Systemic Sclerosis (Scleroderma)

Content of This Page

1- Definition and Classification

2-Pathophysiology

3-Epidemiology and Risk Factors

4- Cutaneous Manifestations

5– Raynaud’s Phenomenon

6- Lung Involvement

7- Gastrointestinal Manifestations

8- Renal Crisis in Systemic Sclerosis

9- Cardiac Involvement

10- Autoantibodies

11- CREST Syndrome

12- Diagnostic Workup

13- Management Overview

14- Prognosis and Monitoring

15-Differential Diagnosis

Definition and Classification

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease marked by:

  • Fibrosis of skin and internal organs

  • Microvascular dysfunction

  • Immune dysregulation

It is classified into:

  • Limited cutaneous SSc (lcSSc) – distal skin involvement, slow progression

  • Diffuse cutaneous SSc (dcSSc) – widespread skin involvement, early visceral disease

  • Subtypes can be further described by antibody profile and clinical manifestations

Left Arm Scleroderma © image from Wikimedia Commons

Pathophysiology

Three main pathological features:

  1. Immune activation → autoantibodies (ANA, anti-Scl-70, anticentromere)

  2. Vascular injury → Raynaud’s, digital ulcers

  3. Fibroblast activation → collagen overproduction → fibrosis of skin/organs

Triggers may include silica exposure, viral infections, or environmental toxins.

Epidemiology and Risk Factors

  • Female:Male = 4:1

  • Peak incidence: age 40–60

  • Risk factors: genetic predisposition (HLA-DR), silica exposure, radiation, certain drugs

Cutaneous Manifestations

  • Sclerodactyly: tight, shiny, thickened skin on fingers → flexion contractures

  • Mask-like facies: loss of facial expression, radial furrowing

  • Telangiectasias, calcinosis

  • Digital ulcers from vasospasm or infarction

Often begins with puffy fingers before progressing to fibrosis.

Telangiectasia

Raynaud’s Phenomenon

  • Present in >90% of patients (often the first sign)

  • Triggered by cold or stress → triphasic colour change (white → blue → red)

  • May progress to digital ulceration or gangrene

-Nailfold capillaroscopy may reveal dilated loops, dropout—used in early diagnosis.

Raynaud’s Phenomenon

Lung Involvement

  • Interstitial Lung Disease (ILD): esp. with anti-Scl-70

    • Symptoms: dry cough, dyspnoea

    • PFTs: restrictive pattern, ↓ DLCO

    • Imaging: HRCT shows fibrosis

  • Pulmonary Arterial Hypertension (PAH): esp. in lcSSc

    • Screen with echocardiogram and NT-proBNP

    • Right heart catheterization is gold standard

-Leading cause of death in systemic sclerosis.

Gastrointestinal Manifestations

  • Esophageal dysmotility → reflux, strictures

  • Delayed gastric emptying

  • SIBO → bloating, diarrhoea

  • Watermelon stomach (gastric antral vascular ectasia – GAVE)

  • Constipation or pseudo-obstruction due to colonic dysmotility

-Barium studies and manometry can aid diagnosis.

Renal Crisis in Systemic Sclerosis

  • Sudden onset malignant hypertension, headache, oliguria

  • Microangiopathic haemolytic anaemia may occur

  • Associated with anti-RNA polymerase III antibodies

-Treat immediately with ACE inhibitors (even if creatinine is rising)

Avoid NSAIDs and high-dose steroids—they can precipitate crisis.

Cardiac Involvement

  • Pericarditis

  • Conduction defects

  • Myocardial fibrosis → arrhythmias, heart failure

  • PAH (as above)

-Monitor with ECG, echocardiogram, troponins if symptomatic.

Autoantibodies in SSc

AntibodyAssociated SubtypeClinical Relevance
ANA>90% casesScreening tool
Anti-centromerelcSScCREST, PAH, good prognosis
Anti-Scl-70 (topoisomerase I)dcSScILD, worse prognosis
Anti-RNA polymerase IIIdcSScRenal crisis, skin involvement

CREST Syndrome

A form of limited SSc with hallmark features:

  • Calcinosis

  • Raynaud’s phenomenon

  • Esophageal dysmotility

  • Sclerodactyly

  • Telangiectasia

Associated with anticentromere antibodies and better overall prognosis.

Diagnostic Workup

  • Clinical diagnosis based on skin thickening, Raynaud’s, and serology

  • Bloods: ANA, Scl-70, centromere, renal profile, CRP

  • Imaging: HRCT for ILD, echo for PAH

  • Lung function tests (↓ DLCO = early PAH)

  • Nailfold capillaroscopy (non-invasive vascular test)

Management Overview

SystemTreatment
Raynaud’sCCBs (nifedipine), sildenafil, iloprost
SkinMTX (for early inflammatory skin changes)
ILDMycophenolate, cyclophosphamide, nintedanib
PAHEndothelin receptor antagonists (bosentan), sildenafil
Renal crisisACE inhibitors (e.g. captopril) – emergency
GIPPIs, prokinetics, rotating antibiotics for SIBO

Prognosis and Monitoring

  • Worse prognosis with:

    • Diffuse skin involvement

    • Early ILD or PAH

    • Anti-Scl-70 or anti-RNA pol III positivity

  • 10-year survival ≈ 70–80%

-Mortality mainly from ILD and PAH

Differential Diagnosis

  • MCTD: overlap with lupus, polymyositis, and scleroderma

  • SLE: ANA+, skin findings, but lacks sclerodactyly

  • Dermatomyositis: skin changes + muscle weakness

  • Eosinophilic fasciitis: mimics scleroderma, no Raynaud’s, no autoantibodies

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