BEHCET DISEASE

AND
TOXOPLASMOSIS
BY DR SHAHZADA KHAN
TMO EYE A WARD HMC
 BEHCET DISEASE
Introduction:
Behcet disease (BD) is a chronic, relapsing, occlusive systemic vasculitis
of unknown etiology.

 Characterised by a triad of oral aphthous ulcers, genital ulcers, and

ocular disease.

The disease was described by a Turkish dermatologist, named Dr.

Hulusi Behcet.
 Epidemiology
BD is most prevalent along the Silk Road.

It is most commonly noted in Turkey, but has high prevalence also in Japan,
Korea, China, Iran, Iraq, and Saudi Arabia.
 
In North America and Northern European countries, the prevalence is much
lower. 
Onset is typically in the second to fourth decades of life . BD is most
commonly sporadic.
 Etiology
Behcet's disease might be an autoimmune disorder, which means the body's
immune system mistakenly attacks some of its own healthy cells.

Abnormal immune activity may be generated by exposure to infectious (viral

and bacterial) or non-infectious (environmental sources, such as heavy metals
or chemicals) antigens in patients with a genetic predisposition.
 Clinical Manifestations
Ocular Manifestations
Ocular inflammation occurs in about 70%, tends to be more severe in men
and is the presenting manifestation in about 10%.

AAU, often bilateral, is typical. It is non granulomatous.

A transient mobile hypopyon in a relatively white eye is characteristic.

Vitritis may be severe and is universal in eyes with active posterior segment
disease.
Hypopyon in a white eye
Retinitis.
Transient superficial white infiltrates that heal without scarring may be seen
during acute systemic disease.
There may be deeper more diffuse retinitis similar in appearance to viral
inflammation.
Exudative detachments can also occur.
Inflammatory deposits analogous to KPs may be seen on the inferior
peripheral retina.
Retinal infiltrates
Retinal vasculitis – arteritis as well as phlebitis, in contrast to pure venous
involvement in sarcoidosis – can manifest with sheathing, perivascular
haemorrhages and occlusion .
Vascular leakage may give rise to diffuse retinal oedema and CMO.

Optic disc hyperaemia and oedema.

 Disc and retinal neovascularization may be seen as a response to

inflammation and ischaemia.
Occlusive vasculitis
Uncommon manifestations include conjunctivitis, , episcleritis, scleritis and
ophthalmoplegia from neurological involvement.

End-stage disease is characterized by optic atrophy, retinal atrophy and

gliosis and sheathing, attenuation and ghosting of affected vessels .
The vitreous tends to clear.
Other complications include PS, cataract, glaucoma and, retinal detachment
and phthisis.
End-stage disease
 Non-ocular systemic manifestations
Oral aphthae are the most frequent finding in BD .
These are recurrent mucosal ulcers that produce significant discomfort and
pain.

They can occur on the lips, gums, palate, tongue, uvula, and posterior pharynx.

They are discrete, round or oval, white ulcerations with red rims that vary in
size from 2 to 15 mm.
They recur every 5- 10 days or every month.
Major aphthous ulceration
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.
They disappear with minimal, if any, scarring.

Acne vulgaris or folliculitis-like skin lesions may frequently appear on the

upper thorax and face.

Early 40% of patients with BD exhibit cutaneous pathergy.

Genital ulcers appear grossly similar to oral aphthous ulcers.
These lesions are associated with variable amounts of pain.

Systemic vasculitis may also occur in up to 25% of patients with BD, and any
size artery or vein in the body may be affected.

Four different vascular complications can develop from the systemic

vasculitis of BD: arterial occlusion, aneurysm, venous occlusion, and varices.
Cardiac involvement from BD can include granulomatous endocarditis,
myocarditis, endomyocardial fibrosis, coronary arteritis, and pericarditis;
these can occur in up to 17% of patients.

 Gastrointestinal lesions can include multiple ulcers involving the esophagus,

stomach, and intestines.

Neurological manifestations (5%) such as meningoencephalitis of the

brainstem, dural sinus thrombosis and cerebral aneurysms .
Arthritis occurs in more than half of all patients with Behcet's Disease.

 Arthritis causes pain, swelling, and stiffness in the joints, especially in the
knees, ankles, wrists, and elbows.

Arthritis that results from Behcet's Disease usually lasts a few weeks and
does not cause permanent damage to the joints.
 Investigation
HLA-B51.
 Pathergy test.
Inflammatory markers (e.g. ESR, CRP, complement levels, white cell count)
may be elevated.
FA delineates ischaemic areas and aids detection of posterior segment
inflammation and monitoring of disease activity.
Imaging such as brain MRI.
OCT for macular edema.
 Diagnosis
Diagnosis of BD is based on clinical findings and the diagnostic criteria.
There are two diagnostic criteria for BD.

