Hydroquinone and Exogenous Ochronosis: What You Need to Know

What is hydroquinone and how does it work?

Hydroquinone is a topical depigmenting agent that has been used in dermatology for over 60 years. It works by inhibiting an enzyme called tyrosinase, which plays a central role in melanin production. By reducing tyrosinase activity within your melanocytes (the pigment-producing cells in your skin), hydroquinone gradually decreases the amount of melanin deposited in the skin, producing a visible lightening effect over weeks to months.[1]

It's most commonly prescribed for melasma, sun spots (solar lentigines), and post-inflammatory hyperpigmentation — those stubborn dark marks left behind after acne, eczema, or skin injuries. Hydroquinone is typically used as a cream or gel at concentrations between 2% and 4%, applied thinly to affected areas once or twice daily. If you're weighing up the differences between strengths, we've covered that in detail in our guide to hydroquinone 2% vs 4% in Australia.

Australian regulation: why hydroquinone is prescription-only

In Australia, the Therapeutic Goods Administration (TGA) classifies hydroquinone at concentrations of 2% or above as a Schedule 4 (Prescription Only) medicine. Products above 10% are classified as dangerous poisons. In late 2025, the TGA proposed removing the over-the-counter (Schedule 2) category for hydroquinone skin-lightening products altogether, aligning Australian regulations with the European Union and the United States.[2]

This means purchasing hydroquinone products online from unregulated overseas sources isn't just risky — in many cases, it's illegal. At Prescription Skin, all prescriptions are issued by AHPRA-registered Australian doctors who assess your skin, medical history, and suitability before prescribing.

So, what exactly is exogenous ochronosis?

Exogenous ochronosis (EO) is a skin condition characterised by a paradoxical darkening of the skin in the areas where depigmenting agents have been applied. Instead of continuing to lighten, the affected skin develops distinctive blue-black, grey-brown, or dark brown discolouration.[3]

This is understandably distressing — the darkening can easily be mistaken for worsening melasma or hyperpigmentation, which sometimes leads patients to apply more hydroquinone, inadvertently making things worse.

The term "ochronosis" was coined in 1866 by the pathologist Rudolf Virchow, referring to the ochre-coloured (brownish-yellow) pigment deposits found in connective tissue. There's an inherited form called endogenous ochronosis (alkaptonuria), which affects multiple organs — but exogenous ochronosis is entirely different. It's a localised skin condition caused by external agents, most commonly hydroquinone, and does not involve internal organs.[3]

How does it develop?

The exact mechanism is still being studied, but the classical theory proposes that hydroquinone inhibits the enzyme homogentisic acid oxidase locally within the dermis. This causes a build-up of homogentisic acid, which polymerises into an ochre-coloured pigment that deposits between collagen fibres in the upper layer of the deeper skin.[3]

Interesting new research published in the British Journal of Dermatology in 2025 suggests tyrosinase — the same enzyme hydroquinone is designed to block — may actually metabolise hydroquinone into reactive compounds that accumulate in the skin and trigger the characteristic pigment deposits.[4] It's a paradox: the very enzyme targeted by the treatment may contribute to the adverse reaction when hydroquinone is used excessively or without appropriate breaks.

Both theories agree on the critical point: duration of uninterrupted use is the dominant risk factor.

The three clinical stages of exogenous ochronosis

Exogenous ochronosis was classified into three progressive stages by the South African dermatologist Dogliotti in 1979. Recognising the early signs is vital, because stopping hydroquinone early can prevent progression.[3]

On skin biopsy, the hallmark at any stage is curved, banana-shaped, ochre-coloured fibres deposited between degenerated collagen in the upper dermis — this is the gold standard for confirming the diagnosis.[5]

Who is at risk?

A 2022 systematic review of 126 published cases found that the overwhelming majority of exogenous ochronosis occurred in middle-aged women using high-concentration or unknown-concentration products for a median of 5 years of continuous use. Only four cases were reported with treatment courses of 3 months or less.[1]

The key risk factors include:

• Prolonged, uninterrupted use — this is the single most important risk factor. Time-limited treatment courses with scheduled breaks dramatically reduce risk.
• High concentrations — most cases involve products at 4% or above, or products of unknown concentration from unregulated sources.
• Darker skin types — Fitzpatrick skin types IV–VI are disproportionately affected, though cases occur across all skin types.[1]
• Inadequate sun protection — ochronosis occurs predominantly on sun-exposed areas. Daily broad-spectrum SPF 50+ is essential during treatment.
• Unsupervised use — products purchased online from overseas, or used without medical oversight, carry significantly higher risk.

Putting the risk in perspective

A major safety review involving over 10,000 patients treated with hydroquinone under clinical supervision found approximately one case of ochronosis per year in the United States — confirming the condition is extremely rare when hydroquinone is used as prescribed.[6]

How is exogenous ochronosis treated?

The most important step is immediate and permanent cessation of hydroquinone. Beyond that, treatment can be challenging and often requires a combination approach over time:

• Strict sun protection: Daily SPF 50+ sunscreen and physical sun avoidance to prevent further pigment darkening.
• Topical treatments: Low-potency topical corticosteroids, retinoids (such as tretinoin), and glycolic acid peels can gradually improve pigmentation.
• Antioxidants: Topical vitamin C and vitamin E may help dilute deposited pigment over time.
• Laser therapy: Q-switched Nd:YAG, fractional CO₂, and picosecond lasers have shown benefit in selected cases, though multiple sessions are typically needed.[3]

Prevention is far more effective than treatment. This is precisely why supervised, time-limited prescribing is so important.

How Prescription Skin keeps you safe

At Prescription Skin, our approach to hydroquinone prescribing is built around minimising risk while maximising results:

• Individualised assessment: Your skin condition, skin type, medical history, and previous treatments are reviewed before any prescription is issued.
• Appropriate concentration: We prescribe the lowest effective strength, typically starting at 2–4%.
• Time-limited courses: Hydroquinone is prescribed for defined periods (usually 3–6 months), with scheduled reviews. Open-ended use is not supported.
• Sun protection counselling: Every patient is advised on daily broad-spectrum SPF 50+ and sun avoidance during treatment.
• Ongoing monitoring: Follow-up reviews assess treatment response and check for early signs of any adverse effects.

Our custom prescription skincare formulations can also include complementary active ingredients like niacinamide, retinoids, and ascorbic acid to support your results while keeping your skin healthy. If you're new to prescription skincare, our guide on your first 8 weeks on prescription skincare walks you through what to expect.

When to contact your doctor

Reach out to your Prescription Skin doctor if you notice any of the following during hydroquinone treatment:

• The treated area is becoming darker rather than lighter, particularly with a blue-grey or brown-black tone
• Small bumps or caviar-like papules appearing on the treated skin
• The skin looks thinner or you notice visible small blood vessels
• Any unusual skin changes or persistent irritation
• You've been using hydroquinone for longer than recommended without a review

Early detection is everything. The sooner changes are identified, the sooner your treatment plan can be adjusted to protect your skin. Have questions? Check out our FAQ page or start a consultation with our team.