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ALL / Rheumatology

Mixed connective tissue disease

Mixed connective tissue disease

Mixed connective tissue disease (MCTD, Sharp's syndrome) is a rare, heterogeneous, multi-system autoimmune disorder. It is a distinct clinical entity, but features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and myositis may all be present. It is associated with anti-U1 ribonucleoprotein (RNP) antibodies.* It is not to be confused with 'undifferentiated connective tissue disease'.**

Epidemiology
  • Male:female ratio 1:3
  • Average age of presentation 30-40, may present in children
  • Rare - incidence in adult population is estimated to be 2.1/million/year in one Norwegian study

Presentation:
  • Raynaud's phenomenon often precedes other symptoms and occurs in 90% of cases
  • Polyarthralgia/arthritis
  • Myalgia
  • 'Sausage fingers'(dactylitis)

Other clinically important features:
  • Dermatological: photosensitive rash, scleroderma-like changes, alopecia
  • Oesophageal dysfunction
  • Respiratory: pleuritis, pulmonary hypertension, interstitial lung disease
  • Haematological: anaemia, lymphadenopathy, splenomegaly, rarely TTP
  • Cardiac: pericarditis, pericardial effusion, accelerated coronary artery disease
  • Renal: glomerulonephritis (tends to be milder than SLE)
  • Neuropsychiatric: seizures, mood disturbance

Investigations:
  • Exclude other connective tissue disease/vasculitis
  • Bloods FBC: anaemia, leucopenia, thrombocytopenia, U+E: renal impairment, CRP/ESR raised
  • ANA (usually) positive, anti Ds-DNA and scleroderma-specific antibodies (e.g. Anti-Scl70) are negative
  • Anti-U1 RNP (an extractable nuclear antigen, ENA), must be positive*.
  • Organ-specific investigations, e.g. ECG, echo, CT chest, MRI brain

Management:
  • No large-scale trials - patients have been included in trials for SLE/SSc and show similar levels of response to immunosuppression/DMARDs
  • Calcium channel blockers may be used for the treatment of Raynaud's
  • Proton pump inhibitors for reflux disease
  • Endothelin receptor antagonists/prostacyclin analogues in pulmonary hypertension
  • Smoking cessation, moderate exercise

Prognosis:
  • 1/3 long-term remission, 1/3 have chronic symptoms, 1/3 develop severe systemic involvement and premature death.


*Note that anti-U1 RNP antibodies are not completely specific and may also be seen in definite SSc and SLE
**Undifferentiated connective tissue disease refers to syndromes in which features of one or more 'classical' connective tissue disease may be present, but do not meet diagnostic criteria. Anti-U1 RNP is absent.
+PassMedicine Notes

Mixed connective tissue disease (MCTD, Sharp's syndrome) is a rare, heterogeneous, multi-system autoimmune disorder. It is a distinct clinical entity, but features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and myositis may all be present. It is associated with anti-U1 ribonucleoprotein (RNP) antibodies.* It is not to be confused with 'undifferentiated connective tissue disease'.**

Epidemiology
  • Male:female ratio 1:3
  • Average age of presentation 30-40, may present in children
  • Rare - incidence in adult population is estimated to be 2.1/million/year in one Norwegian study
Presentation:
  • Raynaud's phenomenon often precedes other symptoms and occurs in 90% of cases
  • Polyarthralgia/arthritis
  • Myalgia
  • 'Sausage fingers'(dactylitis)
Other clinically important features:
  • Dermatological: photosensitive rash, scleroderma-like changes, alopecia
  • Oesophageal dysfunction
  • Respiratory: pleuritis, pulmonary hypertension, interstitial lung disease
  • Haematological: anaemia, lymphadenopathy, splenomegaly, rarely TTP
  • Cardiac: pericarditis, pericardial effusion, accelerated coronary artery disease
  • Renal: glomerulonephritis (tends to be milder than SLE)
  • Neuropsychiatric: seizures, mood disturbance
Investigations:
  • Exclude other connective tissue disease/vasculitis
  • Bloods FBC: anaemia, leucopenia, thrombocytopenia, U+E: renal impairment, CRP/ESR raised
  • ANA (usually) positive, anti Ds-DNA and scleroderma-specific antibodies (e.g. Anti-Scl70) are negative
  • Anti-U1 RNP (an extractable nuclear antigen, ENA), must be positive*.
  • Organ-specific investigations, e.g. ECG, echo, CT chest, MRI brain
Management:
  • No large-scale trials - patients have been included in trials for SLE/SSc and show similar levels of response to immunosuppression/DMARDs
  • Calcium channel blockers may be used for the treatment of Raynaud's
  • Proton pump inhibitors for reflux disease
  • Endothelin receptor antagonists/prostacyclin analogues in pulmonary hypertension
  • Smoking cessation, moderate exercise
Prognosis:
  • 1/3 long-term remission, 1/3 have chronic symptoms, 1/3 develop severe systemic involvement and premature death.
*Note that anti-U1 RNP antibodies are not completely specific and may also be seen in definite SSc and SLE **Undifferentiated connective tissue disease refers to syndromes in which features of one or more 'classical' connective tissue disease may be present, but do not meet diagnostic criteria. Anti-U1 RNP is absent.

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