Pediatric psoriasis and psoriatic arthritis

Psoriasis and psoriatic arthritis (PsA) are not uncommon among the pediatric population. Recognizing and treating these chronic disorders in children present unique challenges for the dermatologist. Paucity of clinical trials and a dearth of available treatment modalities, many of which carry significant risk or adverse effects, can make treating pediatric psoriasis and PsA a daunting task. This review attempts to define and consolidate the current state of knowledge with regards to this disease spectrum. The need for further clinical trials to investigate treatment options in the pediatric population is also discussed.     

Therapeutic hotline. Abatacept: our experience of use in two patients with refractory psoriasis and psoriatic arthritis

The B7 family of molecules on antigen presenting cells (APCs) regulate T cell activation. They deliver stimulatory signals through CD28 and inhibitory signals through CD152, or cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). CTLA4Ig (abatacept) is a soluble chimeric protein consisting of the extracellular domain of human CD152 linked to the modified Fc portion of human IgG1. By binding to B7-1 (CD80) and B7-2 (CD86) molecules on APCs, CTLA4Ig blocks the CD28-mediated costimulatory signal for T cell activation. Success with abatacept has been noted in psoriasis. Abatacept was administered to two patients with refractory psoriasis and psoriatic arthritis after the patients had failed all conventional treatment methods. Both patients experienced very brief improvement in disease. The improvement, however, was not continued, and both patients were taken off the medication. The small patient population limits the extrapolation of the present authors' results to the larger population. Furthermore, the present authors' patients have very severe, refractory disease and do not adequately represent the majority of psoriasis patients. Although the present authors' patients demonstrated brief response to drug, this response was not sustained. No adverse events were reported in the present authors' patients.     

Newly available treatments for psoriatic arthritis and their impact on skin psoriasis

Far from being a "benign" arthropathy, as it was initially characterized, psoriatic arthritis (PsA) affects approximately 0.2% of the US population and can be associated with considerable joint damage, symptomatology, and quality of life impairment. PsA shares many characteristics with rheumatoid arthritis (RA), and new, rationally designed drugs that are effective in RA also are proving active in PsA. Two such drugs, etanercept and infliximab, target tumor necrosis factor (TNF), a key component of the inflammatory response. This review discusses the rationale for and experience with the use of these agents in PsA. Etanercept is a dimeric fusion protein that binds specifically to TNF, blocking its interaction with cell surface TNF receptors. Infliximab is a chimeric (murine/human) monoclonal antibody that binds to TNF and inhibits its binding to its receptor. A randomized placebo-controlled trial of etanercept in PsA found statistically significant benefits for this agent in measures of arthritic activity and psoriatic severity. There have been anecdotal reports of the efficacy of infliximab in PsA, but results from controlled clinical trials of this agent in PsA have not been reported. TNF inhibitors represent new therapeutic options for patients with PsA. The potential advantages of treatment with etanercept and infliximab early in the disease course are discussed.     

Long-term study of infliximab in Japanese patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma

The efficacy and safety of infliximab in patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis (excluding localized type) and psoriatic erythroderma were assessed in clinical practice. Without washout of the existing treatment of psoriasis, treatment was switched to infliximab, which was given at a dose of 5 mg/kg at weeks 0, 2 and 6 and then every 8 weeks up to week 46. The primary end-points were 75% improvement in Psoriasis Area and Severity Index score (PASI 75 response rate) for plaque psoriasis, 20% improvement in American College of Rheumatology criteria (ACR 20 response rate) for psoriatic arthritis, and global improvement in pustular psoriasis and psoriatic erythroderma. The PASI 75 response rate in plaque psoriasis was 72.2% at week 10 and 53.6% at week 50. The ACR 20 response rate in psoriatic arthritis was 66.7% at week 14 and 80.0% at week 46. The response defined as global improvement in pustular psoriasis was between 66.7% and 100.0% during the 2–50-week period. The response defined as global improvement in psoriatic erythroderma was between 75.0% and 100.0% during the week-2–50 period. There were 14 discontinued patients. The most frequently reported reason for discontinuation was the development of adverse events. However, there were no serious respiratory diseases, infections or infusion reactions. In patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma, infliximab was well tolerated, regardless of prior treatment, and also showed superior efficacy over a period of approximately 1 year.     

