Synovitis in psoriatic arthritis: immunohistochemistry, comparisons with rheumatoid arthritis, and effects of therapy

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis that affects the peripheral joints, spine, and entheses. Most patients with PsA present with peripheral synovitis of the oligoarticular or polyarticular subtype. As one of the targets of this disease, studies on the synovium may provide insight into the mechanisms involved in this condition. Key findings from the available studies comparing synovial tissue of PsA and rheumatoid arthritis patients are discussed in this review. Also, changes in the synovial infiltrate, expression of proinflammatory cytokines and adhesion molecules, and vascularity in synovial tissue after treatment with various medications are addressed. Finally, a model for proof-of-principle study design using serial synovial biopsies is described, which could be used to predict clinical (in)efficacy in early clinical trial design in Ps

Ideal target for psoriatic arthritis? Comparison of remission and low disease activity states in a real-life cohort

Background Psoriatic arthritis (PsA) recommendations state that the target of treatment should be remission or low disease activity (LDA). We used a real-life dataset to compare different potential targets. Methods 250 patients with PsA considered in an acceptable disease state according to their rheumatologist were included. Targets for remission were the Disease Activity Index for Psoriatic Arthritis (DAPSA) and clinical DAPSA (cDAPSA) remission (4), very low disease activity (VLDA) and Psoriatic Arthritis Disease Activity Score 1.9. LDA targets analysed were the DAPSA 14, cDAPSA 13, minimal disease activity (MDA) and adjusted MDA targets: MDAjoints with both tender joint count (TJC) and swollen joint count (SJC) mandated, MDAskin (psoriasis area and severity index (PASI) mandated) and MDAjoints&skin with TJC, SJC and PASI mandated. Results Comparison of the several candidate targets demonstrates that VLDA is achieved by the lowest proportion of patients and includes patients with the lowest residual disease activity compared with the other remission targets. The modified MDA measures are the most stringent targets for LDA in terms of residual disease on joints, psoriasis and enthesitis within patients achieving the target. In both remission and LDA, the inclusion of C reactive protein did not show an added value. The exclusion of a skin domain, as in the DAPSA measures, resulted in negligence of skin disease and a negative impact on the quality of life in some patients. Conclusions The different remission and LDA targets show us significant overlap between measures, but these measures targeting the same definition do differ in terms of allowance of residual disease. Inclusion of laboratory markers seems unnecessary, although exclusion of a skin domain may result in psoriasis not being assessed resulting in residual impactful skin diseas

Breast sensibility in bilateral autologous breast reconstruction with unilateral sensory nerve coaptation

Background Patient satisfaction after breast reconstruction is dependent on both esthetics and functional outcomes. In an attempt to improve breast sensibility, a sensory nerve coaptation can be performed. The aim of this study was to objectify the sensory recovery in patients who, by chance, underwent bilateral autologous breast reconstruction with one innervated and one non-innervated flap. It must be emphasized that the intention was to coaptate the sensory nerves on both sides. Methods The cohort study was carried out in the Maastricht University Medical Center between August 2016 and August 2018. Patients were eligible if they underwent bilateral non-complex, autologous breast reconstruction with unilateral sensory nerve coaptation and underwent sensory measurements using Semmes-Weinstein monofilaments at 12 months of follow-up. Sensory outcomes were compared using t tests. Results A total of 15 patients were included, all contributing one innervated and one non-innervated flap. All patients had a follow-up of at least 12 months, but were measured at different follow-up points with a mean follow-up of 19 months. Sensory nerve coaptation was significantly associated with better sensation in the innervated breasts and showed better sensory recovery over time, compared to non-innervated breasts. Moreover, the protective sensation of the skin can be restored by sensory nerve coaptation. Conclusions The study demonstrated that sensory nerve coaptation leads to better sensation in the autologous reconstructed breast in patients who underwent bilateral breast reconstruction and, by chance, received unilateral sensory nerve coaptation.</p

Response to: 'To DAPSA or not to DAPSA? That is not the question' by Schoels et al

We thank the authors for the interest in our paper and are grateful for the opportunity to respond to the points raised1. We agree that there is a clear distinction between composite measures of psoriatic arthritis such as DAPSA and composite measures of psoriatic disease such as MDA/VLDA and PASDAS. As the Vienna group rightly point out, these measures differ in terms of the components included, but not due to disagreement within the outcome measure community as suggested in the letter. The choice of components for each composite measure was decided using different methodology in the development of each one, thus resulting in different measures. We believe that this variation in scores is one reason for the need to compare such scores in different populations to establish the optimal measure or measures for PsA. Indeed when the DAPSA was originally suggested, it was because the same components used in the DAREA were identified in a principal component analysis (PCA) in PsA. Interestingly in this analysis, the variables tested were taken from the OMERACT PsA domains and therefore DAPSA was not, a priori, designed specifically to be a unidimensional composite measure. The fourth component identified in the PCA was the PASI highlighting the importance of skin in PsA despite the fact that patients had a low baseline mean PASI of only 3.3. Whilst PASI was not included in the DAPSA as the eigenvalue was 0.949 and therefore just under the threshold of 12, it is interesting to imagine how the results may have differed if it were developed in a group with slightly more active skin disease

