hla associated uveitis
TRANSCRIPT
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HLA Associated
Uveitis
Speaker:DR. NAFIZ MAHMOODDO student , NIO&H
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.
The term is commonly used to describe
many forms of intraocular inflammation
involving not only the uvea
but also the retina & its vessels.
Uveitis
Inflammation of the uveal tract
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MHC
HLA
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Major Histocompatibility Complex ( MHC) :
Cell surface glycoproteins responsible for regulation of Immune system.
Human Leukocyte antigen ( HLA )
Cell surface glycoprotein encoded by HLA gene located on chromosome 6, responsible for regulation
of Immune system in humans
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At the end of the paper, Dausset wrote that
‘Finally, in a more long time perspective,
the study of leucocyte antigens might
become of great importance in tissue
transplantation, in particular in bone
marrow transplantation’ (translated from French).
The credit for discovery of the first HLA antigen goes to Dausset
Jean Dausset (1916–2009)
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MHC class I( HLA – A , B , C )
Surface of all nucleated cells
MHC class II( HLA – DP , DQ , DR )
Antigen presenting cells (APC)
glycoproteins
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Pathogenesis
A. HLA are peptide binding molecules for etiologic antigens or infectious agentsThus , specific HLA might be predisposed to process certain AgSuch as an infectious agent cross-reacts with a self Ag
B. Molecular mimicry between infectious Ag & epitope of HLA molecule
C. Mutation recognise self as non-self
immunologic reaction
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Functions of MHC/ HLA
Defense
Transplant rejections
Protect against cancers
Associated with Autoimmune diseases
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Diseases associated with HLA
HLA Diseases A3 HaemochromatosisB5 Behcet’s disease
B27 Ankylosing spondylitisReiter’s syndromePsoriatic arthritis
Acute anterior uveitis
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Cont…
HLA DiseasesDR2 Multiple sclerosis
Pernicious anaemiaDR4 Type 1 DM
Rheumatoid arthritisDR5 Pernicious anaemiaDR7 Coeliac disease
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Cont…
HLA DiseasesDR3 Dermatitis herpetiformis
Coeliac diseaseSjogren syndrome
SLEAddison’s diseaseGrave’s disease
Hashimito’s thyroiditisMyasthenia gravis
Type 1 DM
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Uveitic diseases with HLA associations
Diseases HLA associationTubulointestinal nephritis & uveitis (TINU)syndrome
HLA- DRB1
Birdshot retinochoroidopathy HLA- A29Reactive arthritis HLA- B27Acute anterior uveitis HLA- B27
Strong association
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Diseases HLA associationJuvenile idiopathic arthritis HLA- A2,DR5,DR8,DR11Behcet disease HLA- B51Intermediate uveitis HLA- B8,B51,DR2,DR15Sympathetic ophthalmia HLA- DR4Vogt-Koyanagi-Harada Syndrome
HLA- DR4
Sarcoidosis HLA- B8,B13 Multiple sclerosis HLA- B7, DR2Retinal vasculitis HLA- B44
Weaker association
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Ankylosing spondylitis
Inflammation
calcification,
ossification of
ligament & capsules
of joints of
axial skeleton
Male
Presentation • 3rd-4th decades• Insidious onset-
Lower back pain & stiffness
Systemic features • Progressive limitation of spinal movement• Enthesitis• Cardiac complications
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Ocular features o Acute anterior uveitis 25%o Scleritis o Episcleritiso Keratitiso Mechanical ptosis
Bony obliteration of sacroiliac joint
Bamboo spine
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Reiter syndrome
Triad • Non-gonococcal urethritis• Conjunctivitis• arthritis
Systemic featuresPeripheral arthritisSpondyloarthropathyEnthesitisMucocutaneous lesions Genitourinary involvement
Pathogenesis 1–3% after non-specific urethritis,4% of persons after enteric infections by• Shigella, • Salmonella and • Campylobacter • Yersinia
3rd–4th decades
Ocular fetures• AAU – 12%• conjunctivitis
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keratoderma blenorrhagica in Reiter syndrome
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Psoriatic arthritisMale = Female 3rd–4th decades
Signs A. Skin :• Plaque psoriasis• Flexure psoriasis
B. Nail dystrophyC. Arthritis
Ocular featuresAAU – 7%conjunctivitis, marginal corneal infiltrates
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Juvenile idiopathic arthritis
Systemic onset:Characterized by- • Fever • Rash• Lymphadenopathy• Hepatosplenomegay
** uveitis – less than 6%
polyarticular onset:More than 4 joints40% of all JIAANA + in 40%** iridocyclitis – 10%F:M – 3:1
pauciarticular onset:4 joints or lessANA + in 75%** uveitis – 20%F:M – 5:1
ComplicationsBand keratopathyCataractGlaucomaVitreous debrisMECh. Hypotonyphthisis
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Inflammatory bowel disease
Ulcerative colitis
Intestinal menifestations • bloody diarrhoea • lower abdominal cramps • urgency • tenesmus
Extra-intestinal menifestation• Muco-cutaneous lesions• Arthritis• Hepatic disease• Thromboses
2nd–3rd decades
AAU – 12%
diffuse surface ulceration of the mucosa with development of crypt abscesses
and pseudopolyps
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pseudopolyposis, lack of haustration
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Crohn disease
Intestinal menifestations • diarrhoea • abdominal pain.
