From Retinal Vasculitis to Stroke, from Systemic Findings to Diagnosis, the Necessity of Multidisciplinary Management in Behçet’s Disease: A Case Report Open Access

Introduction: Behçet’s disease (BD) is a rare, chronic multisystem disorder characterized by occlusive vasculitis, which can present with a variety of systemic and ocular manifestations. The diagnosis of BD is often challenging, particularly in populations with low prevalence. Retinal vasculitis and stroke can be key indicators, and the early involvement of a multidisciplinary team is essential for accurate diagnosis and management to prevent long-term complications. Case Presentation: A 40-year-old African American female presented with vision changes in her left eye and a history of multiple strokes. Examination revealed retinal ischemia and vasculitis, raising suspicion of an underlying systemic condition. Extensive workup for infectious and inflammatory causes was negative. As her condition progressed, the patient developed genital ulcers, prompting further investigation. A biopsy of the genital ulcer confirmed BD, and a multidisciplinary approach involving ophthalmology, rheumatology, and neurology was initiated. The patient was treated with high-dose corticosteroids, immunosuppressive therapy, and intravitreal corticosteroids, leading to stabilization of her ocular and systemic symptoms. Despite her history of stroke, the collaboration between specialties facilitated better management of her condition and prevention of further complications. Conclusion: It is crucial to include BD as a potential diagnosis in cases of ophthalmic or systemic vasculitis, even in regions and populations with low prevalence. Early referral to a rheumatologist for cases of vasculitis and timely collaboration are essential for accurate diagnosis, prevention of systemic complications, and appropriate management.

Behçet’s disease (BD), a chronic multisystem disorder, is histopathologically characterized by occlusive vasculitis. The disease predominantly affects populations in the Mediterranean, Far Eastern, and Middle Eastern regions, with a prevalence ranging from 15 to 420 cases per 100,000 individuals [1, 2]. Predominantly presents in the third or fourth decade of life, affecting males and females at similar rates. However, research suggests that male patients are more likely to experience an earlier onset and a more severe disease trajectory [3]. Key characteristics encompass oral ulcers (present in 98% of cases), genital ulcers (80%–87%), erythema nodosum (50%), maculopapular rash (45%–90%), positive pathergy test (ranging from 8.6% to 70%), and ocular inflammation [4]. Patients presenting with retinal vasculitis as the primary manifestation of BD rarely present with systemic vasculitis [5]. Here we present a case of isolated primary retinal vasculitis secondary to BD that progressed to systemic vasculitis and, ultimately, stroke. To our knowledge, this is one of few case reports that exhibit definitive progression from a primary retinal vasculitis manifestation of BD to stroke and highlights the importance of multidisciplinary management. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000545635).

A 40-year-old African American female presented to our clinic with a several-day history of vision changes in her left eye (OS). The patient’s medical history included a thalamic stroke in 2018 attributed to papillary fibroelastoma of her mitral valve cordae (now resected), closure of patent foramen ovale in 2019, bilateral pontine strokes in 2021, and a past ocular history of vitreous hemorrhage treated with pars plana vitrectomy and endo laser in her right eye (OD). On examination, the best-corrected visual acuity was 20/20 OD and 20/50 OS with intraocular pressures of 14 mm Hg OD and 15 mm Hg OS. Slit lamp examination was normal with no cells or flare noted in the anterior chamber or vitreous. Her fundus examination OD was notable for laser scars temporally and inferotemporally in midperiphery, while OS showed intra-retinal and sub-internal limiting membrane (ILM) hemorrhage with vascular sheathing in the inferotemporal arcade (Fig. 1a). Fluorescence angiography demonstrated peripheral retinal ischemia OS without neovascularization, staining of the vessel walls, and sub-ILM hemorrhage in the fovea (Fig. 1b). Review of systems was non-revealing. Serum studies including complete blood count, basic metabolic panel, liver function tests, erythrocyte sedimentation rate, C-reactive protein, rapid plasma reagin, fluorescent treponemal antibody absorption, QuantiFERON-TB Gold, human leukocyte antigen B27 (HLA-B27), rheumatoid factor, cyclic citrullinated peptide antibody, antinuclear antibody, antineutrophil cytoplasmic antibodies, immunoglobulin G4 antibody (IgG4 Ab), serum protein electrophoresis, angiotensin-converting enzyme, lysozyme, soluble interleukin-2 receptor (sIL-2R), human leukocyte antigen B51 (HLA-B51), as well as anterior chamber tap for herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus, and toxoplasma gondii for suspected retinitis were negative or unremarkable.

Given the patient’s history of vitreous hemorrhage in one eye and vasculitis in the other, the differential diagnoses include bilateral sequential vasculitis and ischemia from conditions such as tuberculosis, Eales’s disease, neuropsychiatric lupus erythematosus and vasculitic lupus, multiple sclerosis, VZV, HSV, toxoplasmosis, Rift Valley fever, West Nile fever, Behçet’s, Susac syndrome, syphilis, and relapsing polychondritis. A 23-gauge pars plana vitrectomy with ILM peel, endolaser inferotemporally, and Ozurdex injection was administered, resulting in an improvement of the patient’s vision to 20/30. Although her vision remained stable for several months, the patient was later admitted due to another thalamic stroke, prompting a consultation with the rheumatology service. Transesophageal echocardiography revealed a small left-to-right shunt, and four-vessel cerebral angiography demonstrated worsening stenosis in multiple cerebral vessels, indicative of vasculitis. During this admission, the presence of genital ulcers with a positive biopsy for BD and two additional cerebrovascular accidents led the rheumatology service to diagnose BD. Oral prednisone 80 mg was initiated, leading to resolution of the patient’s vascular sheathing. Given her stable vision, the oral prednisone was tapered to 60 mg, an intravitreal injection of triamcinolone 2 mg was administered, and azathioprine 50 mg daily was initiated per rheumatology recommendations. Quiescent status was achieved after keeping the patient on prednisone 60 mg daily and monthly doses of cyclophosphamide for 6 months. Currently, the patient is on azathioprine 50 mg once daily with a best-corrected visual acuity of 20/25-2 OS.

