The competitive nature of signal transducer and activator of transcription complex formation drives phenotype switching of T cells.

Signal transducers and activators of transcription (STATs) are key molecular determinants of T-cell fate and effector function. Several inflammatory diseases are characterized by an altered balance of T-cell phenotypes and cytokine secretion. STATs, therefore, represent viable therapeutic targets in numerous pathologies. However, the underlying mechanisms by which the same STAT proteins regulate both the development of different T-cell phenotypes and their plasticity during changes in extracellular conditions remain unclear. In this study, we investigated the STAT-mediated regulation of T-cell phenotype formation and plasticity using mathematical modelling and experimental data for intracellular STAT signalling proteins. The close fit of our model predictions to the experimental data allows us to propose a potential mechanism for T-cell switching. According to this mechanism, T-cell phenotype switching is the result of the relative redistribution of STAT dimer complexes caused by the extracellular cytokine-dependent STAT competition effects. The developed model predicts that the balance between the intracellular STAT species defines the amount of the produced cytokines and thereby T-cell phenotypes. The model predictions are consistent with the experimentally observed interferon-γ to interleukin-10 switching that regulates human T helper type 1/type 1 regulatory T-cell responses. The proposed model is applicable to a number of STAT signalling circuits.

Initial Experience of Using Dual-Energy CT with an Iodine Overlay Image for Hand Psoriatic Arthritis: Comparison Study with Contrast-enhanced MR Imaging.

Purpose To determine the feasibility of dual-energy (DE) computed tomography (CT) with an iodine overlay image (IOI) for evaluation of psoriatic arthritis in the hand. Materials and Methods Approval from the institutional ethics committee and written informed consent from all patients were obtained. This prospective study included 16 patients who had psoriasis with finger joint symptoms from January 2015 to January 2016. Contrast material-enhanced (CE) DE CT and 1.5-T CE magnetic resonance (MR) imaging were performed within 1 month of each other. DE CT was performed with a tube voltage of 80 kV and 140 kV with use of a 0.4-mm tin filter. Images acquired with both modalities were evaluated by two radiologists independently by using a semiquantitative scoring system. Interreader agreement was calculated for each modality: Weighted κ values were calculated for synovitis, flexor tenosynovitis, and extensor peritendonitis, and κ values were calculated for periarticular inflammation. With consensus scores and CE MR images as the reference, the sensitivity and specificity of IOI DE CT for inflammatory lesions were calculated. Statistical analysis of discordant readings was performed by using the McNemar test. Results Interreader agreement for inflammatory lesions was excellent or good (weighted κ = 0.83 and κ = 0.75 in IOI DE CT; weighted κ = 0.81 and κ = 0.87 in CE MR imaging). The sensitivity and specificity of IOI DE CT were 0.78 and 0.87, respectively. Total agreement was 86.3%; however, there were significantly more lesions detected with IOI DE CT than with CE MR imaging alone (134 vs 20 lesions in 1120 evaluated items; P < .001). Sixty-nine percent of the abnormalities detected with IOI DE CT alone were located in distal interphalangeal joints. Conclusion IOI DE CT is a new imaging modality that may be useful for evaluating psoriatic arthritis in the hand, particularly in the detection of inflammatory lesions in small joints, and may be more useful than CE MR imaging, within the limitation that there is no histopathologic reference. © RSNA, 2017.

Silencing of homeobox A5 gene in the stratum corneum of psoriasis.

Analysis of psoriatic parakeratotic cells is helpful for understanding the pathogenesis of psoriasis. Methylation analysis can be performed on psoriatic scales, but it is unclear whether genes can be silenced by DNA methylation in psoriatic stratum corneum. The present study was conducted to detect genes silenced in psoriatic stratum corneum. Methylation array analysis with 485 577 probes, quantitative real-time methylation-specific PCR (RT-MSP) and bisulphite sequencing were performed for 30 psoriatic scale samples, 6 fully developed psoriatic skin samples and 12 normal skin samples. Immunohistochemical staining of HOXA5 was performed for 29 psoriatic epidermal samples and 13 normal epidermal samples. The genome-wide methylation array detected two CpG sites within CpG islands (CGIs) located in promoter regions of HOXA5 and LIAS that had methylation levels of >0.6 in at least one of the three psoriatic scale samples and of <0.2 in all three normal skin tissue samples (methylation rate range, 0.0-1.0). RT-MSP for HOXA5CGI, in which the primers were successfully developed, revealed that the average methylation level of 27 psoriasis scales (60.2%) is significantly higher than that of 9 normal skin samples (34.6%) (P=.013). Immunohistochemical staining revealed that HOXA5 protein was not expressed in the stratum corneum of fully developed psoriatic epidermis, but the protein was expressed in the stratum corneum of incompletely developed epidermis and normal epidermis. In conclusion, HOXA5 can be silenced in the stratum corneum of psoriasis. The silenced gene was identified by non-invasive methylation analysis of psoriatic scales.

