Systemic glucocorticoid use and the occurrence of flares in psoriatic arthritis and psoriasis: a systematic review

OBJECTIVES: The use of systemic glucocorticoids (SGCs) is traditionally discouraged in the treatment of PsA and psoriasis due to the risk of psoriatic flares. However, despite this recommendation, SGCs are frequently prescribed for these patients. In this study we reappraise the old paradigm that SGCs are contra-indicated in the treatment of PsA and psoriasis. METHODS: A systematic search of MEDLINE, EMBASE and the Cochrane Library databases was performed in November 2019 to identify articles on any SGC use compared with no use in the PsA and psoriasis population. Topical glucocorticoid treatment was excluded. Our two primary outcomes focused on the prescribing characteristics and the occurrence of any type of flare. RESULTS: Our search yielded 4922 articles, and of these 21 full-text articles were eligible for inclusion. There were 11 retro- and prospective cohorts involving a total of 4,171,307 patients. Of these, 6727 (37.82%) of the patients with PsA and 1 460 793 (35.17%) of the patients with psoriasis were treated with any type of SGC. Ten observational/interventional studies did not report an increased risk or occurrence of psoriatic flares related to SGC use. CONCLUSION: Our results indicate that SGCs are frequently prescribed for PsA and psoriasis patients. The occurrence of psoriatic flares appears to be low upon SGC exposure. In patients with a clear indication for SGCs, e.g. in need of rapid anti-inflammatory therapy or bridging of therapies, the use of SGCs should be considered in view of the low risk of skin flaring. It remains of importance to weigh risks for short- and long-term SGC-related side effects in clinical decision making

Suppression of IL-12/IL-23 p40 subunit in the skin and blood of psoriasis patients by Tofacitinib is dependent on active interferon-γ signaling in dendritic cells: implications for the treatment of psoriasis and interferon-driven diseases

Interleukin (IL)-12 and IL-23 are pro-inflammatory cytokines produced by dendritic cells (DCs) and associated with Psoriasis (Pso) and Psoriatic Arthritis (PsA) pathogenesis. Tofacitinib, a Janus kinase inhibitor, effectively suppresses inflammatory cascades downstream the IL-12/IL-23 axis in Pso and PsA patients. Here we investigated whether Tofacitinib directly regulates IL-12/IL-23 production in DCs, and how this regulation reflects responses to Tofacitinib in Pso patients. We treated monocyte-derived dendritic cells and myeloid dendritic cells with Tofacitinib and stimulated cells with either lipopolysaccharide (LPS) or a combination of LPS and IFN-γ. We assessed gene expression by qPCR, obtained skin microarray and blood Olink data and clinical parameters of Pso patients treated with Tofacitinib from public datasets. Our results indicate that in DCs co-stimulated with LPS and IFN-γ, but not with LPS alone, Tofacitinib leads to the decreased expression of IL-23/IL-12 shared subunit IL12B (p40). In Tofacitinib-treated Pso patients, IL-12 expression and psoriasis area and severity index (PASI) are significantly reduced in patients with higher IFN-γ at baseline. These findings demonstrate for the first time that Tofacitinib suppresses IL-23/IL-12 shared subunit IL12B in DCs upon active IFN-γ signaling, and that Pso patients with higher IFN-γ baseline levels display improved clinical response after Tofacitinib treatment

Biomechanical and Dimensional Measurements of the Pulvertaft Weave Versus the Cow-Hitch Technique

Background: In this study, biomechanical strength and bulkiness of the cow-hitch technique and Pulvertaft weave were compared. Our goal was to investigate whether the cow hitch can withstand equal strength in comparison with the Pulvertaft and to see if there is a difference in bulk, which could enhance gliding function and reduce friction and adhesion formation. Methods: Sheep tendons were used to perform 10 cow-hitch and 10 Pulvertaft repairs. Tensile strength was obtained with a cyclic loading tensile testing machine and tendon width and height measurements were obtained through digital analysis by photographs of the repairs. Results: The cow hitch showed significantly better ultimate strength and had less bulk. There was no statistical difference in displacement, defined as gain in total length of the tendon. Conclusions: The results in this study show that the cow hitch outperforms the Pulvertaft weave in both ultimate strength and bulk