Dietary habits in Japanese patients with psoriasis and psoriatic arthritis: Low intake of meat in psoriasis and high intake of vitamin A in psoriatic arthritis

Psoriasis is characterized by T‐helper 17 cell‐dominant abnormal immunity, and hyperproliferation and abnormal differentiation of epidermal keratinocytes. Some patients are associated with arthritis. Dietary habits can modulate the pathogenesis of psoriasis. Previous studies in Western countries showed higher body mass indices, higher intake of fat and lower intake of fish or vegetables in psoriatic patients compared with the reference groups. We evaluated dietary habits in adult Japanese psoriatic patients, using a validated brief‐type self‐administered dietary history questionnaire, and compared the results to those of age‐ and sex‐matched healthy controls. The results in psoriatic patients with arthritis were compared with those in the patients without. Japanese psoriatic patients showed higher body mass indices, higher intake of fish/shellfish, pulses, sugar/sweeteners, vitamin B₁₂ and vitamin D, and lower intake of meat, compared with those of healthy controls. The logistic regression analysis showed that psoriasis was associated with high body mass index and low intake of meat. The intake of confection in patients with high Psoriasis Area and Severity Index was higher than that in those with low index. The intake of β‐carotene, vitamin A and green/yellow vegetables in psoriatic patients with arthritis were higher than those in the patients without. The dietary habits in Japanese psoriatic patients are rather different from those in Western patients. This is the first study showing the differences in dietary habits between psoriatic patients with arthritis and those without. Further studies should elucidate the relationships of these results with skin and joint lesions in psoriatic patients.     

银屑病和银屑病关节炎与溃疡性结肠炎相关性Meta分析

目的:有研究报道银屑病或银屑病关节炎患者溃疡性结肠炎发生率明显高于正常人,本文目的在于进一步明确银屑病、银屑病关节炎与溃疡性结肠炎的相关性。方法:通过Pubmed、Cochrane Library、Embase、知网、万方等数据库检索银屑病、银屑病关节炎并溃疡性结肠炎相关文献,采用Review Manager 5.3软件进行Meta分析。结果:共纳入13篇文献,横断面研究3篇、病例对照研究2篇、队列研究8篇,包含银屑病723 402例,银屑病关节炎37 059例,Meta分析结果显示银屑病与溃疡性结肠炎[RR=1.65(95%CI 1.55～1.76),OR=1.76(95%CI 1.43～2.17)],差异具有统计学意义,银屑病关节炎与溃疡性结肠[RR=2.14 (95%CI 1.72～2.66),OR=2.05 (95%CI 1.50～2.80)],差异具有统计学意义。结论:银屑病、银屑病关节炎可能增加溃疡性结肠炎的发生率。     

中重度银屑病与银屑病性关节炎肌骨超声关节改变的比较

目的：比较中重度银屑病和银屑病性关节炎患者的关节超声表现的差异。方法：纳入2014年2月至2017年8月住院期间接受肌骨超声检查的中重度银屑病和银屑病性关节炎患者。评估两组患者的附着点炎、滑膜炎、骨侵蚀、关节间隙狭窄、甲病变等关节相关病变。结果：与310例中重度银屑病患者相比，112例银屑病性关节炎患者的年龄更大、病程更长、关节超声异常表现比例更高。96.4%（108/112）的银屑病性关节炎患者和81.9%（254/310）的中重度银屑病患者超声显示关节改变。结论：本研究中重度银屑病患者和银屑病性关节炎患者关节超声异常比较均较高，临床上应重视中重度银屑病患者的关节改变筛查。     

Dermoscopy of nail fold and elbow in the differential diagnosis of early psoriatic arthritis sine psoriasis and early rheumatoid arthritis

