乌司奴单抗治疗银屑病的研究进展

银屑病是一种免疫介导的慢性炎症性皮肤病,白介素-12和白介素-23在银屑病发病中起到重要作用。乌司奴单抗作为一种人源化单克隆抗体,能与白介素-12和白介素-23共有的p40亚基特异性结合,阻断各自介导的免疫反应,用于银屑病的治疗。临床试验表明,该药具有良好的耐受性,不良反应轻微,并且疗效迅速、显著,能改善生活质量。目前资料证明,该药适用于成人中重度斑块状银屑病治疗,也可用于其他类型银屑病的治疗。     

Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized,double‐blind,phase III NAVIGATE trial

Psoriasis is a chronic disease causing red and scaling skin lesions. Current treatments, especially biologics, which are either given by injection or intravenous infusion (IV), are very effective in the treatment of moderate to severe plaque psoriasis. However, most patients look to achieve clear skin, so there is room for improvement. One approved biologic, ustekinumab, blocks two of the body's internal proteins, interleukin (IL)‐12 and IL‐23. Blocking these proteins prevents signals that cause inflammation in psoriasis. While ustekinumab is effective in many patients, most will not achieve complete skin clearance. Because recent scientific evidence shows that IL‐23 may be more important than IL‐12 in causing psoriasis, guselkumab, a new treatment that specifically targets IL‐23, but not IL‐12, has been developed and was recently approved in the U.S. to treat moderate to severe psoriasis. In the NAVIGATE trial, 871 patients with moderate‐to‐severe plaque psoriasis received ustekinumab and if, after 16 weeks, patients were not clear or almost clear, they were randomly assigned to either continue ustekinumab or start treatment with guselkumab until week 44. From week 16 until week 40, the average number of visits (maximum = 4) at which patients were clear or almost clear was significantly greater in patients treated with guselkumab (1.5) than with ustekinumab (0.7). In addition, at week 28, twice the proportion of patients on guselkumab (31.1%) were clear or almost clear than on ustekinumab (14.3%). Infections were the most commonly reported adverse event among patients on either guselkumab or ustekinumab. The authors conclude that for patients who do not achieve clear or almost clear skin after ustekinumab treatment, switching to guselkumab could be an effective treatment strategy and did not raise safety concerns.     

Treatment of psoriasis with topical agents: Recommendations from a Tuscany Consensus

Psoriasis is a chronic and relapsing inflammatory skin disease, clinically characterized by erythematous and scaly plaques. Treatment approach is mainly driven by disease severity, though several factors should be considered in order to identify the optimal therapeutic choice. Mild psoriasis may be treated with a wide array of topical agents including corticosteroids, vitamin D analogs, keratolytics, and calcipotriol/betamethasone propionate compound. Because guidelines may not provide practical indications regarding the therapeutic approach, the use of topical agents in psoriasis is more individually tailored. In order to homogenize the standard of care, at least in a local setting, we collected the real‐life‐based recommendations for the use of topical therapies from an expert panel, the Tuscany Consensus Group on Psoriasis, representing all leading centers for psoriasis established in Tuscany. With this document, this consensus group sought to define principles guiding the selection of therapeutic agents with straightforward recommendations derived from a real‐life setting.     

