Systemic Sclerosis

Systemic sclerosis is an autoimmune condition characterised by thickening and hardening of the skin (sclerosis) and other connective tissues. There are 3 distinct patterns of systemic sclerosis, including:

  1. Limited cutaneous SS
  2. Diffuse cutaneous SS
  3. Scleroderma

90% of patients with any form are ANA positive. 

 

Limited cutaneous systemic sclerosis

Clinical Features

  • Typically women aged 30-50 years of age
  • Sclerosis affects the face & distal limbs
  • Raynaud’s phenomenon is common
  • Used to be referred to as CREST syndrome. Features of LCSS therefore include: Calcinosis, Raynaud’s, Esophageal dysfunction, Sclerodactyly, Telangiectasia

Antibody

  • Anti-centromere antibodies, ANA

  

Diffuse cutaneous systemic sclerosis

Clinical Features

  • Typically women aged 30-50 years of age
  • Sclerosis affects the trunk & proximal limbs

Complications

  • Interstitial lung disease (up to 8/10 patients) - SSc-ILD (Scleroderma-related ILD) - pulmonary fibrosis with progressive respiratory failure
  • Pulmonary hypertension 
  • Hypertension, CKD

Antibody

  • SCL-70 antibodies, ANA

 

Scleroderma

Clinical Features

  • Hardened, thickened areas of skin. Tightening of the skin gives a 'shiny' appearance.
  • Plaque morphoea - oval patches of discoloured, hardened skin which might be shiny
  • Linear morphoea: thickened lines of skin along the arms and legs
  • No organ involvement

 

 Sjogren’s Syndrome  

Pathophysiology

  • Autoimmune mediated destruction of exocrine glands
  • Classification
    • Primary Sjogren’s 
    • Secondary Sjogren’s - rheumatoid arthritis, connective tissue disease

Clinical Features

  • Epidemiology: Typically affects middle aged women
  • Generalised features:
    • Fatigue
    • Diffuse, generalised joint pain
  • Exocrine dysfunction results in: 
    • Keratoconjunctivitis Sicca - dry eyes - a foreign body, gritty sensation and light sensitivity
    • Dry mouth - xerostomia - difficulty chewing, swallowing or talking. 
      • Increased risk of oral candidiasis 
    • Parotitis - facial swelling
    • Vaginal dryness
  • Photosensitive rashes

Complications

  • Lymphoid malignancy ( x 50 risk)

Investigations

Antibodies

  • Rheumatoid factor - 50% positive
  • ANA - 70% positive
  • ANTI-RO (SSA) - 70% Primary SS
  • Anti-La (SSB) - 30%

Investigations

  • Schirmer’s test - reduced tear film (<5mm after 5 minutes)
  • Labial (lip) salivary gland biopsy - histology -l focal lymphocytic infiltration 
  • Anti-Ro/La positive

Management

  • Dry eyes and mouth - pilocarpine, artificial tears 

 

Dermatomyositis

Dermatomyositis is an inflammatory condition resulting in symmetrical proximal muscle weakness and skin lesions. 

Causes

  • Underlying malignancy in 25% of patients -  ovarian, breast, lung 
  • Idiopathic

Clinical features

Cutaneous features - 'Dermato...'

  • Heliotrope periorbital rash - redish/purple rash on eyelids
  • Red macular rash affecting back and shoulders
  • Mechanics hands – Gottron’s red papules on extensor surfaces - often overlying the knuckles and PIP/DIP joints
  • Rashes are photosensitive

‘Myositis..’

  • Symmetrical, proximal weakness +/- tenderness
    • Difficult climbing stairs, getting up from chair, holding up a cup of tea or brushing hair etc. 

General symptoms

  • Fatigue
  • Weight loss
  • Night sweats 

Other features: ILD causing shortness of breath, Raynaud’s phenomenon 

Investigations

Bloods

  • Raised CK due to myositis
  • ANA positive (80%)
  • Antibodies:
    • Anti-MI-2 Antibodies
    • Anti-SRP antibodies
    • (Anti-Jo 1 antibodies - more associated with polymyositis) 

Management

  • Steroids - Prednisolone 
  • Patients should be screened for malignancy

 

Polymyositis

  • A variant of dermatomyositis without skin manifestations
  • Antibodies: Anti-JO1 (vs histidine tRNA ligase) 

 

Mixed Connective Tissue Disease / Sharp's Syndrome 

Pathophysiology

  • A multisystem autoimmune disease with mixed features of SLE, systemic sclerosis and myositis.

Clinical Features

  • Myalgia 
  • Shortness of breath due to pulmonary hypertension
  • Polyarthralgia
  • Raynaud's phenomenon
  • Dactylitis "sausage fingers"
  • Rash
  • Oesophageal dysfunction / swallowing difficulties
  • Renal/CNS disease is unlikely

Antibodies

  • Anti-U1 ribonucleoprotein antibodies (Anti-RNP)

Management

  • DMARDs

 

Relapsing Polychondritis

Pathophysiology

  • Episodic inflammation of cartilage, particularly of the ears, nose, joints

Clinical Features

  • Ears - Auricular chondritis, hearing loss, vertigo 
  • Nose - nasal chondritis - saddle nose
  • Respiratory tract -  hoarse voice, aphonia, wheeze
  • Joints - arthralgia

Management

  • Steroids can be used to induce remission
  • Maintenance - DMARDs 

 

Familial Mediterranean Fever

Pathophysiology

  • An autosomal recessive disease resulting in recurrent episodes of acute polyserositis

Epidemiology

  • Increased prevalence in patients of Turkish, Armenian, Arabic descent 

Clinical features

  • Patients have 'attacks' lasting 1-3 days with symptoms including:
    • Fever
    • Pleurisy
    • Abdominal pain, peritonitis 
    • Pericarditis
    • Arthritis
    • Erysipeloid rash on the lower limbs

Management

  • 1st line - colchicine

 

Pseudoxanthoma Elasticum

Pathophysiology

  • An autosomal recessive disease caused by calcium deposition and mineralization of the elastic fibres of connective tissues around the body.

Clinical Features

  • Retinal angioid streaks - red bands radiating from the disc. 
  • 'Plucked chicken skin appearance'
    • Small yellow papules in a liner pattern, in groups forming plaques
    • Loss of elastic tissue and saggy looking skin in neck, axilla etc. 
  • Cardiovascular complications:
    • Intermittent claudication is a common early sign of arterial disease
    • Ischaemic heart disease
    • MV valve prolapse 
  • Gastrointestinal bleeding - melaena/frank bleeding/occult in stool

 

Adult-onset Still’s Disease

Pathophysiology

  • A systemic autoimmune disease

Clinical features

A triad of:

  • Fever
  • Joint pain - especially the knees, wrists and ankles
  • Maculopapular salmon rash 
  • Other - lymphadenopathy, sore throat, hepatosplenomegaly, myalgia, pericarditis. 

Investigations

  • No single diagnostic test - Ferritin, ESR and CRP elevated
  • Autoantibodies: Rheumatoid factor and ANA are negative

Management

  • 1st Line: NSAIDs and corticosteroids
    • NSAIDs for symptomatic control
    • Once diagnosis is confirmed patients can be treated with steroids
  • Long term: DMARDs - Methotrexate 
    • Alternatives: ciclosporin, leflunomide, azathioprine, MMF, cyclophosphamide
  • Alternative: If failure of 2 DMARDs, Anakinra (IL-1 receptor antagonist) is recommended by NICE