ACR Journals

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Official journals of the American College of Rheumatology: Arthritis & Rheumatology Arthritis Care & Research ACR Open Rheumatology SoMe Editor: Karen Costenbader, MD, MPH

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ACR Journals@acr-journals· 24d

In skin of color, dermatomyositis may present with less obvious erythema and more dyspigmentation, making careful evaluation of distribution, texture, and associated findings critical. Early recognition can improve outcomes Letter in Arthritis & Rheumatology doi.org/10.1002/art....

A Fitzpatrick skin type V woman in her 70s presenting with a heliotrope rash characterized by prominent lichenification and eyelid edema, with subtle background erythema

ACR Journals@acr-journals· 24d

Clinical images show a case of dystrophic calcification development in a 50-year-old woman with a 15-year history of systemic lupus erythematosus and overlapping systemic sclerosis Clinical images in ACR Open Rheumatology doi.org/10.1002/acr2...

Image: multiple symmetric subcutaneous indurations on her palms, forearms, hips, thighs, and shins (A). The lesions were nontender but prone to spontaneous rupture with extrusion of yellowish-white material (B). Imaging showed extensive subcutaneous calcinosis (C-D)

ACR Journals@acr-journals· 25d

A 56 y/o woman with 10-year history of RA presented with 2 months of left heel pain & progressive difficulty walking. She had started methotrexate & leflunomide 3 months earlier & received a local glucocorticoid injection around the left ankle. She denied recent trauma ACROR doi.org/10.1002/acr2...

Examination showed ankle swelling, a visible and palpable gap along the Achilles tendon, weak plantar flexion, and absence of passive plantar flexion during calf squeezing, indicating a positive Thompson test (A). MRI confirmed complete Achilles tendon discontinuity with tendon-end retraction and marrow edema in the calcaneus and talus (B and C)

ACR Journals@acr-journals· 26d

Congratulations to the newly appointed Deputy Editors of Arthritis Care & Research: ▪️ Joshua Baker, MD, MSCE ▪️ Bonnie L. Bermas, MD ▪️ Yvonne C. Lee, MD, MMSc ▪️ Todd A. Schwartz, DrPH

ACR Journals@acr-journals· 26d

New papers in Arthritis Care & Research: A VEXAS-specific disease activity index to quantify inflammation over time in VEXAS syndrome doi.org/10.1002/acr.... Trajectory of total body adiposity in youth following injury doi.org/10.1002/acr.... ↓

Weekly recap in ACR journals banner - Arthritis Care & Research

ACR Journals@acr-journals· 26d

New studies this week in Arthritis & Rheumatology: Skin cancer risk with JAKi vs IL-6Ri in RA doi.org/10.1002/art.... Open-label PK study of certolizumab pegol in polyarticular JIA doi.org/10.1002/art.... ↓

Weekly recap in ACR journals banner - Arthritis & Rheumatology cover

ACR Journals@acr-journals· 26d

Challenges persist in defining & assessing renal response to therapy in lupus nephritis. Review examines current limitations of renal outcome definitions & provides a perspective toward uniform definitions of response in LN trials, renal flare/relapse, & refractory disease doi.org/10.1002/acr2...

Existing clinical response criteria and potential unified hierarchical criteria for histologic and clinical definitions of renal response

ACR Journals@acr-journals· 27d

Over the past 50 years, there has been major growth in our understanding of the pathogenesis of juvenile IIM. New review in AC&R looks at the progress that has been made in treatment, development of prognostic tools, & knowledge of the long-term outcomes of juvenile myositis doi.org/10.1002/acr....

A. Classification of Myositis – THEN. This shows the classification of myositis in the early 1990s, with separation of clinical pathologic and myositis autoantibody subgroups. Juvenile dermatomyositis was considered a distinct disease from the adult forms of myositis, other subgroups of juvenile myositis were not recognized, and the number of myositis autoantibodies identified was limited. B. Classification of Juvenile Myositis – NOW. This represents the classification of myositis today, with integration of clinical subgroups and myositis autoantibodies to together define distinct phenotypes. Most of the subtypes present in adult myositis are now recognized in juvenile myositis, and classification is integrated across the age-span. Many more myositis autoantibodies and their associated phenotypes have been identified in recent years.

