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Dermatology Uncovered

Module 9: Dermatology in Systemic Disease

Learning Outcomes

Section titled “Learning Outcomes”

  1. Identify and describe common cutaneous manifestations of systemic diseases, including metabolic (e.g., diabetes mellitus), autoimmune (e.g., systemic lupus erythematosus), neoplastic (e.g., paraneoplastic syndromes), and infective conditions (e.g., HIV-related dermatoses).

  2. Explain the pathophysiological mechanisms linking systemic diseases to their dermatological presentations, emphasizing how skin findings can reflect underlying organ dysfunction or systemic pathology.

  3. Interpret dermatological signs in the context of systemic illness to aid in early diagnosis, differential diagnosis, and formulation of a comprehensive management plan, integrating dermatological and systemic treatment approaches.

1. Cutaneous Manifestations of Systemic Illness

Section titled “1. Cutaneous Manifestations of Systemic Illness”

Overview

Section titled “Overview”

Skin changes may be the first or most visible sign of systemic diseases. These manifestations can be of metabolic, neoplastic, autoimmune, or infectious origin.

Common Conditions and Features

Section titled “Common Conditions and Features”

  • Acanthosis Nigricans: Velvety hyperpigmented plaques in flexural areas. Associated with insulin resistance, obesity, and internal malignancies (especially gastric adenocarcinoma).

  • Amyloidosis: Papular or macular lesions due to amyloid deposition. Often itchy and located on the shins, thighs, or back. Histology confirms the diagnosis.

  • Crohn’s Disease: Cutaneous signs include granulomatous cheilitis, perianal ulceration, and pyoderma gangrenosum. May also present with metastatic skin lesions.

  • Dermatitis Herpetiformis: Intensely pruritic vesicles on elbows, knees, and buttocks. Associated with gluten-sensitive enteropathy. Diagnosed via biopsy and direct immunofluorescence.

  • Diabetes Mellitus:

    • Necrobiosis Lipoidica: Yellowish plaques with telangiectasia, commonly on the shins.

    • Diabetic Bullae: Non-inflammatory blisters on feet and hands.

    • Eruptive Xanthomata: Yellow papules due to hyperlipidemia.

  • Erythema Nodosum: Painful red nodules on the shins, often reactive to infections or systemic inflammation.

  • Livedo Reticularis: Net-like purplish discoloration due to vascular pathology.

  • Porphyria Cutanea Tarda: Photosensitive blisters and hyperpigmentation due to porphyrin metabolism defects.

  • Sarcoidosis: Lupus pernio and other granulomatous skin lesions.

  • Sweet’s Syndrome: Acute febrile neutrophilic dermatosis with painful plaques and systemic symptoms.

Diagnosis

  • Clinical examination
  • Skin biopsy
  • Serological tests (e.g., ANA, anti-dsDNA)
  • Imaging and systemic workup

Treatment

  • Treat underlying systemic disease
  • Topical steroids or immunomodulators
  • Systemic immunosuppressants (e.g., corticosteroids, dapsone)
  • Lifestyle modifications (e.g., weight loss in acanthosis nigricans)

2. Connective Tissue Disorders

Section titled “2. Connective Tissue Disorders”

Overview

Section titled “Overview”

These are autoimmune diseases affecting the skin and other organs. Skin signs often precede systemic involvement.

Major Disorders

Section titled “Major Disorders”

  • Cutaneous Lupus Erythematosus (CLE):

    • Acute CLE: Butterfly rash, photosensitivity, oral ulcers.

    • Subacute CLE: Annular or papulosquamous lesions.

    • Chronic CLE (Discoid LE): Scarring plaques, alopecia.

    • Associated with HLA subtypes and complement deficiencies.

  • Dermatomyositis:

    • Gottron’s Papules: Over knuckles and elbows.

    • Heliotrope Rash: Periorbital violaceous discoloration.

    • Nailfold Telangiectasia and Shawl Sign.

    • Associated with malignancy (breast, ovarian, lung).

    • Muscle weakness and elevated CK levels.

  • Scleroderma (Systemic Sclerosis):

    • Limited Cutaneous: CREST syndrome (Calcinosis, Raynaud’s, Oesophageal dysmotility, Sclerodactyly, Telangiectasia).

    • Diffuse Cutaneous: Rapid skin thickening, organ involvement.

    • Skin becomes tight, shiny, and immobile.

