Risk of All-Cause Mortality, Cardiovascular Disease Mortality, and Cancer Mortality in Patients With Bullous Pemphigoid

Abstract

Importance: The role of bullous pemphigoid (BP) in cardiovascular disease (CVD) mortality remains controversial, and analyses of causes of death among patients with BP based on individual data remain lacking.

Objective: To evaluate the risk of all-cause mortality, CVD mortality, and cancer mortality in patients with BP.

Design, setting, and participants: This cohort study identified patients who received a diagnosis of and treatment for BP during their dermatology clinic visits at a tertiary medical center in central Taiwan between January 1, 2007, and December 31, 2017. Controls were patients without BP and were individually matched to cases (4:1) according to age, sex, and date of the dermatology clinic visit. Data were analyzed from March 6, 2019, to April 2, 2021.

Exposures: Bullous pemphigoid was confirmed pathologically with typical direct immunofluorescence findings or clinically with typical clinical presentation, positive findings of an anti-basement membrane zone antibody test, and corticosteroid use for at least 28 cumulative days.

Main outcomes and measures: Mortality outcomes confirmed by the National Death Registry.

Results: Of 252 patients with BP and 1008 matched control patients (N = 1260), 685 (54.4%) were men and the median age was 78.0 (IQR, 70.3-84.8) years. Patients with BP had higher CVD mortality at 1 year (20 [7.9%] vs 13 [1.3%]), 3 years (28 [11.1%] vs 24 [2.4%]), and 5 years (31 [12.3%] vs 39 [3.9%]) compared with matched control patients. After adjusting for potential confounding variables, patients with BP had a 5-fold higher risk of CVD mortality at 1 year (hazard ratio [HR], 5.29 [95% CI, 2.40-11.68]), 3 years (HR, 5.79 [95% CI, 3.11-10.78]), and 5 years (HR, 4.95 [95% CI, 2.88-8.51]). Subgroup analyses revealed that the CVD mortality risk associated with BP was higher in patients without a history of hypertension (HR, 7.28 [95% CI, 3.87-13.69]) or CVD (HR, 6.59 [95% CI, 3.40-12.79]) and in patients without prior diuretic use (HR, 5.75 [95% CI, 3.15-10.50]) compared with matched control patients. In addition, all-cause mortality associated with BP was higher in patients without prior corticosteroid use than in control patients (HR 5.65 [95% CI, 4.19-7.61]).

Conclusions and relevance: The findings of this cohort study suggest that BP was associated with a 5-fold higher risk of CVD mortality, particularly in patients without underlying hypertension or CVD or those without prior corticosteroid or diuretic use. Future studies should investigate the benefits of routine monitoring and timely management of CVD symptoms and signs in patients with BP.

Figure 1.. Process of Selecting Patients With and Without Bullous Pemphigoid (BP) From 2007 to 2017 at China Medical University Hospital

Anti-BMZ indicates anti–basement membrane zone antibodies; CMUH, China Medical University Hospital. ^aTime frame of corticosteroid (ie, methylprednisolone, prednisolone, or dexamethasone) use is from 7 days before to 60 days after the pathological examination or anti-BMZ test. ^bDiagnostic codes of pemphigoid include 694.2x, 694.5x, and 694.6x from International Classification of Diseases, Ninth Revision (ICD-9), and L12.xx from International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). Diagnostic codes of pemphigus include 694.4x from ICD-9 and L10.xx from ICD-10.

Figure 2.. Adjusted Hazard Ratios (HRs) of All-Cause Mortality, Cardiovascular Disease Mortality, and Cancer Mortality Stratified by Subgroups of Sex, Age, Comorbidities, and Medication History

The sizes of the squares correspond to the inverse of the variance of the HRs. NA indicates not available. ^aFor the cancer mortality of the subgroup with antiplatelet use, the HR could not be calculated because the number of deaths was zero for patients with bullous pemphigoid (BP).