Evidence for neurogenic inflammation in lichen planopilaris and frontal fibrosing alopecia pathogenic mechanism

Abstract

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are lymphocytic scarring alopecias affecting primarily the scalp. Although both diseases may share some clinical and histopathological features, in the last decade, FFA has become an “epidemic” particularly in Europe, North and South America with unique clinical manifestations compared to LPP, thus, raising the idea that this disease may have a different pathogenesis. Symptoms such as scalp burning, pruritus or pain are usually present in both diseases, suggesting a possible role for nerves and neuropeptides in the pathogenesis of both diseases. Based on some previous studies, neuropeptides, such as substance P (SP) and calcitonin gene‐related peptide (CGRP), have been associated with lipid metabolism and many chronic inflammatory disorders. In this study, we asked if these neuropeptides are associated with LPP and FFA scalp lesions. Alteration in the expression of SP and CGRP in affected and unaffected scalp skin from patients with both diseases was found with examination of sections using immunohistochemical techniques and confocal microscopy. We then quantitatively assessed and compared SP and CGRP expression from control, LPP and FFA scalp biopsies. Although LPP and FFA share similar histopathologic findings, opposite results were found in affected and unaffected scalp in the ELISA tests, suggesting that these diseases may have different pathogenic mechanisms. We also found presence of histopathological inflammation irrespective of evident clinical lesions, which raises the possibility that both diseases may be more generalized processes affecting the scalp.

A Cell Membrane-Level Approach to Cicatricial Alopecia Management: Is Caveolin-1 a Viable Therapeutic Target in Frontal Fibrosing Alopecia?

“…It is important to note that Substance P receptor neurokinin (NK1) localizes to caveolae and that caveolae disruption in either cells (by cyclodextrins) or in Cav1 knockout mice significantly reduces Substance P immunoreactivity and activation of NK1 receptor [ 84 ]. Since perifollicular neurogenic inflammation, in which substance P plays a key role [ 85 ], has recently been recognized as an additional feature of FFA pathobiology [ 2 ], the possibility that Cav1 may facilitate substance P-induced bulge IP collapse deserves careful exploration ( Figure 1 b). Considering that Substance P and IFN-γ have been previously demonstrated to be upregulators of MHC-I and to rapidly induce HF-IP collapse [ 73 , 74 ], this further substantiates our hypothesis that downregulation of Cav1 may be an alternative approach to inhibit collapse HF immune privilege and thus be a potential avenue for treatment of FFA.…”

“…Primary lymphocytic cicatricial alopecias (PLCA) are characterized by progressive, permanent hair loss for which there is currently no cure [ 1 , 2 , 3 , 4 ]. PLCA result from irreversible damage to the epithelial stem cells (eSCs) of the hair follicle (HF) due to (1) eHFSC apoptosis, (2) pathological epithelial-mesenchymal transition (EMT), (3) collapse of bulge immune privilege (IP) and (4) interferon-gamma-dominated Th1-type chronic inflammatory response [ 5 , 6 , 7 , 8 ].…”

Histological evidence for epidermal and dermal atrophy of the alopecic band in treatment‐naïve patients with Frontal Fibrosing Alopecia

“…Lastly, the presence of more pronounced follicular inflammation and perifollicular fibrosis in the clinically unaffected area is not surprising, given the fact that the AB is an evolved presentation of the disease and studies have shown that the clinically unaffected skin in lichen planopilaris is histologically affected. 8 The main limitation of this study is the lack of control group. However, as both biopsies were taken from the same scalp, we were able to study also the differences between clinically affected and unaffected areas.…”

New developments in hair research

“…Doche and colleagues demonstrate that perifollicular lymphocytic inflammation can be observed in overtly unaffected scalp skin of LPP and frontal fibrosing alopecia (FFA) patients . The data suggest a much more generalized inflammation is present, extending well beyond the lesion limit.…”

“…And/or something else in the local environ that decides where lesions will develop? In fact, Doche et al also characterize the presence of neurogenic inflammation in LPP and FFA both within and beyond the alopecic lesions . They observed differences in neuropeptide distribution, in LPP versus FFA.…”