HLA Associated

Uveitis

Speaker:DR. NAFIZ MAHMOODDO student , NIO&H

.

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

MHC

HLA

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

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)

MHC class I( HLA – A , B , C )

Surface of all nucleated cells

MHC class II( HLA – DP , DQ , DR )

Antigen presenting cells (APC)

glycoproteins

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

Functions of MHC/ HLA

Defense

Transplant rejections

Protect against cancers

Associated with Autoimmune diseases

Diseases associated with HLA

HLA Diseases A3 HaemochromatosisB5 Behcet’s disease

B27 Ankylosing spondylitisReiter’s syndromePsoriatic arthritis

Acute anterior uveitis

Cont…

HLA DiseasesDR2 Multiple sclerosis

Pernicious anaemiaDR4 Type 1 DM

Rheumatoid arthritisDR5 Pernicious anaemiaDR7 Coeliac disease

Cont…

HLA DiseasesDR3 Dermatitis herpetiformis

Coeliac diseaseSjogren syndrome

SLEAddison’s diseaseGrave’s disease

Hashimito’s thyroiditisMyasthenia gravis

Type 1 DM

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

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

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

Ocular features o Acute anterior uveitis 25%o Scleritis o Episcleritiso Keratitiso Mechanical ptosis

Bony obliteration of sacroiliac joint

Bamboo spine

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

keratoderma blenorrhagica in Reiter syndrome

Psoriatic arthritisMale = Female 3rd–4th decades

Signs A. Skin :• Plaque psoriasis• Flexure psoriasis

B. Nail dystrophyC. Arthritis

Ocular featuresAAU – 7%conjunctivitis, marginal corneal infiltrates

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

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

pseudopolyposis, lack of haustration

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

stricture in the descending colon

Birdshot retinochoidopathy

Idiopathic chronic bilateral

Middle aged women

Clinical feature

Symptoms• Insidious impairment of central vision• Photopsia• Floaters• Nyctalopia• Disturbance of color vision

vitritis

Fundus

• Multifocal,hypopigmented,ovoid, cream-colored choroidal lesions in post-equarorial region• Emanate from optic nerve • Radial distribution

CMEERMCNV

Investigations :• HLA- A29 : sensitive 96% ; specific 93%• OCT• Autofluorescence• FA• ICGA• ERG : rod & cone abnormalities

Treatment : Systemic & intraocular steroids Immunosuppresent

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

Acute uveitic phase

Bilateral granulomatous AU

Multifocal posterior uveitis

Diffuse choroidal infiltration

Dalen-fuchs nodules

Vitritis

Papillitis

Exudative RD

Convalescent phase

Localized alopecia

Poliosis

Vitiligo

Sunset glow fundus

Depigmented limbal lesions

Chronic recurrent phase

Smouldering AU with exacerbation

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

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

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

Other systemic features

• Vascular lesions

• Arthritis

• Dermatographia

• Neurological menifestations

• Gastrointestinal inflammation

• Hepatic & renal lesions

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

End stage disease

• Optic atrophy

• Retinal atrophy

• Gliosis

• Sheathing

• Attinuation & ghosting of vessels

Investigation :• HLA – B51

• Pathergy test

• Inflammatory markers

• Thrombophilia screening

• FA

• Superficial lesion biopsy

• Systemic imaging – MRI/MRA,CTA of brain,

Treatment

Topical steroids

Systemic steroids & azathioprine

Ciclosporin

Infliximab or adalimumab

Interferon alfa

Anticoagulants

Conclusion

Testing for HLA can provide supporting evidence

for a particular diagnosis,

but cannot make

definitive diagnosis.

Remember