scleroderma
SCLERODERMA
Scleroderma is a connective tissue disorder characterized by skin thickening and fibrosis. It is rare, autoimmune and chronic.
It has an idiopathic cause and not contagious.
Early microvascular damage, mononuclear cell infiltrates and slowly developing fibrosis are the important features of the tissue lesions.
The leading causes of death are pulmonary fibrosis and pulmonary arterial hypertension.

Scleroderma Diagnosis

Diagnosis

  • Diagnosis is based on medical history, clinical presentation and laboratory tests

2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria for Scleroderma/Systemic Sclerosis

  • Presence of skin thickening of the fingers extending proximal to the metacarpophalangeal joints
  • If skin thickening is absent, assess for any of the following:
    • General skin thickening of the fingers
    • Fingertip lesions
    • Abnormal nailfold capillaries
    • Telangiectasia
    • Interstitial lung disease or pulmonary arterial hypertension (PAH)
    • Raynaud’s phenomenon
    • Systemic sclerosis-related autoantibodies

Classification

Localized

  • Usually affects only the skin but may spread to the joints, bones and muscles
  • Not associated with Raynaud’s phenomenon or significant internal organ manifestations
    • Morphea
      • Circumscribed (plaque) 
        • ≥1 discolored patches on the skin with sclerotic changes in 1 anatomic site  
        • Involvement confined in the subcutaneous tissue  
        • Very localized form of scleroderma
      • Linear
        • Streaks or band of thick hard skin on the arms and legs, and subcutaneous tissue abnormalities in dermatomal distribution affecting usually 1 side of the body
        • Most common form of morphea in children  
        • Associated with impairment of growth of affected extremity  
        • En coup de sabre is a type of linear morphea in which there are sclerotic lesions on the face, scalp or forehead  
      • Generalized
        • ≥4 plaques (similar to circumscribed morphea) involving at least 2 anatomic sites often on the limbs or trunk  
      • Bullous
        • May occur in other forms of morphea  
      • Deep
        • Most disabling form of morphea primarily involving the subcutaneous tissue
        • Most uncommon form of morphea in children

Systemic (Systemic Sclerosis)

  • Hardening of the skin and Raynaud’s phenomenon are the clinical hallmarks of the disease
  • Usually occurs in women ages 30-50 years old
    • Limited
      • Skin thickening is mainly limited in the forearms, hands, face and feet (acral distribution), has prominent vascular presentation and may also affect the lungs and digestive system [eg PAH, severe gastroesophageal reflux disease (GERD), interstitial lung disease] 
      • Physical exam shows telangiectasia, calcinosis cutis, sclerodactyly and digital ischemic complications
    • Diffuse
      • More extensive skin involvement affecting acral skin and trunk with more serious and extensive internal organ involvement (eg heart, lung, gastrointestinal and kidneys) 
      • Tendon friction rubs and pigment changes are the common physical exam findings
    • Systemic sclerosis sine scleroderma
      • Type of systemic scleroderma that only affects the internal organs with no skin involvement
      • Anti-Scl-70, ACA, or anti-RNA polymerase I, II, or III may be present
    • Overlap syndromes
      • Type of systemic scleroderma with concomitant autoimmune rheumatic disease (eg rheumatoid arthritis, SLE, polymyositis, dermatomyositis, vasculitis, Sjögren’s syndrome)
    • Pre-scleroderma
      • Raynaud’s phenomenon, nailfold capillary changes and antibodies such as anti-Scl-70 and RNA polymerase I, II, or III are present
    • Environmentally-induced scleroderma
      • Positive for history of exposure to a scleroderma-inducing environmental agent and diffuse skin sclerosis

Laboratory Tests

  • There is no definitive diagnostic test for scleroderma
  • Serologic tests confirm but not exclude diagnosis of scleroderma

Anticentromere Antibodies (ACA)

  • Highly specific and moderately sensitive for limited systemic sclerosis
  • Associated with higher risk of esophageal disease or pulmonary hypertension

