Basic information: male, 63 years old.

Main complaint: The psoriasis foci gradually worsened.

History of present illness: 14 years ago, due to localized erythema and scaling, he was diagnosed with psoriasis at an external hospital. The rash intensified, half was diagnosed as "iridocyclitis". a year ago; DLQI: 21 points. Previous treatment: topical ointment such as Fusong cream, phototherapy (strong UVA1, NB-UVB for whole body), acitretin+MTX; hormone (iridocyclitis) 3# qd*2d; maintenance treatment: Yisaipu+ MTX2#qw.

History: No history of allergy to biological agents.

Examination: The spirit is clear, energy is good, superficial lymph nodes of whole body are not enlarged, breath sounds of both lungs are clear, heart rhythm is correct. . Inspection of abdominal cavity without features, spine is normal.

Lab and Imaging Findings: Complete blood count, urinalysis, liver function, kidney function, and electrolytes showed no overt abnormalities; tests for hepatitis B, HIV and tuberculosis did not reveal obvious abnormalities; ANA(-), ENA(-), HLA-B27(-). An electrocardiogram and CT scan of lungs showed no obvious abnormalities.

Dermatological examination: Multiple red papules and plaques with small scales on surface were seen on trunk and extremities, Auspitz's sign was positive. Rashes on anterior and posterior surfaces of both legs merged into large scales with a slight tendency to erythroderma, swelling and deformity of joints were not observed. ✧

Bad Body Surface (BSA): 45%✧

Psoriasis area and severity index - PASI score: 27.6✧

Practical Global Score (PGA): 3

Diagnosis: Severe plaque psoriasis with iridocyclitis.

Treatment and healing effect: Intravenous infusion of yarrow sage and vitamin C, Queshu cream and Queyan Shusong ointment cream were given for external use. Discharged from hospital and continues treatment: celecoxib in capsules, 1 tablet if necessary; topical Keshu cream 1 time per day; topical mometasone furoate cream 1 time per day externally.

Secukinumab 150 mg subcutaneously once every 0, 1, 2, 3, 4 weeks, then once a month, after 5 treatments, PASI score 1.8, PGA score 1, BSA 2%, skin condition improved significantly (Table 1, Fig. 1).

Table 1. Changes in the severity of psoriasis before and after treatment

Figure 1. Changes in skin lesions before and after treatment

Follow-up: Skin lesions continued to improve, iridocyclitis remained stable with no recurrence.

2

Discussion

In this case, patient's concomitant iridocyclitis is a type of uveitis. Uveitis is a common clinical eye disease that has various forms, is very difficult to diagnose and treat, easily recurs, and eventually leads to irreversible blindness, which places a heavy burden on patients and their families [4]. Ocular lesions are quite common in patients with psoriasis. Symptoms and signs are subtle and easy to overlook. They usually occur in active phase of psoriasis or simultaneously with severe psoriasis. Uveitis associated with psoriasis is mainly anterior uveitis, with a small proportion presenting as posterior uveitis and panuveitis, which can be an acute inflammatory response or a chronic inflammatory response [6]. The frequency of hypopyon in patients with psoriasis associated with uveitis is higher than in other types of uveitis; The most common psoriasis associated with uveitis are psoriasis vulgaris and psoriasis arthropathica [15]. In China, 5 cases of psoriasis accompanied by cyclitis (2 cases of erythrodermic, 2 cases of arthropathic, 1 case of widespread) were registered, among which 1 case was accompanied by glaucoma in addition to uveitis and cataracts. Most patients develop uveitis several years after onset of psoriasis, with insidious onset and progressive exacerbation, often involving both eyes, severe visual impairment, and even blindness [1].

A study found a significantly increased risk of uveitis in patients with psoriasis. In 2020, a new meta-analysis included 7 studies, including 2 studies comparing incidence of uveitis in patients with psoriasis and patients without psoriasis, 5 studies comparing incidence of uveitis. Approximately 6 million patients were analyzed by incidence of uveitis (222,083 with psoriasis, 5,643,718 without psoriasis), and by prevalence of uveitis, 1.34 million patients (37,891 patients with psoriasis and 1,305,545 without psoriasis). Patients with psoriasis had a significantly higher risk of developing uveitis than patients without psoriasis, with a pooled hazard ratio of 1.23 (95% CI: 1.05-1.45, I2 = 55%); patients with psoriasis also had a significantly higher risk of developing uveitis. Above, combined risk ratio was 1.97 (95% CI: 1.68-2.31, I2=0%) [7].

