To develop comprehensive recommendations for the treatment of the various clinical manifestations of psoriatic arthritis (PsA) based on evidence obtained from a systematic review of the literature ...and from consensus opinion.
Formal literature reviews of treatment for the most significant discrete clinical manifestations of PsA (skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis) were performed and published by members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Treatment recommendations were drafted for each of the clinical manifestations by rheumatologists, dermatologists and PsA patients based on the literature reviews and consensus opinion. The level of agreement for the individual treatment recommendations among GRAPPA members was assessed with an online questionnaire.
Treatment recommendations were developed for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the setting of PsA. In rotal, 19 recommendations were drafted, and over 80% agreement was obtained on 16 of them. In addition, a grid that factors disease severity into each of the different disease manifestations was developed to help the clinician with treatment decisions for the individual patient from an evidenced-based perspective.
Treatment recommendations for the cardinal physical manifestations of PsA were developed based on a literature review and consensus between rheumatologists and dermatologists. In addition, a grid was established to assist in therapeutic reasoning and decision making for individual patients. It is anticipated that periodic updates will take place using this framework as new data become available.
Summary
Background
The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) was developed for use in clinical trials and longitudinal patient assessment.
Objectives
To characterize ...disease severity using the CDASI and assess the responsiveness of this instrument to clinically meaningful changes in disease activity.
Methods
Patients with cutaneous dermatomyositis at the University of Pennsylvania (UPenn, n = 93) and Stanford University (Stanford, n = 106) were prospectively evaluated using the CDASI, physician global assessment (PGA) Likert scales and a visual analogue scale (VAS). Data was analysed using logistic regression models and receiver operating characteristic curves to select cut‐offs.
Results
Baseline CDASI activity scores for the patients evaluated at UPenn ranged from 0 to 47 (median 17), and baseline PGA VAS scores ranged from 0 to 9·6 (median 1·1). At UPenn a CDASI activity score of 19 differentiated mild from moderate and severe disease. At Stanford baseline CDASI scores ranged from 0 to 48 (median 21), baseline PGA VAS scores ranged from 0 to 9·7 (median 4·2) and CDASI activity scores of 14 or less characterized mild disease. When a 2‐cm change in the PGA VAS was regarded as a clinically significant improvement, a 4‐point (UPenn) or 5‐point (Stanford) change in CDASI reflected a minimal clinically significant response.
Conclusions
The CDASI is a valid and responsive measure that can be used to characterize cutaneous dermatomyositis severity and detect improvement in disease activity. Variations in cut‐offs may be due to differences in disease severity between the two populations or inter‐rater variations in the use of the external gold measures.
What's already known about this topic?
Validated outcome measures are essential for comparative trials.
The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) was created for the assessment of cutaneous dermatomyositis in clinical trials, translational research and clinical practice.
Previous studies have demonstrated the validity and reliability of this instrument.
What does this study add?
Cutaneous dermatomyositis disease severity can be characterized with the CDASI.
Clinical change can be assessed by changes in CDASI activity scores.
Practical and standardized use of the CDASI is now possible.
Linked Comment: Volc‐Platzer, Br J Dermatol 2015; 173: 890–891.
Two of the 3 standardized field sobriety tests that U.S. law enforcement uses at roadside checks have a postural equilibrium component to them. Those tests have been validated to detect impairment ...caused by blood alcohol concentrations (BACs) of 0.08 g/dL or above. Many medical and traffic safety associations support a lower limit, and one state, Utah, has passed a law to lower the limit to 0.05 g/dL. Many studies have examined the effects of alcohol on postural control (of which postural equilibrium is a component), with a consensus emerging that impairment is usually found at BACs greater than 0.06 g/dL. Most of these studies, however, had a relatively small number of subjects, usually between 10 and 30. The current study collected data from a much larger sample.
The objective of this study was to provide additional evidence that posture control is negatively affected at BACs greater than 0.06 g/dL or breath alcohol concentrations (BrACs) of 0.06 g/210 L.
This was a between-subjects study, with BrAC group as the independent variable (5 levels: 0.00, 0.04, 0.06, 0.08, and 0.10 g/210 L); 4 measures of postural control as the dependent variables; and age, height, and weight as the covariates. Posture control was measured with a force-sensing platform connected to a computer. The feet's center of pressure (CoP) on the platform was recorded and the corresponding movement of the body in the anterior-posterior and lateral planes was derived. Participants (N = 96) were randomly assigned to one of the BrAC groups. Positive BrAC groups were compared to the zero BrAC group. Data were examined with hierarchical multiple regression.
Adjusted for age, height, and weight, the main effect of lateral CoP with eyes open was not statistically significant. There was a statistically significant main effect of alcohol on anterior-posterior CoP excursion with eyes open and with eyes closed and lateral CoP excursion with eyes closed. For all 3 of those variables, only BrACs of 0.08 and 0.10 g/210 L produced differences against zero BrAC. Although the main effect of alcohol on Lateral CoP Excursion with eyes open was not statistically significant, the contrasts between 0 and 0.08 and 0 and 0.10 g/210L BrAC were in the hypothesized direction.
