Autoimmune Rheumatologic Disorders and the Eye: Study Guide

Introduction

Autoimmune diseases have a variety of systemic manifestations; the eye is frequently involved in numerous autoimmune and rheumatologic disorders. Ocular manifestations are frequently nonspecific and different diseases may affect different parts of the eye, but early recognition of symptoms can help avoid or delay both systemic and ocular sequelae.

The most common autoimmune diseases that affect the eyes can be separated into four categories:

Rheumatologic
Dermatologic
Endocrine
Vascular

This is part one of a four-part series in which we discuss autoimmune rheumatologic diseases and the eye including:

Rheumatoid arthritis
Sjögren's syndrome
Seronegative spondyloarthropathies

Rheumatoid arthritis ^1-5

Rheumatoid arthritis - epidemiology

Disease
- Incidence in USA:40 per 100,000 persons
- Prevalence
  - .024-1% of population
- 2:1 (women: men)
- Age: 30-50
Eye manifestations
- 27.2% of patients with RA

Rheumatoid arthritis - mechanism

Vasculitis
- Vascular occlusion
- Infiltration
- Fibrinoid necrosis
Immune complex deposition
Complement activation
Autoantibodies
Secretion of collagenases by macrophages and neutrophils
Cytokine production

Rheumatoid arthritis - presentation

General
- Symmetrical inflammatory polyarthritis
  - Joint deformities
  - Nodules (Proximal interphalangeal joints (PIP)>Distal interphalangeal joints (DIP))
- Constitutional symptoms
- Joint stiffness
- Fever
- Weight loss
Anterior segment more commonly affected than posterior segment

Rheumatoid arthritis presenting with keratoconjunctivitis sicca (most common)

Mechanism
- Dysfunction of
  - Meibomian gland
  - Lacrimal gland
  - Accessory lacrimal gland
  - Goblet cells
Characteristics
- Foreign body sensation
- Burning
- Decreased visual acuity
- Photophobia
- Pruritis
Complications
- Superficial punctate keratitis
- Filamentary keratitis
- Corneal ulcer
- Corneal melt
Diagnosis
- 25% meet criteria for secondary Sjögren's Syndrome (SS)
- Schirmer’s Test
  - < 5mm tear extension
- Tear break up time
  - < 5 seconds
- Decreased lacrimal lake
- Staining
  - Fluorescein
  - Rose Bengal
  - Lissamine green
Treatment
- Lubricating drops/ointment
- Topical cyclosporine
- Oral pilocarpine
- Topical Lifitegrast
- Punctal occlusion
- Amniotic membrane
- Tarsorrhaphy

Rheumatoid arthritis presenting with episcleritis

Mechanism
- Inflammation of episclera
Characteristics
- 40% bilateral
- Salmon-pink eyes
- Mild pain
- Occurs in a sectoral or radial distribution
Diagnosis
- Clinical

Below, in Figure 1, you will find an image of a patient with episcleritis.

https://covalentcareers3.s3.amazonaws.com/media/original_images/Episcleritis_.jpeg

^{Figure 1: episcleritis}

Treatment
- Self-limiting
- Symptom relief
  - Topical corticosteroids
  - Oral NSAID

Rheumatoid arthritis presenting with scleritis

Mechanism
- Inflammation of sclera
- Vasodilation of superficial and deep episcleral vessels
Characteristics
- Most common cause of scleritis
- Can present before onset of joint symptoms
- Bilateral in 40-50% of patients
- Anterior Scleritis

Figure 2 shows a non-necrotizing scleritis.

https://covalentcareers3.s3.amazonaws.com/media/original_images/non-necrotizing_scleritis_.jpeg

^{Figure 2: non-necrotizing scleritis}

Pain made worse with eye movement
Blurry vision
Photophobia
Tearing
Posterior Scleritis
- T-sign on B-scan

In Figure 3, you will find an example of T-sign with fluid in Tenon space on B-scan

https://covalentcareers3.s3.amazonaws.com/media/original_images/T-sign_with_fluid.jpeg

^{Figure 3: T-sign with fluid in Tenon space on B-scan}

Complication
- Retinal detachment
- Chorioretinal folds
Scleromalacia Perforans

Figure 4 demonstrates scleromalacia perforans.

