Mechanism of Action of Coal Tar in Psoriasis
Coal tar exerts its antipsoriatic effect through three primary mechanisms: binding of polyaromatic hydrocarbons to the aryl hydrocarbon receptor, suppression of keratinocyte proliferation by inhibiting DNA synthesis, and suppression of inflammation with potential effects on immunologic function 1.
Primary Molecular Mechanisms
The therapeutic action of coal tar operates through the following pathways:
1. Aryl Hydrocarbon Receptor Activation
- Polyaromatic hydrocarbons (PAHs) in coal tar bind to the aryl hydrocarbon receptor 1
- Among the thousands of compounds in coal tar, carbazole (a polycyclic aryl hydrocarbon) has been most extensively studied and is hypothesized to be primarily responsible for treatment efficacy 2
- This receptor binding initiates downstream effects that reduce psoriatic inflammation
2. Antiproliferative Effects
- Coal tar decreases keratinocyte proliferation by suppressing DNA synthesis 1
- This directly addresses the hyperproliferation of keratinocytes that characterizes psoriatic plaques
- The reduction in cell proliferation is enhanced when combined with UV irradiation 3
3. Anti-inflammatory and Immunomodulatory Actions
- Coal tar suppresses inflammation through mechanisms that are not fully elucidated 1
- It may affect immunologic function, contributing to its therapeutic benefit 1
- The compound has additional antibacterial and antipruritic effects 4
Photochemical Mechanisms (When Combined with UV)
When coal tar is used with phototherapy (as in Goeckerman therapy):
- Type I reactions (oxygen-independent): Photoreaction with DNA causing photoconjugation and interstrand cross-links 5
- Type II reactions (oxygen-dependent): Generation of singlet oxygen (¹O₂) leading to cell membrane damage 5
- Coal tar is an efficient producer of singlet oxygen, more so than 8-methoxypsoralen 5
Clinical Context
The 2021 Joint AAD-NPF Guidelines provide Grade A recommendation for coal tar preparations in treating mild to moderate psoriasis 1. The mechanism's complexity—involving thousands of chemical compounds with many unidentified—explains why coal tar remains effective despite our incomplete understanding of all its molecular targets 2, 6.
Important caveat: While the aryl hydrocarbon receptor pathway is well-established for coal tar, biomass-derived tars (which are rich in phenols rather than PAHs) have mechanisms that remain to be fully elucidated 6. This suggests multiple therapeutic pathways may exist within different tar preparations.