Peter Rae
Introduction
Anterior uveitis is a condition in which there is inflammation of the anterior structures of the uvea – the iris and ciliary body. The most common presentation is acute anterior uveitis (AAU), with presenting symptoms of rapid-onset pain, photophobia and red eye, which is most commonly unilateral (1). On slit-lamp examination, inflammatory cells must be present in the anterior chamber to diagnose AAU. There may also be flare, hypopyon, keratic precipitates and posterior synechiae.
AAU is an inflammatory condition, with topical steroids being the cornerstone of anti-inflammatory treatment. Rarely, systemic immunosuppressive drugs are used if topical therapy has failed or is not tolerated (2). Dilating drops such as cyclopentolate are also prescribed to relieve pain and prevent the formation of posterior synechiae.
AAU is most commonly idiopathic, but can be associated with infections such as herpes simplex, varicella zoster, and syphilis. It can also be associated with underlying autoimmune conditions (1).
This review will outline the systemic diseases associated with AAU and discuss approaches regarding further investigations and referral to other specialties.
Associations with systemic disease
The most common diseases associated with AAU are spondyloarthropathies (3). These include ankylosing spondylitis (AS), Reiter syndrome, psoriatic arthritis, and juvenile idiopathic arthritis (JIA). AS and Reiter syndrome are more common in males positive for the HLA-B27 gene, with 90% and 85% of patients respectively positive for the gene (4). AS consists of axial skeletal ankylosis and ossification, with typical radiological changes seen on spinal and hip X-rays. Reiter syndrome consists of a triad of conjunctivitis, urethritis, and arthritis. Psoriatic arthritis is defined as inflammatory arthritis developing in those with psoriasis, and is estimated to affect 20% of those patients with psoriasis. The most common pattern of arthritis is asymmetric inflammation affecting fewer than five joints. Finally, JIA is defined as idiopathic arthritis affecting children under 16 lasting more than six weeks. Uveitis is more common in JIA patients positive for antinuclear antibodies (ANA) (5). All patients with the above conditions should be referred urgently to a rheumatologist for consideration of systemic immunosuppression with disease-modifying antirheumatic drugs (DMARDs) (6). These may be conventional DMARDs, which provide broad immunosuppression, or biologic or targeted DMARDs, which target specific inflammatory pathways and cellular processes.
AAU is also associated with inflammatory bowel disease (IBD) – Crohn’s disease and ulcerative colitis. These conditions usually present in adolescence or young adulthood with gastrointestinal symptoms of diarrhoea and abdominal pain. Patients with IBD should be referred to IBD teams consisting of gastroenterologists, surgeons and IBD nurses, for consideration of immunosuppressive agents to induce and maintain remission (7). Some patients require surgery to remove areas of affected bowel.
Sarcoidosis is a multisystem autoimmune condition known as ‘the great mimicker’ as it can affect a variety of organs and systems. It typically presents in young adults, with a male predominance. It causes granulomatous inflammation, primarily affecting lymphoid organs and the lungs. Patients classically present with a chronic dry cough. However, it can also present acutely with arthritis, uveitis, and painful skin lesions, amongst many others. As well as AAU, other forms of uveitis and development of granulomas in the globe and orbit are commonly seen. Patients with suspected sarcoidosis should be referred to a medical specialist as per the affected organ or system (8). Many patients are managed by a multi-disciplinary team. The condition is often mild and self-limiting, but severe forms can be life-threatening.
Behçet’s disease is strongly associated with the HLA-B51 gene. It is more common in Japanese and West Asian populations, and typically presents with oral and genital ulcers and vasculitis. It often causes bilateral uveitis, and patients characteristically have hypopyon in a relatively white eye. The condition is rare and relatively poorly understood (9). In the UK, patients with suspected Behçet’s should be referred to one of three “Centres of Excellence”, where they are seen in multi-disciplinary clinics. These consist of specialists in ophthalmology and rheumatology, as well as immunology, oral medicine, dermatology, and others.
Investigations for systemic disease
It is important for ophthalmologists to be able to take a focused history to screen for associated conditions. In the UK, the Curriculum for Ophthalmic Specialist Training (OST) states that all ophthalmologists should recognise when a patient’s ocular problem is a manifestation of a systemic disorder, and be competent in diagnosis, investigation and management of patients with uveitis in systemic disease (10).
Patients presenting with a first episode of unilateral anterior uveitis without granulomatous inflammation often need no further investigation (11). These patients can be treated with topical steroids and dilating drops in eye casualty services. When reviewing a patient with AAU, clinicians should ask patients about features which suggest systemic underlying disease. As outlined above, these include any history of or intercurrent arthralgia, gastrointestinal symptoms, or ulcers. Family history of autoimmune conditions can help stratify the risk of systemic inflammatory disease.
At uveitis clinics, further investigations to establish an underlying cause of AAU include blood tests such as full blood count, CRP, HLA-B27, serum ACE, or ANA depending on the suspected underlying cause. All patients with suspected sarcoidosis should have a chest x-ray. Aqueous sampling is occasionally performed when infection and malignancy are suspected (12). If these investigations indicate that systemic disease is likely, patients should be referred to the relevant medical team.
Conclusion
AAU is a condition which can be associated with life-threatening systemic disease. Treatment with topical corticosteroids forms the mainstay of treatment. It is important for ophthalmologists to be aware of associated underlying diseases in order to take an effective focused history and arrange suitable further investigations. Onward referral where necessary ensures optimal patient care and can prevent life-threatening complications.
References
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