Cutaneous Manifestations of Systemic Disease

The answer first

The skin is a window to internal disease. A single recognised lesion can collapse a differential list from dozens of conditions to one — Gottron papules to dermatomyositis, grouped vesicles on the elbows to coeliac disease, an expanding annular lesion after a tick bite to Lyme disease, painful purpuric plaques in a dialysis patient to calciphylaxis. The discipline of cutaneous manifestations of systemic disease is built on this principle: pattern recognition first, then targeted confirmation. [1]

Three ideas frame everything on this page: [1]

1. Recognise the specific lesion, then ask what system it signals. Acanthosis nigricans signals insulin resistance or a GI malignancy; necrolytic migratory erythema signals glucagonoma; palpable purpura signals small-vessel vasculitis; erythema nodosum signals sarcoidosis, IBD, streptococcal infection or a drug reaction; calciphylaxis signals advanced CKD with disordered calcium-phosphate metabolism. Each lesion carries a short, high-yield list of systemic associations — learn the list and you have the answer. [1]

2. A paraneoplastic skin sign often precedes the diagnosis of the underlying cancer. Adult-onset dermatomyositis, malignant acanthosis nigricans with tripe palms, the sign of Leser-Trelat, Trousseau migratory thrombophlebitis, necrolytic migratory erythema and Sweet syndrome can all be the first manifestation of an otherwise occult malignancy. Recognising the cutaneous marker is the event that triggers the cancer diagnosis — this is the highest-stakes application of dermatology in physician medicine [8] [13].

3. Some skin signs are medical emergencies. Calciphylaxis in a dialysis patient carries a one-year mortality above 50 per cent [4]. A new dermatomyositis in an adult mandates an immediate structured malignancy search. Suspected glucagonoma syndrome demands prompt measurement of glucagon and pancreatic imaging. Do not file these under "dermatology referral in outpatients" — they are urgent physician problems.

DWE high-yield: The paraneoplastic dermatology cluster — dermatomyositis (ovarian, lung, gastric), malignant acanthosis nigricans and tripe palms (gastric), sign of Leser-Trelat (GI adenocarcinoma), Trousseau migratory thrombophlebitis (pancreatic), necrolytic migratory erythema (glucagonoma), Sweet syndrome (acute myeloid leukaemia and myelodysplasia) — is the single most tested family of cutaneous-internal disease associations. [1]

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1. [1]van Beek AP, de Haas ER, van Vloten WA, et al. The glucagonoma syndrome and necrolytic migratory erythema: a clinical review Eur J Endocrinol, 2004.PMID 15538929
2. [2]Tolliver S, Graham J, Kaffenberger BH A review of cutaneous manifestations within glucagonoma syndrome: necrolytic migratory erythema Int J Dermatol, 2018.PMID 29450880
3. [3]Yin WB, Gao Y, Lu Y Gastric Cancer Associated With Malignant Acanthosis Nigricans Am J Med Sci, 2017.PMID 28317636
4. [4]Yerram P, Chaudhary K Calcific uremic arteriolopathy in end stage renal disease: pathophysiology and management Ochsner J, 2014.PMID 25249804
5. [5]Westphal SG, et al. Calciphylaxis 2026.PMID 30085562
6. [6]Cohen PR Sweet's syndrome--a comprehensive review of an acute febrile neutrophilic dermatosis Orphanet J Rare Dis, 2007.PMID 17655751
7. [7]Cohen PR, Talpaz M, Kurzrock R Malignancy-associated Sweet's syndrome: review of the world literature J Clin Oncol, 1988.PMID 3058878
8. [8]Yerolatsite M, Kekkou E, Torounidou N, et al. Cancer-associated dermatomyositis: A scoping review of the literature Autoimmun Rev, 2026.PMID 42409300
9. [9]Marckmann P, Skov L, Rossen K, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging J Am Soc Nephrol, 2006.PMID 16885403
10. [10]Bolotin D, Petronic-Rosic V Dermatitis herpetiformis. Part I. Epidemiology, pathogenesis, and clinical presentation J Am Acad Dermatol, 2011.PMID 21571167
11. [11]Schwartz RA Sign of Leser-Trélat J Am Acad Dermatol, 1996.PMID 8682971
12. [12]Bernett CN, Schmieder GJ. Leser-Trélat Sign 2026.PMID 29261959
13. [13]Varki A Trousseau's syndrome: multiple definitions and multiple mechanisms Blood, 2007.PMID 17496204
14. [14]Schwartz RA, Nervi SJ Erythema nodosum: a sign of systemic disease Am Fam Physician, 2007.PMID 17375516