Herjuni OematanDr. dr. Made Wardhana, Sp.KK (K),

FINS-DV

The Relationship between Neurological Disease and

Bullous Pemphigoid: A Population-Based Case Control

StudyJournal of Investigative Dermatology (2011)

131,631-636

JOURNAL READINGFebruary 11th, 2014

Bullous Pemphigoid (BP) is the commonest bullous autoimmune skin disease.

Previous studies, which have not been population-based or adequately controlled, show associations between neurological diseases and

later BP.

It is believed that exposure of the neuronal antigen could lead to an immune reaction against the

epithelial isoform.

BACKGROUND

OBJECTIVESTo test the hypothesis that there was an

associated between previous neurological diseases and the later development of BP in a large population–based case control study

To perform sensitivity analyses to assess whether this relationship was likely to be

causal

MATERIALS & METHODS

• Computerized longitudinal general practice database with demographic data similar to the general population.

• We used contained data from 328 general practices that use the “In Practice Vision” software.

The Health Improvement Network

STUDY PROFILE

All individuals contributing data from the Health Improvement Network database between 1996 and 2006

Identified with recorded neurological disease

868 CASE 3469 CONTROL

MATCHED Age Sex General practice Date of diagnosis

Ethical approval has been obtained from the Nottingham Research Ethics Committee

DATA ANALYSIS

Fulfilling READ CODE 1 year follow up

before

EXCLUSION: 1 YEAR BEFORE DIAGNOSIS BP

STATISTICAL ANALYSISCASE (BP) & CONTROL WITH NEUROLOGICAL DISEASE

CONDITIONAL LOGISTIC REGRESSIONTo calculate ORs and 95% CIs

ADJUSTED FOR COMORBIDITY

SENSITIVITY ANALYSIS

1. ADJUSTED FOR HEALTHCARE UTILIZATION2. WITH 3 YEAR EXCLUSION3. WITH 3 YEARS EXCLUSION ADJUSTED4. INCLUDING ONLY INDIVIDUALS ON SPESIFIC MEDICATIONS

STATA release 10.0 (Stata Coorporation, College Station, TX)

RESULTS

RESULTS

RESULTS

RESULTS

DISCUSSIONThe findings show a significant increase in the odds of

developing BP in people with neurological diseases diagnosed more than 12 months previously

A 3-fold increase in the odds of BP was seen with dementia & Parkinson’s disease

A 2-fold increase for stroke & epilepsy MS was also associated with increased odds of BP

although estimates were somewhat imprecise

These findings are coherent with the results of previous case–control studies & case reports from many different geographical regions, which report strong associations

between previous neurological diseases & the later development of BP

Valid ?

Important ?

Applicable ?

1. Did the study address a clearly focused issue? Yes

Page 631-632 - The aims of this study was to test the hypothesis that there was an association between previous neurological diseases and the later development of BP & to perform sensitivity analyses to assess whether this relationship was causal.

VALIDITY Are the result of this case control study

VALID?

…..VALID

2. Did the authors use an appropriate method to answer their question? Yes

Page 635 - This study use the Health Improvement Network for data,

where a number of studies have confirmed that this network is sufficiently accurate for use in epidemiological research. Recent systematic review confirmed the accuracy & appropriateness of this methodology.

- Ethical approval has been obtained from the Nottingham Research Ethics Committee (reference number: 07/Q2403/28)

…..VALID

3. Were the cases recruited in an acceptable way? Yes

Page 635 - From the version of the Health Improvement Network, the

authors used contained data from 328 general practices that use the “In Practice Vision” software.

- Numerous studies have used this approach for the purposes of identifying and studying a wide range of diseases.

- The authors then identified all individuals consistent with diagnosis of bullous pemphigoid.

…..VALID

4. Were the controls selected in an acceptable way? Yes

Page 635 - A control group of 4 controls per 1 case was selected- Controls was matched randomly by age, sex, and the GP- Controls had to be alive & contributing data to the health

improvement network database on the same date of the matched case.

5. Was the exposure accurately measured to minimize the bias? YesPage 635 - Comprehensive lists were assembled for stroke, dementia,

Parkinson’s disease, MS, and epilepsy. List were manually checked by authors and available on request.

- Sensitivity analyses were also carried out to ensure that observed associations were not merely due to increased ascertainment

…..VALID

……VALID

6. What confounding factors have the authors accounted for?

- Age, sex, general practice, date of diagnosis- The year before the diagnosis of BP- Health care utilization

7. Have the authors taken account of the potential confounding factors in the design and/or in their analysis? YesPage 635 - By design: Matching: Age, sex, GPRestriction: Patient with neurological disease and the year before the diagnosis of BP was excluded in cases & controls to reduce ascertainment bias.Page 635 - By analysis: - Outcomes measures were adjusted for comorbidity.- Sensitivity analysis were carried out adjusting outcomes for

overutilization of health services, by repeating all analyses including only individuals with 1 year follow up before BP diagnosis.

……VALID

This study is VALID

1. What are the result of this study?

IMPORTANTAre the valid results of this case control

IMPORTANT?

Result…

1 5 2 3 4

…..IMPORTANT2. How precise are the results?

Neurological disease

OR 95% CI P-value

Precise

Stroke 1.8 1.3-2.5 <0.001

0.27 precise

Dementia 3.4 2.4-4.8 <0.001

0.29 precise

Epilepsy 1.7 1.0-3.0 <0.001

0.41 less precise

Multiple Sclerosis

10.7 2.8-40.2

<0.001

0.73 less precise

Parkinson’s disease

3.0 1.8-5.0 <0.001

0.4 less precise

Neurological disease

OR 95% CI P-value

Precise

Stroke 1.4 1.0-2.1 <0.001

0,28 precise

Dementia 3.3 2.1-5.4 <0.001

0,36 less precise

Epilepsy 1.8 1.0-3.2 <0.001

0,44 less precise

Multiple Sclerosis

16.0 3.4-75.3

<0.001

0.78 less precise

Parkinson’s disease

3.0 1.6-5.5 <0.001

0.46 less precise

With 3-year exclusion

Neurological disease

OR 95% CI P-value

Precise

Dementia 3.2 2.0-5.2 <0.001

0,37 less precise

Parkinson’s disease

2.9 1.5-5.4 <0.001

0.48 less precise

With 3-year exclusion: adjusted

Neurological disease

OR 95% CI P-value

Precise

Dementia 2.4 1.1-5.1 <0.001

0.54 less precise

Multiple Sclerosis

6.1 3.3-11.5

<0.001

0.45 less precise

Parkinson’s disease

3.4 2.1-5.4 <0.001

0.38 less precise

Including only individuals on spesific medications

This study is IMPORTANT BUT LESS PRECISE

1. Can the results be applied to the local population? YesWe can used this study because the characteristics of our patient is not so different, we also have many bullous pemphigoid in our region. Our challenge probably on the database of patients that haven’t been computerized yet.

APPLICABILITY Can we APPLY this case control study in caring

for our patient?

.…. APPLICABLE 2. Do the result of this study fit with

other available evidence? Yes

Page 635 - Findings show significant increase in the odds of

developing BP in people with neurological diseases diagnosed more than 12 months previously.

- These findings are coherent with the results of previous case-control studies and case reports from many different regions.

This study is applicable

PAFStroke 6,7 %Parkinson 0,6 %Multipel Sclerosis 0,9%Epilepsi 0,9%Dementia 5,1%

Effect + Effect -Risk Factor + a bRisk Factor - c d

OR= ad bc