Epidermal Hyperproliferation With Less Prominent Dermal Inflammation Is the Unique Histopathological Feature of the Refractory Lesions in Psoriasis Treated With Ustekinumab.

ABSTRACT: Although ustekinumab (UST) shows excellent efficacy in treating psoriasis, not all patients have a complete clearance rate. The purpose of this study was to investigate the histopathological characteristics of refractory psoriasis lesions in patients with excellent response to UST. Fifty-seven patients with newly diagnosed psoriasis and 66 patients with a 75% reduction in the Psoriasis Area and Severity Index score after UST treatment were included. Computer-aided image analysis was performed to measure the epidermal thickness, horny layer thickness, number of dermal vessels, and dermal inflammatory cell infiltration rate. Parakeratosis was scored using a 4-point scale. These measurements were compared between the refractory lesions of UST-treated patients and the untreated lesions of newly diagnosed patients after the adjustment for confounding factors. The dermal inflammatory cell infiltration rate was significantly lower in the refractory lesions (P = 0.022). Meanwhile, the epidermal thickness, horny layer thickness, grade of parakeratosis, and dermal vessel count did not differ between the groups (P = 0.125, 0.719, 0.542, and 0.758, respectively). Subgroup analyses were performed within the UST-treated group after dividing them into 2 groups according to the number of treatments or treatment response rates. None of these features were significantly different between the subgroups. This study suggests that the reduction of dermal inflammation by UST was not sufficient to ameliorate the epidermal changes and implies the role of the interleukin-23-independent downstream cytokine pathway in causing the refractory lesions among patients who responded well to UST. The continuation of UST treatment might not further improve epidermal alterations.

Toenail Psoriasis during Ustekinumab Therapy: Results and Limitations.

BACKGROUND: Nail psoriasis is a common clinically significant symptom of psoriasis. However, few studies have focused on the characteristics and course of toenail psoriasis. OBJECTIVE: To investigate the treatment response of toenail psoriasis during a 52-week period of ustekinumab use. METHODS: Patients were evaluated using the Nail Psoriasis Severity Index (NAPSI) at every injection visit. NAPSI score changes throughout the treatment were analyzed. The treatment response in each toenail and each NAPSI characteristic was also analyzed. RESULTS: A total of 22 patients with chronic plaque psoriasis with concomitant toenail psoriasis were examined. Several characteristics such as ridging or onychomycosis that mimic psoriasis or hinder the evaluation were identified. NAPSI significantly improved during the treatment (p<0.05). The big and second toes were significantly improved after 52 weeks of ustekinumab treatment (p<0.05). Pitting and oil-drop discoloration were the only two characteristics that showed significant changes post-treatment (p<0.05). CONCLUSION: Ustekinumab proved to be efficacious in treating toenail psoriasis. Because of the factors that hinder the NAPSI scoring, only NAPSI scores of the first and second toes can be used.

Nail involvement features in palmoplantar pustulosis.

Pathogenesis of palmoplantar pustulosis (PPP) is not fully understood and whether PPP is a variant of plaque psoriasis (PsO) is still controversial. Psoriatic nail changes are among the clinical features common to both diseases, and understanding them could lead to the understanding of the correlation between both diseases. However, only limited numbers of studies have reported nail involvement pattern in PPP. In this study, we conducted a retrospective review of the medical records and photographs of patients diagnosed with PPP to understand the nail involvement features in PPP patients. We compared the results with the data from our previous study that analyzed the pattern of nail involvement in PsO. As a result, nail involvement was observed in 66.3% of the patients and its severity was correlated with the severity of cutaneous lesions (r = 0.34, P = 0.01). Onycholysis and crumbling were more frequent in PPP than in PsO. Crumbling was associated with higher severity of PPP (P = 0.01), while onycholysis was associated with lower severity (P = 0.03). In PPP, nail changes in the first digits were less prominent than those in other digits when compared with PsO. Risk factors for nail involvement in PPP included female sex (odds ratio [OR] = 9.44, P < 0.001), younger age at diagnosis (OR = 1.08, P = 0.01), and higher severity (OR = 1.15, P = 0.01). Presence of psoriatic arthritis did not show significant association with nail involvement (OR = 1.62, P = 0.77). In conclusion, although PPP shares some nail features with PsO, differences were noted in the commonly observed features and in the distribution of involved nails.

Persistent expression of interleukin-17 and downstream effector cytokines in recalcitrant psoriatic lesions after ustekinumab treatment.