Tissue‐Resident Memory CD8+ T Cells From Skin Differentiate Psoriatic Arthritis From Psoriasis

Objective: To compare immune cell phenotype and function in psoriatic arthritis (PsA) versus psoriasis in order to better understand the pathogenesis of PsA. Methods: In-depth immunophenotyping of different T cell and dendritic cell subsets was performed in patients with PsA, psoriasis, or axial spondyloarthritis and healthy controls. Subsequently, we analyzed cells from peripheral blood, synovial fluid (SF), and skin biopsy specimens using flow cytometry, along with high-throughput transcriptome analyses and functional assays on the specific cell populations that appeared to differentiate PsA from psoriasis. Results: Compared to healthy controls, the peripheral blood of patients with PsA was characterized by an increase in regulatory CD4+ T cells and interleukin-17A (IL-17A) and IL-22 coproducing CD8+ T cells. One population specifically differentiated PsA from psoriasis: i.e., CD8+CCR10+ T cells were enriched in PsA. CD8+CCR10+ T cells expressed high levels of DNAX accessory molecule 1 and were effector memory cells that coexpressed skin-homing receptors CCR4 and cutaneous lymphocyte antigen. CD8+CCR10+ T cells were detected under inflammatory and homeostatic conditions in skin, but were not enriched in SF. Gene profiling further revealed that CD8+CCR10+ T cells expressed GATA3, FOXP3, and core transcriptional signature of tissue-resident memory T cells, including CD103. Specific genes, including RORC, IFNAR1, and ERAP1, were up-regulated in PsA compared to psoriasis. CD8+CCR10+ T cells were endowed with a Tc2/22-like cytokine profile, lacked cytotoxic potential, and displayed overall regulatory function. Conclusion: Tissue-resident memory CD8+ T cells derived from the skin are enhanced in the circulation of patients with PsA compared to patients with psoriasis alone. This may indicate that aberrances in cutaneous tissue homeostasis contribute to arthritis development

Tissue-Resident Memory CD8+ T Cells From Skin Differentiate Psoriatic Arthritis From Psoriasis

Objective: To compare immune cell phenotype and function in psoriatic arthritis (PsA) versus psoriasis in order to better understand the pathogenesis of PsA. Methods: In-depth immunophenotyping of different T cell and dendritic cell subsets was performed in patients with PsA, psoriasis, or axial spondyloarthritis and healthy controls. Subsequently, we analyzed cells from peripheral blood, synovial fluid (SF), and skin biopsy specimens using flow cytometry, along with high-throughput transcriptome analyses and functional assays on the specific cell populations that appeared to differentiate PsA from psoriasis. Results: Compared to healthy controls, the peripheral blood of patients with PsA was characterized by an increase in regulatory CD4+ T cells and interleukin-17A (IL-17A) and IL-22 coproducing CD8+ T cells. One population specifically differentiated PsA from psoriasis: i.e., CD8+CCR10+ T cells were enriched in PsA. CD8+CCR10+ T cells expressed high levels of DNAX accessory molecule 1 and were effector memory cells that coexpressed skin-homing receptors CCR4 and cutaneous lymphocyte antigen. CD8+CCR10+ T cells were detected under inflammatory and homeostatic conditions in skin, but were not enriched in SF. Gene profiling further revealed that CD8+CCR10+ T cells expressed GATA3, FOXP3, and core transcriptional signature of tissue-resident memory T cells, including CD103. Specific genes, including RORC, IFNAR1, and ERAP1, were up-regulated in PsA compared to psoriasis. CD8+CCR10+ T cells were endowed with a Tc2/22-like cytokine profile, lacked cytotoxic potential, and displayed overall regulatory function. Conclusion: Tissue-resident memory CD8+ T cells derived from the skin are enhanced in the circulation of patients with PsA compared to patients with psoriasis alone. This may indicate that aberrances in cutaneous tissue homeostasis contribute to arthritis development