Panuveitis BEHCET DISEASE AAO Reading.pptx

BEHÇET
Faradhillah A. Suryadi
AAO READING
INFECTION & IMMUNOLOGY SUBDIVISION DEC

 Behçet disease (BD) is a chronic, relapsing, multisystem
inflammatory disorder of unknown etiology. It can affect both
the anterior and the posterior segments of the eye, often
simultaneously.
 The disease symptoms have been described for more than
2500 years. They were formally characterized in the early
20th century by Adamantiades and Behçet as a triad of
aphthous ulceration, genital lesions, and recurrent uveitis.
It is now known to affect almost any organ system and occurs in
a variety of ethnic populations all over the world.
 It is most common in the Northern Hemisphere in the
countries of the eastern Mediterranean and on the eastern
rim of Asia.

 The prevalence of BD varies from as high as 20–421 cases
per 100,000 inhabitants in Turkey to 8–13.5 per 100,000 in
Japan and 5.2 per 100,000 in the United States.
 The age of onset is typically in the third and fourth
decades but can also occur after age 50 or in childhood. Both
genders are affected equally, but BD may have a more severe
course in males.
 The diagnosis of BD is clinical and is based on the
presence of multiple systemic findings. The diagnostic system
for BD in Table 9-3 was suggested by researchers in Japan,
and another diagnostic system was suggested by the
International Study Group for Behçet’s Disease ( Table 9-4).

 Although BD is a multisystem disease, it can have its predominant
effect on a single system; thus, special clinical types of BD occur namely,
neuro BD, ocular BD, intestinal BD, and vascular BD. However,
importantly, being free from major organ involvement early in the disease
does not protect against its development later on

NONOCULAR SYSTEMIC MANIFESTATIONS
Recurrent, painful oral aphthae are the most
frequent finding and often the presenting sign
in BD (Fig 9-60). They can occur on the lips,
gums, palate, tongue, uvula, and posterior
pharynx. They are discrete, rounded, white
ulcerations with red rims varying in size
from 2 to 15 mm. They typically last 7–10
days and heal with little scarring unless large.
Figure 9-60. Behcet disease. Mucous membrane
ulcers (oral aphthae)
Genital ulcers appear grossly similar to oral aphthous ulcers, but tend to
be deeper and larger and heal with more scarring. In male patients, they
can occur on the scrotum or penis. In female patients, they can appear on
the vulva and vaginal mucosa. Genital scarring may be apparent on
examination even if patients have no acute symptoms.

 Skin lesions can include painful or recurrent erythema nodosum, often
over extensor surfaces such as the tibia, but also on the face, neck, and
buttocks. Acne vulgaris or folliculitis like skin lesions may frequently
appear on the upper thorax and face. Skin lesions may disappear
spontaneously with minimal or no scarring.
 Nearly 40% of patients with BD exhibit cutaneous pathergy, which
is characterized by the development of a sterile pustule at the site of a
venipuncture or an injection but is not pathognomonic of BD.
 Systemic vasculitis affecting any size artery or vein in the body may
occur in up to 25% of patients with BD. Common manifestations are
arterial occlusions and aneurysms, and superficial or deep venous
occlusions and varices.

 Cardiac involvement can include granulomatous endocarditis,
myocarditis, endomyocardial fibrosis, coronary arteritis, and
pericarditis. Gastrointestinal lesions, such as ulcers involving the
esophagus, stomach, and intestines, may be seen in over 50% of BD
patients in Japan, where it is a significant cause of morbidity.
 Pulmonary involvement is mainly pulmonary arteritis with
aneurysmal dilatation of the pulmonary artery. 50% percent of
patients with BD develop arthritis, commonly of the knee, elbow, hand, or
ankle.
 Neurologic involvement is among the most serious of all
manifestations of BD. Lesions of the white matter of the brain and
brainstem may lead to motor dysfunction, stroke, and
cognitive/behavioral changes.

 Headaches and aseptic meningitis have been associated with CNS
vasculitis and meningeal involvement, respectively. 10% percent of
patients with neuro BD can have ocular disease, and 30% of patients with
ocular BD may have neurologic involvement.
 Mortality has previously been reported to be as high as 10% in
patients with neuro BD, but it may be lower currently, especially with the
use of IMT. Neuro ophthalmic involvement can include cranial nerve
palsies, papillitis, and papilledema resulting from thrombosis of the
superior sagittal sinus or other venous sinuses.

