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OP5.2 | Systemic Associations in Episcleritis/Scleritis Referral — SDL Guide (Part 2)

Clinical Clues to Underlying Systemic Disease

The ophthalmologist examining a patient with scleritis should conduct a targeted systemic history and examination, looking for clinical clues to the underlying diagnosis. This is not a full internal medicine work-up — it is a targeted history and focused physical examination guided by the conditions known to be associated with scleritis. The clinical encounter should be framed around 'red flag' features pointing toward each major systemic category: joint disease for RA and ankylosing spondylitis, respiratory-renal vasculitis for GPA, mucocutaneous features for SLE and reactive arthritis, and constitutional symptoms (fever, weight loss, night sweats) for infection or malignancy. Eliciting these clues at the first consultation directs investigations efficiently and avoids the costly practice of ordering a non-targeted panel.

History — key questions:
- Joint symptoms: morning stiffness (RA), back pain and sacroiliac involvement (AS), symmetrical small-joint polyarthritis (RA, SLE)
- Skin symptoms: butterfly rash (SLE), rosacea (flushing, telangiectasias), skin vasculitic lesions (PAN, GPA)
- Ear/nose: ear pinna pain or swelling, hearing loss (relapsing polychondritis — cartilage inflammation); nasal blockage, epistaxis, bloody nasal discharge, saddle-nose deformity (GPA — upper respiratory tract granulomas)
- Respiratory symptoms: haemoptysis, productive cough, dyspnoea (GPA — pulmonary nodules/haemorrhage; Churg-Strauss/EGPA — asthma with eosinophilia)
- Bowel symptoms: diarrhoea, rectal bleeding, abdominal cramping (IBD)
- Previous systemic diagnoses and medications: established RA, SLE, IBD on disease-modifying therapy
- History of infections: recent surgical or penetrating eye trauma (infectious scleritis)

Examination findings:
- Joints: synovitis of small joints, rheumatoid nodules (RA), sacroiliac tenderness (AS)
- Skin: butterfly malar rash (SLE), discoid lupus, vasculitic purpura
- Ear pinna: tender, swollen, red pinna with sparing of the non-cartilaginous earlobe (relapsing polychondritis — the earlobe is not affected because it is non-cartilaginous)
- Nose: saddle-nose deformity (GPA, relapsing polychondritis)
- Eyes: the ophthalmologist should also look for associated uveitis (joint diseases), proptosis/restricted motility (posterior scleritis)

ANCA-associated vasculitis is the must-not-miss diagnosis. Any patient with scleritis and ANY of: nasal/sinus disease, pulmonary symptoms, haematuria, or a raised CRP/ESR without another explanation, must have ANCA serology requested urgently.

Investigations for Systemic Work-Up

All patients with a new diagnosis of scleritis require a systematic investigative work-up to exclude or identify an underlying systemic disease, even when no systemic symptoms are apparent (because the scleritis may be the first overt manifestation). The investigation panel is informed by the systemic associations.

The investigation strategy follows a two-tier logic: first, screen for all plausible systemic associations with a standard panel ordered at the initial visit; second, use targeted investigations if initial results or clinical findings point toward a specific diagnosis. The evidence base for this panel derives from the landmark case series of Sainz de la Maza, Foster, and McGill, which established the prevalence of each systemic condition across scleritis subtypes. The standard investigative panel for scleritis includes:

Inflammatory markers and general:
- Full blood count (FBC) — anaemia of chronic disease (RA, vasculitis); eosinophilia (Churg-Strauss)
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) — non-specific but elevated in active vasculitis and connective tissue disease

Rheumatological screen:
- Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies — anti-CCP has higher specificity for RA and is positive earlier in the disease course
- Antinuclear antibody (ANA) — positive in SLE, drug-induced lupus, mixed connective tissue disease; if positive, proceed to anti-dsDNA and complement levels (C3, C4)
- Anti-dsDNA — highly specific for SLE; elevated titres correlate with disease activity

Vasculitis screen:
- c-ANCA (PR3-ANCA) — specific for GPA (Wegener's granulomatosis); high sensitivity for active systemic GPA
- p-ANCA (MPO-ANCA) — associated with microscopic polyangiitis, Churg-Strauss syndrome

