Pathomechanisms of immune-mediated alopecia

Abstract

The hair follicle (HF) is a complex mini-organ that constantly undergoes dynamic cycles of growth and regression throughout life. While proper progression of the hair cycle requires homeostatic interplay between the HF and its immune microenvironment, specific parts of the HF, such as the bulge throughout the hair cycle and the bulb in the anagen phase, maintain relative immune privilege (IP). When this IP collapses, inflammatory infiltrates that aggregate around the bulge and bulb launch an immune attack on the HF, resulting in hair loss or alopecia. Alopecia areata (AA) and primary cicatricial alopecia (PCA) are two common forms of immune-mediated alopecias, and recent advancements in understanding their disease mechanisms have accelerated the discovery of novel treatments for immune-mediated alopecias, specifically AA. In this review, we highlight the pathomechanisms involved in both AA and CA in hopes that a deeper understanding of their underlying disease pathogenesis will encourage the development of more effective treatments that can target distinct disease pathways with greater specificity while minimizing adverse effects.

Functional complexity of hair follicle stem cell niche and therapeutic targeting of niche dysfunction for hair regeneration

“…Collapse of immune privilege as a result of environmental factors or genetic predisposition puts HFs in risk of immune/inflammatory attack [81,93,94]. An active immune response with the secretion of inflammatory cytokines such as interferon-γ and TNF-α can certainly disrupt proper maintenance of HFSCs, leading to alopecia [94,95]. These cytokines are secreted in abundance by lymphocytes that are not usually present in the physiological state, including CD4 and CD8 T cells (αβ T cells) that surround or infiltrate the HF [94,96].…”

Ocrelizumab-induced alopecia areata—A series of five patients from Ontario, Canada: A case report

“…The prevalence of AA in the general global population is approximately 1.7% to 2.1%. 8,20 It is possible that the diagnosis of AA in our patients presented was unrelated pathologically from ocrelizumab administration, as both AA and MS are autoimmune processes. However, the onset of AA within a few weeks to months of starting ocrelizumab treatment as well as the highly reported side effect of AA following other disease-modifying therapies in the treatment of MS makes it difficult to ignore the likelihood of ocrelizumab treatment being a causative factor in the development of AA in these cases.…”

Coexistence of frontal fibrosing alopecia and alopecia areata: 3 new cases and review of the literature

“…1,2 Pathology demonstrates a lymphocytic inflammatory infiltrate around the bulge of the hair follicle (HF) surrounded by perifollicular concentric fibrosis, leading ultimately to follicular dropout and fibrotic tracts. 1 AA presents with alopecic patches typically involving the scalp, but evolution to alopecia totalis and alopecia universalis is possible. 1 Histopathology demonstrates lymphocytic infiltrate around the bulb of HF (reminiscent of a "swarm of bees"), an increased number of telogen follicles, and in the chronic stage, miniaturization of HFs.…”

“…1 AA presents with alopecic patches typically involving the scalp, but evolution to alopecia totalis and alopecia universalis is possible. 1 Histopathology demonstrates lymphocytic infiltrate around the bulb of HF (reminiscent of a "swarm of bees"), an increased number of telogen follicles, and in the chronic stage, miniaturization of HFs. 1 Herein, we report three patients diagnosed with AA who subsequently developed FFA ( Fig.…”

“…Exacerbation of disease following the first infusion, sometimes quite severe, has been noticed by us and other providers. 1,2 We performed a retrospective case-control study to identify the factors associated with such exacerbations.…”