Autoimmune Diseases (MT2)

Immunological tolerance

Self vs. non-self

Immune privilege for specific tissue (eye + brain)

Autoimmunity

Immune system attacks self

Seropositive disease

Autoantibodies detected in serum (seropositive)

Autoimmune disease etiologies

• Genetic susceptibility: Failure to remove autoreactivity (clonal education), linked to HLA genes

• Environmental Ag: Infections, nuclear Ag, gut microbiome dysbiosis

• Immune system dysregulation: Hypersensitivity, hygiene hypothesis, stress (high cortisol)

Autoimmune disease characteristics

Wide spectrum of severity, temporal pattern, presentations, pathogenesis

Average 5 years for Dx

Tend to be chronic, relapse-remitting, co-morbidity

Incurable - Treatments aimed at immunosuppression

Autoimmune disease ocular presentations

Dry eye, episcleritis or scleritis, anterior uveitis

Serological autoantibodies

• Anti-nuclear antibodies (ANA) positive

• Rheumatoid Factor (RF) positive: Ab against the Fc region of IgG

Seropositive

Have RF

Seronegative

No RF

Dry Eye Disease

Dx: TBUT, fluorescein staining, Schirmer test (filter paper)

Treatment focuses on:

• Symptoms: Humidity goggles, punctual plugs, lipiflow, intense pulsed light

• Inflammation: Restasis (cyclosporine) and Xiidra (lifitegrast), decrease T helper #

Episcleritis

Inflammation of episclera

Asymptomatic

Scleritis

Inflammation of sclera

Deep boring pain

Sectorial or diffuse red eye

Can be necrotizing → Scleral thinning + globe perforation (scleromalacia perforans)

Anterior Uveitis

Uveal tract inflammation, can be acute (acute inflammation) or chronic (type IV DTH)

Signs: Posterior synechiae and circumlimbal injection (acute only)

Presentations: Cells and flare

Cells and flare

Cells: Inflammatory cells that accumulate → keratic precipitates (KPs) and/or hypopyon

Flare: Fibrinous exudate

Keratic Precipitates

Cells that get stuck to the corneal endothelium

Mutton fat KPs: In chronic anterior uveitis, Th1 + macrophages (type IV hypersensitivity)

Osteoarthritis

Wear and tear, bone and on damage, not autoimmune

Most common form after 40

Presentation: Unilateral with use

Treatment: Pain medications and joint replacement

Rheumatoid arthriris

Autoimmune attacks synovium of joints and extraarticular lesions, initiated by T helper cells, increased risk HLA-DR4 = MHCII

Second most common

Presentation: Bilateral

Treatment: Decrease inflammation

Rheumatoid arthritis systemic presentations

• Bilateral hands and feet: Ulnar and swan neck

• Pain worse in morning

• Pannus formation

Ulnar deviation

Pathognomonic for rheumatoid arthritis

Fingers deform outward

Swan-neck deformity

Last digit curves and next digit curves the other way

Pannus

Pathognomonic for rheumatoid arthritis

Abnormal tissue formed by inflammatory cells

Rheumatoid arthritis extra articular presentations

RA presentations beyond the joint

• Skin nodules

• Serositis: Serosa inflammation (heart and lungs)

• Dry eye

• Scleritis/episcleritis

• Anterior uveitits

Positive tests for rheumatoid arthritis

ANA, RF, ACPA, ESR/CRP (if inflamed)

Signs associated with the eyes for Rheumatoid arthritits

Dry eye, epi/scleritis, necrotizing sclera, acute anterior uveitis

Anti-citrullinated peptide antibody (ACPA)

Citrullinated peptides (CP) are common modifications to lysine amino acids found in CT

Common in early RA

RA hypersensitivities

Type II, III, IV

Juvenile Idiopathic Arthritis (JIA)

Present with arthritis before 16

Presentations: Knee pain + swollen joints, morphological change to hands/feet early on

Similarities with RA: Inflammatory arthritis, ANA+, ACPA+

Unique features: Likely RF- (still considered seropositive) and HLA-B27+, most common cause of chronic anterior uveitis in children

Chronic Anterior Uveitis

Type IV DTH, non-granulomatous until mutton fat KPs

Ocular presentations:

• No red eyes, synechiae, mutton fat KPs

• Band keratopathy: Dystrophic calcification

• Posterior subcapsular cataract due to steroid

JIA positive tests

ANA, RF (very little), ACPA, HLA-b27, ESR/CRP (if inflamed)

Signs associated with the eyes and JIA

Dry eye, chronic uveitis

Sjogren Syndrome

Autoimmune disease attacking exocrine glands (lacrimal and salivary) causing dryness (sicca syndrome)