The interleukin (IL)-23/T-helper (Th)17 axis is considered central to the pathogenesis of psoriasis, with IL-36γ considered a marker for histological differential diagnosis. However, expression data regarding key cytokines in the pathogenesis of psoriasis, as well as data on the effects of IL-23 inhibition on downstream cytokines in human psoriatic skin, are limited. We investigated the expression profile of key cytokines and the effect of ustekinumab (UST) on cytokine expression in human psoriatic tissue. Tumor necrosis factor (TNF)-α, IL-23, IL-17A, and IL-22 were highly expressed in the epidermis, dermal papillae, and upper dermis in patients with psoriasis compared with controls; IL-36γ was strongly expressed in the upper epidermis. Compared with the untreated group, expression intensity and area of IL-23 were significantly decreased in the UST group; expression areas of TNF-α, IL-17A, IL-22, and IL-36γ did not differ. This study identified the distribution and quantitative expression levels of key cytokines in psoriatic lesions and demonstrated that only IL-23 was downregulated without blocking downstream effector cytokines in recalcitrant psoriatic lesions during UST treatment. Our results suggest that, although IL-23 is inhibited, the persistent expression of IL-17 through an alternative pathway maintains the vicious cycle of the TNF-α/IL-23/IL-17 axis with IL-36γ, inducing refractory psoriatic lesions in patients with well-controlled psoriasis.

Comparison of NAPSI and N-NAIL for evaluation of fingernail psoriasis in patients with moderate-to-severe plaque psoriasis treated using ustekinumab.

OBJECTIVE: We sought to determine the psoriatic nail feature which responds to ustekinumab treatment more effectively, and evaluate which between the Nail Psoriasis Severity Index (NAPSI) and the Nijmegen-Nail psoriasis Activity Index tooL (N-NAIL) better reflects the clinical improvement of nail psoriasis. METHODS: Thirty patients with moderate-to-severe plaque psoriasis were prospectively enrolled and treated with ustekinumab for 52 weeks. A single investigator evaluated the condition using the NAPSI and the N-NAIL with serial fingernail photographs. RESULTS: Of the 30 patients, 13 (43.3%) had fingernail psoriasis present at baseline. Mean NAPSI scores improved from 9.46 ± 8.7 at baseline to 6.00 ± 5.2 at week 52, but the improvement was not statistically significant (p = .09). Mean N-NAIL scores significantly improved from 5.46 ± 5.1 at baseline to 3.92 ± 3.7 at week 52 (p = .04). Of the psoriatic nail features, only the splinter hemorrhages significantly improved at week 52 compared to baseline. CONCLUSIONS: When comparing the mean scores between week 0 and 52, the N-NAIL score (p = .04) better reflected a significant improvement of nail psoriasis than the NAPSI (p = .09), and ustekinumab treatment resulted in a more rapid and effective improvement of splinter hemorrhages.

A quantitative, objective method for evaluating the surgical outcomes of baggy eyelid correction using orbital gray scale analysis.

BACKGROUND: Baggy lower eyelids (BLEs) are a common cosmetic problem that is treated using various methods. However, validated objective methods for evaluating the treatment are limited. AIMS: A novel BLE correction procedure, transconjunctival fat resection, and subsequent fat grafting, was assessed using the orbital gray scale (OGS), a previously suggested objective measure for BLEs. METHODS: All patients were evaluated using both the tear trough rating scale (TTRS), a surgeon-derived evaluation method, and OGS, an objective computer-derived assessment. Changes throughout the surgery and their relationship to clinical characteristics, as well as the association between the two measurements, were statistically analyzed. RESULTS: A total of 50 patients who underwent surgery were analyzed. No major complications other than wrinkles were observed. All patients showed improvement in both the TTRS scores and OGS values (P < 0.05). Lateral OGS was improved to a greater extent in older patients (P < 0.05). Medial OGS change was associated with improvement of tear trough depression (P < 0.05). Lateral OGS change was related to decreased infraorbital fat herniation (P < 0.05). Total OGS change was related to improvement of both tear trough depression and fat prolapse (P < 0.05). CONCLUSION: The total OGS change was significantly associated with improvements in tear trough depression and fat bulging. Therefore, it could be a convenient objective evaluation measure for eyelid correction procedures.

Economic Factors as Major Determinants of Ustekinumab Drug Survival of Patients with Chronic Plaque Psoriasis in Korea.

