Plasma YKL‐40: a potential biomarker for psoriatic arthritis?

Background Plasma YKL‐40 is an inflammatory biomarker. No useful biomarker exists in patients with psoriasis or psoriatic arthritis. Objective To measure YKL‐40 and high‐sensitivity C‐reactive protein (hs‐CRP) in patients with psoriasis or psoriatic arthritis before and during treatment. Methods In 48 patients with psoriasis, we measured YKL‐40, hs‐CRP and Psoriasis Area and Severity Index (PASI) at inclusion and in a subgroup of 14 patients, we repeated the measurements after four to six weeks of methotrexate treatment. In 42 patients with psoriatic arthritis, we measured YKL‐40 and hs‐CRP at inclusion and during 48 weeks of adalimumab treatment. The patients with psoriatic arthritis were divided into responders and non‐responders. Results In patients with psoriasis, the baseline median PASI score was 10.8 and baseline YKL‐40 was 45 μg/L. Seventeen per cent had elevated plasma YKL‐40 compared with healthy subjects. Baseline PASI and YKL‐40 were not correlated (rho = 0.14, P = 0.347) and YKL‐40 and hs‐CRP remained unchanged after treatment. In patients with psoriatic arthritis, the median pretreatment YKL‐40 was 112 μg/L and 43% had elevated YKL‐40. YKL‐40 decreased in 33 patients who responded to adalimumab (from 112 μg/L to 68 at 48 weeks, P = 0.007). Hs‐CRP decreased (from 4.65 mg/L to 0.91, P = 0.013) in the responders. In the non‐responders (n = 9), YKL‐40 and hs‐CRP remained unchanged. Conclusions YKL‐40 is elevated in many patients with psoriatic arthritis, but not in patients with psoriasis. YKL‐40 decreased in patients with psoriatic arthritis who responded to treatment. YKL‐40 may be a useful biomarker to monitor the effect of treatment with tumour necrosis factor‐α inhibitors in patients with psoriatic arthritis.     

Arthritis as an important determinant for psoriatic patients to develop severe vascular events in Taiwan: a nation‐wide study

Background Psoriasis is an important systemic inflammatory disease that often leads to severe vascular diseases. This study was launched to determine if joint involvement affects incidence of vascular comorbidities in psoriatic patients. In addition, potential vasculo‐protective effects of methotrexate in psoriatic patients were also evaluated. Method A population‐based retrospective cohort study was conducted using the Taiwanese National Health Insurance database spanning from 1996 to 2006. Accordingly, 7648 and 284 psoriatic patients without or with arthritis, respectively, were identified. To ensure the temporal relationship between different events, those with date of first diagnosis psoriasis during the year of 1996 were excluded from subsequent analyses. In addition, those with diagnosis of cerebrovascular or cardiovascular diseases prior to onset of psoriasis were also excluded from relevant subsequent analyses. Result Taking psoriatic patients without arthritis as the referent group, the hazard ratio for incident cerebrovascular disease was 1.82 (95% CI = 1.17–2.82) for psoriatic patient with arthritis. In addition, psoriatic patients without arthritis who had methotrexate treatment showed reduced risks for incident cerebrovascular disease as compared with those with no arthritis and had received no methotrexate/retinoid treatment. Similar analyses were performed on cardiovascular diseases, and equivalent results were obtained. Conclusion Our study indicated that arthritis is a potential determinant for psoriatic patients in terms of incident vascular comorbidities. In addition, methotrexate treatment may be associated with reduced risks for development of severe vascular diseases in psoriatic patients without arthritis. Further studies should focus on the clinical complications associated with psoriatic patients with or without arthritis.     