OCULAR MANIFESTATIONS
 Ocular manifestations affect up to 70% of patients with BD. They
carry serious implications because they are often recurrent and
relapsing, resulting in permanent ocular damage. Severe vision loss can
occur in up to 25% of patients with BD.
 Ocular disease most often presents as panuveitis that appears to be
more severe and more common in men; over 80% of cases are bilateral.
Ocular involvement as an initial presenting problem is relatively
uncommon, and there may be a delay of years between presenting signs
in other organs and the first occurrence of uveitis.
 The intraocular inflammation is characterized by a
nongranulomatous, necrotizing, obliterative vasculitis that can affect
any or all portions of the uveal tract.

 less common anterior segment findings of BD include cataract,
episcleritis, scleritis, conjunctival ulcers, and corneal immune ring
opacities.
 Posterior segment manifestations of ocular BD are often
profoundly sight threatening. The essential finding is an occlusive retinal
vasculitis affecting both arteries and veins, which may be associated
with multifocal areas of chalky white retinitis (Fig 9-62).
 Panuveitis are the most common types of BD ocular
inflammation, seen in 50%–80% of cases of BD patients with uveitis.
Other posterior manifestations can include retinal artery and vein
occlusions, vascular sheathing with variable amounts of vitritis, and
associated uveitic macular edema.

Figure 9-61. Behcet disease. Hypopyon Figure 9-64. Behcet disease. Histologic view of perivascular
inflammation

Figure 9-62. Behcet disease, Fundus photograph of
retinitis and vasculitis.
Figure 9-63. Behcet disease. Fundus photograph of retinitis and
vasculitis with retinal hemorrhage. The retinits shown here
appears similar to necrotizing herpetic retinitis with retinal
whitening and occlusive retinal vasculitis

 Retinal ischemia can lead to the development of retinal and iris
neovascularization with neovascular glaucoma. After repeated
episodes of retinal vasculitis and vascular occlusions, retinal vessels may
become white and sclerotic.
 The ischemic nature of the vasculitis and accompanying retinitis may
produce a funduscopic appearance that may be confused with acute
retinal necrosis syndrome or other necrotizing herpetic entities (Fig 9-
63).
 The optic nerve is affected in 25% of patients with BD. Optic papillitis
can occur, but progressive optic atrophy may occur as a result of the
vasculitis affecting the arterioles that supply blood to the optic nerve.

 Because of the transient nature of posterior segment
inflammatory episodes in BD, serial color photography may be of
benefit in diagnosis. OCT imaging can show structural alterations
caused by the vasculitis in the form of macular edema and disruption of
the retinal architecture (see Fig 9-65). Systemic investigations may be
helpful, as indicated by clinical presentation.
DIFFERENTIAL DIAGNOSIS
 The differential diagnosis for BD includes HLA-B27 associated
anterior uveitis, reactive arthritis syndrome, sarcoidosis, Susac
syndrome, and systemic vasculitides including systemic lupus
erythematosus, PAN, and GPA. Necrotizing herpetic retinitis can also
mimic occlusive BD retinal vasculitis.

Figure 9-65. Behcet disease.
A. Color fundus photograph indicating
vasculitis and localized retinitis.
B. Flourescein angiogram showing disc
starring and perivascular leakage
C. OCT scan revealing macular edema and
inflammatory disruption of the retinal
microarchitecture

PATHOGENESIS
 Many environmental factors have been suggested as potential
causes of BD, but none has been proven. No infectious agent or
microorganism has been reproducibly isolated from the lesions of patients
with BD. The disorder is clinically and experimentally unlike other
autoimmune diseases.
 HLA associations have been found in 2 systemic forms of BD: HLA-
B12 with mucocutaneous lesions and HLA B51 with ocular lesions.
These associations are not reproducible in all populations, and testing
lacks the sensitivity and specificity to support its use for diagnosis.
 Histologically, BD lesions resemble those of delayed type
hypersensitivity reactions early on; late lesions resemble those of
immune complex type reactions. Histopathology may show an
inflammatory occlusive vasculitis (Fig 9-64).

