At the 2017 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members received updates on several ongoing educational and research efforts. Among them were updates on...At the 2017 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members received updates on several ongoing educational and research efforts. Among them were updates on GRAPPA's continued education efforts; GRAPPA's continued research efforts, including the Biomarker Project, a collaborative research effort to identify and study biomarkers of joint damage; treatment recommendations, including recommendations and core principles related to biosimilars; efforts to update GRAPPA's Website and to create a GRAPPA smart-phone application (app); and the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network.
Psoriatic arthritis (PsA) is a heterogeneous disease with various manifestations of musculoskeletal inflammation. Recent advances in imaging, including ultrasound (US) and magnetic resonance imaging (MRI), allow for the...Psoriatic arthritis (PsA) is a heterogeneous disease with various manifestations of musculoskeletal inflammation. Recent advances in imaging, including ultrasound (US) and magnetic resonance imaging (MRI), allow for the accurate evaluation of the extent of inflammation and damage in the peripheral joints, spine, and entheses. The development and validation of outcome measures are critical steps in creating standardized evaluations of musculoskeletal inflammation and damage in psoriatic patients. At the 2017 meeting of the Group for Research and Assessment of Psoriasis and PsA (GRAPPA), recent work on outcome measures from the GRAPPA US and MRI working groups was summarized. The GRAPPA US group has been developing and validating a sonographic enthesitis scoring system in PsA. The GRAPPA MRI group focuses on the evaluation of whole-body MRI for the assessment of musculoskeletal inflammation in the joints and entheses in patients with PsA.
At the 2017 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the International Dermatology Outcome Measures (IDEOM) psoriasis working group presented an overview of i...At the 2017 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the International Dermatology Outcome Measures (IDEOM) psoriasis working group presented an overview of its cutaneous domain of psoriatic arthritis (PsA) projects. First, the group presented an overview of IDEOM's work to establish psoriasis outcome measures that satisfy the needs of all those involved. Second, the group discussed replacements for the Psoriasis Area and Severity Index (PASI) that can be used in clinical practice, including data that support the use of the physician's global assessment × body surface area measurement score as a PASI surrogate. Third, the group discussed the contribution of skin disease to composite measures of PsA. Last, the group summarized the National Psoriasis Foundation's efforts to establish treat-to-target strategies for psoriasis care.
Spondyloarthritis (SpA) encompasses a group of diseases characterized by an inflammatory arthritis involving both joints and entheses. However, extraarticular symptoms constitute a large element of the pathology and shou...Spondyloarthritis (SpA) encompasses a group of diseases characterized by an inflammatory arthritis involving both joints and entheses. However, extraarticular symptoms constitute a large element of the pathology and should not be underestimated. Microscopic gut inflammation is observed in 50% of patients with SpA and has been linked to disease activity, underscoring the effect of gut inflammation in SpA. In this review, we discuss the influence of gut microbiota on SpA pathogenesis. A change in microbiota composition has been linked to the development of various inflammatory arthritides, and dysbiosis is a potential factor in the pathogenesis of multiple inflammatory diseases. In this context, several groups have reported the modulatory effects of gut microbiota-derived metabolites on the effect of immune cells. The gut mucosa is populated by several types of regulatory T cells, but also some specialized unconventional innate-like T cells. These cells are predominantly found at mucosal and epithelial barrier sites, where they serve an essential role in modulating host-microbial interplay. Apart from the close association between the composition of the microbiota and inflammatory diseases, the therapeutic value of dysbiosis needs further investigation, and the identification of a causal inflammatory pathway between gut dysbiosis and musculoskeletal inflammation could revolutionize the therapeutic approach in SpA.
The microbiome is a known and established immunomodulator of many inflammatory disorders, including psoriasis and psoriatic arthritis. Microbes co-evolved with their human hosts and provide them with nutritional, metabol...The microbiome is a known and established immunomodulator of many inflammatory disorders, including psoriasis and psoriatic arthritis. Microbes co-evolved with their human hosts and provide them with nutritional, metabolic, and immunologic support. An accumulating body of evidence has revealed that psoriatic diseases are characterized by a state of intestinal dysbiosis, which has been linked to a decrease in beneficial commensals and fatty acids. This has been shown in both animal models and human samples, and multiple studies have addressed the physiological and potentially pathogenic role of intestinal and cutaneous microbes in human health and disease. In this review, we discuss state-of-the-art literature in the field of the microbiome in psoriatic diseases that was presented during the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2017 annual meeting, with a special emphasis on synovio-entheseal inflammation. A better understanding of these microbe-host interactions can lead to novel diagnostic and therapeutic targets.
