Prognostic factors for mortality in bullous pemphigoid: A systematic review and meta-analysis

Xianxia Chen, Yaqiang Zhang, Zhicheng Luo, Yujuan Wu, Taoxiang Niu, Jiayuan Zheng, Yuanyuan Xie, Xianxia Chen, Yaqiang Zhang, Zhicheng Luo, Yujuan Wu, Taoxiang Niu, Jiayuan Zheng, Yuanyuan Xie

Abstract

Objective: To systematically evaluate the prognostic factors for mortality in bullous pemphigoid.

Methods: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc and Wanfang Database were searched to collect literature on the prognostic factors for mortality in bullous pemphigoid. The quality of studies was assessed by Newcastle-Ottawa Quality Assessment Scale. Two researchers extracted relevant data and scored study quality independently. The hazard ratio (HR) was calculated using the random effects model. Study heterogeneity was assessed using both Cochran's Q test and I2 statistics. The causes of heterogeneity were assessed by subgroup analysis and/ or sensitivity analysis when heterogeneity was significant. When ten or more studies were included as outcome indicators, publication bias was evaluated by funnel plot and Egger's test.

Results: Out of a total of 1,546 articles retrieved, 15 studies involving 2,435 patients were included. The meta-analysis showed that the mortality of patients with bullous pemphigoid increased with positive bullous pemphigoid 180 antibody (HR = 1.85, 95%CI: 1.25~2.75, P = 0.002); concomitant dementia (HR = 2.26, 95%CI: 1.43~3.59, P<0.001); stroke (HR = 2.09, 95% CI: 1.23-3.55, P = 0.007); heart disease (HR = 1.96, 95% CI: 1.41-2.73, P<0.001) and diabetes mellitus (HR = 2.39, 95% CI: 1.55-3.69, P<0.001). Sex, positive indirect immunofluorescence and hypertension were not associated with prognosis.

Conclusion: Positive bullous pemphigoid 180 antibody, dementia, stroke, heart disease and diabetes mellitus were the prognostic factors for mortality in bullous pemphigoid.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

**Fig 1. The flowchart of literature screening.**

Fig 2. Forest plot of the association… — **Fig 2. Forest plot of the association between advanced age and bullous pemphigoid mortality.**

Fig 3. Forest plot of the subgroup… — **Fig 3. Forest plot of the subgroup analysis of the association between advanced age and bullous pemphigoid mortality.**

Fig 4. Funnel plot of the association… — **Fig 4. Funnel plot of the association between advanced age and bullous pemphigoid mortality.**

Fig 5. Egger’s publication bias plot of… — **Fig 5. Egger’s publication bias plot of the association between advanced age and bullous pemphigoid mortality.**

Fig 6. Trim and fill plot of… — **Fig 6. Trim and fill plot of publication bias on the association between advanced age and bullous pemphigoid mortality.**

Fig 7. Forest plot of the association… — **Fig 7. Forest plot of the association between sex and bullous pemphigoid mortality.**

Fig 8. Forest plot of the association… — **Fig 8. Forest plot of the association between disease severity and bullous pemphigoid mortality.**

Fig 9. Forest plot of the association… — **Fig 9. Forest plot of the association between the general condition and bullous pemphigoid mortality.**

Fig 10. Forest plot of the association… — **Fig 10. Forest plot of the association between positive bullous pemphigoid 180 antibody and bullous pemphigoid mortality.**

Fig 11. Forest plot of the association… — **Fig 11. Forest plot of the association between positive IIF and bullous pemphigoid mortality.**

Fig 12. Forest plot of the association… — **Fig 12. Forest plot of the association between dementia and bullous pemphigoid mortality.**

Fig 13. Forest plot of the association… — **Fig 13. Forest plot of the association between stroke and bullous pemphigoid mortality.**

Fig 14. Forest plot of the association… — **Fig 14. Forest plot of the association between hypertension and bullous pemphigoid mortality.**

Fig 15. Forest plot of the association… — **Fig 15. Forest plot of the association between heart disease and bullous pemphigoid mortality.**

Fig 16. Funnel plot of the association… — **Fig 16. Funnel plot of the association between heart disease and bullous pemphigoid mortality.**

Fig 17. Egger’s publication bias plot of… — **Fig 17. Egger’s publication bias plot of the association between heart disease and bullous pemphigoid mortality.**

Fig 18. Forest plot of the association… — **Fig 18. Forest plot of the association between diabetes mellitus and bullous pemphigoid mortality.**