Although BD often presents as panuveitis with retinal vasculitis, leading to significant visual impairment, its most common ocular manifestation is acute anterior uveitis with shifting hypopyon [6]. The patient’s presentation of bilateral retinal vasculitis with inflammation isolated to the posterior segment is unusual and made diagnosis challenging, especially without any other presenting systemic signs or symptoms except sequential strokes. A study of 40 patients with BD isolated to the retina found that, although periphlebitis (92.5%) is more common, periphlebitis and arteritis as seen in this patient may still occur in about 72.5% of cases [7]. The International Study Group for Behçet’s Disease requires at least three hallmark features, particularly recurrent oral ulcers, for a definitive diagnosis [2]. In addition, HLA-B51, which was negative in this patient, is detected in only 60% of cases, while ocular involvement may be present in up to 70% of patients [8, 9]. Given these strict criteria and the relatively high false negative rate of serum markers, diagnosis often requires multidisciplinary collaboration and an algorithmic approach. The patient’s previous history of strokes may have been an important historical clue in conjunction with retinal vasculitis to suspect BD. However, in this patient a definitive diagnosis was made due to the presence of genital ulcers, an important clinical finding, which is highly specific for BD. The diagnosis of BD in this patient was established based on clinical presentation and histopathologic confirmation. Key diagnostic features included recurrent cerebrovascular accidents, ocular vasculitis, and genital ulcers with a positive biopsy. Additional supportive evidence included worsening cerebral vasculitis on angiography and the resolution of vascular sheathing following corticosteroid treatment. The patient met the International Study Group (ISG) criteria for BD, which require recurrent oral ulcers plus at least two additional features. In this case, the presence of genital ulcers (confirmed by biopsy) and ocular vasculitis fulfilled the diagnostic threshold, with a history of recurrent strokes further supporting the diagnosis. Although a clinical scoring system was not explicitly mentioned, the Behçet’s Disease Current Activity Form is typically used to assess disease severity across multiple domains, including mucocutaneous, ocular, vascular, and neurological involvement. Given the patient’s progressive vasculitis and cerebrovascular complications, disease activity was likely high, necessitating intensive immunosuppressive therapy with corticosteroids, cyclophosphamide, and azathioprine. Additionally, although BD is more frequently observed within our patient’s age group, its prevalence is lower among females and African American individuals.

The recent multicenter retrospective study analyzed retinal vascular occlusions (RVOs) in BD, including 303 eyes from 175 patients. RVOs were present in 30.9% of cases, with branch retinal vein occlusion (51.3%) being the most common. Male sex and Jewish ethnicity were identified as significant risk factors (p < 0.05). Occlusive BD cases had worse visual outcomes, more ocular complications, and required more aggressive immunosuppressive treatment. These findings highlight the prognostic significance of RVOs in BD and the need for early recognition and intensive management [3].

Treatment of ocular BD focuses on inducing remission and preventing progressive retinal vasculitis. Since ocular complications in BD can result in significant visual impairment among young individuals, timely identification of the condition can prevent bilateral blindness as well as mitigate systemic complications [10, 11]. Acute, vision-threatening uveitis may respond to high-dose glucocorticoids, immunosuppressive agents, and biologics, necessitating close collaboration between ophthalmologists, internists, and rheumatologists [11]. Further, unilateral exacerbations might benefit from adjunctive intravitreal corticosteroid therapy alongside systemic treatment [2]. Additionally, a study by Palestine et al. [12] shows that ophthalmologists and rheumatologists differ significantly in treatment decisions regarding BD, which highlights the importance of collaboration for maintaining a consistent treatment plan. Follow-up for BD with retinal involvement necessitates regular ophthalmologic monitoring, including periodic assessments of visual acuity, fundoscopic examinations, and adjunctive imaging modalities such as optical coherence tomography and fluorescence angiography. These evaluations are essential for detecting signs of active inflammation, assessing macular involvement, and identifying any progressive visual changes.

It is crucial to include BD as a potential diagnosis in cases of ophthalmic or systemic vasculitis, even in regions and populations with low prevalence. Early referral to a rheumatologist for cases of vasculitis and timely collaboration are essential for accurate diagnosis, prevention of systemic complications, and appropriate management.

This case report was conducted in accordance with the Declaration of Helsinki. The collection and evaluation of all protected patient health information was performed in a Health Insurance Portability and Accountability Act (HIPAA)-compliant manner. Study has been granted an exemption from requiring ethics approval by the IRB of the University of Arkansas for Medical Sciences. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The authors received no financial support for the research, authorship, and/or publication of this article.

Dr. Sayena Jabbehdari reviewed medical record, wrote original draft of case report, and revised intellectual content. Dr. Anthony Oganov contributed to the original draft and manuscript revision. Dr. Sami H. Uwaydat critically revised the manuscript and intellectual content.

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author. All authors attest that they meet the current ICMJE criteria for authorship.