Psoriasis is a chronic, inflammatory immune-mediated skin disease that affects about 2% of the world's population. In 20% of patients with psoriasis, the characteristic skin lesions are accompanied by psoriatic arthritis...Psoriasis is a chronic, inflammatory immune-mediated skin disease that affects about 2% of the world's population. In 20% of patients with psoriasis, the characteristic skin lesions are accompanied by psoriatic arthritis (PsA). Psoriasis arises in genetically predisposed individuals who have a dysregulated immune response to various environmental factors. The human body is home to many microbial species, and both the skin and the gut microbiome influence the development and function of immune tissue development and function. Studies on the cutaneous microbiome show a trend toward an increased relative abundance of and a decreased level of in patients with psoriasis compared to healthy controls. In the gut microbiome, the ratio of and was perturbed in psoriatic individuals compared to healthy controls. was relatively underrepresented in patients with psoriasis compared to healthy individuals. A decrease in skin microbiome flora diversity seems to be a sign that a patient with psoriasis is at elevated risk for developing arthritis. Modulating the skin microbiota for therapeutic reasons can be achieved by antimicrobial (antibiotic) therapy, the application of prebiotics or probiotics, or the transplantation of an entire healthy microbial population.
The members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) have shown great interest in developing a common GRAPPA database. To address this interest, GRAPPA included a symposium a...The members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) have shown great interest in developing a common GRAPPA database. To address this interest, GRAPPA included a symposium at its 2017 annual meeting to examine the concepts of registries and databases. At this symposium, examples of existing databases were reviewed, and their challenges and achievements were discussed.
Holland R, Tillett W, Ogdie A
… +17 more, Leung YY, Gladman DD, Callis Duffin K, Coates LC, Mease PJ, Eder L, Strand V, Elmamoun M, Højgaard P, Chau J, de Wit M, Goel N, Lindsay CA, FitzGerald O, Shea B, Beaton D, Orbai AM
The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Core Set working group is in the process of selecting core instrume...The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Core Set working group is in the process of selecting core instruments for PsA clinical trials. During a 2-h workshop and breakout group discussions at the GRAPPA 2017 annual meeting in Amsterdam, the Netherlands, participants discussed the first set of candidate instruments to be taken through the OMERACT Filter 2.1 instrument selection process: 66/68 swollen/tender joint count (66/68JC), Spondyloarthritis Consortium of Canada (SPARCC) enthesitis index, patient's global assessment (GRAPPA and OMERACT formulations), Health Assessment Questionnaire-Disability Index (HAQ-DI), Psoriatic Arthritis Impact of Disease (PsAID) questionnaires 9 and 12, and Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue. Based on the assessment of domain match (content and face validity) and feasibility according to the OMERACT instrument selection criteria, the working group recommends continuing with appraisal of construct validity and discrimination for 66/68JC, SPARCC, PsAID 9 and 12, HAQ-DI, and FACIT-Fatigue. In addition, it recommends repeating the OMERACT Filter 2.1 process for patient global instruments because of insufficient votes. Additional sets of candidate instruments for the PsA core instrument set will be evaluated in a similar process.
Juvenile psoriatic arthritis (JPsA), a subtype of juvenile idiopathic arthritis (JIA), constitutes 5% of JIA. The literature is inconsistent regarding features of JPsA, and physicians debate whether it is a distinct enti...Juvenile psoriatic arthritis (JPsA), a subtype of juvenile idiopathic arthritis (JIA), constitutes 5% of JIA. The literature is inconsistent regarding features of JPsA, and physicians debate whether it is a distinct entity within JIA. A biphasic age of onset distribution has been noted. Early-onset disease is characterized by female predominance, small joint involvement, dactylitis, and positive antinuclear antibodies. Late-onset JPsA resembles adult-onset psoriatic arthritis (PsA), with male predominance, psoriasis, enthesitis, and axial disease. Recent studies report improved outcomes, likely due to the widespread use of traditional and biologic disease-modifying antirheumatic drugs. Conflicting HLA associations have been reported in JPsA, but notably both HLA class I and II allele associations are suggested. Similar to PsA cohorts, subjects with JPsA have a lower frequency of a protective interleukin 23R allele than controls or other JIA subtypes. Data in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) patient registry suggest the aggressive characteristics of JPsA: 24.6% of children have joint damage 4.6 years after symptom onset. Pediatric and adult PsA classification criteria define different JPsA cohorts within the registry and support a previous suggestion that the International League of Associations for Rheumatology criteria for JPsA may be overly stringent. Increased collaboration between pediatric and adult physicians and comparative research on these clinically related conditions are warranted.