BACKGROUND: Drug survival, defined as the time until discontinuation, is a parameter reflecting real-world therapeutic effectiveness. Few studies have examined the influence of economic factors on the drug survival of biologic agents for psoriasis, particularly in Asian countries. OBJECTIVE: To determine the drug survival for ustekinumab in real-life settings and investigate the factors affecting drug survival for psoriasis patients in Korea. METHODS: We evaluated 98 psoriasis patients who were treated with ustekinumab at a single center. We analyzed the efficacy and drug survival of ustekinumab. Cox proportional hazard analysis and competing risk regression analysis were performed to reveal the factors affecting the drug survival of ustekinumab. RESULTS: The overall mean drug survival was 1,596 days (95% confidence interval [CI], 904~2,288). Among the 39 cessations of ustekinumab treatment, 9 (23.1%) patients discontinued treatment after experiencing satisfactory results. Multivariate Cox proportional hazard analysis revealed that paying on patients' own expense was the major predictor for the discontinuation of ustekinumab (hazard ratio [HR], 9.696; 95% CI, 4.088~22.998). Competing risk regression analysis modeling of discontinuation because of factors other than satisfaction of an event also revealed that ustekinumab treatment at the patient's expense (HR, 4.138; 95% CI, 1.684~10.168) was a predictor of discontinuation rather than satisfaction. CONCLUSION: The results of our study revealed that the cost of biologics treatment affects the drug survival of ustekinumab and suggested that economic factors affect the drug survival of ustekinumab treatment in Korea.

Epidemiology and comorbidities of patients with chronic urticaria in Korea: A nationwide population-based study.

Few population-based studies have focused on the epidemiology and comorbidities of chronic urticaria (CU) or chronic spontaneous urticaria (CSU). The objective of this study was to obtain information on the epidemiology and comorbidities associated with CU and CSU in Korea. We conducted a cross-sectional analysis using a national health insurance database. An algorithm based on the International Classification of Diseases, 10th revision, was used for the identification of patients with CU and CSU, and an age-sex adjusted logistic regression model was used to assess the risk of comorbidities in these patients. The average annual prevalence rates of CU and CSU during the 4-year period between 2010 and 2013 were 3.08% and 1.40%, respectively. The prevalence rates of CU and CSU were higher in women than men (1:1.39 and 1:1.34, respectively) and peaked at 0-9 and 70-79 years, respectively. After adjustment for age and sex, the patients with CU and CSU were found to have a significantly higher prevalence rate of CU/CSU-related diseases, compared with those without CU (mean adjusted odds ratio, 8.46; 95% confidence interval, 8.10-8.83). Allergic rhinitis, drug allergies, asthma, thyroid diseases and cancers were the most common comorbidities. Stomach, thyroid, liver and prostate cancers were the most prevalent cancers. This study provides large epidemiological data on the prevalence rates of CU and CSU, and their comorbidities, in Korea. Patients with CU and CSU impose a higher burden, in terms of specific comorbidities, than those without CU.

Risk Factors Affecting Adverse Effects of Cyclosporine A in a Real-World Psoriasis Treatment.

BACKGROUND: No study to date has focused on the changes in laboratory test results and related risk factors in patients with psoriasis treated with prolonged Cyclosporine A (CsA) therapy. OBJECTIVE: The objective of this study was to investigate the changes of laboratory values and related risk factors in patients with psoriasis treated with CsA in a real-world setting. METHODS: Records of patients with psoriasis treated with CsA at an outpatient clinic were collected, and a Cox proportional hazards regression model was used. RESULTS: Of the 128 patients included in this study, 28 patients (21.9%) showed laboratory test abnormalities over a mean medication period of 11.6 months. Older age (hazard ratio [HR], 1.174; 95% confidence interval [CI], 1.068~1.370; p=0.007) and pre-existing kidney disease (HR, 0.008; 95% CI, 0~0.205; p=0.001) significantly increased the risk of renal dysfunction. Male sex was the only significant risk factor for liver enzyme elevation (HR, 0.284; 95% CI, 0.081~0.784; p=0.026) and uric acid abnormality (HR, 0.048; 95% CI, 0~0.372; p=0.046). CONCLUSION: This is an in-depth analysis of laboratory changes and related risk factors in patients with psoriasis treated with CsA. Liver is the most commonly affected organ of CsA toxicity. Older age, male sex, and presence of kidney disease were risk factors associated with laboratory abnormality during CsA treatment.