Differentiation between psoriatic arthritis (PsA) sine psoriasis and rheumatoid arthritis (RA) may be a challenge, especially in the early stages, hence the need for new instrumental markers to assist their diagnosis. In this study, we investigated possible dermoscopic differences in vascular appearance of nail fold and elbow (a classic site of repeated trauma) in these two conditions. Fifteen patients with PsA sine psoriasis, 12 patients with RA and 12 controls were included in the study. Regarding the nail fold vascular appearance in PsA sine psoriasis and RA cohorts, the presence of diffuse reddish background with or without sparse dotted vessels was significant in the former, whereas the evidence of parallel dotted/short linear vessels (“fish school‐like” pattern) or irregular/ramified, blurry, purple vessels were significant in the latter; none of these patterns were detected in the control group. Regarding the elbow, the pattern significantly associated with PsA sine psoriasis consisted of diffusely distributed, red, dotted vessels. On the other hand, RA patients and controls displayed similar dermoscopic findings, with three possible vascular patterns being observed: (i) irregular, blurry, purple vessels; (ii) avascular appearance; and (iii) sparse, dotted, purple vessels. In conclusion, dermoscopy may be a useful supportive tool for differentiating early PsA sine psoriasis from RA.     

Risk factors and predictors of psoriatic arthritis in patients with psoriasis

Given the potential consequences of joint damage for patients with psoriaticarthritis, we believe that the optimization of screening methods and theinvestigation of arthritis in patients with psoriasis are a medical priority. It isvery useful to identify predictors of arthritis in patients with psoriasis. In fact,there is a consensus among doctors that the large gap between the diagnosis ofpsoriasis and that of psoriatic arthritis should be narrowed. In order to bettermanage patients with psoriasis, the authors review and discuss recent publications onthe evidence of current predictors of arthritis in patients with psoriasis.     

Etanercept for the treatment of psoriasis and psoriatic arthritis

Etanercept is a fully human soluble recombinant p75 TNF receptor that blocks the binding of TNF to cell surface receptors, thereby neutralizing its biologic activity. Data supporting the FDA's approval of etanercept for controlling signs and symptoms and for inhibiting XRAY progression of psoriatic arthritis will be presented. Data supporting the FDA filing of etanercept for the treatment of moderate to severe psoriasis will also be presented. Long term safety data of etanercept in the over 231,000 adults and children with rheumatoid arthritis who have been treated worldwide will be briefly summarized.     

New biologics for psoriasis and psoriatic arthritis

The prevalence of psoriasis is estimated to be 2.2% in the United States, and 6–39% of patients with psoriasis also develop psoriatic arthritis. New advances have been made in developing treatment options. A new human tumor necrosis factor (TNF)-α antibody, golimumab, has been shown to significantly improve symptoms of psoriatic arthritis. In addition, clinical trials of certolizumab pegol, a PEGylated Fab' fragment of an anti-TNF-α monoclonal antibody, show promising results for treating rheumatoid arthritis and suggest that it may be applicable for treating psoriasis and psoriatic arthritis in the future. New biologic therapies also include antibodies to interleukin-12 and interleukin-23. Phase II studies suggest that ustekinumab is effective in alleviating symptoms of psoriasis and psoriatic arthritis. However, longer studies with radiographic evaluation will be required before their impact on joint destruction can be assessed.     

Adalimumab for treatment of moderate to severe psoriasis and psoriatic arthritis

Psoriasis and psoriatic arthritis are common diseases associated with considerable morbidity and disability. Their pathophysiology comprises similar processes leading to inflammation of skin, entheses, and joints. Although traditional systemic agents can be effective, their use may be limited by lack of efficacy and concerns regarding adverse effects. The objective of this study was to assess the efficacy and safety of adalimumab, a fully human antitumor necrosis factor (anti-TNF) monoclonal antibody, over 16 weeks. The present authors report their personal experience in 15 patients with severe plaque psoriasis and psoriatic arthritis, refractory to other treatments, in which a decisive regression of joint/skin involvement was obtained. Psoriasis and psoriatic arthritis are chronic inflammatory disorders resulting from a combination of genetic and environmental factors.     

