Presented at the joint International Eczema Council and National Alopecia Areata Foundation Symposium, "Atopic Dermatitis and Alopecia Areata: Comparison and Contrast”, held during the 2019 Annual American Academy of Dermatology meeting in Washington, DC to explore the similarities and differences between these two common but complex skin diseases and the implications from bench to bedside.

1. Epidemiologic Association
Between Atopic Dermatitis and
Alopecia Areata
IEC-NAAF Symposium
February 28, 2019
Aaron Drucker, MD, ScM, FRCPC
Assistant Professor, University of Toronto
Scientist, Women’s College Research Institute
@aaron_drucker

2. Disclosures
• Research and
institutional funding
• Sanofi
• Regeneron
• Consultant
• Sanofi
• RTI Health Solutions
• CADTH (Canadian
Agency for Drugs
and Technology in
Health)
• Honoraria
• Astellas Canada
• Prime Inc
• Spire Learning
• CME Outfitters
• Eczema Society of Canada
My family has relationships with: AbbVie, Eli Lilly and Company, GlaxoSmithKline, Intarcia Therapeutics, Janssen
Pharmaceuticals, Kallyope, Merck & Co., Novartis, Novo Nordisk, Pfizer, Shire , Zafgen

3. Objective
• Describe the epidemiologic evidence for associations between atopic
dermatitis and alopecia areata

4. Global age-standardized Prevalence
GBD Study. https://vizhub.healthdata.org/gbd-compare/
ATOPIC DERMATITIS – 3%
ALOPECIA AREATA – 0.25%

5. Global Disability-Adjusted Life Years
Non-Communicable Skin diseases
Other
Decubitus ulcer
Urticaria
Alopecia areata
Itch
Acne
Psoriasis
Dermatitis
GBD Study.
https://vizhub.healthdata.o
rg/gbd-compare/

6. Atopic dermatitis and immune-related
comorbidities

7. Atopic march
Atopic dermatitis
(skin barrier
dysfunction and
inflammation)
Food allergy Hayfever Asthma

8. Atopic Dermatitis Pathogenesis Basics
• Outside-in: Epidermal barrier disruption
• Filaggrin, proteases
• Allows antigens and irritants in
• Inside-out: Th2 inflammatory cytokines
(IL-4, IL-13, IL-22, IL-25, IL-31)…
• Suppress epidermal structure protein synthesis
• Induce proteases
Malajian D, Guttman-Yassky E. Cytokine. 2015 Jun;73(2):311-8.

9. Is atopic dermatitis associated with
autoimmune comorbidities?
Alopecia areata Multiple sclerosis
Ankylosing spondylitis Primary biliary cirrhosis
Celiac disease Pulmonary fibrosis
Chronic glomerulonephritis Rheumatoid arthritis
Chronic urticaria Sjögren syndrome
Crohn's disease Systemic lupus erythematosus
Giant cell arteritis Systemic sclerosis
Graves' disease Type 1 diabetes
Hashimoto thyroiditis Ulcerative colitis
Hemolytic anemia Vitiligo
Immune thrombocytopenia purpura
Andersen et al. J Am Acad Dermatol. 2017 Feb;76(2):274-280.

10. Association of atopic dermatitis with any
autoimmune comorbidity
Odds ratio (Log scale)
OR 2.48
OR 3.46
OR 5.32
Andersen et al. J Am Acad Dermatol. 2017 Feb;76(2):274-280.

11. Is atopic dermatitis associated with
autoimmune comorbidities?
Alopecia areata Multiple sclerosis
Ankylosing spondylitis Primary biliary cirrhosis
Celiac disease Pulmonary fibrosis
Chronic glomerulonephritis Rheumatoid arthritis
Chronic urticaria Sjögren syndrome
Crohn's disease Systemic lupus erythematosus
Giant cell arteritis Systemic sclerosis
Graves' disease Type 1 diabetes
Hashimoto thyroiditis Ulcerative colitis
Hemolytic anemia Vitiligo
Immune thrombocytopenia purpura
Andersen et al. J Am Acad Dermatol. 2017 Feb;76(2):274-280.