Risk factors associated with having psoriatic arthritis in patients with cutaneous psoriasis

The aim of this study was to determine if the following characteristics were associated with the presence of psoriatic arthritis in a sample of psoriasis patients: race, family history of psoriasis and psoriatic arthritis, age of onset of psoriasis, smoking, alcohol consumption and the maximum body surface area (BSA) affected by psoriasis. This was a case–control study involving 400 psoriasis patients who attended the Psoriasis and Photo‐medicine clinic in the National Skin Center of Singapore over a 1‐year period. Cases were psoriasis patients with psoriatic arthritis while controls were psoriasis patients without psoriatic arthritis. The diagnosis of psoriatic arthritis was made by rheumatologists and participants completed a self‐administered standardized questionnaire. The maximum BSA involved was determined from the case notes. Psoriatic arthritis was not significantly associated with sex, race, age of onset of psoriasis, a family history of psoriasis, smoking and alcohol consumption but was significantly associated with a family history of psoriatic arthritis (P < 0.001) and the maximum body surface involved (P = 0.05). Using multivariate analysis to control for variables, the presence of psoriatic arthritis was significantly associated with a family history of psoriatic arthritis (odds ratio [OR] = 20.5; 95% confidence interval [CI] = 2.49–169.10) and the maximum BSA involved (OR = 2.52; 95% CI = 1.33–4.75). Indian psoriatic patients were more likely to have psoriatic arthritis compared to the other races. A family history of psoriatic arthritis and a greater maximum body surface involved may be associated with having psoriatic arthritis in this study population of psoriasis patients.     

TNF-α与关节病型银屑病

临床中通过阻断TNF-α治疗关节型银屑病有效,因此TNF-α可能在PsA的发病中起重要作用,本文对TNF-α在关节病型银屑病中的作用机制做一综述。     

Development of MGUS in psoriatic patients: a possible undiagnosed event during anti‐TNF‐α‐treatment

Background Monoclonal gammopathies are haematological conditions characterized by the clonal proliferation of plasma cells which produce a monoclonal immunoglobulin that accumulates in the blood. They have already been reported during treatment with a range of drugs but never before during treatment with the anti‐TNF‐α treatments: adalimumab, etanercept and infliximab currently used in the therapy of moderate‐severe psoriasis and psoriatic arthritis. Objective This is a case series describing the development of MGUS in psoriatic patients treated with anti‐TNF‐α. Methods Three hundred patients receiving an anti‐TNF‐α treatment for chronic plaque psoriasis or psoriatic arthritis in a clinical setting in Italy, These patients were screened through serum protein electrophoresis to investigate the possible development of MGUS. Results Eight patients were found to have developed monoclonal gammopathy of undetermined significance. The median treatment duration for the eight patients was 1 year with excessive IgG present in five patients, IgM accumulation in one patient and a double monoclonal component in two patients. Conclusion Our data suggest that there may be an association between anti‐TNF‐α therapy and development of MGUS.     

Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this second of 5 sections of the guidelines of care for psoriasis, we give an overview of psoriatic arthritis including its cardinal clinical features, pathogenesis, prognosis, classification, assessment tools used to evaluate psoriatic arthritis, and the approach to treatment. Although patients with mild to moderate psoriatic arthritis may be treated with nonsteroidal anti-inflammatory drugs and/or intra-articular steroid injections, the use of disease-modifying antirheumatic drugs, particularly methotrexate, along with the biologic agents, are considered the standard of care in patients with more significant psoriatic arthritis. We will discuss the use of disease-modifying antirheumatic drugs and the biologic therapies in the treatment of patients with moderate to severe psoriatic arthritis.     

New generation biologics for the treatment of psoriasis and psoriatic arthritis. State of the art and considerations about the risk of infection

Psoriasis is a chronic immune‐mediated disease characterized by inflammation of skin (psoriasis) or joints (psoriatic arthritis) or both, resulting from a dysregulation in particular of the T helper (Th)17 functions. There is no available cure for psoriasis, and a life‐long treatment is needed to control signs and symptoms. Research interest is high around the newest biological drugs approved for the treatment of moderate to severe psoriasis and psoriatic arthritis, and especially drugs blocking the IL‐23/IL‐17 axis. Our aim is to review the new biological drugs for the treatment of psoriasis and their adverse effects, focusing on the risk of infections.     

