Recent Advances in Understanding of the Etiopathogenesis, Diagnosis, and Management of Hair Loss Diseases

Abstract

Hair-loss diseases comprise heterogenous conditions with respective pathophysiology and clinicopathological characteristics. Major breakthroughs in hair follicle biology and immunology have led to the elucidation of etiopathogenesis of non-scarring alopecia (e.g., alopecia areata, AA) and cicatricial alopecia (e.g., lichen planopilaris, LPP). High-throughput genetic analyses revealed molecular mechanism underlying the disease susceptibility of hair loss conditions, such as androgenetic alopecia (AGA) and female pattern hair loss (FPHL). Hair loss attracted public interest during the COVID-19 pandemic. The knowledge of hair loss diseases is robustly expanding and thus requires timely updates. In this review, the diagnostic and measurement methodologies applied to hair loss diseases are updated. Of note, novel criteria and classification/scoring systems published in the last decade are reviewed, highlighting their advantages over conventional ones. Emerging diagnostic techniques are itemized with clinical pearls enabling efficient utilization. Recent advances in understanding the etiopathogenesis and management for representative hair diseases, namely AGA, FPHL, AA, and major primary cicatricial alopecia, including LPP, are comprehensively summarized, focusing on causative factors, genetic predisposition, new disease entity, and novel therapeutic options. Lastly, the association between COVID-19 and hair loss is discussed to delineate telogen effluvium as the predominating pathomechanism accounting for this sequela.

Keywords: JAK inhibitor; alopecia areata; androgenetic alopecia; cicatricial alopecia; female pattern hair loss; trichoscopy.

Figure 1

Common classifications for FPHL and representative clinical images. Ludwig’s, Olsen’s, and Sinclair’s classifications are comparatively presented. Image (a) does not demonstrate remarkable frontal accentuation and, thus, is better classified into Ludwig’s II or Sinclair’s 4. Image (b) can be more preferentially classified into Olsen’s II than into Ludwig’s II or Sinclair’s 3, considering frontal accentuation. Image (c) demonstrates mild hair thinning limited to the midline and, thus, is best classified into Sinclair’s 2.

Figure 2

The schema of representative trichoscopic findings of hair loss diseases and trichoscopic images: (a) Pohl-Pinkus constrictions, (b) coudability hair (tapered hair), (c) broken hairs, (d) exclamation mark hairs (tapering hairs), (e) black dots, (f) yellow dots, (g) short vellus hairs, (h) pigtail hairs, (i) hair diameter diversity, (j) peripilar sign, (k) focal atrichia, (l) yellow dots (less prominent than alopecia areata), (m) perifollicular erythema, (n) perifollicular scales, (o) blue-grey dots (targetoid and speckled), (p) perifollicular whitish halo, (q) follicular pustule (more common in neutrophilic conditions), (r) tufted hairs (typical in folliculitis decalvans), (s) absence of follicular openings, (t) follicular keratotic pluggings (more common in discoid lupus erythematosus), (u) white dots, (v) pinpoint white dots, (w) follicular red dots (typical in discoid lupus erythematosus), and (x) white patch. Clinical images of alopecia areata with the findings of (c), (d), (e), and (g); androgenetic alopecia with the findings of (i); and lichen planopilaris with the findings of (n) and (s).

Figure 3

The heterogeneity of female pattern hair loss.

Figure 4

Representative clinical phenotypes of alopecia areata. (a) Typical form of alopecia areata presenting multiple alopecic patches, (b) alopecia ophiasis, and (c) alopecia totalis/universalis.

Figure 5

Representative clinical courses of alopecia areata treated by corticosteroid injection, contact immunotherapy, and intravenous corticosteroid pulse therapy (pulse therapy). Each patient is considered a good responder.

Figure 6

“Modified-AA-cube”, a schema illustrating a strategy for selecting a therapeutic approach in AA after the emergence of JAK inhibitor in market.

Figure 7

Typical clinical course of self-healing acute diffuse and total alopecia (sADTA). Despite rapidly progressive diffuse hair loss, A sADTA patient spontaneously improves without any intervention.

Figure 8

Clinical findings of hair loss two months after COVID-19. This case showed typical manifestation of telogen effluvium: diffuse hair loss (left panel); upright regrowing hairs, as highlighted by white background (middle panel); and trichoscopy (right panel).

Figure 9

Representative clinical and histopathological findings of fibrosing alopecia in a pattern distribution. Hair loss with hair miniaturization on the parietal area mimicking androgenetic alopecia (left panel). Loss of follicular openings and perifollicular erythema were also detected on trichoscopy (middle panel), and histopathological examination showed perifollicular cell infiltration with concentric perifollicular lamellar fibrosis mimicking lichen planopilaris (right panel).