A) Diagnostic System for Behcet Disease (Japan)

B)Diagnostic System for Behcet Disease (International Study Group for
Behcet Disease)
 A) Diagnostic System for Behcet Disease (Japan)
Major Criteria: Minor Criteria

Recurrent Oral aphthous ulcers GI ulceration

Skin lesions (erythema nodosum, Arthritis

acneiform pustules, folliculitis
Recurrent genital ulcers Epididymitis

Ocular Inflammatory disease Systemic vasculitis or associated

complications
Neuropsychiatric symptoms
Types of Behcet Disease
Complete (4 major criteria)

Incomplete (3 major criteria or ocular involvement with 1 other

major complication)

Suspect (2 major criteria with no ocular involvement)

Possible (1 major criterion)

B) Diagnostic System for Behcet Disease (International
Study Group for Behcet Disease)
Recurrent oral aphthous ulcers (at least 3 or more times per year) plus 2 of
the following criteria:
1. Recurrent genital ulcers
2. Ocular inflammation
3. Skin lesions
4. Positive cutaneous pathergy test
 Differential diagnosis
HLA-B27-associated anterior uveitis,
Reactive arthritis syndrome,
Sarcoidosis, and
Systemic vasculitides including systemic lupus erythematosus and
Wegner granulomatosis.
 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,
which is essential.
 Corticosteroids: 
Most useful agent that is used in the treatment of explosive inflammation of
the anterior and posterior segments.
Prednisone doses of 1.5mg/kg/day (with taper) are most beneficial for
controlling acute inflammation.

Resistance to systemic corticosteroids with long-term use, as well as side

effects of high dose steroids limit their usefulness for extended periods.

Corticosteroids also have utility in treating oral or genital ulcers when used
topically.
 Immunomodulatory medications
Patients who present with sight-threatening posterior segment ocular BD
require prompt institution of systemic corticosteroids together with IMT,
which may include;
azathioprine,
infliximab,
cyclosporine,
tacrolimus,
mycophenolate mofetil,
chlorambucil,
Azathioprine has been found in prospective clinical trials to be useful in
preserving visual acuity in patients with established ocular BD and is a
preferred first-line immunomodulatory agent.

The 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.
 Toxoplasmosis
Introduction:
Toxoplasmosis is the most common cause of infectious retinochoroiditis in
both adults and children.

It is caused by the parasite Toxoplasma gondii, a single-cell obligate

intracellular protozoan parasite with a worldwide distribution .

Cats are the definitive hosts of T gondii, and humans and a variety of other
animals serve as intermediate hosts.
Toxoplasmosis can cause severe disease especially in newborns and
immunosuppressed patient while in immunocompetent patients
toxoplasmosis remain asymptomatic in majority cases.

T gondii has a complex life cycle and exists in 3 major forms:

the oocyst, or soil form.
the tachyzoite, or infectious form .
 the tissue cyst, or latent form which contains as many as 3000 bradyzoites
 Transmission of T Gondii
Human infection by T gondii may be either acquired or congenital.
The principal modes of transmission include:
Ingestion of undercooked, infected meat containing Toxoplasma cysts.

Inadvertent contact with cat feces, cat litter, or soil containing oocysts.

Transplacental transmission occurs only when infection is acquired for the

first time during pregnancy.
Blood transfusion or organ transplantation.
Clinical features of ocular toxoplasmosis
Symptoms:
Unilateral acute or subacute onset of floaters, blurring and photophobia.

Anterior uveitis: A mild to moderate granulomatous anterior uveitis is

frequently observed, and up to 20% of patients have acutely elevated lOP at
presentation.
Anterior segment photo showing keratic precipitates
Retinitis : Classically, ocular toxoplasmosis appears as a focal, white
retinitis with overlying moderate vitreous inflammation ("headlight in the
fog"), often adjacent to a pigmented chorioretinal scar.

Focal retinitis in the absence of chorioretinal scarring should raise the

suspicion of acquired disease or another cause for the necrotizing retinitis
Active toxoplasma retinitis lesion adjacent to a pigmented retinochoroidal scar
Active toxoplasma retinitis with marked vitritis
producing the classic appearance of a headlight in the
fog
Vasculitis :Retinal vessels in the vicinity of an active lesion may show
perivasculitis with diffuse venous sheathing and segmental arterial sheathing.

