Aarij Elahi

Introduction

Behçet’s disease (BD) is a chronic, relapsing, systemic vasculitis that affects both arteries and veins. It can involve a range of organ systems, with hallmark features including oral and genital ulcers and ocular inflammation. Due to the lack of a specific biomarker and the heterogeneous presentation, BD is often diagnosed late in its course. Early recognition and treatment are critical to preventing serious complications, particularly vision loss. This article aims to provide an in-depth understanding of BD, with an emphasis on its ophthalmological implications (1).

Epidemiology

BD demonstrates a geographical predilection along the historical Silk Road, with the highest prevalence in Turkey, followed by Japan and Iran. In Turkey, the prevalence is approximately 420 cases per 100,000 individuals, compared to 0.64 cases per 100,000 in the United Kingdom. The disease most commonly affects individuals aged 20–40 years and is generally more severe in young males.

Genetic predisposition plays a significant role in BD. The HLA-B51 genetic marker is present in approximately 60% of cases, and other genes, such as HLA-ERAP1, are increasingly recognized as contributors to susceptibility. Environmental factors, including infections, may act as triggers in genetically predisposed individuals (2).

Clinical Manifestations

BD’s clinical features are highly variable due to its involvement of multiple organ systems. Key manifestations include:

Mucocutaneous Involvement

• Oral Ulcers: Painful, recurrent aphthous ulcers are the most consistent feature, present in nearly all cases.
• Genital Ulcers: These are less common than oral ulcers but are often deeper and more scarring.
• Cutaneous Lesions: Erythema nodosum-like lesions, pseudofolliculitis, and papulopustular eruptions are frequently observed (3).

Ocular Involvement

Ocular inflammation occurs in approximately 70% of BD patients and is a major cause of morbidity:

• Anterior Uveitis: Typically associated with transient mobile hypopyon in 25% of cases. Symptoms include redness, photophobia, pain, and blurred vision.
• Posterior Segment Disease: The most vision-threatening manifestation, involving obliterative necrotizing retinal vasculitis, vitritis, and complications such as cystoid macular oedema and retinal vein occlusion. These features often lead to severe vision loss if left untreated (2).

Diagnosis

BD is diagnosed clinically, as no single pathognomonic test exists. The International Study Group(ISG) Criteria are widely used:

• Mandatory Criterion: Recurrent oral aphthous ulcers (≥3 episodes/year).
• Additional Criteria (two or more required):
  • Recurrent genital ulcers
  • Ocular involvement (anterior/posterior uveitis, retinal vasculitis, or vitritis)
  • Cutaneous lesions
  • Positive pathergy test (papule ≥2 mm after skin needle prick)

The pathergy test, although not specific, supports the diagnosis and is more commonly positive in endemic regions (4).

Differential Diagnosis

BD must be distinguished from other conditions with overlapping features:

• HLA-B27 Associated Uveitis: Seen in ankylosing spondylitis, psoriatic arthritis, and reactive arthritis.
• Sarcoidosis: Multisystem granulomatous disease with ocular and cutaneous manifestations similar to BD.
• Systemic Vasculitides: Disorders such as systemic lupus erythematosus, polyarteritis nodosa, and granulomatosis with polyangiitis can mimic BD’s retinal vasculitis (5).

Management

Management of BD focuses on suppressing inflammation, preventing relapses, and minimizing complications. Treatment is tailored based on disease severity and organ involvement.

Corticosteroids

Corticosteroids remain the cornerstone of treatment for acute inflammation. Prednisolone (1.5 mg/kg/day, tapered gradually) is effective for ocular and systemic inflammation. Topical corticosteroids are used for mucocutaneous lesions.

Immunomodulatory Therapy (IMT)

IMT is essential for managing severe or refractory disease, particularly posterior uveitis and retinal vasculitis (6). Commonly used agents include:

• Azathioprine: First-line for long-term control.
• Infliximab and Adalimumab: TNF-alpha inhibitors with proven efficacy in ocular disease.
• Ciclosporin and Tacrolimus: Effective in refractory cases.
• Mycophenolate Mofetil: Useful for steroid-sparing purposes.

Prognosis

BD is characterized by a relapsing and remitting course. Exacerbations are often more severe in young males and patients of Middle Eastern descent. Vision loss remains the most significant complication, affecting up to 25% of patients with ocular involvement.

Advances in immunomodulatory therapy have improved outcomes, reducing the risk of severe vision loss and systemic complications. Early recognition and prompt treatment are critical for optimizing the prognosis (2).

Conclusion

Behçet’s disease is a complex, multisystem disorder with significant diagnostic and management challenges. Early diagnosis and a multidisciplinary approach are essential to mitigating the morbidity associated with this condition. Advances in immunosuppressive therapies have markedly improved the outlook for patients, particularly those with severe ocular involvement. Ongoing research into the genetic and immunopathological mechanisms of BD holds promise for further improving outcomes

References

1. Shimizu T, Ehrlich GE, Inaba G, Hayashi K. Behçet disease (Behçet syndrome). InSeminars in arthritis and rheumatism 1979 May 1 (Vol. 8, No. 4, pp. 223-260). WB Saunders.
2. Nair JR, Moots RJ. Behcet’s disease. Clinical medicine. 2017 Feb 1;17(1):71-7.
3. Khairallah M, Accorinti M, Muccioli C, Kahloun R, Kempen JH. Epidemiology of Behçet disease. Ocular immunology and inflammation. 2012 Oct 1;20(5):324-35.
4. Bulur I, Onder M. Behçet disease: new aspects. Clinics in dermatology. 2017 Sep 1;35(5):421-34.
5. Ambrose NL, Haskard DO. Differential diagnosis and management of Behçet syndrome. Nature Reviews Rheumatology. 2013 Feb;9(2):79-89.
6. Evereklioglu C. Current concepts in the etiology and treatment of Behçet disease. Survey of ophthalmology. 2005 Jul 1;50(4):297-350.