12. Why?
• Genetic predisposition to inflammatory conditions
• Poorly understood environmental triggers
• Detection (surveillance) bias

13. Atopic dermatitis and alopecia areata:
The evidence

14. Registry study
• Case-control study
• Alopecia areata cases: National Alopecia Areata Registry – self report
• Controls: Non-blood relatives
• Identified through internet ads, participants friends, invetigators…
• Atopic dermatitis: assessed by self-report
• Only included if onset PRIOR to Alopecia areata
Barahmani et al. J Am Acad Dermatol. 2009 Oct;61(4):581-91.

15. Population
Alopecia areata
(n=2,055)
Controls
(n=558)
Age, mean (SD) 38.5 (17.8) 40.8 (14.7)
Sex, N (%)
Female 1476 (71.8) 361 (64.7)
Male 579 (28.2) 197 (35.3)
Race, N (%)
African
American
121 (5.9) 31 (5.5)
Hispanic 106 (5.2) 55 (9.9)
Caucasian 1828 (88.9) 472 (84.6)

16. Association between atopic dermatitis and
alopecia areata
Odds ratio (95% CI)
Atopic dermatitis and alopecia areata 2.61 (1.78-3.83)
Atopic dermatitis and alopecia
totalis/universalis
2.98 (1.95-4.55)
Alopecia totalis/universalis vs milder
alopecia
1.24 (0.95-1.61)

17. Atopic Dermatitis and Alopecia Areata
Modified from Mohan and Silverberg. JAMA Dermatol. 2015 May;151(5):522-8.
OR: 2.57, 95% CI 2.25-2.94

18. Atopic dermatitis and alopecia areata severity
Mohan and Silverberg. JAMA Dermatol. 2015 May;151(5):522-8.
OR: 1.22, 95% CI 1.01-1.48

19. Nurses’ Health Study 2
• Cohort study
• Alopecia areata cases: self-report diagnosis and year of diagnosis
• Atopic dermatitis cases: self-report diagnosis and year of diagnosis
Drucker et al. Allergy. 2017 May;72(5):831-834.

20. Population
No atopic dermatitis
(n=78,172)
Atopic dermatitis
(n=9,234)
Age
*
54.5 (4.7) 54.4 (4.6)
Race
White, % 96 95
Hispanic, % 0.1 0.1
Black, % 1 2
Asian, % 1 2
Drucker et al. Allergy. 2017 May;72(5):831-834.

21. Association between atopic dermatitis and
alopecia areata
Alopecia cases Non-cases Adjusted OR
No AD 121 78,051
AD 26 9,208 1.80 (1.18–2.76)

22. Population-based data (Denmark)
• Cross-sectional study
• Adults with AD matched with 5 controls (age, sex, time)
• Alopecia areata and atopic dermatitis identified through ICD codes
• Secondary analysis: AD patients compared with hyperhidrosis
patients
Andersen et al. J Am Acad Dermatol. 2017 Feb;76(2):274-280.

23. Population
Atopic dermatitis
(n = 8,112)
Controls
(n = 40,560)
Mean age, y (SD) 42.42 (15.16) 42.42 (15.16)
Women, n (%) 4982 (61.42) 24,910 (61.42)

24. Association between Atopic Dermatitis and
Alopecia Areata
AD, n (%) Controls, n (%) Adjusted OR, 95% CI
General population
Alopecia areata 77 (0.95) 13 (0.03) 26.31 (14.48-47.80)
Hyperhidrosis controls
6.51 (3.34-12.72)

25. Gaps to fill
• Large studies in children
• Inclusion of people with different ethnic backgrounds
• Studies with validated case definitions
• High-quality studies examining the impact of comorbid atopic
dermatitis and alopecia areata on:
• Severity
• Prognosis

26. Summary
• Atopic dermatitis is associated with autoimmune comorbidities,
including alopecia areata, in large epidemiologic studies
• Some of this association is explained by detection bias
• It is unclear whether atopic dermatitis is associated with worse
alopecia areata and vice versa