Extra-intestinal menifestation• Muco-cutaneous lesions• Clubbing, arthritis• sacroiliitis • ankylosing spondylitis.
2nd–3rd decades
AAU – 3%
multifocal, full-thickness, non-caseating granulomatous
inflammation of the intestinal wall
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stricture in the descending colon
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Birdshot retinochoidopathy
Idiopathic chronic bilateral
Middle aged women
Clinical feature
Symptoms• Insidious impairment of central vision• Photopsia• Floaters• Nyctalopia• Disturbance of color vision
vitritis
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Fundus
• Multifocal,hypopigmented,ovoid, cream-colored choroidal lesions in post-equarorial region• Emanate from optic nerve • Radial distribution
CMEERMCNV
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Investigations :• HLA- A29 : sensitive 96% ; specific 93%• OCT• Autofluorescence• FA• ICGA• ERG : rod & cone abnormalities
Treatment : Systemic & intraocular steroids Immunosuppresent
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Vogt-Koyanagi-Harada syndrome
Idiopathic multisystem autoimmue disease
Affects: • Uvea• Ear• Meninges
Pigmented individuals
HLA – DR1, DR4
Prodromal phaseMeningitisAuditory menifestations
TinnitusVertigoDeafness
Cranial nerve palsiesOptic neuritis
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Acute uveitic phase
Bilateral granulomatous AU
Multifocal posterior uveitis
Diffuse choroidal infiltration
Dalen-fuchs nodules
Vitritis
Papillitis
Exudative RD
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Convalescent phase
Localized alopecia
Poliosis
Vitiligo
Sunset glow fundus
Depigmented limbal lesions
Chronic recurrent phase
Smouldering AU with exacerbation
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Diagnostic criteria
1. Absence of a history of penetrating ocular trauma 2. Absence of other ocular disease entities 3. Bilateral uveitis 4. Neurological and auditory manifestations 5. Integumentary findings, not preceding onset of central nervous system or ocular disease, such as alopecia, poliosis and vitiligo
In complete VKH, criteria 1–5 must be present. In incomplete VKH, criteria 1–3 and either 4 or 5 must be present. In probable VKH (isolated ocular disease), criteria 1–3 must be present
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Complications
• CNV
• Subretinal fibrosis
• Preretinal & disc new vessels
• Vitreous haemorrhage
• Cataract glaucoma
Investigations Lumbar punctureFAFOCTB-scanFAICGA
Traetment High dose (1-2mg/kg/day) oral prednisolone, tapered over 3-6 monthsPreceeded by IV methylprednisolone(500-1000 mg/day)Topical steroids, Cycloplegics,ImmunosuppressivesBiological blockers
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Idopathic multisystem syndrome
Behcet disease Male predominent
Diagnostic criteria
1. Recurrent oral ulceration ( at least 3 times in 12 months)2. Plus at least two of the following:
• Recurrent genital ulceration
• Ocular inflammation.
• Skin lesions include erythema nodosum, folliculitis, acneiform
nodules or papulopustular lesions.
• Positive pathergy test - formation of a pustule after 24–48 hours
at the site of a sterile needle prick
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Other systemic features
• Vascular lesions
• Arthritis
• Dermatographia
• Neurological menifestations
• Gastrointestinal inflammation
• Hepatic & renal lesions
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Ocular features (75%)
AAU – bilateral, granulomatous
Vitritis
Retinitis – transient superficial white infiltrate heal without
scarring
Retinal vasculitis – sheathing, perivascular Hge,occlusion,CMO
Optic disc hypermia & edema
Uncommon – conjunctivitis, episcleritis, scleritis
ophthalmoplegia
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End stage disease
• Optic atrophy
• Retinal atrophy
• Gliosis
• Sheathing
• Attinuation & ghosting of vessels
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Investigation :• HLA – B51
• Pathergy test
• Inflammatory markers
• Thrombophilia screening
• FA
• Superficial lesion biopsy
• Systemic imaging – MRI/MRA,CTA of brain,
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Treatment
Topical steroids
Systemic steroids & azathioprine
Ciclosporin
Infliximab or adalimumab
Interferon alfa
Anticoagulants
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Conclusion
Testing for HLA can provide supporting evidence
for a particular diagnosis,
but cannot make
definitive diagnosis.
Remember
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