Psoriasis is a chronic immune-mediated skin disease centered on the IL-23/Th17 axis, affecting 1–3% of the world’s population. The most common type is plaque psoriasis (psoriasis vulgaris), accounting for 80% of all psoriasis. It is a multi-organ disease that not only causes skin lesions but also various systemic complications such as joint, eye, and metabolic issues.
The prevalence of uveitis in patients with psoriasis is reported to be 2–9% 1). The proportion of psoriatic uveitis among all uveitis cases is less than 0.7% 2), making it a relatively rare disease. A large Danish cohort study showed that patients with psoriasis had a significantly higher risk of developing anterior uveitis compared to those without psoriasis (HR 2.13; 95% CI 1.83–2.49), and the risk was even higher in those with psoriatic arthritis (HR 4.42; 95% CI 3.61–5.41) 7).
Psoriatic uveitis is slightly more common in men, with an average age of onset in the early 40s. The most common type is psoriasis vulgaris, followed by association with psoriatic arthritis. Many cases are HLA-A2 positive. Most are non-granulomatous anterior uveitis, and in psoriatic arthritis it is often accompanied by hypopyon. Response to steroid treatment is good, but recurrence is frequent and long-term management is necessary.
Ocular symptoms of psoriasis include not only uveitis but also dry eye (often due to meibomian gland dysfunction), blepharitis, conjunctivitis, episcleritis, and cataracts. However, this article focuses on psoriatic uveitis.
Uveitis occurs in 2–9% of patients with psoriasis1). Although it accounts for less than 0.7% of all uveitis cases, it is important to see an ophthalmologist promptly if redness, eye pain, or photophobia appear. The risk of uveitis is even higher in patients with psoriatic arthritis7), and it is advisable to recommend regular eye check-ups when visiting a dermatologist.
Acute onset is common, with main symptoms including redness, eye pain, photophobia, and blurred vision. Severe cases with hypopyon present with intense eye pain and marked vision loss. When posterior segment involvement (macular edema, vitritis) occurs, floaters and gradual vision loss appear. Symptoms often coincide with flares (recurrence of skin lesions).
Other ocular symptoms of psoriasis (dry eye, blepharitis) are perceived as ocular dryness, foreign body sensation, burning sensation, redness of the eyelid margins, and scales.
Non-granulomatous Anterior Uveitis (most common)
Fine dust-like keratic precipitates (KP): Characteristic fine, dust-like deposits. Mutton-fat KP is rare in psoriatic uveitis.
Anterior chamber cells and flare: Moderate inflammation. Recurrence cycles are often longer compared to HLA-B27 positive cases.
Posterior synechiae: Form in chronic or recurrent cases. Can be prevented by early administration of mydriatics.
Cases with Psoriatic Arthritis
Hypopyon: Viscous, irregular white deposits similar to HLA-B27-associated uveitis. May be accompanied by elevated intraocular pressure and corneal edema.
Acute onset, recurrent: Tends to appear as recurrent AAU in a spondyloarthritis pattern.
Risk of severe disease: Increased risk of complications such as elevated intraocular pressure, band keratopathy, and secondary glaucoma.
Posterior Segment Involvement
Macular edema: Occurs as a complication of chronic inflammation. OCT shows cystoid changes and serous retinal detachment.
Optic disc swelling: Rare. Redness and edema of the optic disc are observed.
Retinal vasculitis: Rare. Confirmed by fluorescein angiography (FA) as leakage of dye from vessel walls.
Ocular complications other than uveitis
Dry eye (MGD): Ocular surface dryness, foreign body sensation, burning sensation. Often evaporative type due to meibomian gland dysfunction.
Blepharitis: Redness, scales, and crusting of the eyelid margins. May be associated with bacterial flora imbalance.
Episcleritis: Mild redness and tenderness. Usually resolves spontaneously but may recur.
