Behçet’s disease

Summary

Behçet’s disease is an idiopathic, multisystem disease characterised by recurrent aphthous oral ulcers, genital ulceration and uveitis.

Background

Behçet’s disease is an idiopathic, multisystem disease characterised by recurrent aphthous oral ulcers, genital ulceration and uveitis. Vasculitis of veins and arteries of all sizes is a key pathogenic component.

The precise aetiology of Behçet’s disease is unclear, although it is likely to have an autoimmune component which may be triggered by exposure to a pathogen with subsequent cross-reaction.

Epidemiology

Patients from Turkey, the Middle and Far East (the ancient ‘Silk Road’ route) are at increased risk of developing Behçet’s disease. It is more common and more severe in men overall; there is a possible genetic predisposition to the disease, and it is strongly associated with HLA-B51.

The peak age of onset is in the third decade.

Clinical features

Behçet’s disease is characterised by the classic triad of:

1. Genital ulcers

2. Oral ulcers (these are painful in Behçet’s disease compared to the painless ulcers in reactive arthritis)

3. Anterior uveitis

There are many other possible clinical features beyond this triad, which can be classified as systemic and ocular.

Systemic features

Additional systemic features include:

• Vascular lesions: aneurysms (including pulmonary and coronary) and venous thrombosis/thrombophlebitis

• Arthritis (in 30% of cases): typically a large joint oligoarthritis

• Neurological involvement (5%): cranial nerve palsies, meningoencephalitis of the brainstem, dural sinus thrombosis, cerebral aneurysms

• Gastrointestinal inflammation, especially ileocaecal

• Dermatological involvement: erythema nodosum, dermatographia (formation of erythematous lines on the skin after scratching - similar to the skin pathergy reaction described below)

Photograph showing erythema nodosum. Image courtesy of Coyle et al.

Ocular features

Ocular inflammation occurs in 〜70% of cases, tends to be more severe in men, and is the presenting complaint in 〜10% of cases. Ocular involvement is almost always bilateral eventually. The classic pattern of eye involvement in Behçet’s disease is a relapsing/remitting acute onset panuveitis with retinal vasculitis (which often spontaneously resolves without treatment). Retinal vascular disease (vasculitis and occlusion) is the main cause of visual impairment.

• Acute anterior uveitis: typically bilateral, non-granulomatous, and a transient mobile hypopyon (white blood cells in the anterior chamber) in a relatively white eye is characteristic

• Vitritis

• Retinitis: during acute disease, transient superficial white infiltrates can be seen. Exudative detachments cal also occur. Inflammatory deposits (that look like keratin precipitates) may be seen on the inferior peripheral retina

• Retinal vasculitis: both arteritis and phlebitis (i.e. inflammation of arteries and veins) can occur in Behçet’s disease, in contrast to sarcoidosis, where only phlebitis occurs. Retinal vasculitis can be seen as sheathing, perivascular haemorrhages and occlusion. Leakage from the retinal vessels can cause diffuse retinal oedema and cystoid macular oedema.

• Optic disc hyperaemia and oedema. Note raised intracranial pressure can also cause optic disc swelling and optic atrophy in Behçet’s disease

• Disc and retinal neovascularisation may develop as a consequence of inflammation and ischaemia

• End-stage disease involves optic atrophy, retinal atrophy and gloss and cheating, attenuation and ghosting of affected vessels. Other complications include cataract and glaucoma

Rarer ocular manifestations include conjunctivitis, conjunctival ulcers, episcleritis and scleritis.

Photograph of the eye from a 27-year-old female patient with Behçet’s disease who presented with a hypopyon panuveitis. Image courtesy of Tugal-Tutkun.

(a) Fundus photograph of the right eye of a 23-year-old man with documented Behçet’s disease showing retinal infiltrates. (b) Fluorescein angiogram showing leakage from retinal vessels and the multilobar pattern of cystoid macular oedema. Image courtesy of El-Asrar et al.

Diagnosis

There is no definitive test for Behçet’s disease; it is diagnosed clinically.

However, a positive skin pathergy test (SPT) is suggestive. In a positive SPT, the site of the needle prick develops into an erythematous induration and a small pustule containing sterile pus.

Other investigations that may be useful:

• HLA-B51

• Inflammatory markers (ESR, CRP, complement levels, white cell count) may be raised

• Thrombophilia screening may be appropriate to exclude other causes of thrombosis

• Systemic imaging e.g. brain MRI/magentic resonance angiography (MRA), CT/computed tomography angiography (CTA) and conventional angiography, to identify ischaemia

Useful ophthalmic investigations:

• Fluorescein angiography: to show areas of ischaemia and helps with detecting posterior segment inflammation and monitoring of disease activity

• Laser flare photometry of the anterior chamber: for determining level of inflammatory activity

Management

Behçet’s disease is managed with immunosuppressive agents. The mainstay of treatment involves:

• Topical steroids: for mucocutaneous involvement

• Systemic steroids and azathioprine: for posterior uveitis ****

• Ciclosporin or infliximab (plus systemic steroids + azathioprine): for severe eye disease

• Infliximab or adalimumab should be considered early for vision-threatening Behçet’s disease

• Alternatively to the above, IFN-⍺ may be used for severe disease

N.B. IFN-⍺ should not be administered together with azathioprine due to the risk of myelosuppression.

Prognosis

Mortality at 5-10 years is 〜5%. This mortality rate is largely due to cardiovascular or CNS complications.

References

1. Salmon, John F., and Jack J. Kanski. Kanski’s Clinical Ophthalmology: A Systematic Approach. Ninth Edition, Elsevier, 2020.

2. Coyle, Christopher, et al. ‘Erythema Nodosum as a Result of Estrogen Patch Therapy for Prostate Cancer: A Case Report’. Journal of Medical Case Reports, vol. 9, Dec. 2015, p. 285. PubMed, https://doi.org/10.1186/s13256-015-0776-4.

3. Tugal-Tutkun, Ilknur. ‘Behçet’s Uveitis’. Middle East African Journal of Ophthalmology, vol. 16, no. 4, Oct. 2009, p. 219. www.meajo.org, https://doi.org/10.4103/0974-9233.58425.

4. Abu El-Asrar, Ahmed M., et al. ‘Differential Diagnosis of Retinal Vasculitis’. Middle East African Journal of Ophthalmology, vol. 16, no. 4, 2009, pp. 202–18. PubMed Central, https://doi.org/10.4103/0974-9233.58423.