Hyperpigmentation – Systemic Causes
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Direct answer
Melanin tells you where to look: bronzing concentrated in mucous membranes, palmar creases, pressure points and scars points to Addison disease through high ACTH-driven melanocyte stimulation, while bronze skin with diabetes and gonadal failure points to haemochromatosis, where iron sits in the basal layer. Drug lists complete the exam picture — clofazimine reddening leprosy patients on national-programme therapy, amiodarone's blue-grey photodistributed hue, minocycline's three patterns — and acanthosis nigricans with sudden onset demands a hunt for gastric malignancy. That geography of pigment is high-yield NEET-PG Medicine material.
What you must remember
- Addison disease: generalized bronzing with mucosal pigmentation, palmar creases, extensor surfaces, scars and nipples — driven by elevated ACTH and melanocyte-stimulating hormone activity.
- Nelson syndrome: deepening pigmentation after bilateral adrenalectomy from unrestrained ACTH secretion by a pituitary corticotroph adenoma.
- Ectopic ACTH production (small cell lung carcinoma) can likewise darken a patient.
- Haemochromatosis: "bronze diabetes" — hyperpigmentation with cirrhosis, diabetes and hypogonadism; mucosa usually spared; screen with transferrin saturation and ferritin.
- Acanthosis nigricans: velvet-brown flexural thickening signalling insulin resistance; sudden onset with weight loss and tripe palms suggests malignancy, classically gastric adenocarcinoma.
- Clofazimine (leprosy regimen): dose-dependent reddish-blue to brown discolouration, prominent in conjunctiva and lesional skin — a routine counselling point in patients on multidrug therapy.
- Amiodarone: blue-grey slate discolouration of photoexposed face after long therapy, with corneal microdeposits.
- Minocycline: blue-black pigment in three patterns — periorbital, shins and forearms (with scarring or inflammation), or generalized muddy brown.
- Other classics: chloroquine and quinacrine yellowing, phenothiazines slate-grey on sun-exposed skin, imipramine, bleomycin flagellate bands, and fixed drug eruption recurring at the same site.
- Peutz-Jeghers syndrome: perioral mucocutaneous macules with hamartomatous intestinal polyposis.
How to reason through a pigmented patient
A 48-year-old man is referred for "tanning that will not fade" over eight months, with fatigue, postural giddiness and a 4 kg weight loss. Examination shows bronze skin darker over the knuckles, elbows and palmar creases, pigmentation inside the buccal mucosa, and low blood pressure with a postural drop.
Step one: use the distribution — mucosal and flexural-pressure pigmentation with constitutional symptoms is Addison until excluded; send morning cortisol with ACTH (and a short synacthen test where available), plus electrolytes expecting hyponatraemia with hyperkalaemia. Step two: if the history diverges, redirect by pattern: had this man been a diabetic with bronze skin, arthropathy of the second and third metacarpophalangeal joints and sexual dysfunction, the next test would be transferrin saturation for haemochromatosis. Step three: take a drug inventory — an Indian leprosy cohort on the national multidrug therapy regimen will include clofazimine, whose reddish-brown discolouration is expected, reversible only slowly, and no reason to stop treatment; a cardiac patient on amiodarone for years develops photoexposed blue-grey change; a young woman on minocycline for acne develops periorbital blue-black discolouration. Step four: examine the flexures — velvety acanthosis in an obese young person is insulin resistance and needs lifestyle plus metabolic screening, but new acanthosis with weight loss and "tripe palms" in an older adult triggers upper gastrointestinal endoscopy for gastric cancer. Step five: for unexplained persistent hyperpigmentation with a negative systemic screen, biopsy and review of every medication, including over-the-counter agents, close the loop.
Where students slip
Examinees quote "Addison causes pigmentation" without the specifics examiners seek: the mucosae, palmar creases, pressure points and old scars. The second slip is missing haemochromatosis because the stem emphasises diabetes and fatigue; the MTP arthropathy and gonadal dysfunction are the breadcrumbs. Third, in the Indian setting, clofazimine pigmentation is misread as a drug reaction needing regimen change — the expected answer is reassurance and continuation. Fourth, forgetting that minocycline pigmentation persists after drug withdrawal separates a well-read candidate from the rest. Finally, the acute-onset acanthosis-malignancy link is the single most penalised omission when a stem mentions dyspepsia or weight loss.
Frequently asked questions
Why does Addison disease hyperpigment mucosae and palmar creases?
Cortisol deficiency removes feedback on pro-opiomelanocortin, raising ACTH and melanocyte-stimulating hormone activity, which stimulates melanocytes maximally in areas of friction and mucosa.
Which pigment pattern suggests haemochromatosis?
Generalized bronze discolouration with diabetes, liver disease, hypogonadism and second-third metacarpophalangeal arthritis; mucous membranes are characteristically spared compared with Addison disease.
Which antileprosy drug causes skin discolouration?
Clofazimine, producing dose-related reddish-blue to brown pigmentation of skin and conjunctiva in patients on multidrug therapy — an expected effect, not an indication to stop treatment.
What does sudden-onset acanthosis nigricans signify?
Malignancy, classically gastric adenocarcinoma, particularly with weight loss, new-onset diabetes and tripe palms — mandating upper gastrointestinal evaluation.
How do amiodarone and minocycline pigmentation differ?
Amiodarone produces blue-grey discolouration of photoexposed areas after prolonged therapy with corneal deposits; minocycline produces blue-black pigmentation in periorbital, scarred-extremity or generalized patterns.