Psoriasis and bone mineral density: Implications for long‐term patients

Psoriasis is a chronic inflammatory disease associated with several comorbidities. Osteoporosis is defined as a reduction in bone mineral density with impaired bone microarchitecture. Several mechanisms may be implicated as a possible cause for the association between psoriasis and osteoporosis, such as systemic inflammation, anti‐psoriatic drug intake and joint dysfunction for psoriatic arthritis (PsA). The aim of the present study was to assess bone mineral density (BMD) in patients with psoriasis, correlating the prevalence of osteopenia/osteoporosis with Psoriasis Area and Severity Index (PASI) score, mean duration of psoriatic disease, PsA and previous treatments for psoriasis. Forty‐three consecutive patients with psoriasis, 19 of whom were affected by the arthropathic form, were enrolled. We evaluated the severity of psoriasis as measured by PASI score, the CASPAR criteria and ultrasounds of the joints to verify the diagnosis of PsA and the age of psoriasis onset to estimate mean disease duration. Patients underwent a bone density scan of the lumbar spine and femoral neck by dual‐energy X‐ray absorptiometry to measure BMD. Patients with osteopenia/osteoporosis showed a statistically significant longer average duration of psoriatic disease (17 years), compared to patients affected by psoriasis with normal T‐score (8.8 years) (P = 0.04). The linear logistic regression confirms a significant relation between mean psoriatic disease duration and BMD alterations (P = 0.04). Our results suggest the necessity of an early diagnostic evaluation of bone metabolism in patients with psoriasis, especially if characterized by longer disease duration.     

The use of ustekinumab in a patient with severe psoriasis and positive HBV serology

Psoriasis is a chronic inflammatory, immune-mediated disease that affects 1% to 2% of the world''s population. Immunobiological medications are prescribed for certain patients with severe forms of psoriasis, however, these drugs increase the risk of reactivation of viral diseases such as hepatitis B. We report the case of a patient with severe psoriasis with positive serology for the Hepatitis B virus, who received ustekinumab (a human monoclonal antibody against interleukin 12 and 23). In this patient, the use of ustekinumab did not reactivate the Hepatitis B virus. Given the high prevalence of chronic viral infections in patients who are candidates for biologic therapy, as well as the potential for reactivate chronic viral illness, randomized controlled studies are needed to assess the risks and benefits of such therapy in these populations.     

IL-12/23抑制剂乌司奴单抗在银屑病治疗中的应用

银屑病是一种免疫紊乱介导的以皮肤慢性炎症性改变为主的系统性疾病,临床表现为皮肤红斑鳞屑,可累及指(趾)甲及关节。IL-12和IL-23是参与银屑病发病的重要细胞因子,乌司奴单抗是靶向抑制IL-12和IL-23共有亚基p40的全人源单克隆抗体制剂,多项国内外随机对照临床试验结果表明,乌司奴单抗应用于中重度斑块型银屑病和关节病型银屑病的治疗可显著改善病情,提高患者生活质量,具有良好的有效性、长期稳定性和安全性。     

Psoriasis in those planning a family,pregnant or breast‐feeding. The Australasian Psoriasis Collaboration

The Australasian Psoriasis Collaboration has reviewed the evidence for managing moderate to severe psoriasis in those who are pregnant or are breast‐feeding, or planning a family. The severity of the psoriasis, associated comorbidities and specific anti‐psoriasis treatment, along with other exposures, can have a deleterious effect on pregnancy outcomes. Psoriasis itself increases the risk of preterm and low birthweight babies, along with spontaneous and induced abortions, but no specific birth defects have been otherwise demonstrated. The baseline risk for a live born baby to have a major birth defect is 3%, and significant neuro‐developmental problem is 5%. In Australia, pregnant women with psoriasis are more likely to be overweight or obese, depressed, or smoke in their first trimester, and are also less likely to take prenatal vitamins or supplements. Preconception counselling to improve maternal, pregnancy and baby health is therefore strongly encouraged. The topical and systemic therapies commonly used in psoriasis are each discussed separately, with regards to pregnancy exposure, breast‐feeding and effects on male fertility and mutagenicity. The systemic therapies included are acitretin, adalimumab, apremilast, certolizumab, ciclosporin, etanercept, infliximab, ixekizumab, methotrexate, NBUVB, prednisone, PUVA, secukinumab and ustekinumab. The topical therapies include dithranol (anthralin), calcipotriol, coal tar, corticosteroids (weak, potent and super‐potent), moisturisers, salicylic acid, tacrolimus, and tazarotene. As a general recommendation, effective drugs that have been widely used for years are preferable to newer alternatives with less foetal safety data. It is equally important to evaluate the risks of not treating, as severe untreated disease may negatively impact both mother and the foetus.     