The current study did not directly address the issue of whether the sobriety tests are sensitive to BrACs of 0.05 g/210 L or above; rather, it provides additional evidence that postural control, one of the components of those tests, is relatively unaffected by BrACs lower than 0.08 g/210 L. Additional research is needed on the diagnostic characteristics of the sobriety tests at BrACs lower than 0.08 g/210 L.
To characterise activation of the type I interferon (IFN) pathway in patients with systemic lupus erythematosus (SLE), dermatomyositis (DM), polymyositis (PM), rheumatoid arthritis (RA) and systemic ...scleroderma (SSc) and to evaluate the potential to develop a molecular diagnostic tool from the peripheral blood that reflects this activation in disease-affected tissues.
Overexpressed transcripts were identified in the whole blood (WB) of 262 patients with SLE, 44 with DM, 33 with PM, 28 with SSc and 89 with RA and compared with 24 healthy subjects using Affymetrix microarrays. A five gene type I IFN signature was assessed in these subjects to identify subpopulations showing both activation and concordance of the type I IFN pathway in the peripheral blood and disease-affected tissues of each disease and to correlate activation of this pathway in the WB with clinical measurements.
A common set of 36 type I IFN inducible transcripts were identified among the most overexpressed in the WB of all subjects. Significant activation of the type I IFN pathway in subgroups of each of the five diseases studied was observed. Baseline disease activity measurements correlated with a type I IFN gene signature in the WB of subjects with SLE, PM and SSc, as did various serum autoantibody levels in subjects with SLE and DM. This signature was also well correlated between disease-affected tissue and WB in subjects with SLE, DM, PM and SSc.
The results indicate that the type I IFN pathway is activated in patient subsets of five rheumatic diseases and suggest that these subsets may benefit from anti-IFN therapy.
Summary
Background
R333 is a topical janus kinase and spleen tyrosine kinase inhibitor being evaluated for discoid lupus erythematosus (DLE) treatment. There is no validated measure to assess the ...area of active DLE lesions.
Objectives
To evaluate R333 efficacy and assess a technique to measure responsiveness.
Methods
Fifty‐four patients with DLE were randomized in a double‐blind design to R333 or placebo. Primary end point was the proportion of patients achieving ≥ 50% decrease in erythema and scale based on lesional Cutaneous Lupus Erythematosus Disease Area and Severity IndexTM for all treated lesions at week 4. Two‐dimensional (2D) area measurements for each lesion were recorded at baseline and weeks 1–6. Eighty‐eight photographs (44 pre‐ and 44 post‐treatment) were obtained from the trial and change in size of active areas was analysed by computerized planimetry and physician‐assessed area change (PAAC).
Results
Thirty‐six patients were randomized to R333 and 18 patients were randomized to placebo. Primary end point was not achieved. There was a strong association between lesion activity and physician global assessment (P < 0·001). Photos of 42 patients assessed by computerized planimetry demonstrated excellent inter‐ and intra‐rater reliability. Area change by computerized planimetry showed a strong correlation with PAAC (Spearman r = 0·72). Area change by 2D measurements showed a weak correlation with PAAC (Spearman r = 0·29).
Conclusions
Four weeks of R333 treatment did not result in significant improvement in lesion activity. Lesion activity and area change using computerized planimetry are better determinants of responsiveness than area change using 2D measurements.
What's already known about this topic?
Topical janus kinase (JAK)/spleen tyrosine kinase (Syk) inhibitors may be useful in the treatment of discoid lupus erythematosus (DLE) lesions.
Validated outcome measures are critical in that they enable the objective evaluation of disease for clinical practice, therapeutic trials and translational research.
There is a need to validate an approach that can evaluate individual cutaneous lesions to assess the effects of topical therapies in DLE.
What does this study add?
The topical JAK/Syk inhibitor R333 did not result in clinical improvement of DLE lesions after 4 weeks of treatment.
Computerized planimetry is a reliable technique for measuring the area of DLE lesions.
Lesion activity and area determined by computerized planimetry are better able to assess clinical responsiveness to topical medication for DLE lesions than the area determined using two‐dimensional measurements.
Plain language summary available online
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Digital ulcers (DU), defined as necrotic lesions located at distal digits or overlying bony prominences, occur in up to 50% of patients with limited or diffuse systemic sclerosis (SSc). These lesions ...are extremely painful and lead to substantial functional disability. The pathogenesis of DU differs depending on their location. DU located at distal aspects of digits are thought to be related to tissue ischemia from several processes, including vasospasm secondary to Raynaud's phenomenon, intimal fibro-proliferation, and thrombosis of digital arteries. DU located over bony prominences, such as the phalangeal joints and elbows, are thought to be due to repetitive microtrauma and difficulty healing due to atrophic, avascular tissue overlying the joints. Management of DU include non-pharmacologic and pharmacologic modalities. This review summarizes the current available and investigational therapies for the treatment and prevention of DU in patients with SSc.
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