Dual energy CT iodine map for delineating inflammation of inflammatory arthritis.

Iodine mapping is an image-processing technique used with dual-energy computed tomography (DECT) to improve iodine contrast resolution. CT, because of its high spatial resolution and thin slice reconstruction, is well suited to the evaluation of the peripheral joints. Recent developments in the treatment of inflammatory arthritis that require early diagnosis and precise therapeutic assessment encourage radiological evaluation. To facilitate such assessment, we describe DECT iodine mapping as a novel modality for evaluating rheumatoid arthritis and psoriatic arthritis of the hands and feet. KEY POINTS: • Dual-energy CT iodine mapping can delineate inflammation of peripheral inflammatory arthritis. • DECT iodine mapping has high spatial resolution compared with MRI. • DECT iodine mapping has a high iodine contrast resolution. • DECT iodine mapping may reflect therapeutic effects.

Generalized pustular psoriasis in a child: observation of long-term combination therapy with etretinate and calcipotriol for 16 years.

Generalized pustular psoriasis (GPP) is a rare condition in young children. It is difficult to treat and may require long-term systemic therapy. We report the long-term course of a 3-year-old boy whose onset of psoriasis dated to age 7 months. He was treated with etretinate and psoralen plus ultraviolet A therapy initially and then with etretinate alone, and at age 12, topical calcipotriol was added. At the age of 19, he had been taking oral retinoids for 16 years, with a mean dose of etretinate of 0.22 mg/kg per day, a total amount of approximately 37 g, without evidence of stunted growth, ligamentous calcification, hyperostosis, or hepatic toxicity.

Risk of squamous cell carcinoma in immunosuppressed patients with voriconazole-related actinic keratosis.

Voriconazole is commonly administered for a long period to patients receiving immunosuppressive therapy. Although voriconazole potentially induces skin cancers in association with sun exposure, this has not yet been examined in detail in a single ethnic patient group. Therefore, the present study investigated the risk of developing squamous cell carcinoma (SCC) in Japanese patients with voriconazole-related actinic keratosis (AK) and the prognosis of Japanese patients with voriconazole-related SCC. We retrospectively examined 37 Japanese patients with AK, including five voriconazole-treated patients (mean age, 57.9  ±  16.3  years) and 32 non-treated patients (74.9  ±  9.2  years), and 18 Japanese patients with SCC, including four voriconazole-treated patients (55.4  ±  16.7  years) and 14 non-treated patients (74.1  ±  10.7  years). Among the 37 patients with AK, SCC developed in five, including four with a history of treatment with both voriconazole and immunosuppressive agents, independent of AK progression. In these four patients, the mean period from the diagnosis of AK to that of SCC was 13.8  ±  11.6  months. Kaplan--Meier analyses showed that the risk of developing SCC was significantly higher in patients with both voriconazole and immunosuppressants/corticosteroid-treated patients with AK than in non-voriconazole-treated patients with AK (the Log-rank test, p < 0.001). The analyses also showed that the mortality rate was significantly higher in patients with both voriconazole and immunosuppressants/corticosteroid-treated patients with SCC than in non-voriconazole-treated patients with SCC (p =  0.018). The present results suggest that voriconazole-related AK precedes the development of cutaneous SCC and voriconazole-related SCC leads to a poor prognosis under the immunosuppressive condition.

Ixekizumab 80 mg Every 2 Weeks Treatment Beyond Week 12 for Japanese Patients with Generalized Pustular Psoriasis and Erythrodermic Psoriasis.