References

1. Baigrie D, Nookala V. Bullous pemphigoid [M]. Treasure Island:StatPearls Publishing, 2020. .
1. Langan S M, Smeeth L, Hubbard R, Fleming K M, Smith C J, West J. Bullous pemphigoid and pemphigus vulgaris—incidence and mortality in the UK: population based cohort study[J]. Bmj, 2008, 337(7662):a180. doi: 10.1136/bmj.a180
1. Baican A, Baican C, Chiriac G, Chiriac M T, Macovei V, Zillikens D, et al.. Pemphigus vulgaris is the most common autoimmune bullous disease in Northwestern Romania[J]. Int J Dermatol, 2010, 49(7):768–774. doi: 10.1111/j.1365-4632.2009.04345.x
1. Serwin A B, Musialkowska E, Piascik M. Incidence and mortality of bullous pemphigoid in north-east Poland (Podlaskie Province), 1999–2012: a retrospective bicentric cohort study[J]. Int J Dermatol, 2014, 53(10):e432–7. doi: 10.1111/ijd.12492
1. Thorslund K, Seifert O, Nilzén K, Grönhagen C. Incidence of bullous pemphigoid in Sweden 2005–2012: a nationwide population-based cohort study of 3761 patients[J]. Arch Dermatol Res, 2017, 309(9):721–727. doi: 10.1007/s00403-017-1778-4
1. Kridin K, Ludwig R J. The growing incidence of bullous pemphigoid: overview and potential explanations[J]. Front Med (Lausanne), 2018, 5:220. doi: 10.3389/fmed.2018.00220
1. Miyamoto D, Santi C G, Aoki V, Maruta CW. Bullous pemphigoid[J]. An Bras Dermatol, 2019, 94(2):133–146. doi: 10.1590/abd1806-4841.20199007
1. Kridin K, Shihade W, Bergman R. Mortality in patients with bullous pemphigoid: A retrospective cohort study, systematic review and Meta-analysis[J]. Acta Derm Venereol, 2019, 99(1):72–77. doi: 10.2340/00015555-2930
1. Bernard P, Bedane C, Bonnetblanc J M. Anti-BP180 autoantibodies as a marker of poor prognosis in bullous pemphigoid: a cohort analysis of 94 elderly patients[J]. Br J Dermatol, 1997, 136(5):694–698. doi: 10.1046/j.1365-2133.1997.6581643.x
1. Monshi B, Gulz L, Piringer B, Wiala A, Kivaranovic D, Schmidt M, et al.. Anti BP180-autoantibody levels at diagnosis correlate with 1-year mortality rates in patients with bullous pemphigoid[J]. J Eur Acad Dermatol Venereol, 2020, 34(7): 1583–1589. doi: 10.1111/jdv.16363
1. Rozenblat M, Halaj A, Rozenblat T, Fisher S, Sah M, Dodiuk-Gad RP, et al.. Mortality and risk factors among Israeli bullous pemphigoid patients[J]. Arch Dermatol Res, 2019, 311(1):19–27. doi: 10.1007/s00403-018-1875-z
1. Jeon H W, Yun S J, Lee S C, Won Y H, Lee J B. Mortality and comorbidity profiles of patients with bullous pemphigoid in Korea[J]. Ann Dermatol, 2018, 30(1):13–19. doi: 10.5021/ad.2018.30.1.13
1. Kalinska-Bienias A, Lukowska-Smorawska K, Jagielski P, Kowalewski C, Wozniak K. Mortality in bullous pemphigoid and prognostic factors in 1st and 3rd year of follow-up in specialized centre in Poland[J]. Arch Dermatol Res, 2017, 309(9):709–719. doi: 10.1007/s00403-017-1772-x
1. Lee J H, Kim S C. Mortality of patients with bullous pemphigoid in Korea[J]. J Am Acad Dermatol, 2014, 71(4):676–683. doi: 10.1016/j.jaad.2014.05.006
1. Gual A, MascaróJ M Jr, Rojas-Farreras S, Guilabert A, Julià M, Iranzo P. Mortality of bullous pemphigoid in the first year after diagnosis: a retrospective study in a Spanish medical centre[J]. J Eur Acad Dermatol Venereol, 2014, 28(4):500–506. doi: 10.1111/jdv.12065
1. Cai S C, Allen J C, Lim Y L, Chua S H, Tan S H, Tang M B. Mortality of bullous pemphigoid in Singapore: risk factors and causes of death in 359 patients seen at the National Skin Centre[J]. Br J Dermatol, 2014, 170(6):1319–1326. doi: 10.1111/bjd.12806
1. Zhang L M, Wu J, Xiao T, Jin G Y, Li J H, Geng L, et al.. Treatment and mortality rate of bullous pemphigoid in China: a hospital-based study[J]. Eur J Dermatol, 2013, 23(1):94–98. doi: 10.1684/ejd.2012.1906
1. Li J, Zuo Y G, Zheng H Y. Mortality of bullous pemphigoid in China[J]. JAMA Dermatol, 2013, 149(1):106–108. doi: 10.1001/archdermatol.2012.2994
1. Cortés B, Khelifa E, Clivaz L, Cazzaniga S, Saurat J H, Naldi L, et al.. Mortality rate in bullous pemphigoid: A retrospective monocentric cohort study [J]. Dermatol, 2012, 225(4):320–325. doi: 10.1159/000345625
1. Cortés B, Marazza G, Naldi L, Combescure C, Borradori L. Mortality of bullous pemphigoid in Switzerland: a prospective study[J]. Br J Dermatol, 2011, 165(2):368–374. doi: 10.1111/j.1365-2133.2011.10413.x
