. Kridin K, Kridin M, Amber KT, et al. The Risk of Pulmonary Embolism in Patients With Pemphigus: A Population-Based Large-Scale Longitudinal Study. Front Immunol 2019;10:1559. DOI: https://doi.org/10.3389/fimmu.2019.01559
17. Polansky M, Eisenstadt R, DeGrazia T, et al. Rituximab therapy in patients with bullous pemphigoid: a retrospective study of 20 patients. J Am Acad Dermatol 2019;81:179-86. DOI: https://doi.org/10.1016/j.jaad.2019.03.049
18. Cugno M, Marzano AV, Bucciarelli P, et al. Increased risk of venous thromboembolism in patients with bullous pemphigoid: The INVENTEP (INcidence of VENous Thromboembolism in bullous Pemphigoid) study. Thromb Haemost 2016;115:193-9. DOI: https://doi.org/10.1160/TH15-04-0309
19. Marzano AV, Tedeschi A, Polloni I, et al. Prothrombotic state and impaired fibrinolysis in bullous pemphigoid, the most frequent autoimmune blistering disease. Clin Exp Immunol 2013;171:76-81. DOI: https://doi.org/10.1111/j.1365-2249.2012.04674.x
20. Johannesdottir SA, Schmidt M, Horváth-Puhó E, Sørensen HT. Autoimmune skin and connective tissue diseases and risk of venous thromboembolism: A population-based case-control study. J Thromb Haemost 2012;10:815-21. DOI: https://doi.org/10.1111/j.1538-7836.2012.04666.x
21. Ramagopalan SV, Wotton CJ, Handel AE, et al. Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: Record-linkage study. BMC Med 2011;9:1. DOI: https://doi.org/10.1186/1741-7015-9-1
22. Zöller SB, Li X, Sundquist J, et al. Articles Risk of pulmonary embolism in patients with autoimmune disorders: a nationwide follow-up study from Sweden. Lancet. 2012;379:244-93. DOI: https://doi.org/10.1016/S0140-6736(11)61306-8
23. Langan SM, Hubbard R, Fleming K, West J. A population-based study of acute medical conditions associated with bullous pemphigoid. Br J Dermatol 2009;161:1149-52. DOI: https://doi.org/10.1111/j.1365-2133.2009.09350.x
24. Chen T, Lee L, Huang H, et al. Association of risk of incident venous thromboembolism with atopic dermatitis and treatment with Janus kinase inhibitors: a systematic review and meta-analysis. JAMA Dermatol 2022;158:1254-61. DOI: https://doi.org/10.1001/jamadermatol.2022.3516
25. Chen CL, Wu CY, Lyu YS, et al. Association between bullous pemphigoid and risk of venous thromboembolism: A nationwide population-based cohort study. J Dermatol 2022;49:753-61. DOI: https://doi.org/10.1111/1346-8138.16412
26. Podolec-Rubiś M, Wołek M, Brzewski P, Wojas-Pelc A. Suspicion of pulmonary embolism during treatment of pemphigoid gestationis. Postepy Dermatol Alergol 2013;30:59-61. DOI: https://doi.org/10.5114/pdia.2013.33381
27. Savin JA. The events leading to the death of patients with pemphigus and pemphigoid. Br J Dermatol 1979;101:521-34 DOI: https://doi.org/10.1111/j.1365-2133.1979.tb15095.x
28. Nagareddy P, Smyth SS. Inflammation and thrombosis in cardiovascular disease. Curr Opin Hematol 2013;20:457-63. DOI: https://doi.org/10.1097/MOH.0b013e328364219d
29. Xu J, Lupu F, Esmon CT. Inflammation, innate immunity, and blood coagulation. Hamostaseologie 2010;30:5-9. DOI: https://doi.org/10.1055/s-0037-1617146
30. Allenbach Y, Seror R, Pagnoux C, et al. High frequency of venous thromboembolic events in Churg-Strauss syndrome, Wegener’s granulomatosis and microscopic polyangiitis but not polyarteritis nodosa: A systematic Retrospective Study on 1130 patients. Ann Rheum Dis 2009;68:564-7. DOI: https://doi.org/10.1136/ard.2008.099051
31. Stassen PM, Derks RPH, Kallenberg CGM, Stegeman CA. Venous thromboembolism in ANCA-associated vasculitis - Incidence and risk factors. Rheumatology 2008;47:530-4. DOI: https://doi.org/10.1093/rheumatology/ken035
32. Weidner S, Hafezi-Rachti S, Rupprecht HD. Thromboembolic events as a complication of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res (Hoboken) 2006;55:146-9. DOI: https://doi.org/10.1002/art.21704
33. Cugno M, Tedeschi A, Borghi A, et al. Activation of blood coagulation in two prototypic autoimmune skin diseases: A possible link with thrombotic risk. PLoS One 2015;10:e0129456. DOI: https://doi.org/10.1371/journal.pone.0129456
34. Marzano AV, Tedeschi A, Berti E, et al. Activation of coagulation in bullous pemphigoid and other eosinophil-related inflammatory skin diseases. Clin Exp Immunol 2011;165:44-50. DOI: https://doi.org/10.1111/j.1365-2249.2011.04391.x