At the 2017 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in Amsterdam, the Netherlands, a trainees symposium was held. Rheumatology and dermatology trainees engage...At the 2017 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in Amsterdam, the Netherlands, a trainees symposium was held. Rheumatology and dermatology trainees engaged in psoriasis or psoriatic arthritis research presented their work. This report briefly reviews 6 oral presentations and 25 posters presented at the meeting.
The 2017 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) was held in Amsterdam, the Netherlands, and was attended by rheumatologists, dermatologists, representatives...The 2017 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) was held in Amsterdam, the Netherlands, and was attended by rheumatologists, dermatologists, representatives of biopharmaceutical companies, and patients. As in previous years, GRAPPA members held a symposium for trainees to discuss their research in psoriatic disease with experts in the field. Other subjects featured during the annual meeting included a discussion of the history, clinical features, controversies, and immunogenetics of juvenile psoriatic arthritis; updates from working groups in Outcome Measures in Rheumatology and International Dermatology Outcome Measures; a discussion of the benefits and challenges of setting up a longitudinal psoriatic arthritis (PsA) database; 3 separate discussions of the effects of the microbiome on skin and joints in psoriasis and PsA; a discussion of options for assessing joints and entheses in PsA by ultrasonography and magnetic resonance imaging; an update on GRAPPA's research and educational projects; a discussion of patient centricity, including the incorporation of patient research partners (PRP) into psoriasis and PsA research and educational efforts, from GRAPPA's PRP; and a discussion of the GRAPPA-Collaborative Research Network's inaugural meeting. In this prologue, we introduce the papers that summarize that meeting.
Psoriatic arthritis (PsA) is a systemic inflammatory disease characterized by possible peripheral and axial joint involvement, enthesitis, dactylitis, and skin and nail disease. It affects up to one-third of psoriatic pa...Psoriatic arthritis (PsA) is a systemic inflammatory disease characterized by possible peripheral and axial joint involvement, enthesitis, dactylitis, and skin and nail disease. It affects up to one-third of psoriatic patients, and may be associated with comorbidities such as cardiovascular and metabolic diseases. The usually prescribed initial treatment of moderate-severe PsA is methotrexate, which may be accompanied or replaced by a tumor necrosis factor (TNF) inhibitor such as etanercept, infliximab, or adalimumab. However, some patients may become unresponsive (or have contraindications) to available anti-TNF agents and require alternative treatment. The aim of this review is to describe the potential role of some new immunomodulatory agents.
Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting peripheral and axial joints, usually associated with psoriasis (PsO) and involving various systems and organs (eye inflammation, such as uveitis; and...Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting peripheral and axial joints, usually associated with psoriasis (PsO) and involving various systems and organs (eye inflammation, such as uveitis; and involvement of nail and enthesis), and it usually requires a multidisciplinary treatment approach. Tumor necrosis factor-α (TNF-α) is overexpressed in psoriatic synovium and skin plaques and its selective inhibition by anti-TNF-α agents has been demonstrated to reduce TNF-α levels in the articular environment, reversing the synovial hyperproliferative phenotype. Studies performed on anti-TNF-α agents in PsA demonstrated that they are able to reduce neutrophil and macrophage infiltration as well as vascular cell adhesion protein 1 expression with ensuing synovial thickness normalization. The efficacy of anti-TNF-α agents for all PsA manifestations (peripheral arthritis, axial involvement, enthesopathy, and skin disease) suggests that anti-TNF-α efficacy might be related to the ability to influence angiogenesis and osteoclastogenesis, reduce synovial inflammation, and slow radiological disease progression. This review describes the role of anti-TNF-α in each manifestation of PsA.