DIAGNOSIS
 Laboratory tests for example, HLA typing, cutaneous pathergy
testing, and blood tests for ESR and CRP are of little value in confirming
the diagnosis.
 Fluorescein angiography demonstrates marked dilatation and
occlusion of retinal capillaries with perivascular staining, evidence of
retinal ischemia, leakage of fluorescein into the macula with the
development of macular edema, and retinal neovascularization that
may leak (Fig 9-65).

TREATMENT
 The goal of treatment is not only to treat the explosive onset of acute
disease with systemic corticosteroids but also to control chronic inflammation
and prevent or decrease the number of relapses of ocular inflammation with IMT.
Posterior segment ocular BD is an absolute indication for prompt initiation of
IMT.
 An American expert panel has recommended TNF inhibitor therapy with
infliximab (good- quality evidence) or adalimumab (moderate quality evidence)
as first or second line corticosteroid sparing therapy. A European League Against
Rheumatism panel has recommended using azathioprine (with corticosteroids)
as first line IMT for ocular BD and cyclosporine or infliximab as second line
treatment.
 When other major organs are involved, close collaboration with specialists
in other fields is necessary, as treatment modifications based on severity and
type of BD may be required.

TREATMENT
 Corticosteroids Systemic corticosteroids (eg, 1.0–1.5 mg/kg/day of
prednisone with a gradual taper) are extremely useful in controlling acute
inflammation. Periocular and intravitreal steroids may also be a useful
adjunct in selected patients. Corticosteroid monotherapy should be
avoided in sight-threatening BD uveitis, as severe rebound attacks may
occur during tapering.
 Nonbiologic IMT Only azathioprine and cyclosporine have under
gone randomized clinical trials indicating effectiveness in reducing uveitis
recurrence and preserving vision. Uncontrolled trials have shown benefit
with mycophenolate mofetil and tacrolimus as steroid- sparing agents;
alkylating agents, while effective, are used less frequently due to serious
side effects.
 Chlorambucil administration can help achieve a durable remission in
ocular BD. Cyclophosphamide is an alternative to chlorambucil and can be
used orally or as pulsed intravenous therapy.

TREATMENT
 Both of these alkylating agents have been shown to be more effective than
cyclosporine in the management of posterior segment ocular BD but carry
a greater risk of systemic complications and require complex hematologic
monitoring.
 The availability of biologic drugs has led most experts to reserve the use of
alkylating agents for patients with severe refractory disease.
 Biologic agents The use of systemic TNF inhibitors has heralded a new era
in the treatment of ocular BD.

TREATMENT
 A substantial body of literature has emerged demonstrating the
longterm efficacy and relative safety of systemic infliximab use in severe
refractory ocular BD, often achieving rapid and complete control of
disease, with reduction in retinal vascular leakage, as shown in FA;
preservation of vision; and reduced recurrences.
 Additional data suggest greater benefit of infliximab therapy when
initiated early on in the disease course. Adalimumab has been studied to a
lesser extent, although preliminary data are promising, including a cohort
studied prospectively as a part of the phase 3 clinical trials of adalimumab
for noninfectious posterior uveitis.
 Interferon alfa is a naturally occurring cytokine involved in immune
regulation, which, when administered in ocular BD as interferon alfa-2a,
has been shown in a number of observational studies to be a safe and
effective therapy. Combined with its lower cost and compatibility with
concomitant latent tuberculosis infection, some experts prefer it as first-
line therapy specific to ocular BD.

PROGNOSIS
 The prognosis for vision is guarded in patients with BD. Nearly
25% of patients worldwide with chronic ocular BD have visual acuity
less than 20/200, most commonly caused by macular edema,
occlusive retinal vasculitis, optic atrophy, and glaucoma. Adult men
tend to have poorer vision outcomes.
 Patients appear to have a better visual prognosis because of
earlier and more aggressive use of IMT. The presence of posterior
synechiae, per sis tent inflammation, elevated IOP, and hypotony
are all statistically significant predictive factors for vision loss.
 The chronic relapsing nature of this disease, with frequent
exacerbations after long periods of remission, makes it difficult to
predict visual outcomes.

AAO READING
INFECTION & IMMUNOLOGY SUBDIVISION - DEC
2023

Panuveitis BEHCET DISEASE AAO Reading.pptx

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