Epidemiology and clinical pattern of psoriatic arthritis in Germany: a prospective interdisciplinary epidemiological study of 1511 patients with plaque-type psoriasis

Background  Because psoriatic arthritis (PsA) usually develops years after the first manifestation of skin symptoms, in many cases the initial diagnosis of PsA depends on the dermatologist.
Objectives  To investigate the prevalence and clinical pattern of PsA in a daily practice population of patients with psoriasis.
Methods  Patients were enrolled in an observational prospective cross-sectional cohort study at 48 community and academic centres. Demographic and medical parameters were recorded, including severity of skin symptoms (Psoriasis Area and Severity Index, PASI), previous and current treatments, concomitant diseases, and the impact of psoriasis on productivity and health-related quality of life (Dermatology Life Quality Index, DLQI). Patients with joint symptoms were referred to a rheumatologist for diagnosis and to record the activity and pattern of arthritis.
Results  Among 1511 patients 20·6% had PsA; in 85% of the cases PsA was newly diagnosed. Of these patients more than 95% had active arthritis and 53·0% had five or more joints affected. Polyarthritis (58·7%) was the most common manifestation pattern, followed by oligoarthritis (31·6%) and arthritis mutilans (4·9%). Distal interphalangeal involvement was present in 41·0% and dactylitis in 23·7% of the patients. Compared with patients without arthritis, patients with PsA had more severe skin symptoms (mean PASI 14·3 vs. 11·5), a lower quality of life (mean DLQI 11·6 vs. 7·7) and greater impairment of productivity parameters.
Conclusions  The findings are consistent with a high prevalence of undiagnosed cases of active PsA among patients with psoriasis seen by dermatologists. As many of these patients also have significant skin symptoms, treatment strategies are required that are equally effective in the control of skin and joint symptoms of psoriasis.     

Bilateral upper limb lymphoedema associated with psoriatic arthritis: a case report and review of the literature

Lymphoedema is an unusual extra-articular feature of rheumatoid arthritis and has rarely been described in psoriatic arthritis. We report a 41-year-old man with psoriasis and psoriatic arthritis who developed bilateral lymphoedema of the upper extremities. Lymphoscintigraphy showed absent lymphatic drainage in the right arm and a subnormal increase in lymphatic flow under manual exertion in both arms. Colour Doppler ultrasound studies did not reveal venous or arterial abnormalities. Conservative management and therapy with cyclosporin (for worsening arthritis) resulted in partial resolution of the lymphoedema and improvement of flow parameters on the right side upon repeat lymphoscintigraphy.     

Prevalence and clinical features of psoriatic arthritis and joint complaints in 2009 patients with psoriasis: results of a German national survey

Background  Psoriatic arthritis (PsA) is a chronic, systemic, inflammatory disorder characterized by the association of arthritis with psoriasis. Patients with PsA may have a heterogeneous and variable clinical course. Evidence that affected patients can have significant radiographic joint damage, functional impairment, reduced quality of life and long-term work disability is increasing.
Objectives  This study aims to determine the prevalence and clinical features of psoriatic arthritis and joint complaints in patients with psoriasis examined in a German national survey.
Methods  This study is a non-interventional, cross-sectional analysis on 2009 patients with psoriasis from 13 dermatological hospitals and 129 dermatological private practices and outpatient clinics in Germany. Patients showing rheumatological symptoms were further recorded with respect to active arthritis and PsA symptoms according to Group for Research and Assessment of Psoriasis and Psoriatic Arthritis criteria.
Results  Nineteen per cent of the patients had PsA, including 14.8% previously confirmed and 4.2% newly diagnosed disease. Another 7.7% had intermittent but clinically unspecific joint symptoms, which could not be clearly attributed to PsA. About half (49.7%) of the patients with PsA had at least 1 swollen joint and 84.9% ( n  = 287) suffered from joint pain. Patients suffering from pain marked an average of 8.7 joints on a diagram as painful out of a possible 28. The mean number of swollen joints among the affected patients amounted to an average of 6.8.
Conclusion  Our results show that there is still a significant number of patients suspected of having joint involvement without ever having been diagnosed with PsA. Recently published data indicate that progression of joint damage and functional disability can be prevented if adequate treatment is started promptly. Early diagnosis and interdisciplinary care are thus crucial.     

