Definition:
A group of systemic autoimmune diseases characterized by immune overactivity with autoantibody production targeting connective tissue components such as collagen, muscle, fascia, and glands. These disorders often involve multiple organs.
General Pathophysiology:
- Involves abnormal activation of T and B lymphocytes
- Leads to production of autoantibodies (ANA, RF, anti-dsDNA, anti-RNP, etc.)
- Causes inflammation, fibrosis, and tissue damage in skin, joints, muscles, blood vessels, and organs
Key Autoimmune Connective Tissue Disorders:
1. Autoimmune Myositis
- Includes:
- Polymyositis: inflammation of skeletal muscles → symmetrical muscle weakness
- Dermatomyositis: polymyositis + heliotrope rash, Gottron's papules
- Symptoms: Muscle weakness, fatigue, dysphagia, skin rash
- Diagnosis:
- Elevated CK
- EMG: abnormal muscle electrical activity
- Muscle biopsy: inflammatory infiltrates
- Treatment: Corticosteroids ± immunosuppressants (methotrexate, azathioprine)
2. Eosinophilic Fasciitis
- Definition: Inflammation of fascia of limbs, limited to arms and legs
- Symptoms: Rare; pain, swelling, skin thickening
- Diagnosis: Skin + fascia + muscle biopsy
- Treatment: Corticosteroids
3. Mixed Connective Tissue Disease (MCTD)
- Definition: Overlap of SLE, scleroderma, and polymyositis, defined by high anti-U1 RNP antibodies
- Symptoms: Raynaud’s phenomenon, arthralgia, myositis, sclerodactyly, malaise
- Diagnosis:
- Positive anti-U1 RNP antibody
- May also have anti-dsDNA, anti-SSA
- Treatment: Corticosteroids, NSAIDs, immunosuppressants (in severe organ involvement)
4. Sjögren Syndrome
- Definition: Autoimmune disease affecting exocrine glands (salivary, lacrimal)
- Can be:
- Primary (alone)
- Secondary (with SLE, RA)
- Symptoms:
- Dry mouth (xerostomia)
- Dry eyes (keratoconjunctivitis sicca)
- Parotid gland enlargement
- Diagnosis:
- Positive anti-Ro/SSA, anti-La/SSB, RF, ANA
- Schirmer test (tear production)
- Lip/salivary gland biopsy: lymphocytic infiltrate
- Treatment:
- Artificial tears, saliva substitutes
- NSAIDs, corticosteroids for systemic symptoms
5. Systemic Lupus Erythematosus (SLE)
- Definition: Multisystem autoimmune disease; type III hypersensitivity (immune complex-mediated)
- Symptoms:
- Butterfly rash, arthritis, photosensitivity
- Oral ulcers, pleuritis/pericarditis, nephritis
- Fever, fatigue, hair loss, CNS symptoms
- Diagnosis:
- Positive ANA (sensitive but not specific)
- Anti-dsDNA, anti-Smith (specific)
- Low C3, C4 (due to consumption)
- Direct immunofluorescence of skin
- Treatment:
- NSAIDs, antimalarials (hydroxychloroquine)
- Corticosteroids, immunosuppressants (azathioprine, cyclophosphamide)
6. Scleroderma (Systemic Sclerosis)
- Definition: Systemic autoimmune disorder with fibrosis, vascular dysfunction, and collagen deposition
- Two forms:
- Limited cutaneous (CREST): Calcinosis, Raynaud’s, Esophageal dysmotility, Sclerodactyly, Telangiectasia
- Diffuse cutaneous: rapid skin + visceral involvement
- Symptoms:
- Skin thickening, Raynaud’s, GI reflux, dyspnea (ILD), renal crisis, joint pain
- Diagnosis:
- Positive anti-centromere antibodies (limited)
- Positive anti-Scl-70 (anti-topoisomerase I) (diffuse)
- Nailfold capillaroscopy
- Treatment:
- Vasodilators (e.g. nifedipine for Raynaud)
- PPIs for reflux
- ACE inhibitors for renal crisis
- Immunosuppressants for lung involvement