Clinical Relevance of Sensory Nerve Coaptation in DIEP Flap Breast Reconstruction Evaluated Using the BREAST-Q

INTRODUCTION: Sensory nerve coaptation in autologous breast reconstruction positively affects the sensory recovery in the reconstructed breast. However, patient-reported outcomes are currently lacking and no conclusions on the clinical relevance of nerve coaptation could be drawn. The aim of this study was to evaluate the clinical relevance of nerve coaptation in deep inferior epigastric perforator (DIEP) flap breast reconstruction. METHODS: A prospective cohort study was conducted with patients with innervated or noninnervated DIEP flap breast reconstruction between August 2016 and August 2018, and completed a BREAST-Q questionnaire at a minimum of 12 months postoperative, in combination with a preoperative questionnaire or at 6 months postoperative. The domain "Physical well-being of the chest" was the primary outcome and patients answered additional sensation-specific questions. Sensation was measured using Semmes-Weinstein monofilaments. RESULTS: In total, 120 patients were included (65 innervated and 55 noninnervated reconstructions). A clinically relevant difference was found in BREAST-Q scores in favor of patients with innervated reconstructions in general, and for delayed reconstructions in specific. Patients with sensate breast reconstruction more often experienced better and pleasant sensation. CONCLUSIONS: This study demonstrated that nerve coaptation in DIEP flap breast reconstruction, specifically in delayed reconstructions, resulted in clinically relevant higher patient-reported outcomes for the BREAST-Q domain "Physical well-being of the chest" and that better sensation was perceived pleasantly. However, the BREAST-Q does not adequately address sensation, and the introduction and validation of new scales is required to fill in these gaps to confirm the clinical relevance of nerve coaptation reliably

"Innervation of the Female Breast and Nipple:A Systematic Review and Meta-Analysis of Anatomical Dissection Studies"

BACKGROUND: Primary cadaveric studies were reviewed to give a contemporary overview of what is known about innervation of the female breast and nipple/nipple-areola complex (NAC). METHODS: We performed a PRISMA-compliant systematic review and meta-analysis (PROSPERO number CRD42020150250). We searched four electronic databases for studies investigating which nerve branches supply the female breast and nipple/NAC or describing the trajectory and other anatomical features of these nerves. Inclusion criteria for meta-analysis were at least five studies of known sample size and with numerical observed values. Pooled prevalence (PP) estimates of nerve branches supplying the nipple/NAC were calculated using random-effects meta-analyses; the remaining results were structured using qualitative synthesis. Risk of bias within individual studies was assessed with the Anatomical Quality Assurance (AQUA) checklist. RESULTS: Of 3653 studies identified, 19 were eligible for qualitative synthesis and 7 for meta-analysis. The breast skin is innervated by anterior cutaneous branches (ACBs) and lateral cutaneous branches (LCBs) of the 2nd - 6th and the nipple/NAC primarily by ACBs and LCBs of the 3rd - 5th intercostal nerves. The ACB and LCB of the 4th intercostal nerve supply the largest surface area of the breast skin and nipple/NAC. The LCB of the 4th intercostal nerve is the most consistent contributory nerve to the nipple/NAC (PP 89.0%; 95% CI 0.80-0.94). CONCLUSIONS: The ACB and LCB of the 4th intercostal nerve are the most important nerves to spare or repair during reconstructive and cosmetic breast surgery. Future studies are required to elicit the course of dominant nerves through the breast tissue

Residual disease activity and treatment adjustments in psoriatic arthritis in current clinical practice

Abstract Background With expanding therapeutic possibilities for treatment of psoriatic arthritis (PsA) it will be increasingly important to determine residual disease and define when to adjust treatment. The rationale behind treatment decisions in current daily clinical practice and the relationship with residual disease activity has not been investigated. The aim of this study was to assess current clinical practice on defining residual disease and subsequent treatment decisions made in PsA patients. Methods This cross-sectional study scored disease activity and treatment decisions prospectively in 142 consecutive PsA patients visiting the outpatient clinic for routine follow up. Disease activity parameters were scored by patient and the treating rheumatologist; the rheumatologist additionally registered his opinion on the presence of remaining disease activity despite current treatment (further mentioned as remaining disease) and subsequent treatment decisions. Results Two thirds (90/142) of patients had remaining disease activity according to the treating rheumatologist. Almost half (46%) of these patients had moderate to high disease activity according to the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA). Residual disease activity was determined by joint disease and pain rather than by active psoriasis. Demographic and clinical features were similar between groups with or without residual disease. Among patients with remaining disease activity, 74% were treated with either a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) only or a first TNF-inhibiting biological agent, suggesting opportunities for treatment modification. However, treatment adjustment was initiated in only 21 (23%) of the 90 patients with residual disease. When comparing patients with remaining disease activity with and without treatment adjustment, we found no differences in objective disease activity measures, such as joint counts and patient scores. These data suggest that treatment is not adjusted in a large majority of patients with residual disease activity, although options for treatment changes are available. Conclusions Remaining disease activity is present in almost two thirds of patients with PsA when scored by the treating rheumatologist, but triggers treatment adjustment in only a minority. Further research to understand why disease activity does not lead to treatment adjustment is required to enable implementation of treatment strategies in clinical practice