Antinuclear Antibodies (ANA) Panel

  • Will show homogeneous, speckled or nucleolar staining patterns
  • Nucleolar pattern is most specific for systemic sclerosis

Anti-beta2-glycoprotein I (β2GPI) Antibodies

  • Usually present in scleroderma patients with macrovascular disease
  • Associated with higher risk of active digital ischemia, loss of digits secondary to ischemia and PAH

Anti-DNA Topoisomerase I (Anti-Scl-70)

  • Highly specific and moderately sensitive for diffuse systemic sclerosis
  • Associated with higher risk of severe interstitial lung disease or lung fibrosis

Anti-PM-Scl Autoantibodies

  • Clinically associated with overlap syndromes and usually present in systemic scleroderma patients with myositis

Anti-RNA Polymerase II

  • Also present in patients with diffuse systemic sclerosis and systemic lupus erythematosus (SLE)

Anti-RNA Polymerase III

  • Highly specific and moderately sensitive for diffuse systemic sclerosis
  • Associated with higher risk of scleroderma renal crisis, malignancy or skin involvement

U1-RNP Antibodies

  • Clinically associated with limited systemic sclerosis with muscle involvement  

U3-RNP (Fibrillarin) Antibodies

  • Clinically associated with diffuse systemic sclerosis and poor outcome
  • Associated with higher risk of systemic sclerosis-associated PAH and skeletal muscle involvement

Organ-specific Assessments

  • Joint radiographs for arthritis
  • Barium swallow (cine esophagography), endoscopy, esophageal manometry for gastrointestinal complications
  • Chest radiograph, pulmonary function test, lung CT scan, bronchoscopy with biopsy, gallium lung scan, bronchoalveolar lavage to check for pulmonary complications
  • ECG ambulatory (Holter), ECG monitoring, echocardiography, cardiac MRI, cardiac catheterization to assess for cardiac complications
  • Renal biopsy and urinalysis for renal complications
  • Skin biopsy for localized scleroderma
  • Creatine kinase measurements, erythrocyte sedimentation rate and C-reactive protein measurements for myositis, malignancy or overlap of systemic sclerosis with another autoimmune disease

Screening

Pulmonary Arterial Hypertension (PAH) Screening in Systemic Sclerosis   

  • Early diagnosis and treatment of PAH may improve clinical outcomes in patients with systemic sclerosis 
  • The 6th World Symposium on Pulmonary Hypertension recommends the use of transthoracic echocardiography (TTE) and the DETECT algorithm to annually screen for PAH in patients with systemic sclerosis spectrum disorders and a diffusing capacity of the lung for carbon monoxide (DLCO) of <80% predicted  
    • DETECT algorithm uses the combination of pulmonary function testing (forced vital capacity/DLCO ratio) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels
    • Patients with positive screening tests are referred for right heart catheterization
    • For patients with a DLCO of ≥80% predicted, consider an annual TTE 
  • The Australian Scleroderma Interest Group (ASIG) algorithm requires fewer variables in the initial step with less restrictive inclusion criteria whereas DETECT is a more validated tool for patients meeting the inclusion criteria 
Editor's Recommendations
Most Read Articles
Stephen Padilla, 5 days ago
The novel coronavirus disease (COVID-19) pandemic appears to have a significant impact on oncological care, according to a study, which stresses the need for psycho-oncological support for cancer patients.
01 Aug 2020
Supplementation with probiotics may have positive effects in patients with type 2 diabetes mellitus (T2DM), reports a recent meta-analysis.
5 days ago
Sodium–glucose cotransporter-2 (SGLT-2) inhibitors increase the risk for diabetic ketoacidosis (DKA) by almost threefold, with molecule-specific analyses suggesting a class effect, according to a study.
Jairia Dela Cruz, 19 hours ago
Monthly prophylaxis with the fixed-dose combination of naphthoquine-azithromycin (NQAZ) is well tolerated and confers significant protection against infection with Plasmodium parasites among individuals residing in malaria-endemic areas in Southeast Asia, as shown in the results of a phase III trial.