Retinochoroiditis may be absent in the acute phase of acquired disease, with

activity consisting of anterior uveitis, vitritis and retinal vasculitis.
Typical retinal scars may form later.
Kyrieleis arteritis is present as white plaques within the artery that
appear nodular and do not extend outside the vessel
Active retinitis next to an old chorioretinal scar with diffuse
vasculitis
• Optic disc oedema is common.

• Vitritis may be severe and impair fundus visualization.

• Punctate outer retinal toxoplasmosis: PORT is characterized by small,

multifocal lesions at the level of the deep retina with scant overlying vitreous
inflammation.
Extensive and fulminant retinal involvement is generally confined to the
immunocompromised, in whom it may be bilateral and difficult to distinguish
from viral retinitis.

Others ocular complications include cataract, CME, serous retinal

detachment, CNV and neuroritinitus,
Healing :
Healing in immunocompetent hosts usually occurs spontaneously within 6–8
weeks, although vitreous opacities take longer to clear.

The inflammatory focus is replaced by a sharply demarcated atrophic scar

that develops a pigmented border.
Inactive lesions appear as a chorioretinal scar in the posterior pole
Recurrence
Recurrent lesions tend to occur at the margins of old scars, but they also can
occur elsewhere in the fundus.
The risk of recurrence is highest within the first year of the initial episode.

Older age also predisposes to higher risk of recurrence.

 Congenital toxoplasmosis (CT)
Congenital toxoplasmosis (CT) may present as a mild or severe neonatal
disease.

There is a wide variety of manifestations of congenital infection, ranging

from fetal hydrops and perinatal death , prematurity, peripheral retinal
scars, persistent jaundice, mild thrombocytopenia, cerebro-spinal fluid (CSF)
pleocytosis,

And the characteristic triad of chorioretinitis, hydrocephalus, and cerebral

calcifications.
Macular retinochoroidal lesion of congenital toxoplasmosis
 Investigations
Serology:
The detection of serum IgG and IgM is most commonly performed to
confirm a clinically diagnosed ocular toxoplasmosis .

Toxoplasma-specific IgM detected in the serum is indicative of a recently

acquired infection .

Detection of Toxoplasma-specific IgG alone is of low diagnostic value as it

indicates previous infection and is also found in individuals manifesting no
signs of ocular toxoplasmosis
Presence of IgG and IgM antibodies do not always indicate ocular infection.

The common method used to estimate the local versus systemic Toxoplasma-
specific IgG is the Goldmann-Witmer coefficient.

This index expresses the ratio of specific IgG in aqueous humour to that in
serum .

A value of 2 or above is generally taken as evidence of the intraocular

synthesis of Toxoplasma- specific IgG in response to active ocular infection.
Polymerase Chain Reaction:
Detection of parasitic DNA and toxoplasma specific antibodies in intraocular
fluids(acqueous,vitreous) by polymerase chain reaction is considered highly
sensitive
and should be considered in all patients with atypical presentations and in
patients not responding to anti toxoplasma therapy.

This combined approach has diagnostic sensitivity and specificity of 60% and
90% respectively.
Fundus fluorescein angiography
FA findings include early hypofluorescence and late intense
hyperfluorescence with fuzzy margins of the retinochoroiditis lesion in all
active lesions .

In eyes with inactive lesions, the scar appeared hypofluorescent and the
atrophic areas appeared hyperfluorescent on FA.

FA also helps in identifying CNVM , involvement of optic nerve head, and
leakage from the vessels.
Fundus Autofluorescence:
Autofluorescence of toxoplasmic retinochoroidal scars demonstrates hypo-
autofluorescence due to lack of functional retinal pigment epithelium .

Acute, active lesions may also show hypo-autofluorescence due to the

presence of overlying retinal edema.

In fact, autofluorescence imaging can be used to monitor the effect of medical
therapy, since it better demonstrates resolution of active retinal edema.
Autofluorescence image showing hypo-autofluoroscent old
chorioretinal scar (black arrow) with hyperautofluoroscent active
lesion(white arrow).
 Treatment
In the immunocompetent patient, the disease has a self-limiting course.

In the immunocompromised patient, the disease tends to be more severe and
progressive.
Treatment is aimed to limits chorioretinal scarring and progression, reduces
the frequency of inflammatory recurrences, and minimizes structural
complications associated with intraocular inflammation.
 Treatment indications
 A sight-threatening lesion involving the macula, papillomacular bundle,
optic nerve head or a major blood vessel
Severe vitritis
Immunocompromised patient.
congenital toxoplasmosis.
pregnant women with acquired disease.
 Classic triple therapy
The classic regimen for the treatment of ocular toxoplasmosis consists of
triple therapy: pyrimethamine , sulfadiazine , and prednisone .