The pathogenesis of psoriatic arthritis (PsA) is still under discussion but great advances have been made in the last 2 decades that confirm the central role of tumor necrosis factor-α (TNF-α) in its inflammatory milieu....The pathogenesis of psoriatic arthritis (PsA) is still under discussion but great advances have been made in the last 2 decades that confirm the central role of tumor necrosis factor-α (TNF-α) in its inflammatory milieu. New therapeutic approaches have been proposed, and new molecules with anti-TNF-α activity have been chemically altered to improve their pharmacological properties. Certolizumab pegol (CZP) is a PEGylated Fc-free anti-TNF that has been shown clinically to be effective in the treatment of rheumatoid arthritis (RA), skin psoriasis, and PsA. This article summarizes available data on its clinical efficacy and safety profile in the treatment of patients with PsA.
Treatment with nonsteroidal antiinflammatory drugs (NSAID) is the recommended first-line therapy in patients with axial spondyloarthritis (axSpA); and for those patients who have persistently active disease, the introduc...Treatment with nonsteroidal antiinflammatory drugs (NSAID) is the recommended first-line therapy in patients with axial spondyloarthritis (axSpA); and for those patients who have persistently active disease, the introduction of tumor necrosis factor-α (TNF-α) inhibitors is indicated. Conventional nonbiological disease-modifying antirheumatic drugs (DMARD), although effective and used in clinical practice for peripheral arthritis, are not recommended. Few studies have been conducted with the aim of evaluating the effect of conventional DMARD, either alone or in combination, in axSpA. As for psoriatic arthritis (PsA), DMARD are widely used, but few trials are available about their effects on axial involvement, which is not often assessed as a primary outcome in clinical trials. In rheumatoid arthritis, combination therapy of 2 or more conventional DMARD appears to confer better response than methotrexate monotherapy, and may even be a viable alternative to TNF-α inhibitors. In peripheral PsA, combination therapy can be used after treatment failure with 1 DMARD, but few studies have been conducted. However, available evidence for the combination of conventional DMARD indicates a lack of any significant benefit on axial symptoms; thus this treatment approach does not represent an effective alternative to anti-TNF-α therapy.
We present an update on the effects of methotrexate (MTX), sulfasalazine (SSZ), leflunomide (LEF), and cyclosporine (CSA) in psoriatic arthritis (PsA) by reviewing data published from January 2010 to June 2014. The most...We present an update on the effects of methotrexate (MTX), sulfasalazine (SSZ), leflunomide (LEF), and cyclosporine (CSA) in psoriatic arthritis (PsA) by reviewing data published from January 2010 to June 2014. The most relevant study on MTX, the Methotrexate In Psoriatic Arthritis (MIPA) trial, did not show a significant difference between this drug and placebo in improving peripheral synovitis. The trial, however, had several limitations. A cohort study on a small number of patients found that MTX does not inhibit radiographic progression. In a large observational study, 86% of LEF-treated patients met PsA Response Criteria (PsARC) at Week 24. No studies of sufficient relevance on SSZ were published in the examined time frame. In an open-label trial, CSA alone was compared to adalimumab (ADA) alone and to the combination ADA/CSA. The ADA arms showed a significantly higher response rate, but as many as 65% of CSA-treated patients were PsARC responders at Month 12. No relevant data on the effects of these 4 drugs on psoriatic enthesitis, dactylitis, or spondylitis have recently been published, and no new safety signals have been reported. Observational data from 2 registers suggest that concomitant MTX increases the retention rate of tumor necrosis factor-α inhibitors. The studies published in the examined time frame confirm that MTX, SSZ, LEF, and CSA have moderate symptom-modifying effect on psoriatic synovitis, and probably little effect on the other manifestations of PsA.