New onset or transition of disease state of psoriatic arthritis during treatment with ustekinumab: A single‐center retrospective study

Ustekinumab (UST) is a treatment option for psoriatic arthritis (PsA), but recent observations indicate that some psoriatic patients may experience new onset of PsA or worsening of pre‐existent PsA. We retrospectively analyzed all cases of psoriasis vulgaris (PsV) and PsA treated with UST in our facility between 2011 and 2015. PsA developed in eight out of 179 PsV patients, mostly later than 8 months after initiation of UST. It was generally not severe, and none had received tumor necrosis factor (TNF)‐α inhibitors previously, indicating that the possibility of unmasking pre‐existing subclinical arthritis is minimal. The eruptions were well controlled at the time of the onset of arthritis in most cases. Interestingly, those who developed arthritis showed a significantly lower body mass index. Regarding pre‐existing PsA, nine PsA patients received UST, and at least partial improvement of PsA could be achieved in two out of three bio‐naive and three out of six bio‐switched patients from TNF‐α inhibitors. PsA was largely more refractory to UST than the eruptions. Altogether, our present study is in agreement with the notion that UST may be less efficient than TNF‐α inhibitors for PsA. While UST cannot fully prevent new development of PsA, it is unlikely that UST increases the risk of new onset of PsA as a paradoxical adverse reaction.     

Neutrophil–lymphocyte ratio,platelet–lymphocyte ratio and mean platelet volume in Japanese patients with psoriasis and psoriatic arthritis: Response to therapy with biologics

Recent studies indicate the presence of systemic inflammation in psoriatic patients, and this inflammatory status is significantly associated with a range of comorbidities. The aim of this study was to evaluate the clinical significance of novel inflammatory biomarkers, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) and mean platelet volume (MPV) in Japanese patients with plaque‐type psoriasis (PsV) and psoriatic arthritis (PsA). One hundred and eighty‐six patients with PsV and 50 patients with PsA treated with biologics, including infliximab, adalimumab and ustekinumab, were retrospectively analyzed before and after treatment. At baseline, NLR and PLR, as well as C‐reactive protein (CRP), were significantly higher in PsA patients than those in PsV patients, and a significant correlation was found between NLR and PLR. In PsV patients, the NLR‐high and PLR‐high subgroups exhibited significantly higher Psoriasis Area and Severity Index scores compared with the NLR‐low and PLR‐low subgroups, respectively, and the NLR‐high subgroup also showed higher CRP levels. MPV value was negatively associated with the presence of arthritis, but its association with inflammation was less clear than that of NLR or PLR. After treatment of the patients with biologics for up to 12 months, NLR and PLR decreased promptly in parallel with a decrease of CRP, irrespective of the type of biologics used. Altogether, these results indicate that both NLR and PLR may be useful markers to evaluate systemic inflammation in psoriatic patients. They may serve as simple, convenient and cost‐effective biomarkers to monitor the disease course after systemic therapy.     

Treatment of nail psoriasis with adalimumab: an open label unblinded study

Background Despite numerous advances in the therapeutic management of cutaneous psoriasis, there is a lack of standardized therapeutic regimens for psoriatic nail disease. Objective An open, non‐randomized, unblinded study was designed to evaluate the efficacy and safety of adalimumab in the treatment of nail psoriasis. Patients/methods Seven patients suffering from severe plaque‐type psoriasis and 14 with psoriatic arthritis and cutaneous psoriasis with concomitant nail involvement were enrolled into the study. The applied dose regimen of adalimumab was the same as the one recommended for cutaneous psoriasis. Outcome measures were assessed at baseline and at weeks 12 and 24 using the Nail Psoriasis Severity Index (NAPSI). Patients also filled in a Greek translation of the international onychomycosis‐specific questionnaire to assess the impact of the nail improvement on their quality of life. Results All 21 patients completed the study and were eligible for statistical analysis. Significant improvement was recorded after the eighth injection. Mean NAPSI (NAPSIm) at baseline was 10.57 ± 1.21 for the fingernails and 14.57 ± 2.50 for the toenails in patients with just cutaneous psoriasis and 23.86 ± 2.00 for the fingernails and 29.29 ± 2.87 for the toenails in patients with psoriatic arthritis. NAPSIm at week 12 was 5.57 ± 0.78 for the fingernails and 9.57 ± 2.17 for the toenails in patients with just cutaneous psoriasis and 12.86 ± 1.05 for the fingernails and 19.21 ± 2.07 for the toenails in patients with psoriatic arthritis. NAPSIm after 24 weeks of treatment was 1.57 ± 0.20 for the fingernails and 4.14 ± 1.58 for the toenails in patients with cutaneous psoriasis and 3.23 ± 0.32 for the figernails and 10.00 ± 1.40 for the toenails in patients with psoriatic arthritis. Treatment was well tolerated with minimal and temporary side‐effects limited to the site of injection. All patients were satisfied, while marked improvement in their quality of life was recorded based on the reduction of the scores obtained from the international quality of life questionnaire. Conclusions Despite the lack of a control group, our results demonstrate a beneficial effect of adalimumab on psoriatic nail disease.     

