Comorbidities in Alopecia Areata 

Alopecia areata (AA) is a chronic, relapsing immune-mediated disorder that causes nonscarring hair loss that can significantly impact a patient’s quality of life. The scalp is the primary target, but involvement of other sites such as body hair loss and nail dystrophies are common. Hair loss can range from patchy alopecia to total loss of scalp and body hair. Approximately 2% of the US population is estimated to be affected by AA, with a current prevalence of 6.7 million Americans as of 2023.¹ AA is associated with a wide range of systemic, cardiovascular, psychiatric, autoimmune, gastrointestinal, and malignant diseases.² In this review, we look at the current evidence of comorbid conditions associated with AA as discussed in the introductory article of this series.

Metabolic and Cardiovascular Comorbidities

There are significant associations between AA and various metabolic and cardiovascular comorbidities (see Table). Several studies suggest that patients with AA have a higher prevalence of metabolic syndrome, including abdominal obesity, hypertension, hyperglycemia, and dyslipidemia.³ There is a statistically significant correlation between AA and metabolic syndrome, with individuals showing higher mean waist circumference, fasting glucose, and triglyceride levels compared to controls.⁴ Studies have also shown the prevalence of type 2 diabetes mellitus to be higher in AA patients.⁵ These findings suggest that the chronic systemic inflammation present in AA may disrupt metabolic homeostasis, contributing to insulin resistance and lipid abnormalities.

Cardiovascular comorbidities like coronary artery disease and atrial fibrillation are also increasingly recognized in this population. There is a higher prevalence of ischemic heart disease, hypertension, and stroke in patients with AA compared to the general population.⁶ The pathophysiology of cardiac abnormalities involves inflammatory cytokines such as TNF-α and IL-6 that may promote endothelial cell dysfunction, vascular injury, and atherosclerosis in susceptible individuals. Psychological stress and anxiety are commonly observed in AA patients, which may further contribute to cardiovascular risk through neuroendocrine and behavioral pathways.

Quality of Life Issues

Patients with AA experience higher rates of anxiety, depression, and impaired quality of life compared to individuals without AA.⁷ The emotional distress stems largely from altered self-image, social stigma, and chronic disease unpredictability. A large population-based study identified a significant association between AA and mood disorders (anxiety and depression), as well as severe psychiatric illnesses, including schizophrenia and bipolar disorder.⁸ Obsessive-compulsive disorder (OCD) is an important link, although it is less studied. Obsessive-compulsive traits may emerge early in the disease course of AA. The pathophysiology of AA and psychiatric comorbidities is multifactorial. Emotional and chronic stress can exacerbate both psychiatric symptoms and alopecia activity. Immune dysregulation occurs due to chronic inflammation and cytokine dysregulation that may contribute to autoimmunity and psychiatric disorders.

Endocrinopathic Comorbidities

Endocrinopathic comorbidities are also associated with AA. The most well-established endocrine comorbidity in AA is autoimmune thyroid disease, particularly Hashimoto’s thyroiditis and Graves’ disease.⁵ Type 1 diabetes mellitus also shows significant association, likely due to shared autoimmune mechanisms and genetic predispositions such as HLA-DR and HLA-DQ.⁹ In addition, AA can occur as part of autoimmune polyglandular syndromes (APS), particularly APS type 1 (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy) and more frequently APS type 2, which includes core features: Addison’s disease, autoimmune thyroid dysfunction and type 1 diabetes mellitus. The evidence between AA and PCOS is limited and conflicting. Some cross-sectional studies have reported higher rates of PCOS among women with AA compared to controls, while others have not found significant associations.^5,10

Nail and Atopic Disorders

Nail and atopic disorders are more common in patients with AA than the general population. Common nail changes include: pitting, beau’s lines, trachyonychia, onychorrhexis, and onycholysis. Nail involvement typically correlates with more severe forms of AA such as alopecia totalis or universalis. Nail changes can be a marker of poor prognosis.¹¹ Atopic diseases like atopic dermatitis (AD), asthma, and allergic rhinitis are also more prevalent. There is an important association between chronic or treatment-resistant AA and AD, as they may share a common immunological mechanism, particularly the Th2 response.¹² 

Gastrointestinal Comorbidities

Gastrointestinal comorbidities play a significant role in the clinical course of AA. A clear association between Celiac disease and AA was first noted in 1995 by Corazza et al.¹³ Crohn’s disease (CD) and ulcerative colitis (UC) share immune dysregulation of Th17 with AA leading to systemic inflammation.¹⁴ Helicobater pylori infection and autoimmune gastritis have been reported, suggesting a chronic gastrointestinal inflammation and autoimmunity as a role in AA.¹⁵ The evidence between irritable bowel syndrome (IBS) and AA is less robust. IBS involves gut-brain axis dysfunction and low-grade inflammation along with intestinal microbiota alterations. Patients with AA report higher rates of IBS symptoms.¹⁶ The proposed mechanism between IBS and AA involves systemic inflammation, gut microbiome dysbiosis, increased intestinal permeability, and overlap of psychological comorbidities^.17 

Malignancies

Cohort studies have proposed an increased risk of hematologic malignancy in patients with AA, specifically non-Hodgkin lymphoma and leukemia.¹⁸ Cheng et al found a similar association of lymphoma along with uterine cancers in patients with AA.¹⁹ There is an increased incidence of thyroid cancer and AA.²⁰ No correlation between other solid organ malignancies and AA has been reported.