Diagnosed alone: Primary

Diagnosed after a different autoimmune: Secondary

Key features: More common in females, possibly linked to EBV (likely to develop lymphoma)

Sjogren systemic presentations

• Dry eye due to inflamed lacrimal glands (no CL), blurred vision, corneal melting

• Xerostomia: Dry mouth, difficulty swallowing, weight loss, cavities

• Arthritis

• Malar rash

Positive tests for Sjogrens

ANA, Anti-Ro/SSA/Anti-La/SSB, RF, hypergamma-globulinemia, ESR/CRP (if inflammed)

Signs associated with eyes and Sjogrens

Dry eye, epi/scleritis, acute anterior uveitis

SS treatments

Lubricants, immune modulators, systemic immune modulators

Systemic Lupus Erythematosus (SLE)

Autoimmune diseases affecting multiple organs with array of Ab and type II complement dependent and type III reactions

“Great imitator”: Affects any organ

Affects women more

Positive tests for Lupus

ANA, anti-ds DNA, anti-smith, APA, Anti-Ro/SSA/Anti-SSB, Rf, ESR/CRP (if inflammed)

Signs associated with the eye and Lupus

Dry eye, epi/scleritis, acute anterior uveitis, vasculitis, RVOs

Lupus systemic presentations

• Hematologic abnormalities (anti-phospholipid Ab syndrome, idiopathic thrombocytopenia, anemia)

• Arthritis

• Malar rash, oral ulcers, photosensitivity

• Nephritis (leading cause of death)

• Serosa

• Alopecia

• Lupus retinopathy

Fundus changes and Lupus

Changes in eyes reflect severity of disease in kidney

Immunomodulator Therapy

Decrease inflammation and prevent irreversible tissue and organ damage

3 classes:

• NSAIDs and steroids

• DMARDs (Disease-Modifying Antirheumatic Drugs): Ciclosporin (IL-2 inhibitor), methotrexate, plaquenil (hydroxychloroquine)

• Biologics

NSAIDs and steroids

Puts out fire but has many side effects

NSAIDs: Block COX

Steroids: Stops inflammation

Mechanism: Decrease production of prostoglandins, decreases chemotaxis, stimulate macrophages and lymphocytes

Ocular side effects: Posterior subcapsular cataracts, increased IOP

DMARDs

Prevents fire from starting again

Methotrexate: Interferes with folate metabolism (used by dividing cells for DNA synthesis) and inhibits hematopoiesis and lymphocyte proliferation

Methotrexate

DMARD

Interferes with folate metabolism (used by dividing cells) and inhibits hematopoiesis and lymphocyte proliferation

Plaquenil

DMARD

Mechanism: Inhibits APC activation

Bull’s eye Maculopathy: Ring pattern of damage around fovea and central vision loss, dose and duration dependent, worse when combined with methotrexate

Biologic Therapy

Subset of DMARDs but more targeted, receptors and/or Ab

Rituximab: Targets CD20 → Kills B cells

TNF alpha blockers: Blocks inflammation and increase WBC death

Downsides to imunosuppressants

• Opportunistic infections

• Cancer

• Rx toxic effects

Shared characteristics of seronegative diseases

• Relapsing and remitting

• Seronegative spondyloarthropathies: Inflammation + repair at joint level → Bone fusion

• Acute anterior uveitis: Often unilateral, small KPs (PMNs bc acute inflammation), cells and flare

50% HLA-B27+ AAU → Have or develop spondyloarthropathy

Men more affected

HLA-B27

Encodes MHCI and increases susceptibility

90-100% ankylosing spondylitis HLA-B27+

Ankylosing Spondylitis

Sacroiliitis causing inflammatory lower back pain + progressive loss os movement

Bamboo back: Vertebrae fusion, pathognomonic for AS

100% HLA-B27

Reactive Arthritis (ReA)

Inflammatory arthritis following infection

Preceding infections:

• Chlamydia

• Dysentery

ReA Clinical Triad

• Non-gonococcal urethritis (chlamydia)

• Bilateral conjunctivitis (or acute anterior uveitis)

• Arthritis (dactylitis or achilles tendonitis)

Can’t pee, cant’ see, can’t climb a tree

Psoriatic arthritis (PSA)

Autoimmune arthritis accompanied by psoriasis

Presentation:

• Psoriasis on elbows, knees, scalp, lower back

• Arthritis later (dactylitis)

Treatment: UV-B light

Dactylitis

Whole digit is affected and swollen

Sausage finger or toe

Enteropathic arthritis

Arthritis associated with IBD

Epidemiology: Patients with IBD, Crohn Disease, or Ulcerative Colitis

When gut flares so do joints + eyes