关节病型银屑病生物标志物研究进展

生物标志物在关节病型银屑病（PsA）的发病机制中扮演了重要角色,包括调控T细胞、NK细胞、调节细胞增殖分化等,临床上可作为疾病诊断、活动度判断、临床分型、治疗反应的标志物。本文就可溶性生物标志物、细胞生物标志物、遗传生物标志物对PsA发病机制的研究进展进行了综述。     

Successful management of infliximab‐induced generalized pustular psoriasis without therapy discontinuation in a patient with psoriatic arthritis

While infliximab has been shown to be paradoxically associated with the development of pustular psoriasis in patients with rheumatoid arthritis, spondyloaripathies, juvenile idiopathic, and inflammatory bowel disease, there are few cases of pustular psoriasis induced by infliximab in patients with psoriasis. We here present a 55‐year‐old female patient with longstanding plaque psoriasis and psoriatic arthritis who developed generalized pustular psoriasis 1 month after the fifth infusion of infliximab. Given the lack of other side effects and the rapid initial response of the underlying psoriatic arthritis, we opted against discontinuing infliximab therapy, and the sixth infusion of infliximab was administered 10 days ahead of schedule. Topical corticosteroids were added for the management of pustular lesions on initial presentation. One week after the sixth infusion, the pustular psoriatic lesions almost completely disappeared. No recurrence of pustular psoriasis was observed during the 3‐month follow‐up. Our experience shows that pustular lesions associated with infliximab can be successfully managed with topical corticosteroids without discontinuing infliximab therapy or compromising therapeutic benefit seen upon the underlying condition.     

Hyperuricemia is an independent risk factor for psoriatic arthritis in psoriatic patients

Psoriatic arthritis (PsA) is a spondyloarthritic condition mainly seen in patients with psoriasis. Psoriatic patients with plaques on the scalp, gluteal fold or nail lesions are known to develop PsA more frequently, but other markers for PsA have not yet been identified. To determine which psoriatic patients are at greatest risk of developing PsA, psoriasis vulgaris (PsV) patients who visited the Department of Dermatology, Fukuoka University Hospital in 2015 were enrolled. Patients with and without PsA were statistically compared with respect to age, sex, age at onset, body mass index (BMI), smoking and drinking habits, familial history of psoriasis and comorbidities. Of 331 patients (237 men, 94 women), 55 had PsA (17%; 39 men, 16 women). PsA patients had significantly higher frequencies of nail lesions (PsA vs PsV‐only, 62% vs 29%; P < 0.0001) and hyperuricemia (PsA vs PsV‐only, 22% vs 9%; P = 0.01). These were confirmed as independent risk factors for PsA by logistic regression analysis, with odds ratios of 5.05 for nail lesions (P < 0.0001) and 4.18 for hyperuricemia (P < 0.01). There was no difference in age at onset, sex, BMI and incidence of diabetes mellitus, hypertension or dyslipidemia. Hyperuricemia is also known to be more frequent in psoriatic subjects than the normal population. Uric acid crystals are a strong stimulator of innate immunity. Considering that none of our cohort had gouty arthritis, hyperuricemia may increase uric acid crystallization in and around joints, thereby inducing PsA in psoriatic subjects. Hyperuricemia appears to be an independent risk factor for PsA.     

Use of biological drugs in patients with psoriasis and psoriatic arthritis in Italy: Results from the PSONG survey

This Italian multicenter retrospective study compared the drug survival and efficacy of different anti‐TNF agents in psoriasis (PsO) and psoriatic arthritis (PsA) patients. A database of PsO/PsA patients treated with adalimumab, etanercept, and infliximab from May 2013 to May 2014 was analyzed. PASI 75, 90, and 100 was calculated at each time point to evaluate efficacy. Drug survival rate and probability of maintaining PASI response were evaluated. The impact of dependent variables on probability of PASI 75 loss was evaluated by logistic regression. 1,235 patients were included, 577 with PsO and 658 with PsA. Highest survival rates were observed with adalimumab followed by etanercept and infliximab in PsO and PsA patients. The probability of maintaining PASI response was significantly higher for adalimumab followed by infliximab. For PsO patients, the odds of losing PASI 75 was higher in etanercept‐treated patients (OR: 8.1; 95% CI: 4.2–15.6, p < .001) or infliximab (OR: 6.6; 95% CI: 2.6–16.3, p < .001) vs. adalimumab. Likewise, for PsA patients the odds of losing PASI 75 was higher in etanercept‐treated patients (OR: 2.3; 95% CI: 1.4–3.8, p = .01) or infliximab (OR: 2.2; 95% CI: 1.1–4.1, p = .018) vs. adalimumab. Adalimumab could be the best therapeutic option over other anti‐TNF agents for the treatment of PsO and PsA patients.