INTRODUCTION: In 2018, ixekizumab (80 mg every 2 weeks [Q2W] beyond Week 12) received approval in Japan for patients with generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP). This open-label study evaluated the efficacy and safety of ixekizumab (80 mg Q2W from Week 12 to Week 20) in Japanese patients with GPP and EP. METHODS: Seven patients with GPP and five patients with EP were enrolled. An initial dose of 160 mg (subcutaneous [SC] injection) was followed by 80 mg Q2W SC until Week 12. Primary endpoint assessed global improvement score (GIS) by comparing psoriatic findings, Static Physician Global Assessment, Psoriasis Area and Severity Index score, and other evaluations with those at the baseline and were graded as 1 = resolved, 2= improved, 3 = unchanged, and 4 = worsened. Patients who showed GIS = 1 (resolved) at Week 12 completed the study. Patients with GIS ≥ 2 continued to receive ixekizumab 80 mg Q2W until Week 20. RESULTS: At Week 12, four of seven patients with GPP showed "resolved," two showed "improved," and one showed "worsened." Of five patients with EP, one showed "resolved" and four showed "improved." Two patients with GPP and four patients with EP continued ixekizumab treatment until Week 20. At Week 20, one of the two patients with GPP showed "resolved" and one patient showed "improved." All four patients with EP showed "improved." One non-drug related serious adverse event was reported by one patient with EP at Week 12. From Week 12 to Week 20, no adverse events (AEs) were reported in patients with GPP, but two mild AEs were reported in one of the four patients with EP. CONCLUSIONS: This study indicates that ixekizumab continuous Q2W dosing is efficacious and safe for patients with GPP and EP. CLINICAL TRIAL REGISTRATION: NCT03942042.

Ixekizumab is an anti-interleukin-17 treatment for a skin condition with thick and scaly patches called psoriasis. Ixekizumab (initial dose of 160 mg followed by 80 mg administered every 2 weeks [Q2W] from Week 2 through Week 12 and thereafter 80 mg every 4 weeks [Q4W]) has been approved in Japan; people who have not achieved 100% clear skin after taking ixekizumab for 12 weeks can continue to receive ixekizumab Q2W rather than monthly. However, this approval partially lacked data from people with rare types of psoriasis, generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP). The aim of this study was to look at the effectiveness and safety of continuous Q2W dosing of ixekizumab in Japanese people with GPP and EP beyond Week 12. Researchers aimed to find out whether psoriasis symptoms in this population improved if they continued Q2W treatment for > 12 weeks. Seven people with GPP and 5 with EP participated in the study (12 in total). Participants initially received 160 mg under-the-skin injection of ixekizumab, followed by 80 mg injections Q2W. Two GPP and four EP participants continued to receive ixekizumab after 12 weeks up to Week 20. One GPP participant achieved 100% clear skin, and another GPP participant and all 4 EP participants showed improvement. No participants died, and safety findings were similar to previous ixekizumab studies from both Japanese and non-Japanese people. This study suggests that people with GPP and EP who continue to take ixekizumab Q2W after 12 weeks may show improvements in their psoriasis with a well-tolerated safety profile.

Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Generalized Pustular Psoriasis and Erythrodermic Psoriasis: 52-Week Results.

INTRODUCTION: We report an exploratory analysis of the efficacy and safety of certolizumab pegol (CZP) in Japanese patients with generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) (NCT03051217). METHODS: Patients ≥ 20 years with GPP or EP were randomized 1:1 to open-label CZP 400 mg every 2 weeks (Q2W) or 200 mg Q2W (400 mg weeks 0/2/4) for 16 weeks; patients who achieved "much improved" or "very much improved" on the Global Improvement Score (GIS; for GPP) or a PASI 50 response (≥ 50% reduction from baseline Psoriasis Area and Severity Index; for EP) continued to week 52. Efficacy outcomes assessed included Clinical Global Impression of Improvement (CGI-I), Dermatology Life Quality Index (DLQI 0/1), and Itch Numeric Rating Scale (INRS 0). GIS and Japanese Dermatological Association (JDA) severity index were assessed in patients with GPP, and PASI and Physician's Global Assessment (PGA) in patients with EP. Treatment-emergent adverse events (TEAEs) were evaluated through weeks 0-52. RESULTS: Of 22 patients randomized, 19 completed week 52. At week 16, all reported outcomes improved with both CZP doses and were generally maintained through week 52. At week 52, 6/7 GPP and 12/12 EP patients achieved CGI-I response ("improved" or "remission"). Also, 4/7 GPP and 7/12 EP patients achieved DLQI 0/1; 2/7 GPP and 2/12 EP patients achieved INRS 0. Meanwhile, 6/7 patients with GPP achieved GIS response, and JDA severity index was reduced from baseline. We found that 9/12 and 5/12 patients with EP achieved PASI 90 and PGA 0/1, respectively. Overall, three serious TEAEs were reported in three CZP 400 mg Q2W-treated patients. CONCLUSION: CZP treatment over 16 weeks improved the signs and symptoms of GPP and EP, and improvements were maintained through week 52. No new safety signals were identified. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03051217.

Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: Effect of Demographics and Baseline Disease Characteristics on Efficacy.

INTRODUCTION: We present certolizumab pegol (CZP) efficacy data across patient demographic and baseline disease characteristic subgroups from a phase 2/3 trial investigating CZP treatment in Japanese patients with moderate to severe plaque psoriasis (PSO; ClinicalTrials.gov identifier: NCT03051217). METHODS: Patients were randomised 1:2:2 to placebo once every 2 weeks (Q2W), CZP 400 mg Q2W and CZP 200 mg Q2W (400 mg weeks 0, 2 and 4) for 16 weeks. Patients who achieved ≥ 50% reduction in their baseline Psoriasis Area and Severity Index (PASI 50) score at week 16 continued therapy to week 52. PASI 75/90 (75% and 90% reduction, respectively) and Physician's Global Assessment (PGA) 0/1 responder rates at weeks 16 and 52 were reported for patient demographic and baseline disease characteristic subgroups, including body mass index (BMI), PASI, disease duration and prior biologic use. Non-responder imputation was used. RESULTS: Of the randomised patients, 2/26 patients in the placebo group, 47/53 patients in the CZP 400 mg Q2W group and and 39/48 patients in the CZP 200 mg Q2W group completed week 52. In the subgroups evaluated, week 16 efficacy was generally maintained through week 52. At week 52, PASI 75 was achieved by 84.2, 85.7 and 80.0% of patients receiving CZP 400 mg Q2W in the low (15.0-23.7 kg/m2)/intermediate (> 23.7-27.4 kg/m2)/high (> 27.4-47.0 kg/m2) BMI subgroups, respectively, and by 77.8, 70.6 and 69.2%, respectively of patients treated with CZP 200 mg Q2W. PASI 75 at week 52 was achieved by 92.9, 75.0 and 84.2% of patients receiving CZP 400 mg Q2W in the low (12.0-18.0)/intermediate (> 18.0-27.0)/high (> 27.0-67.2) baseline PASI subgroups, respectively, and by 85.0, 58.3 and 68.8% of patients receiving CZP 200 mg Q2W, respectively. Similar responses were observed across other subgroups evaluated for both CZP doses in PASI 75/90 and PGA 0/1. CONCLUSION: Clinically meaningful improvements in signs and symptoms of PSO were maintained through week 52 for CZP dosed at 400 mg Q2W or 200 mg Q2W, across patient subgroups. In general, a numerically greater response was observed for patients receiving CZP 400 mg Q2W versus those receiving CZP 200 mg Q2W across patient subgroups. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03051217.

A systems model for immune cell interactions unravels the mechanism of inflammation in human skin.

Inflammation is characterized by altered cytokine levels produced by cell populations in a highly interdependent manner. To elucidate the mechanism of an inflammatory reaction, we have developed a mathematical model for immune cell interactions via the specific, dose-dependent cytokine production rates of cell populations. The model describes the criteria required for normal and pathological immune system responses and suggests that alterations in the cytokine production rates can lead to various stable levels which manifest themselves in different disease phenotypes. The model predicts that pairs of interacting immune cell populations can maintain homeostatic and elevated extracellular cytokine concentration levels, enabling them to operate as an immune system switch. The concept described here is developed in the context of psoriasis, an immune-mediated disease, but it can also offer mechanistic insights into other inflammatory pathologies as it explains how interactions between immune cell populations can lead to disease phenotypes.

Psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis. It is found in approximately 10% of psoriatic patients in Japan. PsA mainly affects the peripheral joints, spine, and/or sacroiliac joints. Left untreated, there is progressive, irreversible bone destruction leading to joint deformation and dysfunction. Before the era of biologic treatments, the diagnosis of PsA was difficult and available treatments were limited. Over time the pathology of PsA has become better understood, and many treatments now exist. Early detection and treatment of impending joint deformities are necessary to avoid impairment of PsA patients' quality of life. Most patients develop the arthritis following the onset of the skin manifestations of psoriasis. The process of diagnosing PsA sometimes encounters difficulties because some patients may not show radiographic findings in the early stage, and may have normal levels of C-reactive protein and matrix metalloproteinase-3. For these cases, approaches such as magnetic resonance imaging or ultrasound imaging, as well as symptom questionnaires, are helpful. Currently, non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and several biologics are the main treatments for PsA, which when used with an aggressive approach, will result in better patient outcomes.

Certolizumab Pegol for the Treatment of Moderate to Severe Plaque Psoriasis: 16-Week Results from a Phase 2/3 Japanese Study.

INTRODUCTION: Certolizumab pegol (CZP), the Fc-free, PEGylated anti-tumor necrosis factor, is approved for the treatment of moderate to severe plaque psoriasis (PSO) in Western countries and in Japan, among other indications. METHODS: We report results from the first 16 weeks of a 52-week phase 2/3 trial of CZP in Japanese patients with PSO. Patients ≥ 20 years with PSO ≥ 6 months (Psoriasis Area and Severity Index [PASI] ≥ 12, body surface area affected ≥ 10%, and Physician's Global Assessment [PGA] ≥ 3 on a 5-point scale) were randomized 2:2:1 to CZP 400 mg every 2 weeks (Q2W), CZP 200 mg Q2W (400 mg weeks 0/2/4), or placebo Q2W. Outcomes assessed to week 16: PASI 75, PASI 90, PGA 0/1 (Markov chain Monte Carlo), Dermatology Life Quality Index (DLQI 0/1) and Itch Numeric Rating Scale (INRS 0) (non-responder imputation), and DLQI and INRS change from baseline (last observation carried forward). Safety data were reported for patients receiving ≥ 1 dose of study medication through weeks 0-16; adverse events were evaluated using Medical Dictionary for Regulatory Activities version 18.1. RESULTS: A total of 127 patients were randomized to CZP 400 mg Q2W (N = 53), CZP 200 mg Q2W (N = 48), placebo (N = 26). Week 16 responder rates for CZP 400 mg/200 mg Q2W versus placebo were 87.1%/73.0% versus 7.9% for PASI 75; 75.7%/53.8% versus 0.2% for PASI 90; 66.7%/52.7% versus 0.0% for PGA 0/1 (all p < 0.0001 for both CZP doses versus placebo). Significant improvements in DLQI and INRS were reported at week 16 by patients receiving both CZP doses compared with placebo (p < 0.0001). Incidence of treatment-emergent adverse events within the CZP 400 mg Q2W, CZP 200 mg Q2W, and placebo groups were 326.1, 404.9, and 682.4 per 100 patient-years. No new safety signals were identified compared to previously reported data. CONCLUSION: CZP dosed at 400 mg or 200 mg Q2W was associated with improved PSO signs and symptoms. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03051217.

Effect of anti-interleukin-17 biologics on Krebs von den Lungen-6 level in patients with psoriasis.

Interleukin (IL)-17 plays critical roles in the pathogenesis of both psoriasis and interstitial pneumonia (IP). We hypothesized that anti-IL-17 biologics might suppress both clinically relevant and latent IP activity and decrease Krebs von den Lungen-6 (KL-6) level in psoriasis patients. We aimed to elucidate the effects of anti-IL-17 biologics on KL-6 levels. We retrospectively analyzed the clinical data of psoriasis patients treated with anti-IL-17 biologics. KL-6 levels were measured before treatment (baseline) and at 3 and 6 months after the initiation of the treatment, and ratios of KL-6 levels at each time point to the baseline levels were calculated. Chest computed tomography (CT) was performed on patients with coexisting IP. The clinical characteristics and radiographic findings were evaluated. A total of 294 psoriasis patients were treated with anti-IL-17 biologics. Baseline KL-6 levels were higher than 401 U/mL in 34 patients (high baseline KL-6 group). While anti-IL-17 biologics did not affect KL-6 levels and ratios of KL-6 to the baseline levels at any time point in the overall study population, they decreased both KL-6 levels and ratios at 6 months after the initiation of the treatment in the high baseline KL-6 group. A total of 10 patients with coexisting IP showed decreasing ratios of KL-6 to the baseline levels at 6 months without affecting coexisting IP in CT performed at 3-12 months. Anti-IL-17 biologics decreased KL-6 levels in the high baseline KL-6 group regardless of recognizable IP. A decrease in KL-6 levels was not associated with a radiographic improvement of IP, which should be examined in large numbers with long-term observations in future studies.

Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: 52-Week Results.

INTRODUCTION: Certolizumab pegol (CZP), an Fc-free, PEGylated anti-tumour necrosis factor biologic, dosed at 400 mg every 2 weeks (Q2W) and 200 mg Q2W over 16 weeks, resulted in improvements in Japanese patients with moderate to severe plaque psoriasis (PSO); no new safety signals were identified. We present 52-week efficacy and safety results. METHODS: Patients ≥ 20 years with PSO ≥ 6 months [Psoriasis Area and Severity Index (PASI) ≥ 12, body surface area ≥ 10%, Physician's Global Assessment (PGA) ≥ 3] were randomised 1:2:2 to placebo Q2W, CZP 400 mg Q2W and CZP 200 mg Q2W (400 mg weeks 0/2/4) for 16 weeks. Week 16 PASI 50 responders continued through week 52; CZP 200 mg Q2W-randomised patients were re-randomised 1:1 to CZP 200 mg Q2W or CZP 400 mg Q4W; patients initially randomised to other treatment groups continued in the same group. Outcomes included PASI 75/90/100, PGA 0/1, Dermatology Life Quality Index (DLQI) 0/1, Itch Numeric Rating Scale (INRS) 0, modified Nail Psoriasis Severity Index (mNAPSI), durability of response for week 16 PASI 75/90 responders, and safety. RESULTS: Of 26/53/48 patients randomised to placebo, CZP 400 mg Q2W and CZP 200 mg Q2W, 2/47/39 completed week 52, respectively. PASI 75/90 responses were generally maintained from weeks 16 to 52 for all CZP doses. Most week 16 PASI 75/90 achievers maintained their response through week 52. PASI 75/90/100 responses at week 52 in the CZP 400 mg Q2W and CZP 200 mg Q2W groups were 83.0/81.1/41.5% and 72.9/60.4/18.8%, respectively; DLQI/INRS remission rates were 64.2/50.9% in CZP 400 mg Q2W and 58.3/27.1% in CZP 200 mg Q2W-treated patients. Reductions in mNAPSI observed for CZP-treated groups were maintained through week 52. No new safety signals were identified. CONCLUSION: CZP treatment resulted in improvements in signs and symptoms of PSO, which were maintained through week 52. The 400 mg Q2W dose could provide additional clinical benefit. TRIAL REGISTRATION: NCT03051217.

Characteristics of anti-IL-17/23 biologics-induced interstitial pneumonia in patients with psoriasis.

OBJECTIVES: Anti-IL-17/23 biologics are increasingly used to treat psoriasis. We aimed to elucidate characteristics of drug-induced interstitial pneumonia (DIIP) caused by anti-IL-17/23 biologics. METHODS: We retrospectively analyzed the clinical data of psoriasis patients treated with anti-IL-17/23 biologics. Chest CT was performed to evaluate DIIP. Serum KL-6 levels were measured before treatment (baseline) and during treatment. RESULTS: A total of 603 psoriasis patients were treated with anti-IL-17/23 biologics with mean follow-up of 21.1 months. Six patients developed DIIP at mean 14 months after initiation of the therapy. Older age, higher baseline KL-6 value and more frequent pre-existing IPs were associated with development of DIIP by univariate analysis. At the onset of DIIP, elevated serum KL-6 levels with concomitantly increased ground glass opacity (GGO) in Chest CT were demonstrated. DIIP was improved by only cessation of causative agents in five patients but steroid therapy was needed in one patient. CONCLUSIONS: DIIP is a plausible complication of anti-IL-17/23 biologics. Age, baseline KL-6 level and underlying IP could be the risk factors for DIIP development. Serum KL-6 levels and chest CT are useful for not only predicting but also detecting DIIP caused by anti-IL-17/23 biologics.

Quantitative analysis of therapeutic response in psoriatic arthritis of digital joints with Dual-energy CT iodine maps.