Efficacy and safety of ustekinumab treatment in elderly patients with psoriasis

The ratio of the elderly among psoriasis patients has been increasing. However, satisfactory long‐term management of psoriasis for the elderly is challenging because of the more frequent presence of comorbidities, and the higher risk of adverse events from systemic therapeutic agents than younger patients. The use of ustekinumab (UST) appears to be an appropriate systemic treatment because it is considered less likely to cause adverse events than other systemic treatments, as well as necessitating fewer hospital visits. Our retrospective study aimed to evaluate the efficacy and safety profile of UST in elderly patients with psoriasis. The study included 24 patients aged over 65 years (range, 65–88 years; mean, 73.1 years) with moderate to severe plaque psoriasis with impaired quality of life. Efficacy and safety were assessed over a 1‐year period using the Psoriasis Area and Severity Index (PASI) and the Dermatology Live Quality Index (DLQI). The efficacy was evaluated by the proportion of subjects who achieved ≥75% reduction in PASI score (PASI 75). PASI 75 responses were 56.5% at week 16, 59.1% at week 28, and 60.0% at week 52. None of the patients developed any serious infection during the 1‐year treatment. The mean DLQI score at weeks 0, 16, 28, and 52 was 7.8 ± 6.0, 2.5 ± 3.4, 1.4 ± 1.7, and 1.2 ± 1.7, respectively. UST showed sufficient efficacy for elderly patients with psoriasis without any serious infection over the 1‐year treatment. Our results suggest that UST is the preferable agent for the treatment of elderly patients with psoriasis.     

Ustekinumab treatment for hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a follicular occlusive inflammatory skin disease that occurs in the axilla, groin, buttocks and vulval region. Control of the intractable inflammation is a primary goal of HS treatments. Benefit of anti‐tumor necrosis factor (TNF) antibodies against HS have been reported, and adalimumab has been approved for HS in Europe, the USA and Japan. However, the alternative therapies for anti‐TNF antibodies have not been established yet. We experienced a case of HS which developed during the infliximab treatment for Crohn’s disease (CD) and was well managed by ustekinumab (UST). We reviewed the articles relating to ustekinumab treatments for HS. Twenty‐four HS patients, 16 women and eight men, have been treated with ustekinumab. The average age was 35.7 ± 10.8 years (mean ± SD). All were of Hurley stage II or III. Ten (10/24, 41.6%) had received anti‐TNF drugs including infliximab, adalimumab and etanercept prior to UST treatment for HS. Although the initial doses varied from 45 mg s.c. to 390 mg i.v., all cases were treated with 45 or 90 mg s.c. every 8 or 12 weeks at the regular dose, by following the regimen for psoriasis or CD. HS in most of the cases started to improve after 3–5 months of UST initiation, and some achieved complete remission. To our knowledge, our case is the first Asian HS patient improved by UST. Overall, UST is useful for HS and could be an alternative treatment if HS patients do not respond to other medications including anti‐TNF drugs.     

Serum C‐reactive protein levels in Japanese patients with psoriasis and psoriatic arthritis: Long‐term differential effects of biologics