In an analysis of 117 cases of psoriatic uveitis (anterior 99, intermediate 3, posterior 10, panuveitis 5), complications reported included vitreous opacity 41.1% (65/117), cataract 29.7% (47/117), posterior vitreous detachment 25.9% (41/117), elevated intraocular pressure 17% (27/117), and dry eye 13.3% (21/117)1). In uveitis associated with psoriatic arthritis, the frequency of visual acuity ≤0.5 was higher than in cases with psoriasis alone9).
In cases with psoriatic arthritis (PsA), severe anterior uveitis with hypopyon is more likely to occur, resembling HLA-B27-associated acute anterior uveitis (AAU) complicating ankylosing spondylitis8). It is often recurrent, and the risk of complications such as secondary glaucoma, macular edema, and band keratopathy increases, so systemic treatment with immunosuppressants or biologics may be necessary.
The development of psoriatic uveitis involves a combination of immune, genetic, and environmental factors.
Patients with axial psoriatic arthritis (sacroiliitis, spondylitis) have a particularly high cumulative risk of developing uveitis10), making multidisciplinary collaboration among orthopedics, dermatology, and ophthalmology especially important.
Diagnosis is made based on typical skin findings (well-demarcated erythematous scaly plaques), Auspitz sign (punctate bleeding after scale removal), and Koebner phenomenon (appearance of lesions at trauma sites). When skin lesions are mild or intermittent, nail findings (nail pitting, onycholysis, oil-drop discoloration) can be clues.
Perform basic screening recommended by the uveitis clinical practice guidelines2):
| Disease | Key differentiating features |
|---|---|
| HLA-B27-associated AAU (e.g., ankylosing spondylitis) | Presence of spondylitis/sacroiliitis, no psoriatic skin lesions |
| Behçet’s disease | Oral aphthae, genital ulcers, HLA-B51, hypopyon forming anterior chamber empyema |
| Sarcoidosis | Mutton-fat KP, hilar lymphadenopathy, high ACE levels, granulomatous inflammation |
| IBD-associated uveitis | Intestinal symptoms (Crohn’s disease, ulcerative colitis), confirmed IBD diagnosis |
| Reactive arthritis | Preceding infection (urethritis, enteritis), triad of urethritis, arthritis, and conjunctivitis |
| Infectious uveitis | Positive infection screening (syphilis, tuberculosis, herpes, etc.) |
Psoriasis and HLA-B27-associated AAU may coexist (approximately 5–10% of psoriasis patients are HLA-B27 positive8)), requiring comprehensive assessment combining dermatological diagnosis and HLA typing.
Treatment of psoriatic uveitis is performed stepwise in collaboration with dermatology, orthopedics, and ophthalmology.
Systemic treatment for psoriatic uveitis follows the treatment for psoriasis and is carried out in consultation with a dermatologist.
| Drug class | Representative drug | Effect on uveitis |
|---|---|---|
| TNF-α inhibitors | Adalimumab (Humira®), Infliximab (Remicade®) | Effective for both psoriasis and uveitis4). Adalimumab is covered by insurance for non-infectious uveitis (160 mg → 80 mg → 40 mg every 2 weeks) |
| IL-17 inhibitors | Secukinumab (Cosentyx®), Ixekizumab (Taltz®) | Effective for psoriasis and psoriatic arthritis, but there is a risk of new-onset or exacerbation of uveitis5) |
| IL-23 inhibitors | Guselkumab (Tremfya®), Risankizumab (Skyrizi®) | Options with less concern for uveitis5). Reports of use in psoriasis with uveitis are accumulating |
| IL-12/23 inhibitors | Ustekinumab (Stelara®) | Reports of efficacy for psoriasis + uveitis are accumulating. Blockade of the IL-12 pathway may be effective for uveitis |
Among TNF-α inhibitors, adalimumab is the only one with insurance coverage for non-infectious uveitis (approved in 2019)4). Infliximab is used off-label for refractory cases.
IL-17 inhibitors (secukinumab, ixekizumab) are effective for psoriatic skin lesions and psoriatic arthritis, but there are reports of risk of new-onset or worsening of uveitis 5). When ocular inflammation is present, it is recommended that dermatologists and ophthalmologists discuss selecting a TNF-α inhibitor (e.g., adalimumab) that is also effective for uveitis, or an IL-23 inhibitor with lower uveitis risk.
