Early administration of adalimumab for paediatric uveitis due to Behçet’s disease

An 11-year-old female patient with no previous history presented with right conjunctival injection and photophobia. The patient had previously been treated with fluorometholone 0.1% eye drops; however, the same symptoms recurred twice in 1 year. At presentation, her best-corrected decimal visual acuity (BCVA) was 0.4 in the right eye and 1.2 in the left eye. Intraocular pressures (IOPs) of the right and left eyes were 17 and 16 mmHg, respectively (Normal range: 10–21 mmHg). Slit-lamp examination showed ciliary injection and diffuse fine keratic precipitates. Micro-hypopyon and an anterior chamber cell grade of 3+ (based on the Standardization of Uveitis Nomenclature Working Group classification [13]) were observed; posterior synechiae were also present in the right eye. (Fig. 1) Fundus examination of the right eye was hazy and lacked clarity. The left eye exhibited no apparent abnormalities in the anterior chamber or fundus. Fluorescein angiography (FA) of the right eye revealed diffuse vascular leakage and optic disc leakage. (Fig. 2) The patient did not complain of arthralgia or genital ulcers, but had a history of recurrent oral ulcers. On the basis of these findings, the patient was diagnosed with unilateral panuveitis. The differential diagnosis was as follows: Behçet’s disease, juvenile idiopathic arthritis-related uveitis, HLA-B27-related uveitis, A20 haploinsufficiency, and sarcoidosis. Dexamethasone eye drops (0.1%, instilled hourly), tropicamide/phenylephrine eye drops (four times/day), 1% atropine eye drops (once/day), and prednisolone (15 mg/day orally) therapies were initiated for inflammation of the right eye. Further investigation revealed ileocecal ulcers and HLA-B51 positivity. Interferon-gamma release assay and tuberculin tests for tuberculosis infection, raid plasma regain assay, and Treponema pallidum antibody hemagglutination test for syphilis were negative; angiotensin-converting enzyme, antinuclear antibody, matrix metalloproteinase-3, and anti-citrullinated protein antibody levels were within the normal range. A20 haploinsufficiency was thought to be less likely in this patient, due to the absence of a family history of autoimmune diseases, genital ulcers, and fever spikes [14, 15]. In Behçet’s disease, oral ulcers heal without scars, uveitis typically involves the posterior chamber, and retinal vasculitis manifests with a fern-like pattern; in contrast, A20 haploinsufficiency is characterised by anterior uveitis [14]. Because of the presence of typical ocular symptoms and recurrent oral ulcers, the patient was diagnosed with the incomplete type of Behçet’s disease, in accordance with the Japanese diagnostic criteria for Behçet’s disease (revised in 1987) [16]. Inflammation in the anterior chamber and BCVA gradually improved after the treatment. However, a relapse occurred in the right eye and new-onset uveitis appeared in the left eye during the tapering of prednisolone. Adalimumab was administered subcutaneously to avoid the side effects of systemic corticosteroid. [17] The patient was 12-year-old and weighed 36 kg when adalimumab was started. Since there is no indication regarding the dose of adalimumab for paediatric Behçet’s disease, we administered 40 mg every 2 weeks without a loading dose, in accordance with the recommended dose for treatment of juvenile idiopathic arthritis-associated uveitis. The duration of uveoretinitis prior to starting adalimumab was 11 months. After beginning administration of adalimumab, the patient complained of transient abdominal pain, which resolved spontaneously. BCVA improved to 1.5 in both eyes and the anterior chamber cell grade improved to < 0.5+ within 2 weeks. (Fig. 3) Within 4 weeks, laser flare photometry values dramatically improved from the peak value of 48 ph/ms (physiological value approximately 3 ph/ms) in both eyes, to 3–4 ph/ms in the right eye and 2–3 ph/ms in the left eye. (Fig. 4) FA revealed improvement of retinal vasculitis. (Fig. 2) Oral ulcers healed without scars after adalimumab administration. Ileocecal ulcers were completely resolved on the follow-up colonoscopy, which was performed 3 months after initiation of the therapy. The inflammation has remained well-controlled by administration of adalimumab without local or systemic corticosteroid for 17 months. No side effects of adalimumab have been observed.

A 14-year-old female patient reported blurry vision in the left eye for the past 8 months and had been diagnosed with uveitis at another clinic. Despite the administration of local and systemic corticosteroid, inflammation persisted; therefore, the patient was referred to our clinic. The patient presented with fine keratic precipitates and anterior chamber cell grade of 2+ in the left eye. The vitreous cell grade was 1+ in the right eye and 2+ in the left eye. FA showed diffuse fern-like capillary leakage and optic disc hyperfluorescence of the left eye. (Fig. 5) The BCVA was 1.2 in both eyes, and the IOPs of the right and left eyes were 16 and 22 mmHg, respectively. Non-ocular manifestations were oral ulcers and shoulder arthralgia. Skin or genital lesions were not observed. The differential diagnosis was as follows: Behçet’s disease, A20 haploinsufficiency, and idiopathic retinal vasculitis. Interferon-gamma release assay and tuberculin tests for tuberculosis infection, raid plasma regain assay, and Treponema pallidum antibody hemagglutination test for syphilis were negative; angiotensin-converting enzyme, antinuclear antibody, matrix metalloproteinase-3, and anti-citrullinated protein antibody levels were within the normal range. There was no family history of autoimmune diseases and colonoscopy revealed no abnormality. Behçet’s disease was suspected and the patient was referred to a paediatrician for further investigation. She tested negative for HLA-B51. Additionally, the following treatment (initiated in the previous clinic) was continued: 0.1% dexamethasone eye drops (four times/day), tropicamide/phenylephrine eye drops (once/day), and prednisolone (5 mg/day orally). In accordance with the Japanese diagnostic criteria for Behçet’s disease (revised in 1987), the patient was diagnosed with the incomplete type of Behçet’s disease on the basis of the presence of a typical ocular symptom and recurrent oral ulcers [16]. Retinal vasculitis recurred in both eyes; therefore, initiation of adalimumab was proposed to the patient; however, it was initially declined due to financial restrictions. Thus, prednisolone was increased to 20 mg/day, and methotrexate was initiated at 6 mg/day. (Fig. 6) A maximum of 12 mg methotrexate was administered; however, the patient experienced nausea and the inflammation relapsed. Subcutaneous adalimumab injection was then introduced, and prednisolone was slowly tapered. The patient was 15-year-old and weighed 53 kg when adalimumab was initiated, thus we administered 80 mg as a loading dose, followed by 40 mg every 2 weeks, starting 1 week after the loading dose, in accordance with the recommended dose for treatment of adult uveitis. The duration of uveoretinitis prior to starting adalimumab was 13 months. The anterior chamber cell grade improved from 3+ in both eyes to 0 and 0.5+ in the right and left eyes, respectively, within 7 weeks after beginning adalimumab administration. (Fig. 6) The peak values of laser flare photometry were 131.8 ph/ms in the right eye and 71.4 ph/ms in the left eye; these improved to 4–5 ph/ms and 10–12 ph/ms, respectively. (Fig. 7)  BCVA remained ≥ 1.5 in both eyes. Oral ulcers and arthralgia were improved after adalimumab therapy. The inflammation subsided, and local and systemic corticosteroid therapies were discontinued. The follow-up period of adalimumab was 12 months at the time this report was written, and the patient had not experienced any side effects.