Psoriasis has been shown to accompany systemic inflammation. We aimed to examine serum C‐reactive protein (CRP) levels in Japanese psoriatic patients, and to elucidate their long‐term as well as short‐term changes by treatment with different biologics. A retrospective study was conducted in those who initiated and successfully continued the treatment for up to 24 months with either infliximab, adalimumab or ustekinumab, at the psoriasis special clinic of Jikei University School of Medicine. A total of 212 patients were included, 171 with plaque‐type psoriasis (PsV) and 41 with psoriatic arthritis (PsA). A statistically significant elevation of CRP values was found in the group with a Psoriasis Area and Severity Index (PASI) of 12 or more compared with the PASI of less than 12 for both PsV and PsA. The CRP‐positive patients had a higher proportion of PsA compared with the CRP‐negative patients, and they had significantly higher PASI scores. Serum CRP values declined as early as at 3 months after systemic treatment with biologics. Tumor necrosis factor (TNF)‐α antagonists did lead to a notable and sustained CRP decline up to 24 months. Infliximab showed rapid decline, while CRP decline by adalimumab treatment was time‐dependent. The interleukin‐12/23 p40 antagonist, ustekinumab, appeared to be less potent than TNF‐α antagonists in stabilizing CRP values at low levels despite good control of cutaneous lesions. In conclusion, serum CRP levels can be used to assess disease severity in Japanese psoriatic patients as a marker of systemic inflammation. TNF‐α antagonists may be more beneficial than ustekinumab in this regard.     

Brodalumab in patients who had inadequate response to ustekinumab

Psoriasis is a chronic condition that causes red, scaly patches on the surface of the skin. Treatments may include topical (applied to the skin) creams and oral and injectable medications. Psoriasis can be caused by an autoimmune reaction in which the body's own immune system attacks healthy cells and tissues. To treat moderate-to-severe psoriasis, doctors sometimes use specialized medicines called antibodies, which block different parts of the autoimmune reaction that can lead to psoriasis. Although these antibody treatments can be very effective, they do not work in every patient. This study looked at data from two clinical studies of patients with moderate-to-severe psoriasis. In each study, patients were initially given one of two antibody treatments: ustekinumab or brodalumab. Some patients initially given ustekinumab or brodalumab did not have adequate skin clearance at week 16; these patients either started taking brodalumab (if they were initially given ustekinumab) or continued taking brodalumab (if they were initially given brodalumab) through to week 52. Patients who experienced inadequate response to their initial treatment after week 16 continued to receive their initial treatment until week 52. At week 52, patients who switched to brodalumab after an inadequate response to ustekinumab showed improvement in skin clearance. Skin clearance in patients who continued taking ustekinumab following inadequate response after week 16 was not as complete as skin clearance in those who switched to brodalumab after an inadequate response at week 16. Additionally, side effects were similar between patients who switched to brodalumab and those who remained on ustekinumab. The results of this study suggest brodalumab may be a successful treatment in patients with moderate-to-severe psoriasis who do not experience adequate skin clearance with other psoriasis treatments.     

Secukinumab demonstrates superior efficacy and a faster response in clearing skin in Asian subjects with moderate to severe plaque psoriasis compared with ustekinumab: Subgroup analysis from the CLEAR study

The 52‐week results from the CLEAR (NCT02074982) study showed high and superior efficacy of secukinumab versus ustekinumab in clearing skin and improving patient‐reported outcomes, with comparable safety profile in subjects with moderate to severe psoriasis. Here, we analyzed the efficacy and safety of secukinumab in Asian subjects from the CLEAR study. In this double‐blind, phase IIIb study, eligible subjects with moderate to severe plaque psoriasis were randomized (1:1) to receive s.c. injection of secukinumab 300 mg or ustekinumab as per label. Of 62 subjects included in Asian subanalyses, 23 were randomized to secukinumab and 39 to ustekinumab. A significantly higher proportion of subjects achieved 90% or more improvement in Psoriasis Area and Severity Index (PASI 90) with secukinumab versus ustekinumab at week 16 (78.3% vs 35.9%, P = 0.0010) and at week 52 (60.9% vs 33.3%, P = 0.0196). Similarly, a higher proportion of subjects achieved PASI 100 with secukinumab versus ustekinumab at week 16 (43.5% vs 10.3%, P = 0.0029) and at week 52 (30.4% vs 12.8%, P = 0.0704). The median time to achieve 50% improvement in baseline PASI was 2.8 weeks in the secukinumab group versus 6.3 weeks in the ustekinumab group. The safety profile of secukinumab was in line with the known profile and no deaths occurred. Overall, 95.7% and 84.6% of subjects remained on secukinumab and ustekinumab, respectively. Similar to the core study, secukinumab showed sustained and superior efficacy with faster response versus ustekinumab, and no new or unexpected safety concerns were identified, in Asian subjects with moderate to severe plaque psoriasis.     

