Post-Inflammatory Hyperpigmentation (PIH): Pathogenesis Explained
This post may contain terminology and content that feels unfamiliar or technical to general readers who arrive here via search — but the honest purpose of this post is for me to study and organize this topic for myself. 😄
Post-inflammatory hyperpigmentation (PIH) can be broadly divided into epidermal PIH and dermal PIH. The pathogenesis of each is as follows.
1. Epidermal PIH
1) Caused by an inflammatory reaction in the epidermis (e.g., dermatitis or after laser procedures)
2) Damage to keratinocytes → release of cytokines such as endothelin-1, bFGF, alpha-MSH, and nitric oxide
- Epidermal melanocytes become activated, promoting the maturation of pre-melanosomes into melanosomes and stimulating melanin synthesis.
- Transfer of pigment to surrounding keratinocytes increases, leading to hypermelanosis.
- Wavelengths of 532 nm, 694 nm, 755 nm, and IPL at 515–755 nm have far greater absorption by melanin than 1064 nm. As a result, the fluence required to destroy epidermal melanocytes also damages adjacent keratinocytes. These damaged keratinocytes then secrete cytokines such as endothelin-1, alpha-MSH, MSH-SCF, bFGF, and nitric oxide, which activate melanocytes.
→ As pre-melanosomes mature into melanosomes, melanin synthesis is stimulated and PIH develops.
- Urokinase-type plasminogen activator (u-PA) secreted by keratinocytes converts plasminogen into plasmin. This plasmin in turn promotes the secretion of bFGF (a melanocyte growth factor) from keratinocytes, which further activates melanocytes — ultimately stimulating melanin synthesis and causing PIH. (This is the rationale for using tranexamic acid, which inhibits u-PA and plasmin, as a treatment for melasma.)
- When cells in the upper dermis — including fibroblasts, mast cells, lymphocytes, macrophages, and endothelium — are damaged, fibroblasts notably secrete SCF, while mast cells release arachidonic acid metabolites and histamine. These inflammatory mediators re-activate melanocytes, stimulating melanin synthesis and resulting in PIH.
- Intracellular free radical oxygen species and peroxides also promote melanin synthesis.
(This provides the rationale for the idea that various antioxidants may help reduce melanin synthesis.)
2. Dermal PIH
1. Inflammation disrupts the basal layer.
2. Melanin pigment is released into the papillary dermis (melanin pigment that should remain in the basal cell layer of the epidermis descends downward).
3. It is trapped by macrophages in the papillary dermis.
4. Fibroblast-derived melanogenic growth factors (SCF), via c-Kit, mediate mesenchymal–epithelial interactions that modulate melanocyte function.
=> The key takeaway, therefore, is to minimize epidermal damage in order to reduce keratinocyte injury. Damage to keratinocytes leads to the release of cytokines, which can increase PIH and melanosis.
Accordingly, the important clinical point is to treat using methods that can destroy melanosomes while minimizing keratinocyte damage.