A. Treatment Paradigm for Juvenile Dermatomyositis in 1980s- THEN. Daily oral prednisone therapy was the mainstay of therapy. Second line therapies were limited, and only cyclophosphamide and plasmapheresis were available for severe patients. B. Treatment Paradigm for Juvenile Myositis – NOW. A standardized approach to initial therapy now includes daily oral prednisone in combination with methotrexate, with option to add intravenous methylprednisolone and/or intravenous gammaglobulin. A number of medications are available as second- and third-line therapies, including targeted biologics and drugs and use of combination therapies

ACR Journals@acr-journals· 28d

Documentation of contraception and pregnancy interest is often missing from the clinical notes of rheumatologists. A learning collaborative demonstrated improvements in documentation within community rheumatology clinics with simple and feasible interventions AC&R doi.org/10.1002/acr....

Changes within the NextGen EHR system to implement the collection of current contraception, interest in pregnancy, and current pregnancy. A. Red text added to alert the medical assistant to women within the target age-range for the reproductive health questions. B. Red text added to alert the physician when a woman was interested or unsure about pregnancy desire. A custom list of contraceptive options was created; two forms of current contraceptives could be documented.

ACR Journals@acr-journals· 29d

Study introduces a VEXAS-specific disease activity index (DAI) designed to quantify active inflammation over time in patients with VEXAS syndrome. Prospective validation is ongoing Arthritis Care & Research doi.org/10.1002/acr.... (scoring guide can be found in supplementary downloads)

VEXAS-DAI domains, items, and grading (scoring guide can be found in supplementary downloads)
a Grade range reflects potential clinician-assigned grades, where applicable.
b Maximum score reflects the greatest possible score for each domain (bold) and item (plain text) corresponding to the highest grade of inflammation.

ACR Journals@acr-journals· 29d

New data from an Italian study of 60 autoimmune patients showed women positive for aPL antibodies face increased risk for preterm delivery in presence of high anti-PS/PT titers and low lectin pathway activity since the beginning of pregnancy Arthritis & Rheumatology doi.org/10.1002/art....

The Role of Anti-Phosphatidylserine/Prothrombin Antibodies and the Lectin Complement Pathway in Anti-Phospholipid Antibody-Associated Preterm Delivery. Graphical abstract created using BioRender

ACR Journals@acr-journals· Jul 14

Open-label pharmacokinetics (PK) study of certolizumab pegol (CZP) in polyarticular JIA. CZP showed Rapid and long-term sustained improvement of JIA. PK of CZP was linear, with steady state reached by week 12. No new safety signals detected Arthritis & Rheumatology doi.org/10.1002/art....

Geometric mean certolizumab pegol plasma concentrations for the entire 2 treatment period – original and reduced dose (PK-PPS, OC).

ACR Journals@acr-journals· Jul 13

Analysis of BSRBR-RA linked cancer registry data compared non-melanoma skin cancer risk after JAKi vs IL-6Ri initiation in RA. Findings suggest a clinically small, plausibly higher risk with JAKi, adding to previous evidence on JAKi vs TNFi Arthritis & Rheumatology doi.org/10.1002/art....

Time to first-ever non-melanoma skin cancer in RA patients initiated JAKi compared with IL-6Ri, primary ever-exposed model with a 90-day lag period, Kaplan–Meier failure function

ACR Journals@acr-journals· Jul 11

Editorial in Arthritis & Rheumatology: Are axSpA and PsA merely different clinical phenotypes within a shared disease spectrum, or do they reflect distinct immune programs that determine tissue tropism and therapeutic responses? doi.org/10.1002/art....

Summary of immune signatures in axial spondyloarthritis versus psoriatic arthritis

ACR Journals@acr-journals· Jul 11

New papers this week across the ACR journals: Distinct immune signatures in axSpA and PsA doi.org/10.1002/art.... Peripheral blood DNA methylation changes precede lymphoma in primary SjD doi.org/10.1002/art.... Non‐melanoma skin cancer risk with JAKi vs IL-6Ri in RA doi.org/10.1002/art....

ACR Journals@acr-journals· Jul 10

An epigenome-wide association study identified peripheral blood DNA methylation changes that precede lymphoma diagnosis in primary Sjögren’s disease. Exploratory findings highlight candidate pathways involved in immune regulation & lymphomagenesis and provide foundation for future biomarker studies

DNA methylation differences in peripheral whole blood from patients with Sjögren’s disease (SjD) sampled ≥1 year prior to lymphoma diagnosis (SjD pre-lymphoma) compared with SjD without subsequent lymphoma (SjD only).