People with psoriasis have a higher risk of developing uveitis for two possible reasons. On one hand, psoriasis is a systemic inflammatory disease and its inflammatory burden can induce onset of ocular inflammatory diseases. The researchers found that in aqueous humor of patients with uveitis increaseds concentrations of many pathogenic factors of psoriasis, including inhibitors of TNF, IL-2, IL-6, IL-17, etc. [10,12]. On other hand, psoriasis and uveitis share same genetic basis and pathogenic mechanism that mediate both skin and ocular autoimmune diseases. For example, onset of anterior uveitis and psoriasis is associated with HLA-B27 gene [13, 14]; this gene also mediates diseases such as ankylosing spondylitis, psoriatic arthritis, and inflammatory bowel disease [8].

Uveitis and psoriasis have a common pathological mechanism. Uveitis is a group of diseases characterized by intraocular inflammation, some of which are caused by autoinflammatory or autoimmune reactions, such as VHC syndrome, Behcet's disease, ankylosing spondylitis-associated uveitis, eye nodule disease, sympathetic ophthalmia, and shotgun chorioretinopathy. Although these uveitis have different clinical forms, genetic and biomarker data suggest that they share a common molecular basis, activation of interleukin (IL)-23/IL-17 pathway. Aberrant reactions in this pathway can be caused by various factors, including genetic predisposition, cytokine imbalance, infection, and changes in gut [16]. In addition, studies in an experimental autoimmune uveitis (EAU) model have shown that some populations of Treg cells are also involved in formation and stability of ocular immune microenvironment, and their reduced number and function cannot effectively inhibit IL-23/IL-17. pathway is an important mechanism that leads to permanent activation of Th17 cells and causes uveitis [4]. Increased activity of IL-23/IL-17 pathway is associated with proliferation and pathogenicity of Th17 cells. Animal model studies have also shown that development of pathogenic Th17 cells is responsible for experimental autoimmune uveitis. Further research has shown that retinal pigment epithelial (RPE) cells can be a target for IL-17. IL-17 triggers a downstream inflammatory cascade leading to RPE cell dysfunction, which affects barrier function of retina and promotes intraocular inflammation [16].

Figure 2. IL-23/IL-17 signaling pathway activated in uveitis [16]

Psoriasis patients should be regularly screened for eye disease, and biological agents can control uveitis based on control of skin lesions. The pathogenesis of psoriasis is complex and is associated with autoimmune dysfunction, and uveitis is often accompanied by many autoimmune diseases. When psoriasis and uveitis occur simultaneously, clinicians must be very careful. The 2019 AAD-NPF Joint Guidelines for Management and Treatment of Psoriasis Comorbidities state that dermatologists should be aware of an increased incidence of uveitis in patients with psoriasis with suspicious ocular symptoms such as eye redness (with or without pain). ), blurred vision and increased photosensitivity require further examination by an ophthalmologist [9]. At same time, it is also recommended to establish screening criteria for ocular psoriasis or ocular complications in diagnosis and treatment of specialists or general practitioners, and regularly monitor eye involvement in patients with psoriasis, especially in patients with severe psoriasis Perform routine ophthalmological examination and leaving every year or two to ensure that best opportunity to treat eye diseases and reduce serious consequences such as blindness is missed.

The "Expert Consensus on Clinical Diagnosis and Treatment of Acute Anterior Uveitis in My Country (2016)" states that simple acute anterior uveitis does not require systemic immunosuppressants, but systemic comorbidities can be treated by experienced clinicians.Use under direction of. Depending on systemic diseases associated with patient, referral to appropriate departments for diagnosis and treatment may also be recommended [6]. Immunosuppressants such as cyclosporine, methotrexate, and corticosteroids are commonly used to treat uveitis. In addition to traditional immunosuppressants for treatment of uveitis, some new immunosuppressants and biological agents have also shown certain curative effects, such as tumor necrosis factor-α (TNF-α) inhibitors, interleukin inhibitors, etc. According to numerous literature data, uveitis can be well controlled during treatment period, but many patients still relapse after stopping drug, and long-term effect is still uncertain. The main side effects include redness and swelling at injection site, ulcers, secondary infection, bone marrow suppression, pulmonary embolism, myocardial infarction, congestive heart failure, gastrointestinal reactions, and infusion reactions [2]. In addition, there have been case reports of uveitis in patients with psoriasis and other immune-mediated inflammatory diseases treated with TNF-α inhibitors. Therefore, use of TNF-α inhibitors may also be one of causes of increasedprevalence/incidence of uveitis in patients with psoriasis [7].

Secukinumab is a fully human anti-IL-17A monoclonal antibody. Domestic phase III clinical trials have confirmed that secukinumab has a significant effect in Chinese patients with psoriasis. A randomized controlled trial in 16 patients with non-infectious uveitis showed that after 8 weeks of treatment with secukinumab, most of them improved, manifested by downregulation of inflammation and reduced use of glucocorticoids; adverse reactions such as infections in treatment group The incidence rate was not significantly different from placebo group, demonstrating a good safety profile [11]. In this case, although secukinumab significantly improved patient's skin lesions, it also provided good control of iridocyclitis.