TNF-α inhibitors (adalimumab, infliximab) are effective for psoriatic skin lesions, psoriatic arthritis, and uveitis, allowing simultaneous treatment 4). Adalimumab is approved for non-infectious uveitis. Since IL-17 inhibitors effective for skin lesions carry a risk of worsening uveitis, drug selection based on the presence of ocular complications is important.
The core pathogenesis of psoriasis involves an activation cascade from plasmacytoid dendritic cells to myeloid dendritic cells to IL-23 to Th17 cells. IL-17A/F and IL-22 produced by Th17 cells induce hyperproliferation of skin keratinocytes, forming a positive feedback loop that recruits more immune cells. A similar inflammatory circuit operates in ocular tissues 3).
In uveitis patients, IL-23 and IL-17 concentrations in tears and aqueous humor are significantly higher than in healthy individuals 6). IL-23 is involved in the formation of long-term memory of Th17 cells and promotes chronic recurrent inflammatory patterns. Transcriptional promotion of inflammatory genes via the TYK2/JAK/STAT pathway is also an important pathogenic mechanism.
Gut microbiota dysbiosis alters T cell activation patterns, promoting inflammation in the skin, eyes, and joints. Changes in the composition of skin commensal bacteria (e.g., Staphylococcus aureus) are also involved in psoriasis pathogenesis. Disruption of the intestinal barrier function exposes systemic circulation to gut bacterial antigens, leading to systemic immune activation.
Enthesitis is a common lesion in all spondyloarthropathies, observed in psoriasis, IBD, Behçet’s disease, and ankylosing spondylitis. The “enthesitis-uveitis axis” hypothesis proposes that common autoantigens (collagen, proteoglycans) exist at entheses, skin, and eyes, and immune responses to these lead to ocular inflammation. This explains why uveitis is particularly frequent in cases with psoriatic arthritis.
IL-17A is thought to play a role in maintaining immune privilege in the eye. It has been suggested that IL-17 inhibition may alter intestinal barrier function, leading to increased systemic exposure to gut bacterial antigens. Another hypothesis is that blocking the IL-17 pathway relatively enhances the Th1 response, exacerbating intraocular inflammation 5). On the other hand, IL-23 inhibitors may block upstream of IL-17 while maintaining a more physiological immune balance in the gut and eye.
HLA-A2 positivity is frequently observed in Japanese patients with psoriatic uveitis. It is possible that intraocular activation of CD8+ T cells via MHC class I molecules (HLA-A2) is involved in the pathogenesis, and the genetic background unique to Japanese people is thought to influence the clinical features of psoriatic uveitis.
The effects of upadacitinib (JAK1 inhibitor) and deucravacitinib (TYK2 inhibitor) on psoriasis, psoriatic arthritis, and uveitis are being investigated in clinical trials. JAK inhibitors have a mechanism that comprehensively blocks the Th17/IFN-γ pathway, an inflammatory circuit in uveitis. TYK2 inhibitors selectively suppress IL-23 signaling and show high clinical efficacy for psoriasis. Prospective studies on their impact on psoriasis complicated by uveitis are awaited.
Research is progressing on biomarkers of MHC class I-related T cell responses for risk prediction of psoriatic uveitis. Application to personalized medicine (precision medicine) targeting HLA-A2 is expected.
Studies using optical coherence tomography angiography (OCTA) have reported that even psoriasis patients without clinical inflammation may show decreased retinal capillary density or changes in blood flow. It is expected to become a tool for disease severity classification and treatment efficacy evaluation in the future.
Dry eye and uveitis share multiple molecular signaling pathways, including involvement of Th1 lymphocytes, expression of IL-17/Th17, activation of matrix metalloproteinases, and infiltration of macrophages and dendritic cells 1). It has been pointed out that the coexistence of both diseases may be more frequent than expected in psoriasis patients, and active screening for dry eye (both aqueous tear-deficient and evaporative types) is recommended in patients with anterior uveitis.