Some clinical factors affecting quality of the response to ustekinumab for psoriasis

Ustekinumab has demonstrated efficacy for psoriasis. However, it is known that approximately 30% of patients have shown insufficient response. The aim of the current study is to clarify the specific clinical factors that could be associated with response to ustekinumab treatment. We reviewed the medical records of all patients who were treated with ustekinumab. The Psoriasis Area and Severity Index (PASI) score was calculated, and the efficacy was evaluated at week 0 and week 16. The relationship between clinical efficacy and the patients’ background was investigated. The patients, who showed a <74% reduction in the PASI score, were classified as insufficient‐responders. A total of 74 patients (average 60.3 years old, male to female ratio 54:20) were examined retrospectively. Eighteen patients were identified as insufficient‐responders. Each of the factors, body weight (BW) over 80 kg, body mass index (BMI) over 25, or smoking habit over 20 cigarettes/day showed a higher proportion of insufficient‐responders compared with responders, although the difference was not statistically significant. Patients with previous exposure to biologics showed a significantly lower response to the treatment. Furthermore, a statistical difference was identified between patients with none of these factors and patients with some of these factors. Our data suggest that some factors, such as high BW, high BMI, a smoking habit over 20 cigarettes/day, or exposure previous treatment with biologics are likely to affect the quality of the response to ustekinumab. Therefore, these factors need to be taken into account when ustekinumab is administrated.     

Impact of ustekinumab on health‐related quality of life and sexual difficulties associated with psoriasis: results from two phase III clinical trials

Background Ustekinumab, a human anti‐interleukin‐12/23 monoclonal antibody, has been shown to effectively treat moderate‐to‐severe psoriasis which significantly affects health‐related quality of life (HRQoL), including patients’ sexual lives. Objectives The aim of this study was to determine if sexual difficulties associated with psoriasis are related to disease severity and whether sexual difficulties improve with skin disease during ustekinumab treatment. Methods  In phase III PHOENIX 1 and 2 trials, psoriasis patients were randomized to ustekinumab (n = 1334) at weeks 0 and 4 and q12 weeks thereafter or placebo (n = 662) at weeks 0 and 4 with crossover to ustekinumab at week 12. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were used to assess psoriasis severity and patient‐reported HRQoL respectively. Based on DLQI Question #9, impaired sexual function was defined as ‘very much’ or ‘a lot’ of sexual difficulties. Results At baseline, mean DLQI was 12.0, indicating a very large negative effect on patients’ lives. Impaired sexual function was reported by 22.6% (women = 27.1%; men = 20.8%) and was significantly associated with increased psoriasis severity. At week 12, ustekinumab‐treated patients had a greater mean improvement in DLQI (?9.13 vs. ?0.53 with placebo, P < 0.001) and the proportion of patients with impaired sexual function decreased from 22.4% to 2.7% compared with no change with placebo (P < 0.001). Patients with greater PASI improvement experienced a greater reduction of sexual difficulties due to psoriasis. A similar pattern of improved sexual function was observed at weeks 24–28 in placebo crossover patients. Conclusions Ustekinumab treatment is associated with significant improvement in HRQoL and sexual difficulties due to psoriasis.     

