Pigmentary Disorders
Too little pigment, too much pigment, and the systemic clue behind each
Loss of pigment
Depigmented or hypopigmented? Depigmented skin has no melanin, looks chalk-white, and glows brightly under a Wood lamp. Hypopigmented skin keeps some melanin, looks off-white, and changes little under the lamp.
| Disorder | Key features | Test or treatment |
|---|---|---|
| Vitiligo | Sharp, chalk-white patches; periorificial, acral, Koebner; melanocytes absent | Wood lamp bright; TSH; topical therapy or narrowband UVB |
| Pityriasis alba | Ill-defined, scaly, off-white patches on the cheeks and arms of atopic children, most obvious after tanning | Reassure; emollients, sunscreen, mild steroid |
| Tinea versicolor | Scaly oval macules on the upper trunk that fail to tan | KOH; selenium sulfide or azole |
| Albinism | Diffuse pallor, white hair, nystagmus; normal melanocyte number | Sun protection, skin cancer checks |
| Ash-leaf macules | Three or more lance-shaped hypomelanotic macules (≥5 mm) in an infant | Wood lamp; evaluate for tuberous sclerosis |
Vitiligo. Cytotoxic T cells destroy melanocytes, leaving symmetric depigmented patches around the eyes and mouth, on the hands, feet, elbows, and knees, and at sites of trauma (Koebner phenomenon). Autoimmune thyroid disease is the most common association (screen TSH), along with type 1 diabetes, pernicious anemia, and Addison disease. Limited disease responds to potent topical steroids, calcineurin inhibitors such as tacrolimus (preferred on the face and folds to avoid atrophy), or topical ruxolitinib; widespread or progressive disease is treated with narrowband UVB. Sunscreen prevents burns in depigmented skin. Repigmentation starts around follicles, so white hairs in a patch predict a poor response.
Tinea versicolor. Malassezia, a lipophilic yeast of normal skin, overgrows in heat, humidity, and sweat. Its dicarboxylic acids (such as azelaic acid) inhibit melanocytes, so lesions stay pale after sun exposure; others are pink or brown. KOH shows short hyphae with round yeast ("spaghetti and meatballs"). Topical selenium sulfide or ketoconazole is first-line and oral fluconazole treats extensive disease; oral terbinafine and griseofulvin are ineffective, and oral ketoconazole is avoided because of hepatotoxicity. Color returns only over months, which is not treatment failure.
Albinism. Oculocutaneous albinism is autosomal recessive; in OCA1 a defective tyrosinase leaves a normal number of melanocytes unable to make melanin, whereas in vitiligo the melanocytes are gone. Nystagmus, photophobia, and low vision from foveal hypoplasia accompany the pale skin, and high squamous cell carcinoma risk demands lifelong photoprotection. Hermansky-Pudlak syndrome adds bleeding and pulmonary fibrosis; Chédiak-Higashi syndrome adds recurrent pyogenic infections.
Ash-leaf macules in an infant point to tuberous sclerosis (TSC1/TSC2, mTOR overactivity): look for infantile spasms, cortical tubers on brain MRI, facial angiofibromas, a shagreen patch, ungual fibromas, cardiac rhabdomyomas, and renal angiomyolipomas.
Excess pigment
Melasma. Symmetric brown patches on the cheeks, forehead, upper lip, and chin, most common in women with darker skin and driven by UV and visible light plus estrogen (pregnancy, oral contraceptives). Strict broad-spectrum sunscreen, ideally tinted to block visible light, is the foundation, with hormonal triggers stopped when possible. Hydroquinone 4% or a triple-combination cream (hydroquinone, tretinoin, fluocinolone) lightens lesions, though prolonged hydroquinone can cause exogenous ochronosis; azelaic acid is used in pregnancy. Relapse is common.
Post-inflammatory hyperpigmentation. Darkening after acne, eczema, lichen planus, burns, or procedures is most frequent and persistent in darker skin. Epidermal pigment is brown and fades over months; dermal pigment is blue-gray and lingers. Treat the inflammation, use sunscreen, and add retinoids, azelaic acid, or hydroquinone.
Café-au-lait macules. One or two are common. Six or more larger than 5 mm before puberty (15 mm after), with smooth borders and axillary or inguinal freckling, suggest neurofibromatosis type 1 (neurofibromas, Lisch nodules, optic glioma). A few large, unilateral macules with jagged "coast of Maine" borders that respect the midline suggest McCune-Albright syndrome (mosaic activating GNAS mutation) with polyostotic fibrous dysplasia and precocious puberty.
Solar lentigines. Uniform tan-brown macules on the dorsal hands, face, and forearms of older fair-skinned adults contain more melanocytes and melanin and mark cumulative sun damage; unlike freckles, they do not fade in winter, and cryotherapy or laser is only cosmetic. An enlarging, irregular, variegated facial macule needs biopsy for lentigo maligna. Lentigines on the lips and buccal mucosa with hamartomatous GI polyps indicate Peutz-Jeghers syndrome.
Drugs and systemic disease
Drug-induced pigmentation. Minocycline causes blue-black pigment in acne scars, blue-gray patches on the shins, and discoloration of teeth, sclerae, and nails. Amiodarone causes slate-gray to violaceous discoloration of sun-exposed facial skin with photosensitivity. Antimalarials darken the shins and palate, bleomycin produces flagellate streaks, and silver causes argyria. Pigment fades slowly, if at all, after the drug is stopped.
Addison disease. Low cortisol removes feedback on the pituitary, and POMC is cleaved into ACTH and MSH, which stimulate melanocortin-1 receptors. Pigment gathers in palmar creases, knuckles, gums, scars, and friction sites, with fatigue, weight loss, salt craving, hypotension, hyponatremia, and hyperkalemia; the cosyntropin stimulation test confirms it. Secondary adrenal insufficiency lowers ACTH and causes no pigmentation.
Hemochromatosis. Iron overload from HFE C282Y homozygosity gives bronze-gray skin with diabetes and cirrhosis ("bronze diabetes"). Transferrin saturation above 45% and high ferritin prompt HFE testing, and phlebotomy lowers iron and fades the pigment.