35. Marzano AV, Tedeschi A, Fanoni D, et al. Activation of blood coagulation in bullous pemphigoid: Role of eosinophils, and local and systemic implications. Br J Dermatol 2009;160:266-72. DOI: https://doi.org/10.1111/j.1365-2133.2008.08880.x
36. Echigo T, Hasegawa M, Shimada Y, et al. Both Th1 and Th2 chemokines are elevated in sera of patients with autoimmune blistering diseases. Arch Dermatol Res 2006;298:38-45. DOI: https://doi.org/10.1007/s00403-006-0661-5
37. Timoteo RP, Da Silva MV, Miguel CB, et al. Th1/Th17-related cytokines and chemokines and their implications in the pathogenesis of pemphigus vulgaris. Mediators Inflamm 2017;2017:7151285. DOI: https://doi.org/10.1155/2017/7151285
38. Sun CC, Wu J, Wong TT, et al. High levels of interleukin-8, soluble CD4 and soluble CD8 in bullous pemphigoid blister fluid. The relationship between local cytokine production and lesional T-cell activities. Br J Dermatol 2000;143:1235-40. DOI: https://doi.org/10.1046/j.1365-2133.2000.03894.x
39. Zhang L, Chen Z, Wang L, Luo X. Bullous pemphigoid: The role of type 2 inflammation in its pathogenesis and the prospect of targeted therapy. Front Immunol 2023;14:1115083. DOI: https://doi.org/10.3389/fimmu.2023.1115083
40. Kowalski EH, Kneibner D, Kridin K, Amber KT. Serum and blister fluid levels of cytokines and chemokines in pemphigus and bullous pemphigoid. Autoimmun Rev 2019;18:526-34. DOI: https://doi.org/10.1016/j.autrev.2019.03.009
41. Najem MY, Couturaud F, Lemarié CA. Cytokine and chemokine regulation of venous thromboembolism. J Thromb Haemost 2020;18:1009-19. DOI: https://doi.org/10.1111/jth.14759
42. Bieber K, Ernst AL, Tukaj S, et al. Analysis of serum markers of cellular immune activation in patients with bullous pemphigoid. Exp Dermatol 2017;26:1248-52. DOI: https://doi.org/10.1111/exd.13382
43. Tedeschi A, Marzano AV, Lorini M, et al. Eosinophil cationic protein levels parallel coagulation activation in the blister fluid of patients with bullous pemphigoid. J Eur Acad Dermatol Venereol 2015;29:813-7. DOI: https://doi.org/10.1111/jdv.12464
44. Echigo T, Hasegawa M, Inaoki M, et al. Antiphospholipid antibodies in patients with autoimmune blistering disease. J Am Acad Dermatol 2007;57:397-400. DOI: https://doi.org/10.1016/j.jaad.2006.07.004
45. Sagi L, Baum S, Barzilai O, et al. Novel antiphospholipid antibodies in autoimmune bullous diseases. Hum Antibodies 2015;23:27-30. DOI: https://doi.org/10.3233/HAB-140280
46. Chu KY, Yu HS, Yu S. Current and Innovated Managements for Autoimmune Bullous Skin Disorders: An Overview. J Clin Med 2022;11:3528. DOI: https://doi.org/10.3390/jcm11123528
47. Yang M, Wu H, Zhao M, et al. The pathogenesis of bullous skin diseases. J Transl Autoimmun 2019;2:100014. DOI: https://doi.org/10.1016/j.jtauto.2019.100014
48. Hall RP, Streilein RD, Hannah DL, et al. Association of serum B-cell activating factor level and proportion of memory and transitional B cells with clinical response after rituximab treatment of bullous pemphigoid patients. J Investig Dermatol 2013;133:2786-8. DOI: https://doi.org/10.1038/jid.2013.236
49. Lucchini E, Zaja F, Bussel J. Rituximab in the treatment of immune thrombocytopenia: What is the role of this agent in 2019? Haematologica 2019;104:1124-35. DOI: https://doi.org/10.3324/haematol.2019.218883
50. Orsi FA, Lijfering WM, Geersing GJ, et al. Glucocorticoid use and risk of first and recurrent venous thromboembolism: self-controlled case-series and cohort study. Br J Haematol 2021;193:1194-202. DOI: https://doi.org/10.1111/bjh.17388
51. Chen TL, Huang WT, Loh CH, et al. Risk of Incident Venous Thromboembolism Among Patients With Bullous Pemphigoid or Pemphigus Vulgaris: A Nationwide Cohort Study With Meta-Analysis. J Am Heart Assoc 2023;12:e029740. DOI: https://doi.org/10.1161/JAHA.123.029740
How to Cite
1.
Almutairi AG, Almutairi AG, Almutairi RR, Shadid A, Bin Dakhil AA, Alakrash L. Venous thromboembolism in bullous pemphigoid: current evidence from an updated systematic review. Dermatol Reports [Internet]. 2025 Jan. 29 [cited 2026 Sep. 2];17(3). Available from: https://journals.pagepress.net/dr/article/view/10257
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