Exogenous Ochronosis

Exogenous ochronosis is a blue black or grey brown discolouration of the skin, mainly on the face, caused by long term use of skin lightening products, especially those containing hydroquinone.

It is seen mainly in Africa, South Asia and the Middle East, where hydroquinone creams are widely available, and in patients with melasma. It follows use of hydroquinone at 2 to 5% for 6 months or more (or lower strength used for years).

Other causes are resorcinol, phenol, mercury, picric acid, quinine and the antimalarial drugs. Endogenous ochronosis (alkaptonuria) is a different, inherited disease.

Pathophysiology.

Hydroquinone inhibits homogentisic acid oxidase locally, so homogentisic acid accumulates in the dermis. It then polymerises into ochre coloured pigment that deposits in collagen and elastic fibres and causes inflammation and fibre damage.

Sun exposure and high concentrations of hydroquinone increase the risk.

• Slowly increasing grey brown to blue black hyperpigmentation on the cheeks, forehead, temples and neck, with a "caviar like" papular appearance in advanced cases.
• Colloid milium like papules and sometimes nodules and atrophic scars. A paradoxical darkening in patients who continue to use the product to treat melasma.
• Usually no symptoms except cosmetic concern, and distress.

• Clinical diagnosis from history of lightening products and the typical pattern. Dermoscopy shows brown grey globules and structureless areas.
• Biopsy: yellow brown, banana shaped ochre fibres in the papillary dermis, which are diagnostic.
• Urine homogentisic acid if joint disease or dark urine suggests alkaptonuria.

Differential diagnosis.

• Melasma and post-inflammatory hyperpigmentation.
• Hori naevus, lichen planus pigmentosus and ashy dermatosis.
• Argyria, minocycline and amiodarone pigmentation, and endogenous ochronosis.

• Stop all hydroquinone and other suspected products, and explain that improvement is slow and may be incomplete.
• Strict sun protection (broad spectrum SPF 30 or more, with a physical filter and hats).
• Topical options with modest benefit: tretinoin 0.025 to 0.05% nightly, azelaic acid 15 to 20% twice daily, and chemical peels (glycolic acid 30 to 50%, or trichloroacetic acid 10 to 20%) at monthly intervals.
• Q-switched lasers (alexandrite, neodymium doped yttrium aluminium garnet) give good improvement in many cases, though they have caused paradoxical darkening in some, so test first. Fractional carbon dioxide laser and dermabrasion can help papular lesions.
• Counsel about alternatives for melasma that do not contain hydroquinone (tranexamic acid 250 mg twice daily for 3 to 6 months where no thrombosis risk, with sun protection).

Special groups. Pregnancy and breastfeeding: avoid tretinoin, tranexamic acid and hydroquinone.

Monitoring. Review every 2 to 3 months, with photographs.

Referral and escalation. Dermatology.