18.6 Sjogren's Syndrome & Inflammatory Myopathies

7. Sjögren's Syndrome

Sjögren's syndrome is a chronic autoimmune epithelitis characterized by progressive CD4+ T-cell and B-cell lymphocytic infiltration of exocrine glands, predominantly the lacrimal and salivary glands.

Clinical Features & Diagnostic Assessment

• Sicca Complex:
  • Xerophthalmia (Keratoconjunctivitis Sicca): Sensation of gritty ocular foreign body, burning, photophobia, and dry eyes. Assessed clinically using Schirmer's test (a strip of filter paper placed in the lower conjunctival sac; < 5 mm wetting after 5 minutes is abnormal) or Rose Bengal / fluorescein corneal staining revealing punctate epitheliopathy.
  • Xerostomia: Severe oral dryness, requiring water to swallow dry food, dysgeusia, accelerated rampant dental caries (particularly cervical and incisal caries), and recurrent oral candidiasis.
• Glandular Enlargement: Bilateral, firm, non-tender or mildly tender parotid gland enlargement in 30–40% of patients.
• Extraglandular Features: Arthralgias, fatigue, Raynaud's phenomenon, cutaneous purpuric vasculitis, and renal tubular acidosis (Type 1 distal RTA causing hypokalaemic metabolic acidosis, nephrocalcinosis, and osteomalacia).
• Diagnostic Autoantibodies: Anti-Ro/SSA (positive in 60–80%) and Anti-La/SSB (positive in 40–60%). Positive Rheumatoid Factor is present in 70% of primary Sjögren's patients, along with polyclonal hypergammaglobulinaemia.
• Histopathological Gold Standard: Minor salivary gland lip biopsy demonstrating focal lymphocytic sialadenitis, defined by a Chisholm-Mason focus score >= 1 (at least one dense aggregate of >= 50 mononuclear cells per 4 mm² of glandular tissue).

Major Neoplastic Complication: B-Cell MALT Lymphoma

Patients with primary Sjögren's syndrome carry an extraordinary up to 44-fold increased relative risk of developing Non-Hodgkin Lymphoma, specifically marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue [MALT] lymphoma), typically arising within the salivary glands, stomach, lungs, or thyroid.

• Red Flags for Lymphomatous Transformation:
  1. Persistent, firm, asymmetrical or expanding enlargement of a parotid or submandibular gland;
  2. Disappearance of previously elevated Rheumatoid Factor levels;
  3. Development of new hypocomplementaemia (particularly low C4);
  4. Presence of type II mixed cryoglobulinaemia or a new serum monoclonal paraprotein spike (M-band);
  5. Development of cutaneous palpable purpura, lymphadenopathy, or systemic B-symptoms (unexplained fever, drenching night sweats, weight loss).

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8. Inflammatory Myopathies: Polymyositis, Dermatomyositis & Antisynthetase Syndrome

Idiopathic inflammatory myopathies are autoimmune disorders targeting skeletal muscle and surrounding microvasculature.

Clinical Presentation

• Proximal Symmetrical Muscle Weakness: Insidious or subacute progressive weakness affecting proximal limb-girdle musculature (pelvic and shoulder girdles). Patients report difficulty rising from a low chair, climbing stairs, lifting objects into overhead cupboards, and combing their hair. Distal muscles are preserved until late. Facial and extraocular muscles are characteristically SPARED (in stark contrast to myasthenia gravis, which classically causes ptosis, diplopia, and ocular paresis).
• Bulbar & Respiratory Involvement: Oropharyngeal and upper oesophageal striated muscle weakness causes dysphagia, dysarthria, and aspiration pneumonia. Diaphragmatic and intercostal weakness precipitates ventilatory failure.
• Serum Enzymes: Markedly elevated Creatine Kinase (CK), frequently 10 to 50 times the upper limit of normal (often 5,000–20,000 U/L). Elevated aldolase, AST, ALT, and LDH.

Pathognomonic Cutaneous Hallmarks of Dermatomyositis

• Heliotrope Rash: Violaceous (purplish-pink) macular erythema of the upper eyelids and periorbital tissues, frequently accompanied by periorbital oedema.
• Gottron's Papules: Pathognomonic erythematous or violaceous, flat-topped, lichenoid scaly papules and plaques overlying the dorsal aspect of the metacarpophalangeal (MCP) and interphalangeal (PIP, DIP) joints. CRUCIAL EXAM CONTRAST: Gottron's papules affect the skin overlying the joints, whereas the rash of SLE characteristically spares the knuckle joints and affects the skin in between the joints!
• Gottron's Sign: Symmetrical macular violaceous erythema over extensor bony prominences (elbows, knees, medial malleoli).
• Shawl Sign & V-Sign: Poikiloderma (mottled erythema, telangiectasia, dyspigmentation) in a photosensitive distribution across the upper back, posterior neck, and shoulders (shawl sign) or anterior lower neck and chest (V-sign).
• Mechanic's Hands: Hyperkeratotic, cracked, painful fissuring and scaling along the radial and palmar aspects of the fingers and palms, resembling the hands of a manual laborer.

Diagnostic Autoantibodies & Clinical Associations

• Anti-Jo-1 (Anti-Histidyl-tRNA Synthetase): The prototypical myositis-specific antibody (20–30% of patients). Defines the Antisynthetase Syndrome, characterized by the clinical pentad:
  1. Inflammatory myositis;
  2. Rapidly progressive interstitial lung disease (ILD);
  3. Raynaud's phenomenon;
  4. Non-erosive inflammatory arthritis; and
  5. Mechanic's hands.
• Anti-Mi-2: Directed against a helicase involved in transcription. Strongly associated with classic dermatomyositis, prominent cutaneous Gottron's/heliotrope lesions, excellent response to systemic corticosteroids, and a very low malignancy risk.
• Anti-TIF1-gamma (TRIM33) & Anti-NXP-2: Strongly associated with cancer-associated dermatomyositis in adults. Up to 50–70% of adult dermatomyositis patients harboring anti-TIF1-gamma have an underlying occult malignancy (ovarian, lung, breast, colorectal, or lymphoma). Mandatory clinical action: Any adult diagnosed with dermatomyositis (especially if anti-TIF1-gamma or anti-NXP-2 positive) must undergo comprehensive occult malignancy screening (CT chest/abdomen/pelvis, mammography, pelvic ultrasound/CA-125, PSA, and colonoscopy).
• Anti-SRP: Associated with severe, rapidly progressive necrotizing autoimmune myopathy, profound weakness, cardiac involvement, and poor steroid response.
• Anti-HMG-CoA Reductase (Anti-HMGCR): Associated with statin-induced necrotizing autoimmune myopathy. Persistent, progressive muscle weakness and massive CK elevation that continues to deteriorate despite statin discontinuation; requires aggressive immunosuppressive therapy.

Muscle Biopsy: Polymyositis vs. Dermatomyositis

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9. Comparative Synthesis: Limited vs. Diffuse Systemic Sclerosis