Diagnosis

  • Autoantibody profiles (ANA, anti-Ro, anti-La, anti-Scl-70)
  • Skin and muscle biopsy
  • Nailfold capillaroscopy
  • Imaging for systemic involvement

Treatment

  • Immunosuppressants: Methotrexate, Azathioprine, Mycophenolate
  • Antimalarials (Hydroxychloroquine for CLE)
  • Physical therapy for mobility
  • Sun protection and skin care

3. Skin in Endocrine and Metabolic Conditions

Section titled “3. Skin in Endocrine and Metabolic Conditions”

Overview

Section titled “Overview”

Hormonal imbalances affect skin via changes in vascular tone, collagen metabolism, and immune responses.

Key Conditions

Section titled “Key Conditions”

  • Diabetes Mellitus:

    • Diabetic Dermopathy: Brown atrophic patches on the shins.

    • Scleredema Adultorum: Thickened skin on the upper back.

    • Acanthosis Nigricans: Marker of insulin resistance.

    • Skin Infections: Furuncles, carbuncles, candidiasis.

    • Diabetic Bullae: Spontaneous blisters on feet/hands.

  • Thyroid Disorders:

    • Hyperthyroidism: Warm, moist skin, palmar erythema, pretibial myxedema (Graves’ disease).

    • Hypothyroidism: Dry, coarse skin, periorbital puffiness, loss of lateral eyebrows (Hertoghe sign), carotenemia.

  • Cushing’s Syndrome:

    • Skin thinning, striae, bruising, acne, hirsutism.

    • Due to excess cortisol from pituitary/adrenal origin or exogenous steroids.

  • Addison’s Disease:

    • Generalized hyperpigmentation due to increased ACTH/MSH.

  • Hyperlipidemia:

    • Xanthelasma: Yellow plaques on eyelids.

    • Tuberous Xanthomas: Nodules on elbows/knees.

  • Polycystic Ovary Syndrome (PCOS):

    • Acne, hirsutism, seborrhea, acanthosis nigricans.

Diagnosis

  • Hormonal assays (TSH, cortisol, insulin, glucose)
  • Lipid profile
  • Skin biopsy if needed

Treatment

  • Control underlying endocrine disorder
  • Topical treatments for skin lesions
  • Systemic therapy (e.g., insulin, thyroxine)
  • Cosmetic interventions (e.g., laser for xanthelasma)

Multiple Choice Questions

Section titled “Multiple Choice Questions”

Tap an answer to check yourself — the correct option and an explanation appear once you choose.

Q1 Which of the following is most commonly associated with acanthosis nigricans?

Q2 Gottron's papules are characteristic of which condition?

Q3 Which skin condition is most commonly associated with diabetes mellitus?

Q4 Which autoantibody is most specific for systemic sclerosis?

Q5 Which of the following is a cutaneous manifestation of internal malignancy?

Short Answer Questions (SAQs)

Section titled “Short Answer Questions (SAQs)”

SAQ 1: Cutaneous Features of Dermatomyositis

Section titled “SAQ 1: Cutaneous Features of Dermatomyositis”

SAQ

Describe the cutaneous features of dermatomyositis.

Reveal model answer
Model answer
  • Gottron’s papules: flat-topped violaceous papules over the knuckles and elbows
  • Heliotrope rash: periorbital violaceous discoloration with oedema
  • Shawl sign: erythema over the shoulders, upper back, and chest (V-sign anteriorly)
  • Nailfold telangiectasia: dilated capillary loops at the proximal nail fold
  • May be associated with underlying malignancy (breast, ovarian, and lung cancers)

SAQ 2: Pathophysiology of Skin Changes in Hypothyroidism

Section titled “SAQ 2: Pathophysiology of Skin Changes in Hypothyroidism”

SAQ

Explain the pathophysiology of skin changes in hypothyroidism.

Reveal model answer
Model answer
  • Reduced thyroid hormone leads to decreased metabolic activity in skin cells
  • Accumulation of glycosaminoglycans (mucopolysaccharides) in the dermis causes non-pitting puffiness (myxoedema)
  • Decreased eccrine gland activity results in dry, coarse skin
  • Reduced keratinocyte turnover leads to thickened stratum corneum
  • Loss of lateral eyebrows (Hertoghe sign) results from reduced hair follicle cycling
  • Carotenemia may occur due to impaired hepatic conversion of carotene to vitamin A

SAQ 3: Skin Manifestations of Systemic Lupus Erythematosus

Section titled “SAQ 3: Skin Manifestations of Systemic Lupus Erythematosus”

SAQ

List three skin manifestations of systemic lupus erythematosus (SLE).

Reveal model answer
Model answer
  1. Malar (butterfly) rash: erythematous rash over the cheeks and nose bridge, sparing the nasolabial folds — characteristic of acute CLE in SLE
  2. Discoid lesions: scarring plaques with follicular plugging, hypopigmented centres, and hyperpigmented borders
  3. Photosensitivity: exaggerated skin response to UV light, producing or worsening rashes on sun-exposed areas
  4. Oral ulcers: usually painless, on the hard palate
  5. Alopecia: diffuse or patchy, often at hairline (lupus hair)

SAQ 4: Dermatological Signs of Cushing’s Syndrome

Section titled “SAQ 4: Dermatological Signs of Cushing’s Syndrome”

SAQ

What are the dermatological signs of Cushing’s syndrome?

