Uveitis Occurring in a Patient with Psoriasis during Adalimumab Therapy: A Case Report.

Here we report a case of a 34-year-old patient with psoriasis who developed uveitis induced by adalimumab. After receiving two subcutaneous injections of adalimumab, the patient suffered from a sudden onset of ocular pain and blurred vision in her left eye, which was diagnosed with acute anterior uveitis. Adalimumab therapy was discontinued and the patient was hospitalised for the treatment of acute anterior uveitis with systemic corticosteroids. This paradoxical adverse event was alleviated after timely interventions and went into remission during a 6-month follow-up period. To the best of our knowledge, this is the first case of uveitis occurring in patients with psoriasis under adalimumab treatment. It indicates that paradoxical uveitis, although rare, is one of the adverse events of adalimumab therapy. Early recognition and prompt intervention would lead to a good outcome. Copyright:

Introduction

Psoriasis is an immune-mediated inflammatory disease with complex genetic susceptibility.[1] It typically affects the skin but can also affect the joints and has been associated with a number of diseases. It is now widely accepted that immune dysregulation and inflammatory responses underlie the pathological changes of psoriasis.[2] In particular, cellular and molecular factors, such as tumour necrosis factor-alpha (TNF-α), dendritic cells and T-cells, contribute substantially to psoriasis pathogenesis.[2] Thus, anti-psoriatic therapies specific targeting to these pathological entities will be effective in treating this notorious disease.

Case History

In November 2019, a 34-year-old Chinese woman was referred to our department for a 9-year history of psoriasis. During the past 9 years, several anti-psoriatic treatment regimens were given, including acitretin, UVB, topical corticosteroids and calcipotriol. However, all of these treatments became inefficient and the disease evolved overtime. She did not have any pre-existing comorbidities. On physical examination, diffuse erythematous plaques with overlying scale on the head, trunk and extremities were found [Figure 1]. The psoriasis area and severity index (PASI) score was 20.5 and body surface area (BSA) was 24%. All routine laboratory investigations were performed, including tuberculosis, hepatitis B, antinuclear antibodies and tumour markers; no abnormality was detected. She was treated with generic adalimumab 80 mg subcutaneous injection on week 0 and 40 mg on week 1. However, during the adalimumab therapy, she had redness of the left eye and was diagnosed with acute anterior uveitis. Her eye symptoms were not well controlled by using corticosteroid eye drops. The patient even suffered sudden ocular pain and blurred vision in her left eye after the second injection. She was referred to an ophthalmologist. Physical examination revealed conjunctival congestion, fine keratic precipitates (KPs) and cells grade 2+ and flare 2+ on slit-lamp examination. The examination of the ocular fundus indicated a normal macula [Figure 1 SuppInfo]. Microbial culture of eye secretions performed before any administration of antibiotics was negative. Adalimumab was discontinued and she was hospitalised for the treatment of acute anterior uveitis. The therapeutic strategies included retrobulbar injection of methylprednisolone, corticosteroid eye drops and intravenous dexamethasone and vancomycin. Two weeks later, the patient presented to our clinic for evaluation of psoriasis severity. As a result, the PASI was reduced to 0.4 and the BSA was reduced to 4% [Figure 2]. Ophthalmologic examination 1 month later demonstrated the recovery of visual acuity, which remained stable at the 6-month follow-up examination. In addition, the condition of psoriasis remained stable without any therapeutic support during this follow-up interval.

Figure 1

Skin involvement on first presentation and before adalimumab therapy

Figure 2

Skin involvement after 1 month of adalimumab therapy

Discussion

Adalimumab, a fully humanised monoclonal antibody that binds and neutralises tumour necrosis factor-alpha (TNF-α), is the most widely used biological for psoriasis, especially for moderate to severe cases. In general, adalimumab is considered to be a safe and well-tolerated treatment option for psoriasis.[3] However, adverse effects still require specific attention during adalimumab therapy in patients with psoriasis, from commonly observed events such as nonserious infections, nasopharyngitis and headache to rare events such as lupus-like syndrome,[3] autoimmune haemolytic anaemia, ulcerative colitis, hair re-pigmentation and multiple sclerosis or other neurological diseases.[4]

Adalimumab was approved for the treatment of non-infectious uveitis. However, previous studies reported that TNF-α inhibitors, especially etanercept, can induce the development of uveitis, a rare paradoxical effect of anti-TNF-α treatment.[5] Other rare ocular manifestations following adalimumab administration include necrotizing fasciitis, orbital sarcoid-like granuloma, uveal melanoma, central retinal vein occlusion and optic neuritis.[6] To date, it has been reported that only seven cases developed uveitis when treated with adalimumab, including two cases of rheumatoid arthritis, two cases of juvenile idiopathic arthritis and three cases of ankylosing spondylitis.[7] In our case, The Naranjo probability scale is graded by score, when 5-8 is rated as “probable”. To the best of our knowledge, this is the first case of uveitis occurring in a patient with psoriasis during adalimumab treatment.

However, the mechanisms behind anti-TNF agent-induced uveitis are still unclear. It is hypothesised that an inverse and interdependent relationship between TNF-α and interferon levels underlie the development of autoimmune diseases.[8] Such an inverse correlation between TNF-α and interferon can affect immune cell activation, autoantibody production and immune complex deposition, leading to immunopathology and autoimmunity.[9] Moreover, differences in pharmacokinetics and pharmacodynamics among different anti-TNF drugs may underlie differential alteration of local cytokine milieu and distinct risk of uveitis occurrence among various TNF inhibitors. This phenomenon may be a “class effect” linked to the dysregulatory features of TNF-α inhibition rather than a molecule side effect.[10]

Taken together, we reported drug-induced uveitis in a patient with psoriasis receiving adalimumab treatment. It suggests that such adverse events can still happen, though rarely, during adalimumab therapy. Early recognition and prompt intervention are particularly important, which can lead to a good outcome for these patients.

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 the Young Scientists Fund of the National Natural Science Foundation of China (No.: 81801992) and the Medical and Health Science and Technology Project of Zhejiang Province (No.: 2018256428).

Conflicts of interest

There are no conflicts of interest.