Cutaneous Manifestations of Systemic Disease

Autoimmune Manifestations - Immune System Alerts

• Systemic Lupus Erythematosus (SLE)
  • Malar (butterfly) rash, discoid lesions, photosensitivity.
  • Oral ulcers, non-scarring alopecia, Raynaud's. ANA often positive.
• Dermatomyositis
  • Heliotrope rash (eyelids), Gottron's papules (knuckles).
  • Shawl sign, V-sign, mechanic's hands. Periungual telangiectasias.
  • Associated with internal malignancy (adults > 40 yrs). Anti-Jo-1, Anti-Mi-2.
• Scleroderma (Systemic Sclerosis)
  • Skin thickening/fibrosis (sclerodactyly), Raynaud's (often first).
  • Telangiectasias, calcinosis cutis, "salt-and-pepper" dyspigmentation.
  • 📌 CREST: Calcinosis, Raynaud's, Esophageal dysmotility, Sclerodactyly, Telangiectasia. Anti-centromere Ab.
• Pemphigus Vulgaris
  • Flaccid bullae, erosions (oral mucosa often first).
  • Nikolsky sign positive. Intraepidermal acantholysis.

  ⭐ Antibodies against desmoglein 1 & 3 (anti-Dsg1, anti-Dsg3).

• Bullous Pemphigoid
  • Tense bullae on erythematous/urticarial base (elderly).
  • Nikolsky sign negative. Subepidermal split with eosinophils. Anti-BPAG1/2.

Metabolic & Endocrine - Inside‑Out Clues

• Diabetes Mellitus:
  • Necrobiosis lipoidica (atrophic plaques, shins)
  • Diabetic dermopathy (shin spots)
  • Acanthosis nigricans (velvety, flexures)
  • Eruptive xanthomas (↑ triglycerides)
  • Bullosis diabeticorum
• Thyroid Disorders:
  • Hypo: Myxedema, dry skin, madarosis (outer eyebrow loss)
  • Hyper (Graves'): Pretibial myxedema, acropachy, Plummer's nails
• Adrenal Disorders:
  • Cushing's: Violaceous striae (>1 cm), moon facies, buffalo hump, atrophy
  • Addison's: Hyperpigmentation (oral, palmar, scars)
• Xanthomas:
  • Xanthelasma palpebrarum (eyelids; normolipidemic common)
  • Tuberous, tendinous, eruptive (hyperlipidemia)
• Porphyria Cutanea Tarda (PCT): Photosensitivity, bullae (sun-exposed), fragile skin, hypertrichosis, port-wine urine.

  ⭐ Acanthosis nigricans can be a sign of insulin resistance (e.g., diabetes) or internal malignancy (especially gastric adenocarcinoma).

GI & Nutritional - Gut‑Skin Signals

• IBD (Crohn's/UC):
  • Erythema nodosum (EN), Pyoderma gangrenosum (PG).
  • Oral aphthae, cutaneous Crohn's.
• Celiac Disease:
  • Dermatitis herpetiformis (DH): intensely pruritic vesicles (extensors); IgA at DEJ.
  • Angular cheilitis, glossitis.

⭐ Dermatitis herpetiformis is a highly specific cutaneous marker for Celiac Disease, responding to a gluten-free diet.

• Nutritional Deficiencies:
  • Zinc (Acrodermatitis Enteropathica): Periorificial/acral dermatitis, alopecia, diarrhea.
  • Niacin/B3 (Pellagra): 📌 3 D's: Dermatitis (photosensitive, Casal's necklace), Diarrhea, Dementia.
  • Vit C (Scurvy): Perifollicular hemorrhage, corkscrew hairs, gingivitis.
• Liver Disease: Pruritus, jaundice, spider nevi, palmar erythema.
• Pancreatic Disease: Enzymatic panniculitis (painful nodules), Trousseau's sign (migratory thrombophlebitis with malignancy).

Paraneoplastic & Vascular - Cancer & Vessel Alarms

• Paraneoplastic Syndromes (Skin signals of internal cancer):
  • Acanthosis Nigricans: GI (stomach), lung. Velvety skin (axilla, neck).
  • Leser-Trélat sign: Sudden ↑ seborrheic keratoses. GI (stomach, colon).
  • Tripe Palms: Gastric/Lung cancer. Rugose palms.
  • Dermatomyositis: Gottron's papules, heliotrope rash. Ovarian, lung. 📌 "Got Heli?"
  • Necrolytic Migratory Erythema: Glucagonoma. Annular crusted plaques.
  • Sweet's Syndrome: AML. Tender red plaques.
• Cutaneous Vasculitis (Vessel inflammation):
  • Palpable purpura: Hallmark. Non-blanching. Lower limbs.
  • Leukocytoclastic Vasculitis (LCV): Small vessels. Drugs, infections, malignancy.
  • IgA Vasculitis (HSP): Purpura, arthritis, abdominal pain, renal.
  • Polyarteritis Nodosa (PAN): Medium vessels. Livedo reticularis, nodules, ulcers. HBV.

⭐ Leser-Trélat sign: abrupt onset of multiple seborrheic keratoses, strongly linked to internal malignancy, especially GI adenocarcinoma.

High‑Yield Points - ⚡ Biggest Takeaways

• Acanthosis nigricans: Velvety plaques; linked to insulin resistance and gastric cancer.
• Dermatomyositis: Gottron's papules, heliotrope rash; signals underlying malignancy.
• Erythema nodosum: Tender shin nodules; associated with sarcoidosis, infections, IBD.
• Pyoderma gangrenosum: Painful ulcers with violaceous borders; linked to IBD.
• Porphyria cutanea tarda: Sun-exposed blisters; associated with liver disease, HCV.
• Necrobiosis lipoidica: Atrophic shin plaques; strongly indicates diabetes mellitus.
• Sweet's syndrome: Tender plaques, fever; consider Acute Myeloid Leukemia (AML).