Reveal model answer
Model answer
  • Skin thinning: due to collagen catabolism from excess cortisol
  • Purple striae: wide, violaceous stretch marks on the abdomen, thighs, and axillae
  • Easy bruising: fragile capillaries with impaired healing
  • Acne: due to androgen excess and immunosuppression
  • Hirsutism: excess androgen-driven hair growth on the face and trunk
  • Facial plethora: ruddy, rounded “moon face” with telangiectasia

OSCE Stations

Section titled “OSCE Stations”

OSCE 1: Dermatomyositis

Section titled “OSCE 1: Dermatomyositis”
OSCE

Scenario: A 45-year-old woman presents with a violaceous rash around her eyes and scaly papules over her knuckles. She reports progressive proximal muscle weakness over two months. Task: Take a focused history, perform a skin examination, suggest investigations, and provide a management plan.

Self-assess against checklist

Tick each point you covered, then check your score.

  • Takes focused history: onset, muscle weakness, photosensitivity, systemic symptoms, weight loss.
  • Asks about associated malignancy risk factors (age, family history, smoking).
  • Examines for heliotrope rash and periorbital oedema.
  • Examines for Gottron’s papules over knuckles, elbows, and knees.
  • Examines for shawl sign and V-sign on chest.
  • Examines nailfold capillaroscopy for telangiectasia.
  • Assesses proximal muscle strength (hip flexors, shoulder abductors).
  • Requests CK to assess muscle inflammation.
  • Requests ANA and autoantibody profile; requests skin and muscle biopsy.
  • Raises association with underlying malignancy (breast, ovarian, lung) and discusses need for workup.
  • Discusses immunosuppressants (methotrexate, azathioprine) for ongoing management.
  • Provides sun protection advice and refers to rheumatology.

OSCE 2: Necrobiosis Lipoidica in Diabetes

Section titled “OSCE 2: Necrobiosis Lipoidica in Diabetes”
OSCE

Scenario: A 60-year-old man with poorly controlled diabetes presents with yellowish plaques on his shins. Task: Describe the lesion, suggest differential diagnoses, recommend investigations, and outline treatment.

Self-assess against checklist

Tick each point you covered, then check your score.

  • Describes lesion accurately: well-demarcated, atrophic, yellowish-brown plaques with central telangiectasia on the shins.
  • Correctly identifies necrobiosis lipoidica as the most likely diagnosis.
  • Lists appropriate differentials: granuloma annulare, xanthomas, pretibial myxoedema.
  • Requests HbA1c and fasting glucose to assess glycaemic control.
  • Requests lipid profile.
  • Recommends skin biopsy for confirmation (necrobiosis of collagen on histology).
  • Advises optimisation of glycaemic control as primary intervention.
  • Discusses topical potent corticosteroids or tacrolimus for active lesions.
  • Advises wound care if ulceration is present.
  • Counsels on the chronic, relapsing nature of the condition.

OSCE 3: Systemic Sclerosis

Section titled “OSCE 3: Systemic Sclerosis”
OSCE

Scenario: A 35-year-old woman presents with thickened, shiny skin on her fingers and episodic colour changes of the fingers in the cold (Raynaud’s phenomenon). Task: Perform a focused examination, suggest relevant investigations, discuss systemic implications, and propose management.

Self-assess against checklist

Tick each point you covered, then check your score.

  • Examines for sclerodactyly: tightened, shiny skin on the fingers and hands.
  • Looks for calcinosis cutis (subcutaneous calcium deposits) over bony prominences.
  • Examines for telangiectasia on the face and hands.
  • Performs nailfold capillaroscopy for dilated or absent capillary loops.
  • Checks for restricted mouth opening (microstomia).
  • Requests ANA and anti-Scl-70 autoantibody profile.
  • Discusses systemic imaging for organ involvement as guided by symptoms.
  • Discusses GI implications: oesophageal dysmotility (part of CREST).
  • Discusses immunosuppressants (methotrexate, azathioprine, mycophenolate) for skin and organ disease.
  • Recommends multidisciplinary care (rheumatology, respiratory, gastroenterology).
  • Provides patient education on skin care and cold protection.

© 2025 Professor Dato’ Dr Sivalingam Nalliah & Navin Anand Sivalingam. This work is licensed under CC BY-SA 4.0. You may share and adapt it freely, with attribution, under the same license.