Page 1034 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 74 Immunological Ocular Disease 997

Prevention and Patient Management
Uveitis can be the first sign of systemic disease (e.g., sarcoidosis,
syphilis, or central nervous system [CNS] lymphoma). It is
essential to identify the cause of uveitis as accurately as possible.
A targeted approach is preferable, with a limited workup guided
by the type and severity of uveitis and the presence of systemic
findings. The history is of great importance. The minimal workup
for uveitis of unknown etiology requires an extensive and careful
review of systems, a syphilis serology, and a chest X-ray. 15
Most practitioners use a stepladder approach to treat uveitis.
The first step is corticosteroids for all patients with noninfectious
uveitis (topical, especially for anterior uveitis, regional injection,
or systemic administration). A surgically implantable intravitreal
device to release fluocinolone for approximately 2.5 years is an
option that is limited by cost and complications, which can
include cataract, glaucoma, and scleral thinning. New delivery FIG 74.8 Hypopyon. Intense inflammation has resulted in a
approaches include injectable corticosteroids complexed with creamy exudate (pus), seen as whitening over the inferior portion
polymers to prolong the beneficial effects; iontophoresis to deliver of the anterior chamber. In this example, hypopyon was secondary
medication across the sclera; and small molecules, which seem to rifabutin, not ankylosing spondylitis.
to have a much broader biodistribution within the eye compared
with topical prednisolone. Systemic immunosuppressive therapy
should be used in cases of inadequate benefit from corticosteroids
22
or unacceptable steroid side effects. Immunosuppression is usually In frequently recurrent cases, therapy with sulfasalazine or TNF
reserved for bilateral forms of uveitis with a severity sufficient inhibitors is effective in reducing the frequency of the attacks. 23
to alter activities of daily living and is frequently chosen for eye Several studies have emphasized that spondyloarthritis may
involvement with Behçet disease. Immunosuppression may be be overlooked in patients with acute anterior uveitis (AAU). A
contraindicated by active infection in the eye or elsewhere. study from Ireland evaluated patients with AAU in the emergency
The role for therapy with biologics to treat uveitis is being room. About 40% had spondyloarthritis that had not been
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assessed in randomized controlled trials. Antibodies to IL-1β recognized. A study from Spain included 798 patients who had
or to anti–IL-17A have proven disappointing in the treatment either HLA-B27–associated AAU or recurrent, HLA-B27–associ-
of uveitis. 16-20 However, adalimumab (an anti-TNF-α biologic) ated anterior uveitis. As in the Irish study, all patients with known
was shown to be effective in a randomized clinical trial for active spondyloarthritis were excluded. The study utilized the Assessment
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uveitis and as a corticosteroid sparing agent in inactive uveitis. In of Ankylosing Spondylitis (ASAS) criteria. Fifty percent of this
an open label trial, infliximab has proven effective but had frequent large group had axial spondyloarthritis and close to an additional
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severe toxicities for this indication. The authors frequently 20% had peripheral spondyloarthritis. 26
prescribe infliximab to treat Behçet disease (see below). Biologic
therapy for uveitis might also be guided by the underlying disease, Inflammatory Bowel Disease–Associated Uveitis
such as Crohn disease, juvenile idiopathic arthritis, or psoriatic Ocular manifestations of inflammatory bowel disease (IBD)
arthritis, all of which are particularly responsive to biologics. (Crohn disease and ulcerative colitis; Chapter 75) include anterior
uveitis, episcleritis, and scleritis (1–9% of all cases). Less common
Overview of the Most Common Uveitis Diagnoses ocular inflammatory manifestations include peripheral keratitis,
Ankylosing Spondylitis–Associated Uveitis intermediate uveitis, optic neuritis, and retinal vasculitis. Twenty
27
Ankylosing spondylitis (AS) is the most common systemic percent of patients with IBD may have sacroiliitis; 60% of them
diagnosis associated with uveitis in Western nations. A genetic are HLA-B27 positive. The anterior uveitis in patients with IBD
predisposition with the HLA-B27 allele is found in 88–96% of is often similar to that seen with the HLA-B27 spectrum of joint
patients. About 30–50% of patients with AS develop anterior diseases: sudden in onset, unilateral, and self-limiting. Like
uveitis transiently during their lifetime. Approximately 50% of sarcoidosis, it may result in intraocular inflammation that is
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patients with sudden-onset anterior uveitis are HLA-B27 positive. insidious in onset, bilateral, posterior to the lens, chronic, or
In some studies, 80–90% of individuals with HLA-B27–associated associated with a retinal vasculitis. 28
iritis have spondyloarthritis. AS should be considered in any Crohn disease is a complex genetic disease—that is, multiple
patient with sudden-onset, primarily anterior, unilateral uveitis genes contribute to susceptibility. One of the best characterized
associated with redness and pain. Recurrent disease, fibrin in of these genes is NOD2. This gene functions as an intracellular
the anterior chamber, posterior synechiae, relatively brief inflam- Toll-like receptor (TLR) that recognizes muramyl dipeptide from
mation that resolves in <2 months, and lowered intraocular bacteria. The NOD2 gene is also implicated in autoinflammatory
pressure are additional hallmarks that help to distinguish diseases. A mutation in the portion of the NOD2 gene known
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HLA-B27–associated iritis from other categories. Inflammation as the nucleotide-binding domain results in a rare autosomal
is sometimes so severe that a hypopyon (Fig. 74.8) develops. dominant form of uveitis known as Blau syndrome.
The posterior segment of the eye is not commonly involved in
this disease except for the development of a vision-reducing Psoriatic Arthritis–Associated Uveitis
cystoid macular edema (see Figs. 74.2 and 74.4). HLA-B27–associ- According to one study in the UK, 1–2% of the population have
ated anterior uveitis usually responds to topical corticosteroids. psoriasis (Chapter 64); roughly 10% of patients with psoriasis