13th February 2025

Uveitis and rheumatic disorders

Ankylosing spondylitis

Ankylosing spondylitis is an HLA-B27-associated spondyloarthropathy characterised by joint inflammation, calcification and ultimately ossification, with a predilection for the axial skeleton. It commonly affects the sacroiliac joint and also may lead to spinal fusion in later stages. Onset is usually between 20-30 years and is significantly more common in males.

Patients typically present with chronic lower back pain or stiffness (for over 3 months) which is worse in the mornings and does not improve with rest but improves with exercise and a trial of NSAIDs. A family history of ankylosing spondylitis may also be present. Enthesitis and arthritis are common and usually occur asymmetrically and in the lower limbs. Extra-articular manifestations are varied in patients with ankylosing spondylitis; importantly, the lifetime prevalence of anterior uveitis is 30-40%, which means patients may present with symptoms of a unilateral red, painful eye. It is also associated with psoriasis and inflammatory bowel disease.

Cases of suspected ankylosing spondylitis should be referred to rheumatology for further assessment. ESR, CRP and HLA-B27 testing may be appropriate in addition to imaging of the sacroiliac joints and spine. NSAIDs, exercise and physiotherapy are the mainstay of treatment, but biological treatments may be considered in refractory cases. All patients with uveitis should be referred urgently to an ophthalmologist.

Reactive arthritis

This is the triad of urethritis, eye sequelae such as conjunctivitis and uveitis, and arthritis. The prevalence of  HLA-B27 positivity in reactive arthritis varies but is estimated to be between 30-50%. Reactive arthritis is more common in males. It may present in the days or weeks following either a bacterial genitourinary or gastrointestinal infection.

Joint pain and swelling is most common in the knee or ankle and is often worse in the mornings. Enthesitis (e.g. Achilles tendonitis and plantar fasciitis) or dactylitis may also be a feature. Skin features include keratoderma blennorrhagica on the palms or soles and painless mouth ulceration. Ocular features include self-limiting conjunctivitis, acute anterior uveitis and occasionally episcleritis. Management is typically with NSAIDs, corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs).

Psoriatic arthritis

Characterised by arthritis which usually develops around 10 years after the onset of preceding psoriasis. Patients can present with asymmetrical oligoarticular or monoarticular joint involvement and may also have dactylitis and sacroiliitis. Nail changes such as pitting or onycholysis may be present. Acute anterior uveitis develops in around 7% of patients with psoriatic arthritis, with conjunctivitis also being associated. Psoriatic arthritis is also associated with HLA-B27. Management of psoriatic arthritis includes NSAIDs and corticosteroids, with DMARDs and biological treatments considered for more severe cases.

Sarcoidosis

Sarcoidosis is one of the most common systemic associations of uveitis. It is a multi-systemic inflammatory disorder of unknown cause, characterised by non-caseating granuloma formation. It is more common in females and has a bimodal age of onset between 20-40 years, and again in older age. Respiratory symptoms such as a dry cough and shortness of breath are common and attributed to variable disease progression from hilar adenopathy to significant pulmonary fibrosis. Malaise and arthralgia may also be present. Skin manifestations are reasonably common and may be specific and granulomatous or non-specific, such as erythema nodosum.

Ocular involvement (usually bilateral) may be seen in 20-75% of patients, most commonly granulomatous anterior uveitis. There are several key findings in ocular sarcoid; ‘mutton fat’ keratic precipitates are large grey-white inflammatory deposits of cells on the corneal endothelium and are a key sign of ocular sarcoid. Trabecular meshwork nodules, vitreous opacities (which may have a ‘snowball’ or ‘string of pearls’ appearance) and optic disc granulomas may also be seen.

Findings in sarcoidosis include elevated serum ACE (angiotensin converting enzyme) levels, deranged liver enzymes (most commonly ALP is raised) and bilateral hilar lymphadenopathy on chest X-ray. Tuberculosis should be ruled out. Treatment of sarcoidosis is by respiratory specialists. Spontaneous remission can occur (with likelihood inversely related to the severity of the disease), and therefore, treatment is not always indicated. If treated, this is usually with corticosteroids.

Behçet’s disease

Behçet’s disease is a multi-system vasculitis characterised by aphthous ulcers of the mouth and genitals, ocular manifestations, and skin lesions such as erythema nodosum. There are a range of CNS, gastrointestinal and other vasculitic manifestations, including pulmonary artery aneurysm. Ocular manifestations are usually bilateral and affect the entire uveal tract (panuveitis), which can be recurrent and may involve a range of sight-threatening complications such as retinal vasculitis and angle-closure glaucoma.

Typically, Behçet’s affects younger patients aged 20-40 years old, with a relatively equal gender distribution. It is more commonly found in people of Turkish, Mediterranean, Israeli or East Asian descent. HLA-B51 is a frequent association.

Investigations may reveal HLA-B51 positivity, a positive pathergy skin test and raised inflammatory markers. Full autoimmune screening should be carried out, and further investigations as appropriate to the clinical findings. Treatment is often with corticosteroids and immunosuppressive therapies.