1. Cancer is not a risk factor for bullous pemphigoid
Cancer is not a risk factor for bullous pemphigoid. A ten-year population-based cohort study
CT Chen, MD,1,2 HY Hu, PhD,3,4 YT Chang, MD, PhD,1,2 CP Li, MD, PhD 2,5 and CY Wu, MD, PhD1,2,3*
1 Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan
2 National Yang-Ming University School of Medicine, Taipei, Taiwan
3 Institute of Public Health and Department of Public Health, National Yang-Ming University, Taipei, Taiwan
4 Department of Education and Research, Taipei City Hospital, Taipei, Taiwan
5 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
British Journal of Dermatology. DOI: /bjd.17197

2. Lead researcher Chen-Yi Wu M.D., Ph.D. Attending Physician
Department of Dermatology, Taipei Veterans General Hospital
No. 201, Section 2, Shih-Pai Road, Taipei, 11217, Taiwan
Associate Professor
National Yang-Ming University School of Medicine
No. 155, Sec.2, Li-Nong Street, Taipei, 11221, Taiwan

3. Introduction What’s already known about this subject ?
Patients with cerebrovascular or neurologic diseases (e.g. dementia, Parkinson’s disease) have a higher risk of developing bullous pemphigoid (BP)
Whether cancer is also a risk factor for BP remains unclear

4. Objective
Is cancer associated with an increased risk of subsequently developing BP?
Which types of cancer are most strongly associated with developing BP?

5. Methods (I) Design Retrospective cohort study Data sources
Longitudinal Health Insurance Database 2000, a subset of Taiwan’s National Health Insurance Research Database containing medical records from 1 million randomly sampled beneficiaries
Defining incident cases of cancer
Subjects required a diagnosis of cancer (ICD-9 codes 140–239) + Catastrophic Illness Card (issued for pathology proven cancers), from
Patients with cancer diagnosis before 2002 were excluded
Index date was the date of the first diagnosis of cancer
Analysis included 36,838 cancer patients

6. Methods (II) Control group
Each cancer patient was matched to 4 age-, sex- and index date-matched controls without cancer
Subjects with BP diagnosed before the index date were excluded
Defining incident cases of bullous pemphigoid
ICD-9 code 694.5
At least three diagnosis codes in outpatient clinic records or at least one in admission records
Covariates
Socioeconomic status, urbanity, and comorbidities (hypertension, diabetes mellitus, hyperlipidaemia, renal disease, chronic liver diseases and cirrhosis, cerebrovascular disease, dementia, and coronary artery disease)

7. Methods (III) Statistical analyses Incidence rate ratio Hazard ratio
Fine-Gray competing risk regression model (with mortality as the competing event) to eliminate the influence of higher mortality rates in the cancer group
P-value <0.05 considered statistically significant

8. Results (I) Risk of BP stratified by age Age (years)
Patients with cancer
Controls
IR ratio
No.
No. of BP IR
(95% CI)
Total
36,838 22
17.2
147,352
171
19.8
0.87 ( )
<40
2,864 1
6.9
11,456
1.3
5.54 ( )
40-49
5,463
4.1
21,852
N/A
50-59
8,116
32,464 7
3.7
60-69
8,033 2
7.3
32,132 21
10.7
0.68 ( )
70-79
8,381 11
46.3
33,524 76
40.1
1.16 ( )
≥80
3,981
83.7
15,924 66
93.6
0.89 ( )
BP: bullous pemphigoid; py: person-years; CI: confidence interval; Incidence rate (IR);
No. of BP/100,000 py
The average observation time was 3.48 years for the cancer group and 5.87 years for the control group.

9. Fine-Gray competing risk regression model
Results (II)
Multivariate analysis for prediction of bullous pemphigoid development
Variable
Fine-Gray competing risk regression model HR
95% CI P
Cancer
0.47
0.03
Age, year
1.05
< 0.001
Sex (male/female)
1.28
0.27
Hypertension
1.33
0.26
Diabetes mellitus
1.69
0.02
Hyperlipidaemia
1.31
Renal disease
1.24
0.48
Chronic liver disease and cirrhosis
1.00
0.99
Cerebrovascular disease
2.14
0.001
Dementia
3.78
0.06
Coronary artery disease
1.01
0.98
HR: hazard ratio; CI: confidence interval

10. Results (III) Incidence for BP stratified by cancer type Cancer type
Number
Mean age (year)
Number of BP
No. of BP/100,000 py
Stomach cancer
1,722
67.3 3
61.6
Colon and rectum cancer
5,067
65.5
15.9
Prostate cancer
1,678
72.6 6
80.5
Bladder cancer
1,125
67.9 2
38.7
Brain and other nervous system
430
49.8
128.3
Liver and intrahepatic bile ducts
4,642
62.8 1
8.9
Lung cancer
4,195
67.7 14
Other skin tumour
521
68.6
39.8
Cervix cancer
995
56.9
18.2
Kidney cancer
961
64.4
25.8
Others
2,094
58.7
14.4
BP: bullous pemphigoid; py: person-years

11. Discussion (I)
No increased risk for BP among cancer patients (HR 0.47)
The average observation time of BP development in cancer group was shorter than for the control group (likely due to the high mortality rate in cancer patients)
Analysed by Fine-Gray competing risk regression model, which describes the direction of the effect, but not the magnitude of the effect
The interpretation should be that cancer is not a risk factor for BP (rather than that cancer is a protective factor for BP)

12. Discussion (II)
The authors observed a high risk for subsequent BP in patients with brain or other nervous system tumours
The main target antigen in BP is BpAg1, with three major forms in the nervous system, epidermis and muscles
A damaged blood brain barrier due to the presence of a brain tumour, or associated treatment e.g. surgery or radiation, could result in the exposure and cross-reactivity of the nervous system antigen to the epidermal antigen
Age, diabetes mellitus, and cerebrovascular disease were independent risk factors for BP, similar to findings from other studies

13. Conclusions What does this study add?
In this population-based study, there was no increased risk of BP seen in cancer patients
Age, diabetes mellitus, and cerebrovascular disease were independent risk factors for BP

14. Research team
HY Hu
CY Wu
YT Chang
CP Li
CT Chen

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