Psoriasis and psoriatic arthritis (PsA) are inflammatory immune-mediated conditions which can cause considerable disability and reduced quality of life. Management can be complex as clinical heterogeneity may lead to different treatment pathways. Tofacitinib is a novel, oral Janus Kinase (JAK) inhibitor with proven efficacy in rheumatoid arthritis. Areas covered: This review analyzes recent studies of tofacitinib in psoriatic disease treatment. The relevant literature was identified using clinicaltrials.gov, PubMed, and Google Scholar. Tofacitinib efficacy was demonstrated in PsA by the OPAL Broaden and OPAL Beyond phase-III studies, and received FDA and EMA approval. Tofacitinib was superior to placebo for the treatment of moderate-to-severe plaque psoriasis in the OPT Pivotal 1 and 2, OPT Retreatment studies, but FDA approval was declined for this indication based on issues of clinical efficacy and long-term safety. Expert commentary: Tofacitinib is an important oral drug for the treatment of PsA. However, the long-term safety data require further evaluation. Tofacitinib and other JAK inhibitors show potential to broaden the treatment options in PsA and other inflammatory conditions.

The IL-1 family member cytokine IL-36γ is recognised as key mediator in the immunopathology of psoriasis, hallmarks of which involve the activation of both resident and infiltrating inflammatory myeloid cells and aberrant angiogenesis. This research demonstrates a role for IL-36γ in both myeloid activation and angiogenesis. We show that IL-36γ induces the production of psoriasis-associated cytokines from macrophages (IL-23 and TNFα) and that this response is enhanced in macrophages from psoriasis patients. This effect is specific for IL-36γ and could not be mimicked by other IL-1 family cytokines such as IL-1α. IL-36γ was also demonstrated to induce endothelial tube formation and branching, in a VEGF-A-dependent manner. Furthermore, IL-36γ-stimulated macrophages potently activated endothelial cells and led to increased adherence of monocytes, effects that were markedly more pronounced for psoriatic macrophages. Interestingly, regardless of stimulus, psoriasis monocytes showed increased adherence to both the stimulated and unstimulated endothelium when compared with monocytes from healthy individuals. Collectively, these findings show that IL-36γ has the potential to enhance endothelium directed leucocyte infiltration into the skin and strengthen the IL-23/IL-17 pathway adding to the growing evidence of pathogenetic roles for IL-36γ in psoriatic responses. Our findings also point to a cellular response, which could potentially explain cardiovascular comorbidities in psoriasis in the form of endothelial activation and increased monocyte adherence.

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The traditional diagnostic gold standard for inflammatory skin lesions of unclear etiology is dermato-histopathology. As this approach requires an invasive skin biopsy, biopsy processing and analysis by specialized histologists, it is a resource intensive approach requiring trained healthcare professionals. In many health care settings access to this diagnostic approach can be difficult and outside emergency cases will usually take several weeks. This scenario leads to delayed or inappropriate treatment given to patients. With dramatically increased sensitivity of a range of analysis systems including mass spectrometry, high sensitivity, multiplex ELISA based systems and PCR approaches we are now able to “measure” samples with unprecedented sensitivity and accuracy. Other important developments include the long-term monitoring of parameters using microneedle approaches and the improvement in imaging systems such as optical coherence tomography. In this review we will focus on recent achievements regarding measurements from non-invasive sampling, in particular from plucked hair and skin tape-strips which seem well suited for the diagnosis of lupus erythematosus and psoriatic inflammation, respectively. While these approaches will not replace clinical observation—they can contribute to improved subgroup diagnosis, stratified therapeutic approaches and have great potential for providing molecular and mechanistic insight in to inflammatory skin diseases.

The skin barrier would not function without IL-1 family members, but their physiological role in the immunological aspects of skin barrier function are often overlooked. This review summarises the role of IL-1 family cytokines (IL-1α, IL-1β, IL-1Ra, IL-18, IL-33, IL-36α, IL-36β, IL-36γ, IL-36Ra, IL-37 and IL-38) in the skin. We focus on novel aspects of their interaction with commensals and pathogens, the important impact of proteases on cytokine activity, on healing responses and inflammation limiting mechanisms. We discuss IL-1 family cytokines in the context of IL-4/IL-13 and IL-23/IL-17 axis-driven diseases and highlight consequences of human loss/gain of function mutations in activating or inhibitory pathway molecules. This review highlights recent findings that emphasize the importance of IL-1 family cytokines in both physiological and pathological cutaneous inflammation and emergent translational therapeutics that are helping further elucidate these cytokines.

