Vogt-Koyanagi-Harada Disease and Systemic Lupus Erythematosus Occurring during Adalimumab Therapy for Ulcerative Colitis.

We report the case of a 36-year-old male patient known to have ulcerative colitis on adalimumab treatment for 2 years who presented with initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease. Uveitis was treated successfully with systemic corticosteroids combined with mycophenolate mofetil. The patient had complete resolution of posterior segment inflammation and exudative retinal detachment. One year after the initial presentation, the patient was diagnosed to have systemic lupus erythematosus and adalimumab was discontinued. This case suggests that adalimumab could induce severe autoimmune inflammatory diseases. Copyright:

Introduction

Uveitis associated with Vogt–Koyanagi–Harada (VKH) disease is an autoimmune disease directed against one or more antigens found on or associated with uveal melanocytes.[1] The initial-onset acute disease typically exhibits granulomatous choroiditis with exudative retinal detachment in addition to optic disc hyperemia and swelling. The inflammation subsequently involves the anterior segment and finally develops into chronic recurrent granulomatous anterior uveitis if not properly treated with typical “sunset glow fundus” and chorioretinal atrophy.[1] VKH disease can develop in association with other autoimmune disorders, such as diabetes mellitus, psoriasis, celiac disease, Hashimoto's thyroiditis, and autoimmune polyglandular syndrome type 1.[2] In addition, VKH disease was reported to occur in association with ulcerative colitis (UC)[345] and Crohn's disease.[6]

Recently, the use of anti-tumor necrosis factor-alpha (TNF-α) agents in patients with uveitis associated with VKH disease was reported.[7] However, the response to these agents was variable. Here, we report the case of a 36-year-old male patient known to have UC treated with adalimumab who presented to our emergency room with initial-onset acute uveitis associated with VKH disease.

Case Report

A 36-year-old male patient with a history of UC for the last 8 years was treated initially with azathioprine and shifted to adalimumab therapy 40 mg administered subcutaneously every other week for the last 24 months. He presented to our emergency room with a history of progressive decrease of vision in both eyes over 10 days. On the day of examination, his best-corrected visual acuity (BCVA) was 20/200 in both eyes. Intraocular pressure was 11 mmHg in both eyes. Slit-lamp examination showed clear cornea and occasional cells in the anterior chambers of both eyes. Dilated fundus examination showed bilateral exudative retinal detachment and optic disc hyperemia. Fundus fluorescein angiography showed bilateral multiple pinpoint hyperfluorescence at the level of the retinal pigment epithelium in the early phases and late pooling of dye in the areas of exudative retinal detachment, in addition to optic disc leakage and staining. Indocyanine green angiography showed multiple hypofluorescent spots in the early and late frames, in addition to fuzzy choroidal vessels and late widespread punctate hyperfluorescent dots. Optical coherence tomography showed subretinal fluid in both eyes [Figure 1].

Figure 1

Color fundus photograph of the right/left eyes showing bilateral optic disc hyperemia and multiple exudative macular detachment ( first row). Optical coherence tomography of the macula showing bilateral exudative retinal detachment at presentation (second row). Fundus fluorescein angiography showing bilateral multiple pinpoint hyperfluorescence at the level of the retinal pigment epithelium and late pooling of dye in the areas of exudative retinal detachment. The optic nerve heads show leakage and staining (third row – right eye, fourth row – left eye). Indocyanine green angiography showing multiple hypofluorescent spots representing choroidal granulomas (fifth row), in addition to fuzzy choroidal vessels (fifth row – white arrows) and late widespread punctate hyperfluorescent dots (fifth row – yellow arrows)

The patient was admitted with a diagnosis of initial-onset acute uveitis associated with VKH disease. Uveitis workup including complete blood count with differential, erythrocyte sedimentation rate, electrolytes, blood sugar, blood chemistry, liver function tests, tuberculin test, and chest X-ray all came to be unremarkable. The patient was treated with intravenous methylprednisolone 1 g daily for 3 days, in addition to mycophenolate mofetil 1 g twice/day. Oral prednisone 1 mg/kg body weight was started on the 4th day. Sixteen months after this treatment, his examination revealed completely quiet eyes with a total resolution of exudative retinal detachment and the BCVA reached 20/20 bilaterally [Figure 2]. Adalimumab was discontinued 4 months before the last visit by his treating physician and replaced by tofacitinib (Janus Kinase inhibitor) as the patient developed systemic lupus erythematosus (SLE).

Figure 2

Color fundus photograph of the right/left eyes showing resolved exudative retinal detachment and mild optic head hyperemia at the last follow-up visit ( first row). Optical coherence tomography of the macula showing complete resolution of the exudative retinal detachment at the last follow-up visit (second row)

Discussion

In the current report, we present a case of initial-onset acute uveitis associated with VKH disease that occurred 8 years after the development of UC. To the best of our knowledge, the association of VKH disease and UC has been reported previously in only three cases.[345]

The exact cause of VKH disease remains unknown, but evidence suggests that it involves a T-lymphocyte-mediated autoimmune process directed against one or more antigens found on or associated with melanocytes. Several studies demonstrated that tyrosinase family proteins are the antigens specific to VKH disease and that VKH disease is characterized by an immune response mediated by T helper (Th) 1 and Th17 cells.[8] In addition, recent studies suggested that B lymphocytes are also involved in the pathogenesis of the uveitis associated with VKH disease and sympathetic ophthalmia.[910] Similarly, there is increasing evidence that B lymphocytes play an essential role in the pathogenesis of other autoimmune diseases, such as rheumatoid arthritis, SLE, multiple sclerosis, and myasthenia gravis.[11]

Adalimumab is a humanized monoclonal anti-TNF-α agent that suppresses the Th1 cell-mediated immunity. In this report, despite that the patient was on adalimumab therapy for UC, he developed uveitis associated with VKH disease. This finding suggests that in our patient with initial-onset acute uveitis associated with VKH disease, adalimumab therapy was not effective to prevent the development of acute uveitis. This finding also suggests that TNF-α might not be a key player in the pathogenesis of initial-onset acute uveitis associated with VKH disease. In a previous study, we demonstrated that TNF-α level in the aqueous humor of patients with uveitis was significantly lower in patients with uveitis associated with VKH disease than in patients with Behçet's disease and human leukocyte antigen-B27-associated uveitis[8] On the other hand, our report suggests an etiologic role for adalimumab therapy in the development of VKH disease. It is known that the use of anti-TNF-α agents is associated with an increasing number of autoimmune diseases such as cutaneous vasculitis, lupus-like syndrome, SLE, and interstitial lung disease.[12] Interestingly, our patient developed SLE 1 year after the initial presentation with the initial onset of acute VKH disease. Therefore, adalimumab was discontinued and replaced with tofacitinib.

Conclusions

VKH disease occurred during adalimumab treatment was not previously reported. This report suggests that adalimumab could induce severe autoimmune disorders.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

This work was supported by King Saud University through Vice Deanship of Research Chair, Dr. Nasser Al-Rashid Research Chair in Ophthalmology (Abu El-Asrar MA).

Conflicts of interest

There are no conflicts of interest.