Chapter 39 Uveitis


This chapter will include endogenous childhood ocular inflammation including uveitis and the vasculitides. The differential diagnosis of childhood uveitis includes infection, hereditary anatomic abnormalities, and degenerations that may be accompanied by inflammation and tumors of childhood (Box 39.1). Ocular inflammation also accompanies systemic vasculitides; following infection (“reactive uveitis”); and accompanying congenital immunodeficiency syndromes and systemic autoinflammatory diseases.

Uveitis is a relatively common feature of several localized autoinflammatory diseases that have both unique and shared genetic associations (Table 39.1). There is often a family history of a wide range of autoimmune and autoinflammatory conditions in children with idiopathic uveitis unaccompanied by systemic disease. However, despite the wide variety of identified genetic associations, uveitis patients only rarely cluster in families, other than those with a high prevalence of HLA-B27, and there must be many environmental triggers and other genetic causes that remain unidentified.

Experimental models of uveitis have concentrated upon antigen-specific autoimmune mechanisms of inflammation. Sympathetic ophthalmia and phacoanaphylaxis may be examples of ocular organ-specific autoimmunity but the majority of childhood uveitis syndromes are secondary to localized or generalized disorders of the control of inflammation. The phenotypes of human uveitis are more varied than the range of available animal models of autoimmunity; there is increasing interest in the variety of mechanisms, other than antigen-specific autoimmunity, that may underlie ocular inflammation. Advances in genetics and study of the differential response to treatment with non-specific and lymphocyte-specific or cytokine-specific immunosuppressants has led to a continuing reappraisal of disease classifications and the therapeutic implications of newly discovered genetic associations.

Epidemiology of pediatric uveitis

Childhood uveitis is uncommon; rising with age. In 0- to 4-year-olds, the incidence is 3/100 000, in 10- to 14-year-olds 6/100 000, and in adults aged 17–25/100 000. It comprises 5% of most series of uveitis patients.2

The most common type of pediatric uveitis at a population level is idiopathic. The most common pattern in young children is chronic anterior uveitis; in those aged 8–16 it is intermediate uveitis. After age 16, the pattern of uveitis types is similar to that in adulthood (Box 39.3). Idiopathic chronic painful bilateral anterior uveitis, idiopathic anterior and intermediate uveitis, and idiopathic panuveitis are also not uncommon in children. Specific uveitis syndromes, such as birdshot retinochoroidopathy, are exceptionally rare in children.3

Juvenile idiopathic arthritis (JIA) is the most common extraocular disease reported in tertiary referral series followed by those with no systemic disease (idiopathic uveitis), enthesitis related arthritis (ERA), sarcoidosis,4 inflammatory bowel disease (IBD), and Behçet’s disease. Even in countries with high rates of Behcet’s disease, Behcet’s uveitis is uncommon in childhood.5 VKH6 and tubulointerstitial nephritis and uveitis syndrome (TINU)7 can begin in childhood. Behçet’s disease and VKH syndrome are 10–100 times more common in some Oriental, Asian, and Mediterranean groups than in Caucasians.

HLA-B27 related diseases, multiple sclerosis (MS), and sarcoidosis are more common in North Europeans; there are also high rates of sarcoidosis in Afro-Caribbeans and high rates of ERA in Middle America. MS-associated uveitis is very rare in this age group although children with intermediate uveitis may well have the same genotype predisposing to the development of MS.

Epidemiology of vasculitis

The commonest type of childhood systemic vasculitis is Henoch-Schonlein purpura which does not have ocular involvement;8 giant cell arteritis does not occur in childhood. The incidence of SLE is 0.8/10 000 and juvenile dermatomyositis 0.4/100 000. Childhood polyarteritis nodosa (PAN) is the fourth most common and ocular involvement is not uncommon. Wegener’s granulomatosis, Behçet’s disease, and microscopic polyangiitis are very rare – each less than 0.1/100 000.

Takayasu’s disease and Kawasaki’s disease are more common in Asians and Orientals. In Japan, the incidence of Kawasaki’s disease in under 5s is 110/100 000: in the UK it is about a hundred times less frequent.