It is important to recognize these comorbidities for essential management of patients, as it can lead to improved quality of life in patients with AA. Early screening and multidisciplinary care are crucial for detecting metabolic syndrome, cardiovascular disease, psychiatric disorders, and autoimmune thyroid diseases along with gastrointestinal conditions. While AA is mainly an autoimmune disorder, there is a small association with certain malignancies, which requires routine cancer screening and increase surveillance. 

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2. Lee S, Lee H, Lee CH, Lee WS. Comorbidities in alopecia areata: a systematic review and meta-analysis. J Am Acad Dermatol. 2019;80(2):466-477. doi:10.1016/j.jaad.2018.07.013

3. Leszynska A, Kubasik J, Gluszak P, et al. Metabolic syndrome and associated comorbidities in alopecia. Forum Derm. 2024;10(4):120-128.

4. Singdia H, Bhargava P, Nijhawan S, Mathur DK. A study of correlation of alopecia areata and metabolic syndrome in northwest Indian population: a case-control study. Int J Trichology. 2023;15(2):63-69.

5. Conic RZ, Tamashunas NL, Damiani G, et al. Comorbidities in alopecia areata: a systematic review and meta-analysis. J Am Acad Dermatol. 2019;80(2):466-477.

6. Conic RRZ, Chu S, Tamashunas NL, Damiani G. Prevalence of cardiac and metabolic disease among alopecia areata patients. J Eur Acad Dermatol Venereol. 2021;35(2):e128-e129.

7. Toussi A, Barton VR, Le ST, Agbai ON, Kiuru M. Psychosocial and psychiatric comorbidities and health-related quality of life in alopecia areata: a systematic review. J Am Acad Dermatol. 2021;85(1):162-175.

8. Tzur Bitan D, Berzin D, Kridin K, Cohen A. The association between alopecia areata and anxiety, depression, schizophrenia, and bipolar disorder: a population-based study. Arch Dermatol Res. 2022;314(5):463-468.

9. Petukhova L, Christiano AM. The genetic architecture of alopecia areata. J Investig Dermatol Symp Proc. 2013;16(1):S16-S22.

10. Yilmaz N, Gok I, Isik B, et al. Evaluation of autoimmune and hormonal profiles in patients with alopecia areata. Postepy Dermatol Alergol. 2016;33(5):359-362.

11. Chelidze K, Lipner SR. Nail changes in alopecia areata: an update and review. Int J Dermatol. 2018;57(7):776-783. doi:10.1111/ijd.13866

12. Diaz MJ, Haq Z, Abdi P, Tran JT, Guttman-Yassky E, Ungar B. Association between alopecia areata and atopic dermatitis: a nested case-control study of the All of Us database. J Am Acad Dermatol. 2024;90(3):607-609. doi:10.1016/j.jaad.2023.10.031

13. Corazza GR, Andreani ML, Venturo N, Bernardi M, Tosti A, Gasbarrini G. Celiac disease and alopecia areata: report of a new association. Gastroenterology. 1995;109(4):1333-1337. doi:10.1016/0016-5085(95)90597-9

14. Conic RRZ, et al. Alopecia areata and associated systemic comorbidities: a cross-sectional study. J Am Acad Dermatol. 2020;82(2):400-403.

15. Ozkaya E, et al. Alopecia areata and Helicobacter pylori infection. J Eur Acad Dermatol Venereol. 2011;25(8):990-991.

16. Trüeb RM. Association between alopecia areata and gastrointestinal disorders. Int J Trichology. 2013;5(2):112-113.

17. Raj SM, et al. Dysbiosis in alopecia areata: a scoping review. Clin Cosmet Investig Dermatol. 2021;14:1661-1674.

18. Conic RRZ, et al. Risk of malignancy in patients with alopecia areata. J Am Acad Dermatol. 2018;78(2):276-282. doi:10.1016/j.jaad.2017.08.055

19. Chen CC, Chang YT, Liu HN, Chen YJ. Cancer risk in patients with alopecia areata: a nationwide population-based matched cohort study. Cancer Med. 2018;7(5):2153-2159. doi:10.1002/cam4.1448

20. Aboalola D, Aouabdi S, Ramadan M, et al. An update on alopecia and its association with thyroid autoimmune diseases. touchREV Endocrinol. 2023;19(2):54-59. doi:10.17925/EE.2023.19.2.10