Systemic Sclerosis

 

• Background

  Pathophysiology

  • Multi-system autoimmune disease characterised by microvascular inflammatory damage, and fibrosis of skin ± internal organs.
  • In the skin, fibrosis begins in lower dermis and upper subcutaneous layer, with over-production of collagen and other connective tissue proteins such as fibrilin.
  • 'Scleroderma' refers to the skin features, and occasionally these occur in isolation. However, there is usually some degree of internal organ involvement, so the term systemic sclerosis (SSc) is generally preferred.

  Sub-types

  • Limited cutaneous systemic sclerosis (lcSSc): skin fibrosis restricted to hands, distal arms, face, and neck.
  • Diffuse cutaneous systemic sclerosis (dcSSc): skin fibrosis includes chest, abdomen, and upper arms. Internal organ disease more common.

  Epidemiology

  • 1/10,000 UK prevalence.
  • 5x commoner in women.
  • Peak onset in 40s.

• Presentation

  Thickened, firm, tight skin (scleroderma):

  • Commonly affects the fingers, 'sclerodactyly'. May lead to finger flexion contractures. Other finger changes in SSc include abnormal nailfold capillaries, fingertip pitting scars or ulcers, and puffiness. Similar changes seen in toes.
  • In the face, it can lead to microstomia (small mouth).
  • May be pruritic.
  • Often has a shiny appearance, and skin may become hyper/hypopigmented.

  While 'CREST syndrome' is no longer considered a clinically distinct sub-type of SSc, it is a useful mnemonic of some key features, especially in lcSSc:

  • Calcinosis (cutaneous).
  • Raynaud's. Often the first sign.
  • Esophageal dysmotility, which may lead to reflux, dysphagia, and oesophageal strictures or dilation. Commonest internal organ affected (90%). SSc can also affect the rest of the GI tract, causing abdo pain, bloating, diarrhoea, vomiting, malabsorption, and weight loss.
  • Sclerodactyly
  • Telangectasia: usually on hands, face, and mucous membranes. In the GI tract, includes gastric antral vascular ectasia (GAVE).

  In addition to the GI tract, almost any internal organ can be affected, including:

  • Lungs: interstitial lung disease (SOB, cough, crackles), pulmonary hypertension.
  • Kidneys: scleroderma renal crisis, presenting with AKI, hypertension, and microangiopathic haemolysis or thrombocytopaenia.
  • Heart: heart failure (esp. RHF due to pulmonary HTN), pericardial disease, myocardial fibrosis, arrhythmias.

  Connective tissue disease:

  • Tendon or bursal friction rubs.
  • Arthritis
  • Sicca symptoms: dry mouth, dry eyes.
  • Carpal tunnel syndrome.
  • Muscular pain/cramps. May be due to inflammatory myositis.

  Non-specific symptoms, including fatigue, weakness, and sleeping difficulties, are also common.

• Investigations

  Diagnosis

  Diagnosis requires presence of bilateral finger skin thickening, or a combination of other clinical features and auto-antibodies. Skin thickening which spares the fingers is unlikely to be SSc.

  90% are anti-nuclear Ab +ve, including the following sub-types:

  • Anti-centromere Ab (50%). Associated with lcSSc.
  • Anti-Scl-70, aka anti-topoisomerase I (30%). Associated with dcSSc.
  • Anti-RNA polymerase III (20%).

  Capillaroscopy – magnified nailfold visualisation to look for abnormal capillaries – can aid diagnosis.

  Assessing disease extent

  Basics bloods:

  • FBC: Hb may be low due to GI bleeding.
  • ↑ESR/CRP suggests ongoing inflammation.

  Organ involvement:

  • Kidneys: U&E, urinalysis.
  • Heart: ECG, echo.
  • Lungs: PFTs, CXR, CT chest.
  • GI tract: barium swallow, endoscopy.

• Management

  Skin and connective tissue disease:

  • Skin thickening: cyclophosphamide, methotrexate, or mycophenolate mofetil. Emollients or antihistamines for itch.
  • Raynaud's: 1st line calcium channel blockers (e.g. amlodipine), 2nd line add/switch to PDE-5 inhibitors (e.g. sildenafil, tadalafil).
  • Calcinosis: consider surgical resection if severe.

  Internal organ disease:

  • Oesophageal dysmotility: PPIs, prokinetic agent (e.g. metoclopromide, erythromycin).
  • Scleroderma renal crisis: ACEi, renal replacement therapy if severe.
  • ILD: cyclophosphamide, transplantation if severe.
  • Pulmonary HTN: PDE-5 inhibitor, endothelin receptor antagonist (bosentan, ambrisentan, macitentan).
  • Ongoing inflammation (synovitis, myositis, arthritis): low dose steroids.

• Prognosis

  • dcSSc: 30% 10 year mortality, usually due to internal organ involvement, especially the lungs.
  • lcSSc: better prognosis, but requires monitoring for progression to diffuse disease.