Episode 21 - Tyrosinase-catalysed metabolism of hydroquinone

In this episode of BJD Talks, Sam and Meera discuss the article ‘Exogenous ochronosis by hydroquinone is not caused by inhibition of homogentisate dioxygenase but potentially by tyrosinase-catalysed metabolism of hydroquinone’ by Ito et al. The full article can be accessed at https://doi.org/10.1093/bjd/ljaf273 

*This podcast was generated by an AI tool created by 67Bricks for the British Association of Dermatologists* 

Transcript

SPEAKER_01 0:00

Welcome to BJD Talks, the official podcast of the BJD. I'm Sam.

SPEAKER_00 0:04

And I'm Mira. In this episode, we will be discussing the article by Shossika Ito et al. Exogenous ocrinosis by hydroquinone is not caused by inhibition of homogentisate dioxygenase, but potentially by tyrosinase catalyzed metabolism of hydroquinone, published in July 2025 and included in the November 2025 issue.

SPEAKER_01 0:27

That's quite a title. Hydroquinone, long a staple in dermatology for treating hyperpigmentation, is now being reassessed. This paper links hydroquinone to exogenous ocrinosis through tyrosinase activity, not homogentosate dioxygenase or HGD as previously thought.

SPEAKER_00 0:44

Exactly. Hydroquinone targets melanocytes, but prolonged use has been tied to exogenous ocrinosis, bluish-black patches on the skin. For years it was thought to work via HGD inhibition, yet this study shows no evidence for HGD's involvement.

SPEAKER_01 1:00

Instead, the researchers highlight tyrosinase as central. Tyrosinasee, already well known in melanogenesis, accepts hydroquinone as a pseudosubstrate in vitro. This leads to harmful metabolites capable of initiating ocronotic particle formation.

SPEAKER_00 1:16

Precisely. The study identifies two pathways, the HBQ pathway and the P-benzoquinone pathway. The latter is the main concern as it involves tyrosinase-mediated oxidation of hydroquinone, leading to hazardous compounds like cystinyl hydroquinone, which eventually triggers ocrinosis.

SPEAKER_01 1:36

Fascinatingly, this process was observed in pigmented sun-exposed areas, but not in vitiligo-affected skin, a clear indication that active tyrosinase is a key player. Sun exposure seems to amplify tyrosinase activity, increasing the risk in those regions.

SPEAKER_00 1:52

They further tested for HGD activity in human skin and, unsurprisingly, found none. While HGD plays a role in liver detoxification, it is not expressed in the skin. This dismantles the long-standing HGD inhibition theory for hydroquinone-induced ocarnosis.

SPEAKER_01 2:11

A major finding, definitely. Clinically, it reinforces the need for alternatives to hydroquinone. Safer melanogenesis inhibitors like thiamidol or butoresosinol might offer similar efficacy without posing such risks.

SPEAKER_00 2:25

Yes, and the study flags that other agents metabolized by tyrosinos could pose similar risks. Take rhododendron, for instance, which is already linked to leucoderma.

SPEAKER_01 2:36

So, does this call for stricter regulations? Perhaps hydroquinone should only be reserved for very short-term use, if at all.

SPEAKER_00 2:43

Absolutely. These findings suggest it's time to shift towards alternatives. Researchers should prioritize developing highly specific tyrosinase inhibitors, while clinicians use hydroquinone sparingly and educate patients accordingly.

SPEAKER_01 2:56

Patient education is crucial, especially concerning sun protection and the dangers of extended hydroquinone use.

SPEAKER_00 3:04

In sum, this study reveals tyrosinase's unexpected role in hydroquinone-induced oquinosis, discredits the HGD theory, and underscores the need for safer alternatives.

SPEAKER_01 3:15

A timely reminder that even established treatments must be scrutinised through rigorous science. For now, safety should be paramount.

SPEAKER_00 3:23

That's all for this episode of BJD Talks. Thanks for listening, and we'll see you next time. Stay informed, stay critical.