Biomarkers in alopecia Areata: A systematic review and meta-analysis.

BACKGROUND: Alopecia areata (AA) is an autoimmune non-scarring alopecia that affects the scalp or any hair-bearing areas in the body. The pathophysiology of AA is complex, but Th1, Th2, and Th17 cytokines dysregulation, as well as chemokines, immunoglobulins and other biomarkers have been shown to play a role in the pathogenesis of the disease. OBJECTIVE: To conduct a systematic review and Meta-analysis to identify biomarkers that reflect AA activity and severity that could be used to better assess disease activity and response in both trials and clinical practice. METHODS: A literature search was conducted using the PUBMED, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from inception to December 2021. Articles reporting on associations between AA and serum clinical biomarkers (cytokines, chemokines, antibodies, immunoglobulins, and others) were included. Serum biomarkers were identified in patients with AA and were correlated with disease severity and patient characteristics (ex. age, sex, comorbidities). The quality of the studies was assessed using the National Heart, Lung, and Blood Institute's Quality Assessment Tool for Case-Control Studies. Meta-analysis pooling of the standardized mean differences (SMD) by the method of Cohen using the common-effect inverse-variance model was performed. For the Meta-analysis, data was pulled for all the markers with a minimum of 4 studies with means and standard deviations. Analysis of data reported as Median with range or inter-quartile range (IQR) revealed that the data was too skewed to recommend calculation and use of mean with standard deviation (SD). If the data were not skewed, mean and SD were calculated. RESULTS: One thousand seven hundred fourteen studies were screened, with 91 included, reporting on a total of 52 biomarkers. Meta-analyses revealed pooled SMD that were significant for interleukin 6 (IL6), C-reactive protein (CRP) and vitamin D. CONCLUSIONS: Serum IL6 and CRP levels are significantly increased in patients with AA compared to healthy age and sex matched controls. Conversely, serum vitamn D levels are significantly decreased in patients with AA compared to healthy age and sex matched controls. This data has the potential to influence the clinical guidelines for the diagnostic workup of AA to include testing the serum levels of CRP and vitamin D.