The aim of this study was to investigate the feasibility of quantitative assessment of the therapeutic response in psoriatic arthritis (PsA) by measuring iodine uptake using a Dual-energy CT (DECT) iodine map. The study included 74 symptomatic and 74 matching non-symptomatic joints of 26 consecutive PsA patients who underwent two contrast enhanced DECTs of the hand or foot, pre and post medical interventions. Symptomatic and matched non-symptomatic control joints were scored with the PsA DECT Scoring System (PsADECTS), which was derived by modifying the PsA MRI Scoring System (PsAMRIS), a recently validated scoring system that assesses PsA changes on MRI. Quantified iodine uptake measured using the DECT iodine map was compared to the PsADECTS score. Efficacy of PsA treatment was confirmed by the improved clinical findings. Both PsADECTS and iodine uptake also showed significant improvement after treatment (Wilcoxon signed-rank test: z = 7.38, p < 0.005; z = 6.20, p < 0.005, respectively). The treatment effects of PsADECTS score and iodine uptake showed a good correlation with each other (Spearman's ρ = 0.58 p < 0.005). Inter-reader agreement for PsADECTS score and iodine uptake were either moderate or good. In conclusion, our study showed that the DECT iodine map is a valid tool for quantitative assessment of the therapeutic response of PsA.

Stability of folding structure of Zic zinc finger proteins.

Zic family proteins have five C(2)H(2)-type zinc finger (ZF) motifs. We physicochemically characterized the folding properties of Zic ZFs. Alteration of chelation with zinc ions and of hydrophobic interactions changed circular dichroism spectra, suggesting that they caused structural changes. The motifs were heat stable, but electrostatic interactions had little effect on structural stability. These results highlight the importance of chelating interactions and hydrophobic interactions for the stability of the folding structure of Zic ZF proteins.

Relationship between the Degrees of Itch and Serum Lipocalin-2 Levels in Patients with Psoriasis.

BACKGROUND: Lipocalin-2 (LCN2), a protein secreted mainly by activated neutrophils, has been associated with neurodegeneration, obesity, and inflammatory responses. Serum LCN2 concentration has been reported elevated in patients with psoriasis, but lower in patients with atopic dermatitis (AD). Spinal astrocyte-derived LCN2 was found to be involved in enhancement of itch in a mouse model of AD. However, the relationship between LCN2 and itch in patients with psoriasis has not been determined. Objective. This study examined the correlation between serum LCN2 levels and the degrees of itch in patients with psoriasis. METHODS: Serum LCN2 concentrations were measured by enzyme-linked immunosorbent assays (ELISA) in patients with psoriasis and AD and in healthy controls. The degree of itch was assessed using a visual analog scale (VAS), and disease severity was determined by measuring psoriasis area and severity index (PASI) and scoring atopic dermatitis (SCORAD). Correlations among serum LCN2 level, VAS, PASI, and SCORAD were analyzed statistically. We further examined the serum LCN levels in psoriasis patients before and after biological treatment. RESULTS: Serum LCN2 concentrations were significantly higher in patients with psoriasis and AD than those in healthy controls. In patients with psoriasis, serum LCN2 concentrations were significantly correlated with VAS, but not with PASI. In contrast, serum LCN2 concentrations did not correlate with VAS or SCORAD in patients with AD. Serum LCN2 levels in psoriasis patients significantly decreased after the biological treatment along with improvement of VAS. CONCLUSION: Serum LCN2 concentration is associated with the degree of itch in patients with psoriasis, suggesting that serum LCN2 may be a useful clinical marker for itch in psoriasis.

Seborrheic keratosis that follows Blaschko's lines.

A 66-year-old Japanese man had skin lesions on the left side of his trunk and the left upper extremity for approximately 10 years. The skin lesions were asymptomatic but increased gradually, which brought the patient to our hospital. On the initial examination, we noticed 5 mm x 5 mm to 15 mm x 5 mm, round or oval, light to dark brown keratotic papules on the left side of chest and abdomen and the left upper extremity. The papules were aligned in an S-shaped line on the trunk and in a straight line on the upper extremity. Clinical and histopathological findings led to a diagnosis of seborrheic keratosis that followed Blaschko's lines. To our knowledge, no such a case has been reported previously. Our case supports the hypothesis that seborrheic keratosis can be associated with genetic mosaicism.