Clinical types of uveitis

Intermediate uveitis

This refers to vitritis with a variable retinal inflammation and a minimal anterior segment inflammation (Table 39.2). The average age of onset is 9–13 years. Young children present late, and there may be extensive retinal complications rarely seen in adults. Children are less likely to develop macular edema but it is more difficult to resolve. Optic disk edema with chronic vitritis is more common than in adults. Peripheral vascular abnormalities are difficult to detect and may only be suspected when they cause hemorrhage. Neovascularization of the optic disk and retina may be caused solely by inflammation and subside with immunosuppression.10

Table 39.2 Structural complications of JIA-uveitis and IU

JIA-uveitis Intermediate uveitis
Anterior segment changes  
AC cells and flare AC signs only in “anterior and intemediate uveitis,” and usually confined to cells only
Band keratopathy  
Extensive posterior synechiae  
Progressive anterior synechiae  
Iris hyperemia and rarely vascularization  
Unexplained hyphema  
Iris vascularized membrane  
Pupillary membrane  
Early irreversible ciliary body damage with chronic hypotony and phthisis Hypotony rare
high risk glaucoma Low risk glaucoma
Early cataract formation Late developing despite persistent inflammation
Persistent diffuse vitreous flare and opacities with minimal vitritis Vitritis necessary for diagnosis
Opacities tend to be dependent and aggregate – snowballs, snowbanks
Diffuse macular and disk edema and subretinal fluid with minimal vitritis Disk edema can be marked in absence of macular edema
Disk neovascularization Disk and peripheral retinal neovascularization
Vitreous hemorrhage Vitreous hemorrhage
Retinal detachment rare without  
Coexisting hypotony Retinal detachment, pars plana cysts, localized peripheral detachments
Postoperative complications  
IOL membrane formation Usually tolerates IOL
Universal posterior capsular opacification  
Membrane formation following capsulotomy  

Changing signs in the inferior fundus are useful to monitor disease progression as the level of vitritis is difficult to monitor in children and visual acuity may be maintained despite progressive extramacular damage. Sarcoidosis produces aggregates of white cells in the inferior vitreous (“snowballs”) rather than pars planitis (“snow bank”) and multifocal choroiditis is characteristic. IU associated with MS rarely produces vitreous opacities. Focal retinal pigment epithelial scars can develop inferiorly at sites of previous retinal inflammation and do not necessarily indicate the development of choroiditis. Retinal vascular leakage and periphlebitis may be marked in acute IU but are not diagnostic of any specific cause.

Localized autoinflammatory diseases

Juvenile idiopathic arthritis

JIA describes chronic joint inflammation starting before 16 years and lasting more than 6 weeks. Early onset rheumatoid arthritis, vasculitides, and ERA are extremely rare causes of arthritis under the age of 7.

JIA types associated with CAU

The ILAR classification of arthritis starting before the age of 16 years uses a personal or family history of psoriasis, a family history of HLA-B27-related disease and rheumatoid factor to aid classification. The classification was designed primarily to aid the epidemiologic study of arthritis. Antinuclear antibody (ANA) and age at onset are not used in the classification but are major independent risk factors for uveitis.

Genetic studies suggest similarities between oligoarticular and polyarticular JIA in the youngest groups.11 Older children with ANA-negative polyarticular JIA may have a distinct pattern of disease and appear to be at a much lower risk of CAU. JIA is found in all races; JIA-uveitis may be more common in Caucasians.

Several genes, including HLA, are associated with different clinical types of JIA.13,14 Oligoarticular onset JIA is associated with HLA genes common to polyarticular JIA (DRB1*08), psoriatic arthropathy (DRB1*1301), and systemic onset JIA (DRB1*11), as well as unique associations such as DPB1*02. Uveitis appears to be associated primarily with the DRB1*13 haplotype, which is most frequent in oligoarticular JIA, and DPB1*02. ERA and early onset rheumatoid arthritis are clinically and genetically distinct from the types of JIA associated with CAU.

Oligoarticular JIA is defined by the involvement of less than five joints at the onset of disease. If more joints are later involved it is classified as extended oligoarticular JIA. If more than five joints are involved at onset it is classified as polyarticular. The cut-off is artificial and age at onset of arthritis and ANA status are as important as the number of joints in defining JIA phenotypes.

All children with chronic painless AU are screened for joint abnormalities and to exclude other systemic diseases. Uveitis is associated with oligoarticular, ANA-positive JIA of early onset: the highest risk groups may have a frequency of uveitis of over 50%. The risk of uveitis diminishes to zero in those whose arthritis starts after age 13, and the cut-off may be much younger in those with polyarticular ANA-negative JIA. ANA status does not change the risk sufficiently to alter screening policy.

In those developing uveitis, arthritis typically starts at 28 months and uveitis 13 months later: 86% have oligoarticular onset JIA, 75% are female, and 80% are ANA-positive.10,12

Jun 4, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Uveitis
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