Table 2.

Common skin lightening agents, mode of use, adverse effects, and country of use.

Ingredient	Mode of use	Adverse effectsa	Severe adverse reactions	Popular region found (past and present)
Hydroquinone (2% or 4%)	Topical	Contact dermatitis; exogenous ochronosis; corneal melanosis; conjunctival hyperpigmentation; nail hyperpigmentation	Peripheral neuropathy; fetal growth retardation; fish odor syndrome	North America; Middle East; South Asia; Southeast Asia; Africa; East Asia; South America
Class I Steroids (Clobetasol, betamethasone)	Topical	Atrophy; striae; contact dermatitis; perioral dermatitis; telangiectasias; acne; purpura; folliculitis; hypertrichosis	Hypothalamic-pituitary-adrenal axis disruption; Cushing syndrome; adrenal insufficiency; diabetes; hypertension; glaucoma and cataracts; steroid addiction syndrome	North America; Middle East; South Asia; Southeast Asia; Africa; East Asia; South America
Mercury	Topical	Gastrointestinal discomfort; dermatitis; hyperpigmentation; nail dyspigmentation	Neuropsychiatric toxicity (mad hatters disease); nephrotoxicity; pneumonitis; mercurial baboon syndrome	Middle East; South Asia; Southeast Asia Africa; East Asia
Glutathione	Topical, oral, injectable	Contact dermatitis; cramping and bloating	Hepatic, neurologic and renal toxicity; Stevens–Johnson syndrome; air emboli; thyroid dysfunction	North America; Middle East; South Asia; Southeast Asia; Africa; East Asia
Retinoids	Topical, oral	Erythema and peeling; retinoid dermatitis; Photosensitivity	Teratogenic and fetal complications; thyroid dysfunction; hepatic toxicity	North America; Middle East; Africa; East Asia; Southeast Asia; South Asia; South America
Cysteamine	Topical	Burning sensation; sulfur odor; xerosis and irritation		North America; South Asia; Southeast Asia; East Asia
Arbutin 1%	Topical	In alkaline conditions, will hydrolyze into hydroquinone; irritation and erythema; contact dermatitis; paradoxical hyperpigmentation		North America; Middle East; South Asia; Southeast Asia; East Asia; South America
Kojic acid 1%–4%	Topical	Contact dermatitis; photosensitivity		Middle East; South Asia; Southeast Asia; East Asia; South America
Camphor	Topical	Contact dermatitis; irritation	Neurotoxicity-seizures and vision loss; burns when heated; hepatic toxicity	Middle East; South Asia; Southeast Asia; East Asia; Africa
Azelaic acid	Topical	Contact dermatitis; burning and tingling		North America; Southeast Asia; East Asia; Middle East; South America
Tranexamic acid	Oral/topical	Abdominal bloating; abdominal pain Contact dermatitis (topical formulation); alopecia	Vascular thrombosis; pulmonary embolism	North America; South Asia; Southeast Asia; East Asia; South America; Africa

^aCommon or less severe.