STEPTRACKERSKIN + MULTISYSTEM | PATHOLOGY + ENDOCRINE + NUTRITION | HIGH-YIELD REVIEW

Skin Signs of Systemic Disease

The skin as a window — rashes and lesions that point to diabetes, cancer, bowel disease, lipids, autoimmunity and missing nutrients.

FOCUS ON
Acanthosis nigricans: insulin resistance (or sudden, extensive → gastric cancer). Leser-Trélat: eruptive seborrheic keratoses → GI cancer. Erythema nodosum: tender shin nodules — sarcoid, IBD, strep, TB, fungi, pregnancy/OCPs. Pyoderma gangrenosum: IBD, don't debride. Xanthomas: lipids. Nutrients: niacin (Casal necklace), zinc (perioral/acral), vitamin C (perifollicular bleeds).
SIGN
MECHANISM
APPEARANCE
THINK
Acanthosis nigricans
Insulin → IGF-1 receptors on keratinocytes/fibroblasts; tumor TGF-α (malignant form)
Velvety hyperpigmented plaques in neck folds, axillae
T2DM, obesity, PCOS · sudden + extensive → gastric adenocarcinoma
Leser-Trélat sign
Tumor growth factors
Sudden eruption of many seborrheic keratoses
GI adenocarcinoma
Erythema nodosum
Septal panniculitis (hypersensitivity)
Tender red-violet nodules on the shins; heal without ulceration
Sarcoid, IBD, strep, TB, coccidioidomycosis, histoplasmosis, pregnancy, OCPs, Behçet
Pyoderma gangrenosum
Neutrophilic dermatosis; pathergy (worsens with trauma)
Painful ulcer with violaceous, undermined border
IBD (UC), RA, myeloid disorders · steroids, no debridement
Xanthomas
Lipid-laden macrophages in skin and tendons
Eruptive (very high TG — pancreatitis risk), tendinous (Achilles — familial hypercholesterolemia), xanthelasma, palmar crease (dysbetalipoproteinemia)
Plane xanthomas → PBC
Necrobiosis lipoidica
Collagen degeneration with granulomas
Yellow-brown atrophic shiny plaques with telangiectasias on shins
Diabetes
Autoimmune rashes
Immune complex or interface dermatitis
SLE: malar rash sparing nasolabial folds, discoid scars · dermatomyositis: heliotrope, Gottron · scleroderma: sclerodactyly, telangiectasias, calcinosis
Photosensitivity → SLE
Endocarditis signs
Emboli (Janeway) and immune complexes (Osler)
Painful Osler nodes on finger pads, painless Janeway lesions on palms/soles, splinter hemorrhages
Blood cultures, echo
Liver disease
↓ estrogen clearance, ↓ bilirubin excretion
Spider angiomas, palmar erythema, jaundice, caput medusae
Cirrhosis
Endocrine pigment
↑ ACTH/MSH or iron deposition
Addison: creases, gums, scars · hemochromatosis: bronze · glucagonoma: necrolytic migratory erythema
Check cortisol, ferritin
Nutritional deficiencies
Missing cofactors for skin turnover and collagen
Niacin: photosensitive dermatitis (Casal necklace) · zinc: perioral/perianal/acral dermatitis, alopecia · vitamin C: perifollicular hemorrhage, corkscrew hairs
Pellagra: dermatitis, diarrhea, dementia
Celiac skin
IgA to epidermal transglutaminase
Dermatitis herpetiformis: itchy vesicles on elbows, knees
Detail: 18.02

Mechanism — acanthosis nigricans

Insulin resistance
→
Hyperinsulinemia
→
IGF-1 receptor activationKeratinocytes, fibroblasts
→
Papillomatosis, hyperkeratosisVelvety dark folds
Tumor TGF-αGastric cancer
→
EGFR in skin
→
Sudden, widespread, mucosal involvement

Skin clue → disease

CLUE
DISEASE
Velvety dark neck folds
Insulin resistance
Painful shin nodules
Sarcoid, IBD, strep, TB, OCPs
Undermined violaceous ulcer
IBD (pyoderma gangrenosum)
Yellow Achilles nodules
Familial hypercholesterolemia
Crops of yellow papules on buttocks
Severe hypertriglyceridemia
Migratory blistering perioral/groin rash
Glucagonoma
Dermatitis in sun-exposed neck
Niacin deficiency
Violet eyelids + knuckle papules
Dermatomyositis

How it's tested

COMMON CONFUSIONErythema nodosum (tender, no ulcers, shins) vs pyoderma gangrenosum (ulcers with undermined edges) — both occur with IBD; only pyoderma ulcerates.
THE TRAPDebriding pyoderma gangrenosum makes it worse (pathergy). It is treated with immunosuppression, not surgery.
YOUR APPROACHIdentify the lesion → its site → the systemic disease it points to → the confirming test (glucose, lipids, colonoscopy, cultures, cortisol, nutrient level).

If you see… think…

Obese teen with velvety dark neck skin → insulin resistance
Older man with sudden widespread acanthosis nigricans and weight loss → gastric adenocarcinoma
Tender red shin nodules + bilateral hilar adenopathy → sarcoidosis (Löfgren)
UC patient with an enlarging ulcer after minor trauma → pyoderma gangrenosum
Achilles tendon xanthomas in a 30-year-old with MI → familial hypercholesterolemia
Eruptive yellow papules + pancreatitis → severe hypertriglyceridemia
Shiny yellow-brown shin plaques in a diabetic → necrobiosis lipoidica
Painful finger-pad nodules + new murmur → Osler nodes (endocarditis)
Diarrhea, dementia, dermatitis on the sun-exposed neck → pellagra (niacin)
Infant with perioral and perianal rash after weaning, alopecia → zinc deficiency