ObjectiveWhen faced with clinical symptoms of scarring alopecia—the standard diagnostic pathway involves a scalp biopsy which is an invasive and expensive procedure. This project aimed to assess if plucked hair follicles (HFs) containing living epithelial cells can offer a non-invasive approach to diagnosing inflammatory scalp lesions.MethodsLesional and non-lesional HFs were extracted from the scalp of patients with chronic discoid lupus erythematosus (CDLE), psoriasis and healthy controls. RNA was isolated from plucked anagen HFs and microarray, as well as quantitative real-time PCR was performed.ResultsHere, we report that gene expression analysis of only a small number of HF plucked from lesional areas of the scalp is sufficient to differentiate CDLE from psoriasis lesions or healthy HF. The expression profile from CDLE HFs coincides with published profiles of CDLE from skin biopsy. Genes that were highly expressed in lesional CDLE corresponded to well-known histopathological diagnostic features of CDLE and included those related to apoptotic cell death, the interferon signature, complement components and CD8+ T-cell immune responses.ConclusionsWe therefore propose that information obtained from this non-invasive approach are sufficient to diagnose scalp lupus erythematosus. Once validated in routine clinical settings and compared with other scarring alopecias, this rapid and non-invasive approach will have great potential for paving the way for future diagnosis of inflammatory scalp lesions.

Abstract Background Psoriatic disease (PsD) is a complex systemic disorder with cutaneous and musculoskeletal (MSK) manifestations. Current evidence on pharmacological interventions –effective Across-The-Spectrum-Of-Clinical-Manifestations (ATSOCM) of early, systemic treatment-naïve PsD- is limited. This review aims to appraise such evidence. Methods This systematic review examined seven Patient-Intervention-Comparator-Outcome (PICO) research questions to address the interventions’ efficacy on: ATSOCM PsD activity; peripheral arthritis; dactylitis; spondylitis; enthesitis; skin; and nails. Early PsD was defined as a disease duration of ≤ 2 years, except for studies investigating outcomes restricted to the skin. Eligible references were clinical trials or well-designed prospective studies/series reporting on: adult humans, untreated, with cutaneous and/or MSK features of PsD. Results Nine references (out of 160 319, publication range 1946–2019) fulfilled the eligibility criteria. No study adopted comprehensive (that is, simultaneous assessment of different PsD manifestations) composite indices as primary outcome measures. Individual studies reported that apremilast and biologics successfully improved outcomes (DAPSA, MDA, PASDAS, PASI, PsARC) when efficacy analyses were restricted to single manifestations of untreated PsD. Only qualitative synthesis of evidence was possible, due to: a) data heterogeneity (disease classification criteria, outcome measures); b) unavailable data subsets -focused on early, untreated PsD- at single study level; c) insufficient data on the participants’ exposure to previous treatment. Conclusions Effective interventions –albeit limited in scope- for early, treatment-naïve PsD were found. No study provided evidence about the management of co-occurring cutaneous and MSK manifestations in early, treatment-naïve PsD. This review highlighted an unmet need in research on early PsD.

BackgroundPsoriatic disease (PsD) refers to a systemic condition, probably driven by chronic and complex inflammatory mechanisms. PsD patients experience a fickle mixture of cutaneous (nail dystrophy, psoriatic lesions spectrum) and musculoskeletal (MSK: arthritis, enthesitis, dactylitis, spondylitis) inflammatory features, variously associated with other co-morbidities (ocular or bowel inflammatory disease, increased cardiovascular risk and metabolic syndrome).Current evidence is limited in respect of the management of early, treatment-naïve PsD.ObjectivesTo assess the literature with a focus on pharmacological interventions in early, treatment-naïve PsD.MethodsSeven research questions were formulated according to the PICO approach: are interventions effective in obtaining control of overall PsD activity? Are interventions effective on peripheral arthritis? On dactylitis? On spondylitis? On enthesitis? On skin and nails?The search was designed as a systematic review of the literature. Early PsD was defined as disease duration ≤2 years, except for studies investigating outcomes restricted to the skin.Criteria for including records were: adult human participants; participants with cutaneous features of PsD; participants with MSK features of PsD; double blind, single blind and non-blinded RCT; well-designed prospective studies/series.The search protocol was registered on PROSPERO [1], the search was performed between June 2018 and January 2019.ResultsResources available were widely explored (4 databases, 5 trial registers, 5 conference archives; see figure). The search retrieved 156,348 references (publication range 1946–2019) of which 308 (0.2%) qualified for full-text-assessment (FTA, figure); 7 (0.0004%) fulfilled the selection criteria and only 4 underwent data extraction.FigureRef. typePsD feature targetedIntervention (success)Primary outcome1 RCTSkinSecukinumab (yes) vs fumarates (no)PASI752 cohortMSKMTX part of T2T (yes)Unclear3 RCTMSKMTX (partial)Joint count4 RCTSkinApremilast (yes)PGAxBSAMeta-analysis was impossible due to data heterogeneity (disease classification criteria, outcome measures and intervention durations). Although no clinical study adopted comprehensive composite indexes as primary outcome measures, 40% of FTA references described more than one component of PsD (i.e.: cutaneous and MSK) at least within the baseline characteristics. A substantial proportion of FTA references did describe, among participants recruited, many who were early untreated PsD at baseline. Unfortunately, separate analyses were not possible due to unavailability of the original datasets. A subset (10%) of the FTA references did not report on the participants’ exposure to previous treatment.ConclusionFew studies addressed early, treatment naïve PsD. The underrepresentation of such data may be related to trial-enrolment criteria. More studies are needed to investigate this identified unmet need.References[1] http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018097366AcknowledgementThe authors wish to thank lib...