 Because sulfonamides and pyrimethamine inhibit folic acid metabolism,

folinic acid (5 mg every other day) is added to try to prevent the leukopenia
and thrombocytopenia that may result from the pyrimethamine therapy.

Systemic corticosteroids are generally begun either at the time of

antimicrobial therapy or within 48 hours in immunocompetent patients.
 Leukocyte and platelet counts should be monitored weekly.

Potential side effects of sulfa compounds include skin rash, kidney stones,
and StevensJohnson syndrome.

Some clinicians advocate adding clindamycin (300 mg 4 times daily) to this

regimen as "quadruple" therapy or in the instance of sulfa allergy.
Azithromycin 250–500 mg daily shows evidence of reducing the rate of
recurrence of retinochoroiditis and its use in combination with
pyrimethamine, folinic acid and prednisolone is a promising new regimen.
Clarithromycin may be a good alternative to azithromycin.

Clindamycin 300 mg four times daily may be added to triple therapy or used
instead of pyrimethamine.
Pseudomembranous colitis is a potential adverse effect.
Intravitreal therapy with clindamycin (1 mg) and dexamethasone (400
µg) may be as effective as triple therapy in reactivated infection.

Two to three injections (at 2-weekly intervals) may be required.

It may be preferred in recurrent infection in pregnancy, but would not

generally be used in isolation in the immunocompromised and in newly
acquired (IgM-positive) infection systemic therapy has superior efficacy.
Co-trimoxazole (trimethoprim 160 mg/sulfamethoxazole 800 mg) twice daily
in combination with prednisolone is a low-cost and better-tolerated option
but might not be quite as effective as classic therapy.

Topical steroid and mydriatic may be given for anterior uveitis.

 Treatment of Congenital toxoplasmosis

To treat CT two types of regimen are available: prenatal and postnatal.

The first is aimed at preventing the infection of the fetus and, in case of
documented infection, hasten the treatment before birth, while the second is
designed to treat the infection and to prevent the sequelae.
PrenatalTreatment :
When pregnant women seroconvert, spiramycin is administered in order to
prevent the mother-to-child transmission.
When the fetal infection is confirmed the association of pyrimethamine and
sulfadiazine is prescribed.
Postnatal Treatment :
The combination of pyrimethamine and sulfadiazine is use after birth for one
year.
MCQ 1
A 20-year-old Brazilian man presents with a history of decreased vision in his
left eye for 1 week. Visual acuity is 20/70 and moderate vitritis is present. On
dilated examination, a pigmented scar in the posterior pole with adjacent
focal white chorioretinitis is present. What is the most appropriate
treatment?
a) oral corticosteroids
b) pyrimethamine, sulfadiazine, and prednisone
c) intravenous acyclovir
d) amphotericin B
MCQ 2
A 20 year old male patient presented with recurrent panuveitis associated
with painful buccal and genital ulcers, subcutaneous nodules and pustules on
the trunk, and positive pathergy (skin hypersensitivity to needle pricks) test. .
This patient meets the criteria for Beçhets' Disease.
What is the most common non-ocular finding iBehcet disease?
a) Arthritis
b) Central nervous system vasculitis
c) Oral or genital ulcers
d) HLA-B51 positivity 
MCQ 3
A 30 year old pregnant lady visits her gynaecologist for first trimester pre
natal check up.She has no complaints.Routine physical exame is for only mild
cervical lymphadenopathy.On serology toxoplasma specific IGM
detected.Which are the best druge to be prescribed in this patient:
a) Combination of pyrimethamine and sulfadiazine
b) Spiramycin
c) Systemic corticosteroids
d) Oral Azithroprine
MCQ 4
A 21-year-old male patient presented with on and off blurring of vision in
right eye during last 2 years. Slit lamp findings was normal anterior segment
with quiet AC, no hypopion.Right eye media was hazy due to grade 2 vitreous
cells, left eye was normal. On systemic evaluation ofpatient multiple nodular
pyoderma gangrenosum ulcers noticed on ventral and dorsal surface of left
leg. Also multiple, round, whitish aphthous ulcers in oral cavity were noticed,
scrotal swelling was present.
What is the most probable diagnosis:
a) Multiple sclerosis-associated uveitis
b) Systemic lupus erythematosus
c) Behcet disease
d) Ocular sarcoidosis
THANKS
Next lecture: Dr Shakeel
Topic:Diabetic
retinopathy(Pathogenesis,classification,clicical feature).

Next journal: Dr Alina

Topic :?