Psoriasis is a lifelong chronic inflammatory disease affecting 2-3% of the worldwide population. Current understanding of the pathogenesis of psoriasis assigns central importance to an interaction between acquired and in...Psoriasis is a lifelong chronic inflammatory disease affecting 2-3% of the worldwide population. Current understanding of the pathogenesis of psoriasis assigns central importance to an interaction between acquired and innate immunity. The disease is characterized by a series of linked cellular changes in the skin, including hyperplasia of epidermal keratinocytes, angiogenesis, and infiltration of T lymphocytes, neutrophils, and other types of leukocytes in the affected skin. Plaque psoriasis is the most common clinical form and is characterized by red and scaly plaques generally localized at extensor sites such as elbows and knees. Major determinants of psoriasis severity include the extent of skin involvement; localization in highly affected areas such as scalp, palms, and soles; pruritus; presence of comorbidities including psoriatic arthritis; and impairment on quality of life. About one-third of patients have moderate to severe psoriasis defined as PASI (Psoriasis Area and Severity Index) and/or Dermatology Life Quality Index>10, and/or affected body surface area>10%. The optimal treatment goal is to safely achieve complete or almost complete skin clearance. Treatments available are various and they are chosen according to disease features, comorbidities, and patient characteristics and priorities. Topical treatments including corticosteroids and Vitamin D analogs are reserved for mild disease. Phototherapy, cyclosporine, methotrexate, acitretin, or biologics such as tumor necrosis factor-α antagonists and ustekinumab are reserved for the moderate to severe forms.
By providing additional and more sensitive information over clinical examination, imaging techniques are useful in the assessment of patients with psoriatic arthritis (PsA) and have been increasingly used to obtain addit...By providing additional and more sensitive information over clinical examination, imaging techniques are useful in the assessment of patients with psoriatic arthritis (PsA) and have been increasingly used to obtain additional clues to its pathogenesis. This review describes the current status and future development of conventional radiography, computed tomography, magnetic resonance imaging, positron emission tomography, and other novel techniques in the evaluation of PsA, with a focus on their use in diagnosing, monitoring, and predicting disease course and followup treatment response. The role and applications of ultrasonography are outside the scope and are reviewed elsewhere in these proceedings.
Fiocco U, Martini V, Accordi B
… +18 more, Caso F, Costa L, Oliviero F, Scanu A, Felicetti M, Frallonardo P, Facco M, Boso D, Molena B, Zambello R, Ramonda R, Cozzi F, Scarpa R, Basso G, Semenzato G, Dayer JM, Doria A, Punzi L
We assessed signaling protein mapping in total T cells, to analyze the proportions of T regulatory (Treg) and TCD4+ effector (Teff) cell phenotypes, and the respective interleukin 6Rα (IL-6Rα) expression in the inflammat...We assessed signaling protein mapping in total T cells, to analyze the proportions of T regulatory (Treg) and TCD4+ effector (Teff) cell phenotypes, and the respective interleukin 6Rα (IL-6Rα) expression in the inflammatory microenvironment of synovial fluid (SF) of patients with sustained psoriatic arthritis (PsA). Our approach was to measure the IL-6 level in SF using a multiplex bead immunoassay. Reverse-phase protein array was used to assess Janus kinase (JAK) 1 and JAK2, extra-cellular regulated kinase (ERK) 1 and 2, protein kinase Cδ (PKCδ), signal transducer and activator and transcription (STAT) 1, STAT3, and STAT5 phosphoproteins in total T cell lysates from SF of patients with PsA. Frequencies of CD4+IL-17A-F+IL-23+ CD4+ Th cells producing IL-17A and IL-17F (Th17) and CD4+CD25high intracellular forkhead box transcription factor+ (FOXP3+) phenotypes, and the percentage of Treg- and Teff- cells were quantified in SF and matched peripheral blood (PB) of patients with PsA and PB of healthy controls (HC) by flow cytometry. Our results were the following: In PsA SF samples, a coordinate increase of JAK1, ERK1/2, STAT1, STAT3, and STAT5 phosphoproteins was found in total T cells in SF of PsA; where IL-6 levels were higher than in PB from HC. Expanded CD4+IL-17A-F+IL-23+ Th17, CD4+ CD25- Teff- and CD4+CD25(high) FoxP3+Treg subsets, showing similar levels of enhanced IL-6Rδ expression, were confined to PsA joints. In our studies, the transcriptional network profile identified by ex vivo signaling protein mapping in T lymphocytes in PsA joints revealed the complex interplay between IL-1, IL-6, and IL-23 signaling and differentiation of Th17 cells and CD4+Tregs in sustained joint inflammation in PsA.