Bilateral optic neuritis as an atypical presentation of juvenile Behcet syndrome: A case report

Abstract

Behcet syndrome is a systemic vasculitis characterized by relapsing uveitis, oral aphthous, and genital ulcers. We present a rare case of a 14-year-old male with juvenile Behcet syndrome (JBS) presenting as bilateral optic neuritis with oral aphthous. Initial treatment with methylprednisolone did not improve the patient's condition. Serum plasmapheresis was performed, resulting in improved visual acuity and papillitis. The patient was discharged with azathioprine, which led to symptom regression. This case highlights the atypical neurologic presentation of JBS and the potential efficacy of plasma exchange in refractory cases.

Highlights

• •Neuro-Behcet can appear as optic neuritis.
• •Behcet syndrome should be considered in pediatric patients with optic neuritis.
• •Approach to the juvenile Behcet syndrome, including plasma exchange

1. Introduction

Behçet syndrome is a systemic vasculitis characterized by relapsing uveitis, oral aphthae, and genital ulcers [1]. While the typical onset of the disease is in the second to fourth decade of life, a subset of patients experience symptoms before the age of 16, known as juvenile-onset Behçet syndrome (JBS) [1]. Although juvenile cases present similarly to adult-onset cases, the incidence of central nervous system involvement, referred to as Neuro-Behçet's syndrome (NBS), is more common in males [2]. NBS often manifests as a subacute brainstem syndrome and hemiparesis due to vascular-inflammatory etiology [3]. However, optic neuritis (ON) is a rarely reported symptom in BS [2]. Herein, we present a case with bilateral optic neuritis, later diagnosed with JBS.

2. Patient description

A previously healthy 14-year-old male adolescent was admitted to the emergency department with acute blurred vision and painful eye movement. His symptoms started six days ago and had a progressive pattern. He also declared that he had oral aphthous occasionally but he did not mention any history of uveitis. He did not have a history of fever, headache, vomiting, or neurological deficits. He was not febrile and fully orientated, with no neck stiffness. No oral or genital aphthous was detected in the physical examination. He also had no remarkable medical history except last year's craniotomy surgery, and there was no neurologic or rheumatologic disease in his family history. His right eye was completely normal, but visual acuity was light perception in his left eye, and bilateral papillitis was seen in fundoscopy. The patient had a left relative afferent pupillary defect (RAPD). The pupillary reflex was normal in the right eye, but the pupillary light reflex and the pupillary dilation response had decreased in his left eye. Ocular findings of slit lamp didn't show keratitis or uveitis. Goldmann perimeter evaluation showed scotoma in his left eye (Fig. 1). Other examination findings were normal.

Fig. 1.

Goldmann perimetry of left eye which shows scotoma.

He was admitted to further investigations. Blood cell count, serum electrolytes, renal and liver function tests, erythrocyte sedimentation rate, and serum levels of C-reactive protein were within normal limits. There was evidence of right-side craniotomy and cranioplasty in the brain magnetic resonance imaging (MRI) with and without contrast, but no parenchymal pathology was seen. Orbital, cervical, thoracic, and lumbar MRI with and without contrast revealed no abnormal findings. There was no evidence of venous thrombosis on magnetic resonance venography. A lumbar puncture showed an opening pressure of 17 cm cerebrospinal fluid (CSF). The CSF sample was acellular, with a glucose level of 63 mg/dl and protein concentration of 42 mg/dl, and later proved negative for herpes simplex virus, cytomegalovirus, and varicella zoster virus. Optical coherence tomography (OCT) was normal. The Pathergy test was negative.

Intravenous methylprednisolone at a dose of 1 g daily was started for the patient for five days. There was no improvement in the patient's condition, the visual acuity of his left eye did not improve, and he complained of blurred vision in his right eye the next day and during the days of hospitalization, the patient suffered from oral aphthous. Further laboratory workup, which included Anti-Aquaporin-4(NMO Antibody) and myelin oligodendrocyte glycoprotein (MOG) antibody were negative. Antinuclear antibody (ANA), extractable nuclear antigens (ENA), anti-neutrophil cytoplasmic antibodies (ANCA), protein electrophoresis, angiotensin-converting enzyme (ACE), serum immunoglobulins, Protein C, Protein S, lupus anticoagulant antibodies, Anti phospholipid antibodies, Anti thrombin antibodies, Beta2 Glycoprotein antibodies, Anti ds DNA antibodies, Anticardiolipin antibodies, HBS Ag, HCV AB, C3, C4, and CH50 were within normal range. He tested positive for HLA—B5. Pathologic Visual Evoked Potential (VEP) was confirmed by prolonged p100 time (Right eye: 122 ms, Left eye: 119 ms). The patient was diagnosed with bilateral optic neuritis caused by Behcet's disease based on The International Criteria for Behçet's Disease (ICBD) criteria and serum plasmapheresis commenced for the patient. Ten sessions of serum plasmapheresis were performed on an everyday basis, without any adverse reactions. Following serum plasmapheresis treatment, bilateral papillitis was improved on fundus examination, and visual acuity was 10/10 on the right and 8/10 on the left. The patient was discharged with azathioprine and was referred to a rheumatology clinic. Three months later the patient developed arthralgia of his left ankle without any tenderness swelling or impairment in range of motion. Radiography revealed no abnormal findings. Dose of azathioprine increased and the signs regressed after two weeks. The schematic timeline of the case is presented in Fig. 2.

