Scleroderma (Systemic Sclerosis)

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Scleroderma (Systemic Sclerosis, SSc)

Scleroderma (Systemic Sclerosis, SSc) is a chronic autoimmune connective tissue disease characterized by vascular dysfunction, immune activation, and progressive fibrosis of the skin and internal organs, most commonly affecting females with a 3:1 ratio between ages 30 and 50. Pathogenesis begins with endothelial injury and abnormal angiogenesis leading to increased vascular endothelial growth factor production and vascular leakage, followed by autoantibody formation including anticentromere antibodies, anti topoisomerase 1 antibodies, and anti RNA polymerase 3 antibodies. These processes drive autoantigen mediated T cell activation and cytokine release, particularly TGF beta, resulting in fibroblast activation and collagen deposition with progressive fibrosis. Diagnosis is based on weighted clinical criteria requiring a score of at least 9 and includes proximal finger skin thickening, digital edema progressing to induration and atrophy, non pitting sclerosis, sclerodactyly, digital ulcers and ischemic pitting scars, telangiectasias, abnormal nailfold capillaries, pulmonary arterial hypertension, interstitial lung disease, Raynaud’s phenomenon, and autoantibody positivity. Limited systemic sclerosis involves distal extremities and face with a better prognosis and includes the CREST variant, while diffuse systemic sclerosis involves proximal and distal extremities and trunk with severe visceral involvement and worse prognosis. Additional cutaneous features include microstomia, beaked nose, salt and pepper dyspigmentation, and pterygium inversum unguis.

Epidemiology

  • Female dragon slayer = Female predominance with 3:1 ratio
  • Ages 30 to 50 = Typical age of onset

Pathogenesis

  • Leaky vascular hose = Vascular dysfunction and abnormal angiogenesis
  • Bucket of VEGF veggies = Increased VEGF production
  • Leaking hose = Vascular leakage
  • Centromere shaped dragonfly = Anticentromere antibodies
  • Top hat = Anti SCL 70 antitopoisomerase 1 antibodies
  • Polymerase printer = Anti RNA polymerase 3 antibodies
  • Tree growth factor beta fertilizer = TGF beta cytokine production
  • Fibrotic tree = Fibrosis development

Clinical Diagnostic Criteria

  • Dragon’s thick claws = Skin thickening of fingers extending proximal to MCP joints
  • Wet hands = Edematous phase with pitting edema
  • Tight shiny dragon claws = Indurated phase
  • Stone claw statue = Non pitting skin thickening
  • Contracted claws = Atrophic phase with flexion contractures
  • Scaly finger skin = Sclerodactyly distal to MCP joints but proximal to PIP joints

Digital Ulcers and Pitting Scars

  • Ulcer in ground = Digital tip ulcers due to trauma
  • Blue pit = Fingertip pitting scars due to ischemia

Telangiectasias

  • Red mat = Matted telangiectasias of face lips and palms
  • Squared mat edges = Smooth squared off telangiectasia borders
  • Loop and dropout towel = Dilated capillary loops with dropout

Lung Findings

  • High tension vascular belt = Pulmonary arterial hypertension
  • Fibrotic lung tree = Interstitial lung disease

Raynaud’s Phenomenon

  • Blue gloves = Raynaud’s phenomenon and secondary Raynaud’s

Autoantibody Positivity

  • Centromere shaped dragonfly = Anticentromere antibodies
  • Top hat = Anti SCL 70 antibodies
  • Polymerase printer = Anti RNA polymerase 3 antibodies

Subtypes

Limited Systemic Sclerosis

  • Dragon mask and claws = Distal extremity and facial involvement
  • Thumbs up = Better prognosis without severe renal or pulmonary disease

CREST Syndrome

  • CREST shield = CREST syndrome
  • Glass of calcium milk = Calcinosis cutis
  • Blue gloves = Raynaud’s phenomenon
  • Esophagus shaped snake = Esophageal dysmotility
  • Dragon claws = Sclerodactyly
  • Telangiectasia mat = Telangiectasias

Diffuse Systemic Sclerosis

  • Sad dragon slayer in full body suit = Diffuse systemic sclerosis with worse prognosis