1. Parker S R, Dyson S, Brisman S, Pennie M, Swerlick R A, Khan R, et al.. Mortality of bullous pemphigoid: an evaluation of 223 patients and comparison with the mortality in the general population in the United States[J]. J Am Acad Dermatol, 2008, 59(4):582–588. doi: 10.1016/j.jaad.2008.07.022
1. Rzany B, Partscht K, Jung M, Kippes W, Mecking D, Baima B, et al.. Risk factors for lethal outcome in patients with bullous pemphigoid: low serum albumin level, high dosage of glucocorticosteroids, and old age[J]. Arch Dermatol, 2002, 138(7):903–908. doi: 10.1001/archderm.138.7.903
1. Roujeau J C, Lok C, Bastuji-Garin S, Mhalla S, Enginger V, Bernard P. High risk of death in elderly patients with extensive bullous pemphigoid[J]. Arch Dermatol, 1998, 134(4):465–469. doi: 10.1001/archderm.134.4.465
1. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses[J]. Eur J Epidemiol, 2010, 25(9):603–605. doi: 10.1007/s10654-010-9491-z
1. Tierney J F, Stewart L A, Ghersi D, Burdett S, Sydes M R. Practical methods for incorporating summary time-to-event data into meta-analysis[J]. Trials, 2007, 8:16. doi: 10.1186/1745-6215-8-16
1. Dersimonian R, Laird N. Meta-analysis in clinical trials[J]. Control Clin Trials, 1986, 7(3):177–188. doi: 10.1016/0197-2456(86)90046-2
1. Higgins J P, Thompson S G, Deeks J J, Altman D G. Measuring inconsistency in meta-analyses[J]. BMJ, 2003, 327(7414):557–560. doi: 10.1136/bmj.327.7414.557
1. Friendlander A H, Ettinger R L. Karnofsky performance status scale[J]. Spec Care Dentist, 2009, 29(4):147–148. doi: 10.1111/j.1754-4505.2009.00088.x
1. Liu Y D, Wang Y H, Ye Y C, Zhao W L, Li L. Prognostic factors for mortality in patients with bullous pemphigoid: a meta-analysis[J]. Arch Dermatol Res, 2017, 309(5):335–347. doi: 10.1007/s00403-017-1736-1
1. Di Lernia V, Casanova D M, Goldust M, Ricci C. Pemphigus vulgaris and bullous pemphigoid: update on diagnosis and treatment[J]. Dermatol Pract Concept, 2020, 10(3):e2020050. doi: 10.5826/dpc.1003a50
1. Lai Y C, Yew Y W, Lambert W C. Bullous pemphigoid and its association with neurological diseases: a systematic review and meta-analysis[J]. J Eur Acad Dermatol Venereol, 2016, 30(12):2007–2015. doi: 10.1111/jdv.13660
1. Ali A, Hu L, Zhao F, Qiu W X, Wang P, Ma X, et al.. BPAG1, a distinctive role in skin and neurological diseases[J]. Semin Cell Dev Biol, 2017, 69:34–39. doi: 10.1016/j.semcdb.2017.06.005
1. Papakonstantinou E, Limberg M M, Gehring M, Kotnik N, Kapp A, Gibbs B F, et al.. Neurological disorders are associated with bullous pemphigoid[J]. J Eur Acad Dermatol Venereol, 2019, 33(5):925–929. doi: 10.1111/jdv.15444
1. Försti A K, Jokelainen J, Timonen M, Tasanen K. Risk of death in bullous pemphigoid: A retrospective database study in Finland[J]. Acta Derm Venereol, 2016, 96(6):758–761. doi: 10.2340/00015555-2347
1. Kridin K, Bergman R. Assessment of the prevalence of mucosal involvement in bullous pemphigoid[J]. JAMA Dermatol, 2019, 155(2):166–171. doi: 10.1001/jamadermatol.2018.5049
1. Joly P, Roujeau J C, Benichou J, Picard C, Dreno B, Delaporte E, et al.. A comparison of oral and topical corticosteroids in patients with bullous pemphigoid[J]. N Engl J Med, 2002, 346(5):321–327. doi: 10.1056/NEJMoa011592
1. Joly P, Benichou J, Lok C, Hellot M F, Saiag P, Tancrede-Bohin E, et al.. Prediction of survival for patients with bullous pemphigoid: a prospective study[J]. Arch Dermatol, 2005, 141(6):691–698. doi: 10.1001/archderm.141.6.691
1. Sticherling M, Franke A, Aberer E, Gläser R, Hertl M, Pfeiffer C, et al.. An open, multicentre, randomized clinical study in patients with bullous pemphigoid comparing methylprednisolone and azathioprine with methylprednisolone and dapsone[J]. Br J Dermatol, 2017, 177(5):1299–1305. doi: 10.1111/bjd.15649
1. Zeiser R. Immune modulatory effects of statins[J]. Immunology, 2018, 154(1):69–75. doi: 10.1111/imm.12902

Source: PubMed

Prognostic factors for mortality in bullous pemphigoid: A systematic review and meta-analysis

Abstract

Conflict of interest statement

Figures

References

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue