CONNECTIVE TISSUE DISEASES (CTDs)
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
Systemic Lupus Erythematosus (SLE)
• Autoantibodies:
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
Sjögren’s Syndrome
• 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
Systemic Sclerosis (Scleroderma)
• Diffuse cutaneous (dcSSc):
o Anti-Scl-70 (topoisomerase I)
o Widespread skin thickening, early visceral involvement (lungs, kidneys)
o Complication: scleroderma renal crisis
• Limited cutaneous (lcSSc / CREST):
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)
Polymyositis / Dermatomyositis
• 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
Mixed Connective Tissue Disease (MCTD)
• 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