Additional Cutaneous Findings

  • Beaked bird with small mouth = Beaked nose and microstomia
  • Salt and pepper dragon = Salt and pepper dyspigmentation
  • Downward bending claws = Pterygium inversum unguis

Quiz

Question 1
Which of the following best describes the underlying pathogenesis of systemic sclerosis?
A. Neutrophilic inflammation only
B. Vascular dysfunction, immune activation, and fibrosis
C. Immune complex deposition only
D. Isolated keratinocyte apoptosis

Question 2
What is the typical demographic affected by systemic sclerosis?
A. Males age 10 to 20
B. Females age 30 to 50
C. Equal gender distribution in elderly
D. Children under age 5

Question 3
Which of the following is an early event in the pathogenesis of systemic sclerosis?
A. Keratinocyte necrosis
B. Endothelial injury
C. Neutrophil infiltration
D. Fibrosis without inflammation

Question 4
Which growth factor is upregulated in systemic sclerosis leading to vascular changes?
A. PDGF
B. VEGF
C. EGF
D. FGF

Question 5
Which cytokine is primarily responsible for fibrosis in systemic sclerosis?
A. IL 1
B. TNF alpha
C. TGF beta
D. IL 6

Question 6
Which autoantibody is most associated with limited systemic sclerosis?
A. Anti SCL 70
B. Anti RNA polymerase 3
C. Anticentromere
D. Anti dsDNA

Question 7
Which autoantibody is associated with diffuse systemic sclerosis?
A. Anticentromere
B. Anti SCL 70
C. Anti Ro
D. Anti histone

Question 8
What is the minimum score required for classification of systemic sclerosis?
A. 5
B. 7
C. 9
D. 12

Question 9
Which of the following is a hallmark skin finding in systemic sclerosis?
A. Vesicles
B. Proximal skin thickening of fingers
C. Nodules with ulceration
D. Scaling plaques

Question 10
What is sclerodactyly?
A. Swelling of proximal limbs
B. Thickening limited to distal fingers
C. Nail destruction
D. Palmar erythema

Question 11
Which of the following vascular findings is characteristic of systemic sclerosis?
A. Petechiae
B. Telangiectasias
C. Purpura
D. Livedo reticularis

Question 12
Which nailfold capillary finding is seen in systemic sclerosis?
A. Increased density
B. Dilated loops with dropout
C. Thickened nails
D. Nail pitting

Question 13
Which pulmonary condition is associated with systemic sclerosis?
A. Asthma
B. Pulmonary arterial hypertension
C. COPD
D. Pneumothorax

Question 14
Which of the following is part of CREST syndrome?
A. Calcinosis cutis
B. Keratinocyte necrosis
C. Granulomas
D. Neutrophilic infiltrate

Question 15
Which subtype of systemic sclerosis has a worse prognosis?
A. Limited systemic sclerosis
B. CREST syndrome
C. Diffuse systemic sclerosis
D. Localized scleroderma

Question 16
Which of the following cutaneous features is seen in systemic sclerosis?
A. Hypertrichosis
B. Beaked nose and microstomia
C. Vesiculobullous lesions
D. Target lesions

Question 17
What is salt and pepper dyspigmentation?
A. Hyperpigmented plaques only
B. Mixed hypo and hyperpigmentation
C. Depigmented patches only
D. Erythematous macules

Question 18
Which nail finding is associated with systemic sclerosis?
A. Onycholysis
B. Nail pitting
C. Pterygium inversum unguis
D. Subungual hematoma

Answers:
1 B. Vascular dysfunction, immune activation, and fibrosis
2 B. Females age 30 to 50
3 B. Endothelial injury
4 B. VEGF
5 C. TGF beta
6 C. Anticentromere
7 B. Anti SCL 70
8 C. 9
9 B. Proximal skin thickening of fingers
10 B. Thickening limited to distal fingers
11 B. Telangiectasias
12 B. Dilated loops with dropout
13 B. Pulmonary arterial hypertension
14 A. Calcinosis cutis
15 C. Diffuse systemic sclerosis
16 B. Beaked nose and microstomia
17 B. Mixed hypo and hyperpigmentation
18 C. Pterygium inversum unguis