Efficacy and safety of systemic treatments in psoriatic arthritis: a systematic review,meta‐analysis and GRADE evaluation

Twenty per cent of patients with plaque psoriasis also have psoriatic arthritis – a disease affecting joints and entheses. Different treatment options exist but currently no succinct systematic overview exists. A systematic review of approved systemic treatments for psoriatic arthritis was conducted. We systematically searched in three databases (last update September 2017). Data were extracted for ACR20/50, HAQ‐DI, SF‐36 and adverse/serious adverse events after 16–24 weeks. We assessed the quality of evidence using GRADE. Twenty trials were included. Three trials compared two active substances. Results for ACR20 were infliximab + methotrexate vs. methotrexate: RR 1.40 (95% CI 1.07–1.84) very low quality evidence; ixekizumab Q2W vs. adalimumab Q2W: RR 1.08 (95% CI 0.86–1.36) very low quality, leflunomide vs. methotrexate: RR 1.01, (95% CI 0.84–1.21) low quality. Eighteen drug vs. placebo comparisons were included. For ACR20/50, HAQ‐DI and SF‐36, the active treatment was efficacious and the quality of the evidence was mostly moderate to low (15 of 18 comparisons). The quality of evidence for (serious) adverse events was mostly low; differences were rare. In three placebo‐controlled comparisons, leflunomide, MTX and sulfasalazine failed to show statistical superiority for ACR. Besides the established treatment of anti‐TNF antibodies and ustekinumab for psoriatic arthritis, the newer treatment options of IL17 antibodies and apremilast are also effective for the treatment of psoriatic arthritis. Based on just one comparative trial and one drug each, the new class of anti‐IL 17 antibodies appears to be equally effective as the group of anti‐TNF antibodies; for apremilast, this is yet unclear.     

Anti‐tumour necrosis factor treatment of severe psoriasis complicated by Epstein–Barr Virus hepatitis and subsequently by chronic hepatitis

A case is described of severe acute hepatitis in 47‐year‐old woman with chronic psoriasis and psoriatic arthritis treated with infliximab. Although clinical, serological and laboratory results were compatible with acute EBV hepatitis, it was difficult to differentiate between EBV infection and other non‐infectious causes of hepatitis. The patient gradually developed chronic hepatitis with liver steatosis and efficient treatment with adalimumab had to be stopped. This case presents an uncommon complication that may arise from the use of biologic therapy and calls for caution in long‐term management of psoriatic patients with internal comorbidities.     

Clinical predictors of nonresponse to anti‐TNF‐α agents in psoriatic patients: A retrospective study

Although the heterogeneity of the therapeutic response to TNF‐α blockers seems to be mainly due to genetic factors, several studies showed that a range of factors may influence it. The aim of our study was to investigate the impact of patients' demographic and clinical characteristics on primary response to an anti‐TNF‐α therapy in psoriatic patients. We retrospectively examined the relationship between various clinical and demographic features and response to treatment with etanercept, adalimumab, and infliximab, evaluated as PASI75 and average PASI improvement at weeks 12, 16, and 14, respectively. We analyzed data obtained from 199 patients. A better response to the treatment was significantly associated with male gender (OR = 2.59), coexistence of psoriatic arthritis (OR = 1.97), and PASI ≤15 at baseline (OR = 0.91). The present study supports that some clinical factors may be potential predictors of response to anti‐TNF‐α agents in psoriatic patients.     

Psoriatic arthritis and the dermatologist: An approach to screening and clinical evaluation

Psoriatic arthritis is a common form of inflammatory arthritis that frequently accompanies psoriasis of the skin—up to 30% of patients with psoriasis are affected. Recognition of the clinical features of psoriatic arthritis is critical, as delayed detection and untreated disease may result in irreparable joint injury, impaired physical function, and a significantly reduced quality of life. Recent epidemiologic studies have also supported that psoriatic arthritis is associated with cardiometabolic and cerebrovascular comorbidities, including coronary heart disease, diabetes mellitus, hypertension, dyslipidemia, and cerebrovascular accidents, further highlighting the importance of identifying affected patients. Dermatologists are poised for the early detection of psoriatic arthritis, as psoriasis predates its development in as many as 80% of patients. In an effort to further acquaint dermatologists and other clinicians with psoriatic arthritis, this review provides a detailed overview, emphasizing its salient clinical features, and discusses classification criteria, validated screening tools, and simple musculoskeletal examination maneuvers that may facilitate earlier detection and treatment of the disorder.     

Psoriasiform exfoliative erythroderma induced by golimumab

Golimumab is a fully human anti‐tumour necrosis factor (TNF)‐α monoclonal antibody approved for use in the treatment of active rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Psoriasis induced by treatment with anti‐TNF drugs is well documented, but to our knowledge, the development of clinical features of psoriasiform exfoliative erythroderma during treatment with golimumab has not been previously described.     

Etanercept therapy for patients with psoriatic arthritis and concurrent hepatitis C virus infection: report of 3 cases

Psoriasis and psoriatic arthritis are exacerbated by interferon alfa and other treatments for hepatitis C virus infection. Immunosuppressants and hepatotoxic drugs are relatively contraindicated in hepatitis C. Data in the literature suggest that etanercept is a safe option in the treatment of patients with rheumatoid arthritis and concurrent hepatitis C. We present three cases in which we have successfully used etanercept to treat psoriatic arthritis/psoriasis in patients with hepatitis C without worsening their hepatitis or interfering with their hepatitis treatment. With close monitoring of viral load and hepatic enzymes, etanercept may be a safe option for treating psoriatic arthritis/psoriasis in patients who also have hepatitis C.     

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.     

TNF‐alpha‐Antagonisten in der Therapie der Psoriasis – Nutzen und Risiken

Summary: Anti‐TNF‐α agents including etanercept, a fusion protein of the p75 TNF receptor and IgG1 and infliximab, a chimeric human‐mowie monoclonal antibody. They have been approved for the treatment of rheumatoid arthritis and/or Crohn's disease. New understanding of the importance of the inlammatory cytokine TNF‐α in the pathophysiology of psoriasis led to the use in open‐label and randomized studies in patients with psoriasis and psoriatic arthritis. Although larger randomized trials are needed to confirm early results, both anti‐TNF‐α agents, have demonstrated activity in improving the signs and symptoms of psoriatic arthritis and psoriasis. Further investigations will fully elucidate the role of infliximab in these and other dermatological diseases.     

Severe infliximab‐induced psoriasis treated with adalimumab switching

Background Antitumor necrosis factor (anti‐TNF) agents are a well‐established treatment for various medical conditions, including psoriasis and psoriatic arthritis. However, anti‐TNF agents may themselves induce psoriasis in some patients. Methods The authors report two cases of patients with severe and refractory infliximab‐induced psoriasis. Results The patients had good clinical responses after switching to another TNF blocker. Conclusion For severe cases, infliximab withdrawal combined with conventional immunosuppressive psoriasis drugs or with adalimumab may be a therapeutic option.     

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.