(A) Manhattan plot showing –log10 transformed p values for autosomal CpG site associations with SjD pre-lymphoma status. The most significantly differentially methylated CpG positions (DMPs) are annotated with their corresponding gene symbols.
(B) Volcano plot showing hypomethylated DMPs in SjD pre-lymphoma (blue) and hypermethylated DMPs (red). The x-axis represents effect size (Δβ) and the y-axis –log10 p values. The horizontal dashed line indicates the Bonferroni-corrected significance threshold (p≤1.3x10-7), and vertical dashed lines denote the effect size threshold (|Δβ|>0.05).
(C) Box plots of methylation β values for selected DMPs in SjD pre-lymphoma (purple) and SjD-only (green). DMPs and corresponding gene annotations are shown on the y-axes. Boxes represent the interquartile range with median indicated; whiskers denote the range, excluding outliers.
(D) Bar plot of functional pathway enrichment analysis for all unique genes (n=336) annotated to autosomal DMPs. Significantly enriched pathways and their –log10 FDR-adjusted p values are shown.
(E) Genomic distribution of all autosomal DMPs (n=473) relative to all CpG sites passing quality control

ACR Journals@acr-journals· Jul 9

Comparing the performance of seven code-based algorithms in EHR data to identify cases of idiopathic inflammatory myopathies showed PPVs ranging from 77% to 84% but with lower sensitivity (14%–63%) ACR Open Rheumatology doi.org/10.1002/acr2...

Comparison of Rule-Based Algorithms to Identify Patients With Idiopathic Inflammatory Myopathies in Electronic Health Records. Graphical abstract created using BioRender

ACR Journals@acr-journals· Jul 9

International survey asked patients with systemic sclerosis about unmet needs in managing orofacial manifestations. Most commonly reported were xerostomia, facial appearance concerns, restricted mouth opening, dysphagia, denture-related problems Arthritis Care & Research doi.org/10.1002/acr....

Orofacial manifestations reported (A) and sources of advice sought (B) concerning orofacial manifestations in SSc

ACR Journals@acr-journals· Jul 9

Can efficacy & target drug exposure data be extrapolated from adults w/ axSpA to children w/ axJSpA? Review in AC&R synthesizes clinical, imaging, & pathophysiology parallels between adult axSpA & axJSpA and argues extrapolation could safely expand therapeutic options for youth with axial disease

Criteria for axSpA in adults and children
†For the axJSpA criteria: The Maximum AxJSpA score is 100, and scores of 55 and above meet the threshold for classification as AxJSpA. Levels within each domain are mutually exclusive. The highest level achieved within each domain contributes to the overall score.
^Level only applicable in absence of pelvic MRI.
# FABER = Flexion Abduction External Rotation of the hip (SIJ pain should be on contralateral side); Mennell’s maneuver: application of SIJ pressure with the patient in prone position, leg straight, and hip extended; Gaenslen’s test: patient is supine with one hip and knee flexed, and the examiner applies downward force to hyperextend the other leg along the edge of the examining table, with SIJ pain on the ipsilateral side that is being hyperextended.
ASAS = Assessment of Spondyloarthritis International Society

ref 8: doi:10.1136/ard.2009.108233
ref 4: doi:10.1002/art.42959

ACR Journals@acr-journals· Jul 8

Analysis of data from 3 large SLE cohorts identified and validated 6 reproducible SLE molecular subtypes spanning IFN, B cell/plasmablast, and neutrophil axes, which were linked to serum proteomic patterns and serological features ACR Open Rheumatology doi.org/10.1002/acr2...

Transcriptomic and proteomic characterization of six molecular subtypes across cohorts. (A) Heatmap of Gene Set Variation Analysis (GSVA) enrichment scores for eight representative immune gene modules across K1 to K6 in ILLUMINATE (whole-blood microarray), LOTUS (whole-blood RNA sequencing [RNA-seq]), and Genuity Science (peripheral blood mononuclear cell RNA-seq). (B) Association of baseline glucocorticoid (GC) use with neutrophil module enrichment (M5.15, M6.20), adjusted (adj.) for cluster (GC use coefficient ± 95% confidence interval [CI]). ***P < 0.001. (C) Cluster-specific neutrophil module effects in LOTUS from multivariable models adj. for baseline GC use and lupus nephritis (LN), shown as cluster means ± 95% CI. *P < 0.05; **P < 0.01; ***P < 0.001. (D) Cluster prevalence in each cohort. (E) Cross-platform proteomic patterns by cluster, showing representative differentially abundant proteins measured by Olink (Genuity Science) and SomaLogic SomaScan (LOTUS); proteins not measured on a given platform are shown in gray brown