Other targeted tests:
- Serum uric acid — if gout is suspected (recurrent episcleritis with joint symptoms)
- VDRL / RPR — to exclude syphilitic scleritis (rare but important; syphilis is the great masquerader in ophthalmology)
- Chest X-ray — GPA (cavitating nodules), sarcoidosis (hilar adenopathy), TB (upper lobe cavities — rare cause of scleritis)
- Urine analysis — haematuria and proteinuria in ANCA-associated vasculitis with renal involvement; an abnormal urinalysis in a patient with scleritis is a medical emergency (urgent nephrology referral)
- HLA-B27 — if ankylosing spondylitis is suspected

Ocular-specific:
- B-scan ultrasonography — essential for posterior scleritis; T-sign confirms the diagnosis when posterior segment involvement is suspected (deep posterior boring pain, proptosis, restricted motility, disc oedema on funduscopy)

In episcleritis, the above panel is NOT performed on the first episode. Targeted testing (e.g. serum uric acid for gout, ESR/CRP for connective tissue disease) is reasonable when: there are systemic symptoms suggesting a specific diagnosis; there are frequent recurrences; or the episode is unusually severe or bilateral.

Indications for Referral: When to Refer and to Whom

Referral decisions in episcleritis and scleritis are based on the diagnosis, the severity subtype, the presence of systemic disease, and the response to initial treatment. The referral hierarchy is stratified and should be communicated clearly when training junior colleagues. A critical error that junior clinicians make is either to refer every red eye to the ophthalmologist, or conversely to reassure and discharge every episcleritis patient without considering whether a systemic disease screen is warranted. The correct approach is risk-stratified: low-risk presentations are managed in primary care or by the general ophthalmologist; moderate-risk presentations (scleritis confirmed, first episode, no systemic diagnosis yet) require ophthalmology-rheumatology co-assessment; high-risk presentations (necrotising scleritis, scleromalacia perforans, or scleritis with known GPA or RA) require urgent specialist input with potential for immunosuppression within days.

Episcleritis — referral indications (selective, not routine):
- No referral for the first episode of uncomplicated simple episcleritis in a young, otherwise healthy patient → manage conservatively with lubricants/NSAIDs and review in 2-3 weeks
- General medicine review if: recurrent episodes (≥3/year), systemic symptoms present, bilateral involvement, or atypical features suggesting scleritis
- Gastroenterology if IBD is suspected
- Dermatology if rosacea is the suspected driver

Scleritis — referral indications (ALL patients with confirmed scleritis require rheumatology referral):

Urgent (within 24-48 hours) referral:
- Necrotising anterior scleritis with inflammation → urgent rheumatology (risk of corneal melt, globe perforation; often GPA or severe RA)
- Any scleritis with peripheral ulcerative keratitis (PUK) → urgent surgical review + rheumatology
- Scleritis with haematuria or abnormal renal function → urgent nephrology (may be ANCA-associated renal vasculitis)
- Suspected GPA with pulmonary or renal involvement → emergency internal medicine/rheumatology

Routine (within 1-2 weeks) referral:
- All other confirmed scleritis → rheumatology (to exclude and manage systemic associations)
- Posterior scleritis → rheumatology + consider oculoplastics if proptosis
- Scleromalacia perforans → rheumatology (RA management); no effective ocular surgery usually; protective spectacles for trauma prevention

To whom:
- Rheumatology — for ALL scleritis (primary partnership for most connective tissue diseases and vasculitides)
- Nephrology — for renal involvement (haematuria, proteinuria, elevated creatinine)
- Pulmonology — for pulmonary involvement (GPA with pulmonary nodules, haemoptysis)
- ENT/Head and Neck Surgery — for GPA with sinonasal disease
- Haematology — for rare lymphoma-associated scleritis
- Oculoplastics — for posterior scleritis with proptosis or restricted motility

Timing principle: the subtype of scleritis dictates the urgency. Diffuse anterior scleritis in an otherwise well patient can be referred routinely. Necrotising scleritis or scleritis with systemic vasculitic features is a medical emergency.