Substance P and CGRP neuropeptides were altered in scalp biopsies from patients with lichen planopilaris and frontal fibrosing alopecia, but in opposite directions — suggesting these similar-looking diseases have different underlying mechanisms.
Opposite neuropeptide patternsLPP and FFA showed opposite substance P and CGRP expression despite looking similar histologically, suggesting different disease mechanisms
What the researchers found
Immunohistochemistry and confocal microscopy revealed altered expression of substance P and CGRP in both affected and unaffected scalp skin from LPP and FFA patients compared to controls. However, ELISA quantification showed opposite patterns in LPP versus FFA — suggesting different pathogenic mechanisms despite similar histopathological features. Notably, inflammation was present in clinically unaffected scalp skin in both diseases, indicating these may be more generalized scalp processes than previously thought.
Why it matters
FFA has reached epidemic levels in recent years with no clear cause identified. If neurogenic inflammation drives these scarring hair loss conditions, it opens the door to targeted treatments — potentially including drugs that block substance P or CGRP (some of which already exist for other conditions like migraines). Understanding the distinct mechanisms of LPP vs FFA is crucial for developing disease-specific therapies.
How the study worked
Scalp biopsies from patients with LPP, FFA, and healthy controls were analyzed using immunohistochemistry and confocal microscopy to visualize substance P and CGRP expression. ELISA was used to quantitatively compare neuropeptide levels between affected and unaffected scalp tissue across all three groups.
What this study cannot tell us
This was a small study with scalp biopsies from a limited number of patients. The abstract does not specify exact sample sizes or the magnitude of neuropeptide differences. The opposite ELISA patterns are suggestive but need replication in larger cohorts. The study cannot determine whether neuropeptide changes cause the disease or are a consequence of it.
How to read the evidence
This is a small translational study using human scalp biopsies with both qualitative (immunohistochemistry) and quantitative (ELISA) analysis. While it provides important mechanistic insight, the limited sample size and cross-sectional design prevent definitive conclusions about causation.
When this study was published
Published in 2020, this study was among the first to provide neuropeptide evidence for distinct pathogenic mechanisms in LPP versus FFA, during a period of rapidly growing interest in the FFA epidemic.
The bigger picture
Neurogenic inflammation — where nerve-derived peptides drive inflammatory processes — is increasingly recognized in skin diseases. The fact that CGRP-blocking drugs are already FDA-approved for migraines raises the intriguing possibility that similar approaches could be explored for scarring alopecia. This study provides mechanistic groundwork for that direction.
Questions still open
- Could CGRP-blocking migraine drugs (like erenumab) have therapeutic benefit in frontal fibrosing alopecia?
- What drives the opposite neuropeptide patterns in LPP versus FFA despite their histopathological similarity?
- Does the finding of subclinical inflammation in unaffected scalp mean earlier treatment could prevent progression of these diseases?
Common questions
What are substance P and CGRP, and how do they relate to hair loss?
Why is FFA considered an epidemic?
Read the original research
Evidence for neurogenic inflammation in lichen planopilaris and frontal fibrosing alopecia pathogenic mechanism.
Experimental dermatology, 29(3), 282-285
Citation
Doche, Isabella; Wilcox, George L; Ericson, Marna; Valente, Neusa S; Romiti, Ricardo; McAdams, Brian D; Hordinsky, Maria K. (2020). Evidence for neurogenic inflammation in lichen planopilaris and frontal fibrosing alopecia pathogenic mechanism.. Experimental dermatology, 29(3), 282-285. https://doi.org/10.1111/exd.13835