Autoimmune Rheumatic Diseases and the Eye: B. Caffery
Definitions and terms:
1. Rheumatic diseases are inflammatory diseases of the joints, soft
tissue and allied connective tissue. Often, their underlying aetiology is
autoimmune and therefore they are a part of the autoimmune disease
classification. The term autoimmune rheumatic diseases helps to further
define a subgroup of the rheumatic diseases.
2. Connective tissue disease is also used to describe some of the
rheumatic diseases in which the connective tissue is the major target. An
older term that is sometimes still used is collagen vascular disease.
These include: rheumatoid arthritis (RA), Sjogren’s syndrome (SS),
systemic lupus erythematosus (SLE), scleroderma, ankylosing spondylitis,
mixed connective tissue disease (CTD), systemic sclerosis (SSc),
dermatomyositis (DM), polymyositis (PM), CREST (which includes
Calcinosis, Raynauds, Esophageal dismotility, Sclerodactyly and
Telangecstasia), polymyalgia rheumatica.
3. Autoimmune diseases are characterized by the presence of autoantibodies in the blood. These antibodies are believed to be responsible
for the inflammation that occurs at various sites in the body including the
eyes.
Why Rheumatic autoimmune diseases are important in the
optometric office.
1. The most prevalent autoimmune diseases, RA, SS and SLE are often
associated with ocular surface disorders
2. Patients with significant systemic discomfort and fatigue often overlook
their ocular symptoms and therefore will not present with problems.
3. Serious inflammation at the ocular surface can lead to severe vision
loss.
Autoimmunity 101: How does our body learn to destroy itself?
Let’s use Sjogren’s syndrome as an example of this
pathophysiology.
1. The etiology of autoimmune diseases is still unknown. However, 2
major theories exist: a viral attack and a local loss of immune protection
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2. Viral etiology: The ocular mucosal tissues are exposed to all forms of
viral species. Viruses can travel from the surface to invade the lacrimal
gland could certainly cause an autoimmune response. Changes in
cytokine expression of lacrimal acinar cells would activate both T and B
immune cells that are present in the healthy lacrimal gland.
3. Failed local immunity: Inflammation in and around the lacrimal gland
from any cause could create a breakdown in immune protection. Sjogren’s
syndrome, then, becomes a disease of failed local immunity as stimulated
acinar cells become antigen presenting cells. MHC class II positive
epithelial cells initiate an autoimmune response by presenting their own
internal proteins on their surfaces to reactive T lymphocytes and thus
activate these cells at the local level. This form of inflammation has been
noted in several ocular conditions including corneal transplant rejection,
uveitus and proliferative vitreoretinopathy. Dendritic, T and B cells also
play a role in this process.
4. This same sort of pathophysiology applies to our understanding of RA
and SLE with different organs being affected.
Epidemiology of rheumatic autoimmune diseases
1. It is generally believed that rheumatic autoimmune diseases affect 5%
of the population. The most prevalent of these diseases are RA, SS and
SLE . There is a predominance of women affected by these diseases.
2. A recent CDC analysis demonstrated that the prevalence of RA has
lessened and that the prevalence of SS may be higher than previously
thought in the US. This review of surveys suggests that up to 3.1 million
adult Americans (approximately 1%) suffer from Sjogren’s syndrome. It is
also believed that 9 out of 10 of them are women.
What we need to do in our eye examinations
1. A thorough history that identifies autoimmune disease. Ask about
fatigue, myalgia, arthralgia, dry mouth and family history.
2. A series of questions of those patients presenting with prolonged and
significant dry eye or acute red eyes that might identify autoimmune
disease. Ask about fatigue, dry mouth and family history. Other systemic
problems like joint pain or stiffness.
3. If suspicious, a look at the hands of patients with suspected or
confirmed autoimmune disease to assess joint inflammation.
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4. An observation of the tongue of those patient in whom you suspect
Sjogren’s syndrome.
5. Extra attention to the ocular surface and anterior chamber to assess:
corneal staining with fluorescein, conjunctival staining with lissamine
green or rose bengal, Schirmer testing, close observation of episclera and
sclera, anterior chamber observation to rule out cell and flare.
6. Findings of Schirmer scores <= 5mm in 5 min in 1 eye and/or total
staining scores of <= 4/9 in at least 1 eye suggests the possibility of
primary or secondary Sjogren’s syndrome. Assess the dry mouth status
and refer where appropriate.
7. Significant peripheral corneal staining with inflammation and/or cell and
flare requires immediate attention with topical and/or oral steroids.
Hospitalization may be required.
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8. Uveitis presentation requires careful observation and a thorough
ophthalmic AND systemic workup.
Mechanism of ocular involvement in rheumatic autoimmune
diseases.
1. The cornea: alterations in epithelial phenotype as dry eye features such
as reduced tear flow, increased osmolarity and inflammation cause
disease. This is seen as staining of the ocular surface
2. The cornea: peripheral corneal melting caused by acute autoimmune
inflammation near the limbus. This is likely a vasculitis which is a serious
sign of increased and acute complications of autoimmune disease
3. The conjunctiva: changes in cell phenotype as dry eye factors cause
trauma. MUC1 and MUC16 show increased expression in SS.
4. Scleritis and episcleritis: local autoimmune inflammation
5. Uvea: the systemic aspects of chronic autoimmune disease are
classically displayed in the anterior chamber where cells and proteins from
the uveal blood vessels are seen in the anterior chamber. More serious
are the posterior uveitis cases.
Uveitis
1. Definition: inflammation of the uveal tract, the vascular layer of the
eye composed of iris, ciliary body and choroid.
2. Classification:
a. Anatomic
Anterior uveitis
Primary site of inflammation: anterior chamber
Intermediate uveitis
Primary site of inflammation: vitreous
Posterior uveitis
Primary site of inflammation: retina or choroid
Panuveitis
Primary site of inflammation: anterior chamber, vitreous,
retina or choroid
b. Course and onset: sudden, insidious, acute, recurrent, chronic
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c. Grade: 0-4+ by cells in field
d. grade of flare: 0-4+
If uveitis is the presenting sign a thorough investigation of possible
systemic cause is warranted. However, 35% or more will be idiopathic.
Blood work can be diagnostic:
FTA-ABS for syphilis
IgG and IgM
ANA: JRA shows ANA Hep-2, SLE shows double stranded DNA,
polyartheritis nodosum and RA
IL-1 and IL-2: in RA, ankylosing spondylitis, IBD
SED rate
Complement for vasculitis
TNF-α for Crohns disease, ank spondylitis, psoriasis
Anti-Ro and anti-La for Sjogren’s syndrome
ACE (angiotensin converting enzyme) for sarcoid
Treatment and Management
1. If autoimmune disease is suspected refer to rheumatology or ask the
family practitioner for specific antibody testing of RA, Ro and La.
2. treat the dry eye. Explain the problem and that it will not affect long term
visual function, prescribe lubricants, gels, anti-inflammatories, nutritional
and supplement counselling, eye protection, humidification and general
health.
3. Treat corneal melts immediately with referral when necessary.
Hospitalization with IV steroids may be needed.
4. Treat the episcleritis and scleritis topically with steroids and frequent
followups
5. Treat iritis with your usual protocol: cycloplegia, steroids. Uveitis
requires a referral and possible invasive treatment. All uveitis deserves a
systemic workout.
Chronic rheumatic autoimmune diseases are a large part of optometric
care. All patients with RA, SLE, SS etc should be queried for possible
anterior segment involvement. All red, sore and dry eyes should be
analyzed with the possibility of systemic autoimmune conditions in mind.
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