Fig. 2.

Schematic timeline of the presented case.

3. Discussion

We reported an unusual neurologic presentation of juvenile Behcet syndrome with optic neuritis. Bilateral optic neuritis in BD, as an early presentation of neuro-Behçet's disease in children, is a rare clinical condition. Patients with JBS are more likely to have gastrointestinal symptoms, neurological and ocular involvement, and arthralgia, while adult-onset Behcet patients are more likely to develop genital and vascular lesions [4,5]. Oral aphthous is the first symptom in nearly all JBS patients, it is the initial presentation in 1/3 of adult patients [4]. As mentioned before, no tests can determine Behcet's disease, so the diagnosis is based on core clinical signs. However, all core clinical signs of JBS may not be present on disease onset [5]. Ocular involvement is less common among JBD patients, appearing (mostly) bilaterally and few years after diagnosis [4]. Uveitis is a common finding in JBS patients with Ocular involvement [5] which is also with worse clinical outcomes [4].

Neurologic involvements in BD are of two forms; parenchymal involvement and non- parenchymal involvement [5]. Neurologic involvement is seen in 3.6–59.6 % of JBS cases [5]. In addition, acute onset headache, hemiparesis, ataxia, and epilepsy are also reported in these patients [5].

Previous studies have reported bilateral ON in patients with BD. Parentin et al. reported JBS in a 12-year-old patient presented with acute episcleritis and papillitis who was responding to treatment with oral corticosteroid [6]. Kardum et al. reported a 24-year-old man with bilateral sequential optic neuritis as a first symptom of the BD [7]. As far as we know, this is the first pediatric case with bilateral optic neuritis as a presenting symptom of JBS. This presentation was without any neurological involvement. Although JBS usually has familial aggregation [4,8], our case did not have any relatives with Behcet's disease. He has a negative pathergy test, which is not an uncommon finding. Pathergy test is not pathognomonic for BD but 50–60 % of JBS showed positive results [4].

About 20–40 % of JBS patients have Musculoskeletal findings which can be seen in the early phase of the disease. Knee and ankle are affected usually and improves without deformity [1,9].

Our patient tested positive for HLA—B5. It is known that people with positive HLA-B5 are at risk for BD; 5.78 times more than the general population [10].

So far, there is no universal guideline for the management or treatment of JBS [10]. Treatment for JBS requires a multidisciplinary approach in most cases [5]. Treatment is used to stop the inflammation process and aims to prevent organ damage [5,10]. More than 50 % of cases need systemic immunosuppression [11]. Corticosteroids, cyclophosphamide, methotrexate, colchicine, azathioprine, and cyclosporine A are reported to be beneficial in JBS patients [8]. Corticosteroids are the most prescribed drug for JBS and are administered in systemic or topical forms [11]. Although high-dose corticosteroid is the most accepted treatment for acute exacerbation of BD [4], especially in neurological involvement, our patient did not respond to it. His symptoms were revealed after therapeutic plasma exchange and did not recur under azathioprine. Beneficial use of therapeutic plasma exchange in BD was previously reported by Erdogan et al. [12]. Some studies have considered anti-tumor necrosis factor (TNF) agents i.e., etanercept, adalimumab, and Infliximab as appropriate treatment options for BD, especially in severe forms and patients who do not respond to or do not tolerate usual treatments. Infliximab may be reserved for severe eye involvement and is reported to be highly effective. There is scarce evidence about Anakinra, canakinumab, tocilizumab, ustekinumab, secukinumab, apremilast, and mycophenolate mofetil in BD, but not investigated in JBS [5].

ICBD criteria is more sensitive than other sets of criteria [13,14]. While the sensitivity of ICBD was reported 70.9–97.1 % in different studies [11,15], International Study Group for Behçet's Disease (ISGBD) criteria sensitivity ranges between 17.4 and 73.7 % [11,16]. The Pediatric Behçet's Disease (PEDBD) study group developed criteria specifically for use in pediatric patients with Behçet's disease. The sensitivity of these criteria in adult patients was reported to be between 45.5 % and 91.7 % [11,17].

In pediatric patients with sequential or bilateral optic neuritis, especially those with atypical presentations, Behcet disease should be considered as a possible diagnosis, especially in regions with higher prevalence of BD. Mucocutaneous manifestations may be absent in early phases. In patients with inappropriate response to corticosteroids plasma exchange may be an effective treatment.

In conclusion this case report highlights the rare presentation of JBS with bilateral optic neuritis which may benefit from plasmapheresis and emphasizes the importance of considering Behcet disease in pediatric patients with atypical optic neuritis. It also underscores the need for a multidisciplinary approach to the treatment of JBS, including systemic immunosuppression.

Funding

This research was conducted without funding.

CRediT authorship contribution statement

Armin Adibi: Writing – review & editing, Writing – original draft, Visualization, Data curation. Iman Adibi: Writing – review & editing, Writing – original draft, Supervision, Conceptualization. Saeed Bahramian: Writing – original draft. Saba Naghavi: Writing – original draft. Fatemeh Gholami: Writing – original draft.

Declaration of competing interest

The authors declare no conflict of interest.