CONNECTIVE TISSUE DISEASES (CTDs)
Disease Autoantibody
SLE ANA, anti-dsDNA, anti-Sm
Sjögren’s syndrome ANA, anti-Ro, anti-La
Systemic sclerosis (diffuse) ANA, anti-Scl-70
Systemic sclerosis (limited) ANA, anti-centromere
Polymyositis/Dermatomyositis ANA, anti-Jo-1, anti-Mi-2
Mixed CTD ANA, anti-RNP
Drug-induced lupus ANA, anti-histone
o ANA: sensitive (99%), but not specific
o Anti-dsDNA: specific, correlates with renal disease
o Anti-Sm: specific, not sensitive
• Clinical features:
o Constitutional: fatigue, fever
o Skin: malar rash, photosensitivity, discoid rash
o Mucosa: oral ulcers
o Arthritis (non-erosive), serositis (pleuritis, pericarditis)
o Nephritis (proteinuria, casts, ↓C3/C4)
o CNS: seizures, psychosis
• Investigations:
o FBC: anaemia, leukopenia, thrombocytopenia
o ESR ↑, CRP often normal (unless infection)
o U+Es, urinalysis ± PCR ratio
o Complement: ↓C3, ↓C4 during flare
o Renal biopsy for lupus nephritis classification
• Management:
o Hydroxychloroquine (first-line for all)
o Steroids ± immunosuppressants:
Azathioprine, mycophenolate, cyclophosphamide (esp. nephritis)
o Monitor for bone health, CV risk, and infections
• Autoantibodies: Anti-Ro, Anti-La, ANA+
• Features:
o Dry eyes (keratoconjunctivitis sicca)
o Dry mouth (xerostomia)
o Parotid gland enlargement
• Associated with: RA, SLE, PBC
• Investigations:
o Schirmer’s test (tear production)
o Salivary gland biopsy (lymphocytic infiltrate)
• Complication: ↑ risk of non-Hodgkin lymphoma
• Management: symptomatic (artificial tears/saliva); systemic immunosuppression if organ involvement
o Anti-Scl-70 (topoisomerase I)
o Widespread skin thickening, early visceral involvement (lungs, kidneys)
o Complication: scleroderma renal crisis
o Anti-centromere
o Features: Calcinosis, Raynaud's, Esophageal dysmotility, Sclerodactyly, Telangiectasia
o Pulmonary hypertension common
• Shared features:
o Raynaud’s, oesophageal reflux, skin fibrosis
• Investigations:
o HRCT + PFTs → ILD
o Echo → pulmonary arterial hypertension
o U+Es → screen for renal crisis
• Management:
o Raynaud’s: CCBs (e.g. nifedipine)
o ILD: mycophenolate, cyclophosphamide
o Renal crisis: ACE inhibitors (even if creatinine rising)
• Autoantibodies:
o Anti-Jo-1: antisynthetase syndrome
o Anti-Mi-2 (dermatomyositis)
• Clinical features:
o Proximal muscle weakness
o Dermatomyositis: heliotrope rash, Gottron’s papules, V-sign/shawl rash
• Investigations:
o CK ↑↑, ALT/AST ↑, LDH ↑
o EMG: myopathic pattern
o Muscle biopsy: confirms diagnosis
• Association with malignancy: esp. dermatomyositis (ovarian, GI, lung, breast)
• Management:
o Steroids first-line
o Immunosuppressants: methotrexate, azathioprine
o Cancer screening
• Autoantibody: anti-RNP
• Overlap of: SLE + systemic sclerosis + polymyositis
• Features:
o Raynaud’s
o Arthritis
o Myositis
o Pulmonary hypertension
• Often ANA+ and may evolve into one dominant CTD
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Author & Educational Disclaimer
Author:
Dr Phillip Cockrell BM FRCP DipClinEd
Dr Phillip Cockrell is a UK Consultant Physician in Internal Medicine, currently working at Queen Alexandra Hospital, Portsmouth University Hospitals NHS Trust. He has previously worked as a registrar across Intensive Care Medicine, Gastroenterology, Cardiology, Stroke Medicine, Acute Medicine, and Respiratory Medicine.
He has held senior leadership roles including Associate Clinical Director of the Acute Medical Unit, Clinical Director of Internal Medicine, and Chief of Medicine. Dr Cockrell has over 15 years’ experience in postgraduate medical education, having lectured extensively across the MRCP syllabus and contributed to MRCP revision teaching and course development.
Dr Cockrell holds a Bachelor of Medicine (BM), Fellowship of the Royal College of Physicians (FRCP), and a Diploma in Clinical Education (DipClinEd). His teaching approach is based on structured consolidation of complex medical topics to support efficient and effective revision for postgraduate examinations.
Purpose of this content:
The material on this page is intended solely for educational purposes to support revision for the MRCP (UK) Part 1 examination. It reflects examination-relevant principles of internal medicine and is designed to aid learning and pattern recognition.
Medical disclaimer:
This content is designed for postgraduate medical examination revision and does not constitute medical advice, diagnosis, or treatment guidance and must not be used as a substitute for professional clinical judgement, local guidelines, or specialist consultation. Clinical decisions should always be made in the context of individual patient circumstances and current national guidance.