Efficacy and safety of guselkumab in psoriasis patients who failed ustekinumab and/or anti‐interleukin‐17 treatment: A real‐life 52‐week retrospective study

Recent major research advancements have significantly expanded our understanding of psoriasis pathophysiology, resulting in the development of highly effective, targeted therapies. Guselkumab is the first interleukin (IL)‐23 inhibitor approved for the treatment of moderate‐to‐severe‐psoriasis, providing a new therapeutical option for psoriasis. The aim of our study was to evaluate the efficacy of guselkumab in psoriatic patients who previously failed anti‐IL‐12/23 and/or anti‐IL‐17 treatment. A 52‐week single‐center retrospective study was performed enrolling moderate‐to‐severe patients attending our Psoriasis Care Center from October 2018 to May 2020. Study population included 13 patients; 46.1% have been previously treated with ustekinumab, while 69.2% have previously failed an anti‐IL‐17 treatment (38.5% secukinumab, 30.8% ixekizumab, and 38.5% both). At baseline, mean Psoriasis Area and Severity Index was 13.2 ± 6.8, reducing up to 0.5 ± 0.7 at week 52 (P < .001). Body surface area reduced from 22.3 ± 10.5 (baseline) to 0.8 ± 1.1 at week 52 (P < .001). No statistically significant differences have been found between patients previously treated with anti‐IL‐12/23 compared to anti‐IL‐17 or both. Only one patient discontinued guselkumab at week 36 due to secondary inefficacy. This is a single institution study with a relatively small sample size. Our real‐life data confirm trial results, showing guselkumab as a safe and effective option in patients with moderate‐to‐severe psoriasis even in those who previously failed ustekinumab and/or anti‐IL‐17 treatment.     

Treatment with 311-nm ultraviolet B enhanced response of psoriatic lesions in ustekinumab-treated patients: a randomized intraindividual trial

Background Treatment with the interleukin‐12/23 antibody ustekinumab produces a satisfactory response [i.e. 75% reduction in Psoriasis Area and Severity Index (PASI) compared with baseline (PASI 75)] in the majority of patients with moderate to severe chronic plaque‐type psoriasis. Objectives To determine whether concomitant 311‐nm ultraviolet (UV) B therapy can further enhance the response in patients with psoriasis treated with ustekinumab. Methods Ten patients (five women and five men; mean age 58 years, range 48–66) with moderate to severe plaque‐type psoriasis were treated with ustekinumab at a standard dosage of 45 or 90 mg subcutaneously depending on body weight (below or above 100 kg) at weeks 0 and 4. Within 2 days after ustekinumab initiation, the minimal erythemal dose (MED) was determined and suberythemal MED 311‐nm UVB‐based phototherapy was thereafter administered to one randomly selected body half (left or right, excluding the head) three times weekly for 6 weeks. Treatment response was monitored weekly in terms of half‐body PASI. Results Nine patients completed the study. Analysis of their data showed that 311‐nm UVB significantly accelerated the therapeutic response. At baseline (i.e. start of 311‐nm UVB therapy), the mean PASI was similar in both irradiated and unirradiated body halves (13·6 vs. 13·3). At week 6, however, it was lower on irradiated body halves (2·5 vs. 6·1). This difference of 3·6 (95% confidence interval 1·3–5) was statistically significant and corresponded to an overall mean PASI reduction from baseline of 82% vs. 54%, respectively. At week 6, PASI 75 was achieved significantly more often on UV‐irradiated body halves than on unirradiated body halves [7/9 patients (78%) vs. 1/9 (11%)] (McNemar test, P = 0·007). At week 12, this synergistic effect of 311‐nm UVB was still apparent although not significantly so. Conclusions Treatment with 311‐nm UVB accelerates the clearance of psoriatic lesions in ustekinumab‐treated patients.     

