Key Facts

Hyperpigmentation is extremely common and has diverse aetiologies. It is important to distinguish localised pigmentary disorders from systemic causes that may require urgent investigation (e.g. Addison's disease). Hyperpigmentation causes significant cosmetic concern and disproportionately affects darker skin types.

Epidemiology

• PIH: extremely common; affects all skin types but more visible/persistent in Fitzpatrick IV–VI
• Melasma: affects ~1% of population overall; up to 50% of pregnant women
• Drug-induced pigmentation: common in elderly with polypharmacy

Aetiology

Localised:

• Post-inflammatory hyperpigmentation (PIH)
• Melasma
• Freckles (ephelides), lentigines, café-au-lait macules
• Acanthosis nigricans (insulin resistance)

Generalised/Systemic:

• Addison's disease (primary adrenal insufficiency)
• Haemochromatosis
• Chronic renal failure
• Primary biliary cholangitis
• Ectopic ACTH (small cell lung cancer)

Drug-induced:

• Amiodarone, minocycline, hydroxychloroquine, phenothiazines, heavy metals, chemotherapy (bleomycin)

Pathophysiology

• Epidermal pigmentation (brown): increased melanin in epidermis — e.g. melasma, PIH, freckles
• Dermal pigmentation (blue-grey): melanin trapped in dermis (melanophages) or exogenous pigment — e.g. drug-induced, dermal melanocytosis
• Mixed: combination of epidermal and dermal — e.g. melasma
• Melanogenesis upregulated by: UV exposure, MSH/ACTH, oestrogen, inflammation, iron deposition

Post-Inflammatory Hyperpigmentation

• Brown/dark patches at sites of previous inflammation (eczema, acne, psoriasis, burns)
• Matches distribution of preceding condition
• More common and persistent in darker skin types

Melasma

• Symmetrical brown/grey-brown patches on face
• Malar, centrofacial, or mandibular pattern
• Triggered by UV, pregnancy (mask of pregnancy), OCP, hormone therapy
• More common in women and darker skin types

Addison's Disease

• Generalised hyperpigmentation, especially:
  • Palmar creases
  • Buccal mucosa
  • Scars and pressure areas
  • Nipples and genital skin
• Associated: fatigue, weight loss, postural hypotension, hyponatraemia, hyperkalaemia

Drug-Induced

• Distribution varies by drug
• Amiodarone: blue-grey, sun-exposed areas
• Minocycline: blue-black, scars, shins, mucous membranes

Red Flags

• New generalised hyperpigmentation — investigate for Addison's, ectopic ACTH, haemochromatosis
• Buccal mucosal pigmentation — Addison's, Peutz-Jeghers (perioral freckling + GI polyps)
• Acanthosis nigricans — insulin resistance/type 2 diabetes; rarely paraneoplastic (gastric cancer)

Bedside

• Wood's lamp: enhances epidermal pigmentation (appears darker); dermal pigmentation unchanged — helps classify depth
• Clinical photography: baseline for monitoring treatment response

Bloods

• 9 am cortisol + short synacthen test: if Addison's suspected
• ACTH: elevated in primary adrenal insufficiency
• Ferritin + transferrin saturation: haemochromatosis screen
• LFTs: liver disease, PBC
• HbA1c/fasting glucose: if acanthosis nigricans (insulin resistance)
• TFTs: thyroid dysfunction can cause pigmentary changes

Biopsy

• Rarely needed for common pigmentary disorders
• May help distinguish melanin from drug-related pigment deposition
• Fontana-Masson stain for melanin; Perls' stain for iron

Special Tests

• HFE gene testing: if haemochromatosis suspected
• Skin biopsy with special stains: if drug-induced pigmentation uncertain

Non-Pharmacological

• Sun protection: SPF 50+ broad-spectrum sunscreen — cornerstone of ALL hyperpigmentation management; reapply every 2 hours
• Treat underlying cause: address inflammation (PIH), discontinue causative drug, treat endocrine disorder
• Camouflage cosmetics: available on NHS for disfiguring pigmentation

Pharmacological — Melasma/PIH

• Topical hydroquinone 2–4%: first-line depigmenting agent — apply OD for 3–6 months; avoid prolonged use (>6 months) — risk of exogenous ochronosis
• Topical tretinoin 0.025–0.05%: promotes epidermal turnover; often combined with hydroquinone
• Topical azelaic acid 15–20%: alternative/adjunct; safe in pregnancy
• Triple combination (Kligman's formula): hydroquinone 4% + tretinoin 0.05% + fluocinolone acetonide 0.01% — most effective topical regimen for melasma
• Topical vitamin C (ascorbic acid): antioxidant; adjunctive
• Chemical peels: glycolic acid peels — specialist use for resistant melasma

Pharmacological — Systemic Causes

• Addison's disease: hydrocortisone replacement (15–25 mg/day in divided doses) + fludrocortisone 50–200 mcg OD
• Haemochromatosis: venesection; iron chelation if venesection not possible
• Drug-induced: withdraw causative drug — pigmentation may take months–years to fade

Referral Criteria

• Dermatology: melasma refractory to first-line treatment, diagnostic uncertainty
• Endocrinology: suspected Addison's disease, Cushing's (ectopic ACTH)
• Hepatology: suspected haemochromatosis
• Genetics: Peutz-Jeghers syndrome

• PIH: usually resolves over months–years; faster with treatment and sun protection; may be very persistent in darker skin
• Melasma: chronic, relapsing; pregnancy-related may improve post-partum; often persists
• Drug-induced: gradual improvement over months–years after drug withdrawal; some (amiodarone, minocycline) may be permanent
• Addison's: pigmentation improves with adequate cortisol replacement
• Haemochromatosis: pigmentation may improve with venesection

Causes of Hyperpigmentation — Summary Table

Drug-Induced Pigmentation