Scleral Manifestations of Systemic Disease

CTDs & Sclera - Joint & Eye Woes

Connective tissue diseases (CTDs) frequently manifest in the sclera, causing inflammation (scleritis, episcleritis) and structural changes. Systemic workup crucial.

• Major CTD Associations:
  • Rheumatoid Arthritis (RA): Most common systemic cause of scleritis, esp. necrotizing.
  • Granulomatosis with Polyangiitis (GPA): Necrotizing scleritis, often with Peripheral Ulcerative Keratitis (PUK).
  • Systemic Lupus Erythematosus (SLE): Episcleritis more frequent than scleritis.
  • Relapsing Polychondritis: Episcleritis, scleritis, chondritis (auricular/nasal).
  • Ankylosing Spondylitis, Inflammatory Bowel Disease (IBD).
• Types of Scleral Involvement:
  • Episcleritis: Superficial, sectoral/diffuse redness, mild discomfort. Often self-limiting.
  • Scleritis: Deep, violaceous hue. Severe, boring pain (radiates, nocturnal).
    • Anterior: Diffuse, Nodular, Necrotizing (high visual loss risk).
      • Necrotizing with inflammation: Most severe.
      • Necrotizing without inflammation (Scleromalacia Perforans): In long-standing RA, perforation risk. 📌 "Painless perforation".
    • Posterior: Pain, ↓vision, proptosis, choroidal folds.

⭐ Scleromalacia perforans, a necrotizing scleritis without significant inflammation, is classically seen in women with long-standing, seropositive Rheumatoid Arthritis.

Vasculitis & Infections - Vessel & Bug Alerts

• Vasculitis-Associated Scleritis:
  • Granulomatosis with Polyangiitis (GPA): Necrotizing scleritis common, often bilateral; c-ANCA/PR3-ANCA positive.
  • Polyarteritis Nodosa (PAN): Necrotizing scleritis; Hepatitis B association.
  • Relapsing Polychondritis: Affects cartilage (ears, nose) & sclera; varied scleritis types.
  • Behçet's Disease: Scleritis can occur, often with uveitis.
  • SLE: Less common, typically diffuse/nodular scleritis.
• Infectious Scleritis: Intense pain, redness, photophobia; purulent discharge signals infection.
  • Bacterial:
    • Pseudomonas aeruginosa: 📌 Post-Surgical Problem. Most common after surgery/trauma; aggressive.
    • Staphylococcus aureus, Streptococcus pneumoniae.
    • Tuberculosis (TB): Nodular or necrotizing; requires systemic Anti-Tubercular Therapy (ATT).
  • Viral:
    • Herpes Zoster Ophthalmicus (HZO): Scleritis, often with keratitis/uveitis. Hutchinson's sign (tip of nose vesicles) is key.
    • Herpes Simplex Virus (HSV).
  • Fungal: Aspergillus, Candida. Immunocompromised or post-trauma (e.g., vegetative injury).
  • Protozoal: Toxoplasma, Acanthamoeba (rare for scleritis).

⭐ Infectious scleritis, especially bacterial (e.g., Pseudomonas), can rapidly progress to scleral perforation if not treated aggressively with appropriate antimicrobials.

Metabolic & Rare Links - Oddball Sclera Signs

• Alkaptonuria (Ochronosis):
  • Bluish-black scleral pigmentation (near muscle insertions). Homogentisic acid.
• Gout:
  • Scleral/episcleral urate tophi; recurrent inflammation.
• Porphyria (e.g., PCT):
  • Scleral thinning, photosensitivity; risk of scleromalacia.
• Osteogenesis Imperfecta (OI):
  • Blue sclera (thin sclera, uvea visible). 📌 Brittle Bones, Blue Sclera.
• Ehlers-Danlos Syndrome (EDS):
  • Blue sclera, scleral fragility, ↑ globe rupture risk.
• Scleral Icterus (Jaundice):
  • Yellow sclera (↑ bilirubin).

  ⭐ Often first sign of jaundice; visible if serum bilirubin > 2-3 mg/dL.

• Other Rare Links:
  • Cystinosis: Corneal crystals primary; scleral deposits possible.
  • Mucopolysaccharidoses (MPS): Scleral thickening (some types).
  • Ligneous Conjunctivitis: May extend to sclera, cornea (woody pseudomembranes).

High‑Yield Points - ⚡ Biggest Takeaways

• Rheumatoid Arthritis is the most common systemic association with scleritis, especially necrotizing scleritis.
• Ankylosing Spondylitis often presents with anterior uveitis and scleritis.
• Wegener's Granulomatosis (GPA) can cause necrotizing scleritis and peripheral ulcerative keratitis (PUK).
• Inflammatory Bowel Disease (IBD), like Crohn's and Ulcerative Colitis, is linked to episcleritis and scleritis.
• Sarcoidosis may manifest as granulomatous scleritis or nodular episcleritis.
• Blue sclera is characteristic of Osteogenesis Imperfecta; also seen in Ehlers-Danlos syndrome and Marfan syndrome.
• Scleromalacia perforans is a severe, painless necrotizing scleritis often seen in long-standing Rheumatoid Arthritis women.