https://covalentcareers3.s3.amazonaws.com/media/original_images/Scleromalacia_Perforans.jpeg

^{Figure 4: scleromalacia perforans}

Severe anterior necrotizing scleritis without inflammation
Painless
Complications
- Visual loss
- Astigmatism
- Globe perforation
Treatment
- Topical therapy ineffective
- Need to manage systemic RA
- Medications
  - Oral NSAID
  - Corticosteroids
  - Methotrexate
  - Azathioprine
  - Mycophenolate mofetil
  - Cyclosporine
  - Biologics (infliximab, adalimumab, rituximab, anakinra)
  - **Co-management with rheumatologist is essential
- Necrotizing scleritis
  - Debridement

Rheumatoid arthritis presenting with peripheral ulcerative keratitis (PUK)

Mechanism
- Immune complexes infiltrate vascular arcades in the corneal periphery
Characteristics
- Corneal melt
- 35% of cases occur secondary to RA
  - Complication of Necrotizing scleritis
- Stromal thinning
- Secondary overlying epithelial defect
- Neovascularization of corneal periphery
- Crescent shaped juxta-limbal ulcers
- Symptoms
  - Pain
  - Photophobia
  - Tearing
  - ↓ visual acuity (induced irregular astigmatism, corneal opacity)
- Complications
  - Corneal perforation
Treatment
- Topical therapy usually ineffective as a cure
- Need to manage systemic RA
  - Systemic corticosteroids best
- Ocular support
  - Topical medroxyprogesterone
  - Topical acetylcysteine
  - Oral tetracycline
  - Amniotic membrane or corneal glue in some cases
Diagnosis
- Common Lab Findings
  - ↑ Rheumatoid factor
  - ↑ HLA-DR4
  - ↑ Anti-cyclic citrullinated antibody (most specific)
  - ↑ Cytokine Th17
  - ↑ CRP
  - ↑ ESR
Management
- As above, based on effected segment of eye

Sjögren's syndrome ^{1, 6-13}

Sjögren's syndrome - epidemiology

Disease
- Incidence: 7 per 100,000 person-years
  - Female::male: 9-14::1
- Prevalence: 42 per 100,000
  - Female::male: 9::1
- Age (Average)
  - 56

Sjögren's syndrome - mechanism

Chronic autoimmune inflammation characterized by diminished lacrimal and salivary gland function

Sjogren's syndrome - presentation

General Disease
- Dry eye
- Dry mouth
- Constitutional symptoms
Ocular
- Dry eye
- Burning
- Sandy-gritty sensation
- Ocular irritation, fatigue
- Pain
- Fluctuating blurry vision
- Pressure sensation behind the eye
Severity
- Mild
  - Dry eye
- Moderate
  - Variable corneal or conjunctival staining
  - Mild debris in the tear film
  - ↓ tear breakup time
  - ↑ tear osmolarity
  - Abnormal Schirmer test (below 5mm)
- Severe
  - Severe punctate corneal erosions
  - Filamentary keratitis
  - Significant conjunctival vital dye staining
  - Low Schirmer levels (may be 0mm)
  - Significantly ↑ tear osmolarity

Sjögren's syndrome - diagnosis

ACR/EULAR Classification Criteria for Primary Sjögren's Syndrome

Item	Weight/Score
Labial salivary gland with focal lymphocytic sialadenitis and focus score => 1 foci/mm2	3
Anti-Ro/SSA positive	3
Ocular staining score => 5 (or van Bijsterveld score =>4) in at least one eye	1
Schirmer test => 5 mm/5 minutes in at least one eye	1
Unstimulated whole saliva flow rate <= 0.1 mL/minute	1

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References

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Hernández-Molina G, Nuñez-Alvarez C, Avila-Casado C, et al. Usefulness of IgA Anti-α-fodrin Antibodies in Combination with Rheumatoid Factor and/or Antinuclear Antibodies as Substitute Immunological Criterion in Sjögren's Syndrome with Negative Anti-SSA/SSB Antibodies. J Rheumatol. 2016;43(10):1852-1857. doi:10.3899/jrheum.151315
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Zagora SL, McCluskey P. Ocular manifestations of seronegative spondyloarthropathies. Curr Opin Ophthalmol. 2014;25(6):495-501. doi:10.1097/ICU.0000000000000098