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 
Figure 225: Ear inflammation in a patient with relapsing polychondritis. John C. Starr et al., CC BY 3.0.

  

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
Figure 226: Patients with Familial Mediterranean Fever also present with erysipeloid skin rashes on the legs which mimic cellulitis. Dr. H.J. Lachman, CC BY 4.0.

   

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
Figure 226: Pseudoxanthoma elasticum of the posterior lateral neck. Note the characteristic 'plucked chicken appearance'. kilbad, CC BY 3.0.

   

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