ReviewCurrent therapeutic approaches to autoimmune chronic uveitis in children
Introduction
Uveitis is an inflammatory disorder involving inflammation of the uveal tract. It is classified as anterior, intermediate, posterior or panuveitis, depending on the part of eye affected by the inflammatory process.
In children, non-infectious, chronic uveitis is a relatively uncommon but serious disease, with the potential for significant long-term complications and possible blindness.
Although frequently associated with an underlying systemic disease, e.g. juvenile idiopathic arthritis (JIA) or many other rarer diseases [1], a significant number of cases in children show no associated signs or symptoms, and are labelled as idiopathic. Strong evidence supports the genetic background to play a major role in the susceptibility of this group of diseases, together with environmental factors, leading to the release of proinflammatory cytokines such as TNF-α [2].
An autoimmune pathogenesis can be advocated for the ocular damage during uveitis: an inflammatory process during immune response activation takes place against ocular self antigens, driven by cellular and/or humoral mechanisms [3]. Taking into account this evidence, an anti-inflammatory therapy based on an immuno-modulatory approach seems a reasonable strategy for non-infectious chronic uveitis, in children as well as in adults. However, there is much less experience and cumulative data in treating children with uveitis or other inflammatory ocular diseases [4]. A lack of controlled studies regarding uveitis in children means that treatment with immunosuppressive drugs is supported only at evidence level III (expert opinion, clinical experience or descriptive study), while studies on certain TNF-α-blocking agents achieve evidence levels II–III.
However, it now seems clear that even in children, the use of immunosuppressive therapy is a reasonable approach to control/reduce inflammation, achieve a corticosteroid-sparing effect and decrease the risk of sight-threatening ocular complications, i.e. hypotony, glaucoma and blindness.
The aim of this review is to report currently available medical strategies for treatment of childhood sight-threatening chronic uveitis; in addition, a step-by-step approach to the use of immunosuppressants in this context is suggested.
Section snippets
Corticosteroids
In children as in adults, corticosteroids are the first-line treatment for non-infectious intraocular inflammation. Main indications for the use of topical corticosteroids are acute or chronic anterior uveitis and/or concomitant anterior chamber inflammation in children with intermediate or posterior uveitis [4]. Corticosteroids are the most rapid and most effective ocular immunosuppressant available.
Mechanism of action: The anti-inflammatory action involves phospholipase A2 inhibitor protein,
Methotrexate (MTX)
MTX it is a folate analog that inhibits the enzyme dihydrofolate reductase, thus inhibiting production of tetrahydrofolate, leading to inhibition of DNA replication and RNA transcription. It acts on T and B cells and it mainly works against rapidly dividing immune cells. At low doses, it acts more as an anti-inflammatory agent than as an antimetabolite. It is recommended as a low-dose regimen in the long-term treatment of inflammatory ocular disease. MTX is given to children at a dosage of 10
Biological modifier drugs (biologics)
Biologic drugs are a group of drugs acting directly against specific cytokines or their receptors, blocking substacte(s) directly responsible of the tissue damage.
Tumor necrosis factor-alpha (TNF-α), a protein secreted by T cells, monocytes and macrophages, is a pro-inflammatory cytokine involved in the pathogenesis of several autoimmune diseases. The protein binds at specific cell membrane receptors and activates a signalling cascade that leads to the generation of pro-inflammatory cytokines
General therapeutic approach to childhood chronic uveitis
To date, as far as we know, there are no generally approved treatment guidelines for childhood chronic uveitis derived from prospective controlled clinical trials.
The following proposed approach is not meant to represent a guideline but simply to report the general step-by-step drug therapy for childhood chronic uveitis found in the current available literature [4], [62], [93], [94].
The first common step in treating non-infectious uveitis in children is topical application of corticosteroids.
Take-home messages
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Childhood, non-infectious, chronic uveitis is a serious disease, with the potential for significant long-term complications and possible blindness. For this reason an immuno-modulatory approach seems to be a reasonable strategy for non-infectious uveitis.
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A lack of controlled studies regarding uveitis in children means that treatment with immunosuppressive drugs is supported only at evidence level III (expert opinion, clinical experience or descriptive study); approved treatment guidelines are
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