The interpretation of long‐term trials of biologic treatments for psoriasis: trial designs and the choices of statistical analyses affect ability to compare outcomes across trials

Psoriasis is a chronic disease requiring long‐term therapy, which makes finding treatments with favourable long‐term safety and efficacy profiles crucial. The goal of this review is to provide the background needed to evaluate properly long‐term studies of biologic treatments for psoriasis. Firstly, important elements of design and analysis strategies are described. Secondly, data from published trials of biologic therapies for psoriasis are reviewed in light of the design and analysis choices implemented in the studies. Published reports of clinical trials of biologic treatments (adalimumab, alefacept, etanercept, infliximab or ustekinumab) that lasted 33 weeks or longer and included efficacy results and statistical analysis were reviewed. Study designs and statistical analyses were evaluated and summarized, emphasizing patient follow‐up methods and handling of missing data. Various trial designs and data handling methods are used in long‐term studies of biologic psoriasis treatments. Responder analyses in long‐term trials can be conducted in responder enrichment, re‐treated nonresponder or intent‐to‐treat trials. Missing data can be handled in four ways, including, from most to least conservative, nonresponder imputation, last‐observation‐carried‐forward, as‐observed analysis and anytime analysis. Long‐term clinical trials have shown that adalimumab, alefacept, etanercept, infliximab and ustekinumab are efficacious for psoriasis treatment; however, without common standards for these trials, direct comparisons of these agents are difficult. Understanding differences in trial design and data handling is essential to make informed treatment decisions.     

Childhood Psoriasis—An Analysis of German Health Insurance Data

This study explored the epidemiology, treatment, and comorbidities of juvenile psoriasis in Germany using health insurance data. Psoriasis is a chronic inflammatory skin condition that affects approximately 2% to 3% of the world's population. Data were obtained from a database of approximately 6.7 million individuals registered with health insurance organizations throughout Germany. The analysis considered all individuals age 18 years and younger with psoriasis who were registered in 2007. Comorbidities were identified using software based on a morbidity‐based risk adjustment model. A total of 138,338 patients with a diagnosis of psoriasis were identified in the database, yielding a prevalence of 2.1%. Within this group there were 4,499 children and adolescents (≤18 years of age), a prevalence of 0.4%. The prevalence ranged from 0.1% at the age of 1 year to 0.8% at the age of 18 years. Most of the patients were treated with topical corticosteroids (72.2%) and antipsoriatics (e.g., tars, psoralen; 20.0%). Immunosuppressants were used in 3.3% of the cases. Juvenile psoriasis was associated with numerous significant comorbidities such as rheumatoid arthritis and inflammation (2.1%); delirium, psychosis, and psychotic and dissociative disorder (1.1%); and heart disease (0.6%). Our study demonstrated that psoriasis is more prevalent in children and adolescents than some older international investigations have documented. Analysis of the health insurance data showed that juvenile psoriasis is associated with a range of comorbidities. The data also may suggest an unrecognized burden of mental health problems in young persons with psoriasis.     

Topical application of anti-angiogenic peptides based on pigment epithelium-derived factor can improve psoriasis

BackgroundPsoriasis is a common chronic inflammatory skin disorder with a high prevalence (3–5%) in the Caucasian population. Although the number of capillary vessels increases in psoriatic lesions, there have been few reports that have specifically examined the role of angiogenesis in psoriasis. Angiogenic factors, such as vascular endothelial growth factor (VEGF), may dominate the activity of anti-angiogenic factors and accelerate angiogenesis in psoriatic skin.ObjectiveWe investigated to identify small peptide mimetics of PEDF that might show anti-angiogenic potential for the topical treatment for psoriasis.MethodsWe examined the expression of PEDF in skin by immunohistochemical staining, immunoblotting, and RT-PCR. To identify potential PEDF peptides, we screened peptides derived from the proteolytic fragmentation of PEDF for their anti-proliferative action. Anti-psoriatic functions of these peptides were analyzed using a mouse graft model of psoriasis.ResultsThe specific low-molecular weight peptides (MW < 850 Da) penetrated the skin and showed significant anti-angiogenic activity in vitro. Topical application of these peptides in a severe combined immunodeficient mouse model of psoriatic disease led to reduced angiogenesis and epidermal thickness.ConclusionsThese data suggest that low-molecular PEDF peptides with anti-angiogenic activity may be a novel therapeutic strategy for psoriasis.