ACR Journals@acr-journals· Jul 8

Among 25 patients w/ SSc, The Hand Test System (HTS) engineered glove provided objective measures that correlated w/ PROMs, mRSS, & high-frequency skin ultrasonography-measured dermal thickness. The HTS glove may be a promising tool for monitoring hand outcomes in SSc ACROR doi.org/10.1002/acr2...

An Engineered Glove for the Objective Assessment of Hand Dexterity in Patients With Systemic Sclerosis. Graphical abstract created using BioRender

ACR Journals@acr-journals· Jul 8

Are axial spondyloarthritis and psoriatic arthritis immunologically distinct? New study used deep immunophenotyping to identify disease-specific immune signatures, revealing differences in innate/inflammatory and adaptive immune pathways Arthritis & Rheumatology doi.org/10.1002/art....

Deep Immunophenotyping Reveals Distinct Immune Signatures in Axial Spondyloarthritis and Psoriatic Arthritis. Graphical abstract created using BioRender

ACR Journals@acr-journals· Jul 6

New study found DNMT3A acts in autoreactive CD4+ T cells to support T follicular helper responses. Reduced DNMT3A function attenuated joint inflammation in a mouse model of rheumatoid arthritis Arthritis & Rheumatology doi.org/10.1002/art....

DNA (cytosine-5)-methyltransferase 3A (Dnmt3a) mutations limit normal and autoreactive CD4+ T follicular helper responses and attenuate T cell-driven joint inflammation. Graphical abstract created using BioRender

ACR Journals@acr-journals· Jul 5

A 56-year-old man presented with 2-month history of periorbital edema and skin rash on his chest, back, and upper extremities with skin sloughing (A,B), without mucosal involvement. Labs showed ANA titer of 1:640, ESR 25 mm/hr, and CRP 33.6.

Periorbital edema and skin rash on his chest, back, and upper extremities with skin sloughing (A,B). Periorbital edema recurred and the rash spread in the setting of tapering glucocorticoids down to prednisone 50 mg daily (C,D).
E, MRI of the thighs with STIR showed muscle edema (white asterisks indicate muscle edema, and white arrows indicate perifascial edema) .
(F) Punch biopsy of the right upper chest demonstrated mild perivascular and periadnexal inflammation on hematoxylin and eosin (H&E) stain (black arrows) and (G) interstitial mucin on Alcian Blue–periodic acid–Schiff (AB-PAS) stain (blue staining, black arrows).

ACR Journals@acr-journals· Jul 5

ACR Open Rheumatology Editor's Pick Positive and Negative Cardiovascular Effects of JAK Inhibitors in Inflammation https://doi.org/10.1002/acr2.90074

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ACR Journals@acr-journals· Jul 4

July Arthritis Care & Research Editor's Pick Clinical Practice Guideline for Evaluation and Management of Peripheral Nervous System Manifestations in Sjögren’s Disease https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr.70004

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ACR Journals@acr-journals· Jul 4

July Arthritis & Rheumatology Editor's Pick PEPITEM Regulates the Synovial Microenvironment During Immune-Mediated Inflammatory Arthritis to Limit Disease https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.70108

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ACR Journals@acr-journals· Jul 3

July A&R Clinical Connections: • First-Year IgG Dynamics in IgG4-Related Disease • Serum Proteomic Signatures of Rheumatoid Arthritis Risk and Response acrjournals.onlinelibrary.wiley.com/doi/epdf/10....

First-Year IgG Dynamics in IgG4-Related Disease. Figure created using BioRender

Serum Proteomic Signatures of Rheumatoid Arthritis Risk and Response. Figure created using BioRender

ACR Journals@acr-journals· Jul 3

July A&R In This Issue • HCQ Adherence and Future Acute Care Use • Late-Onset Rheumatoid Arthritis and Air Pollution • Natural Killer Cell Signature in Still Disease 🔎 Journal Club: Performance of the PREVENT Calculator in Rheumatoid Arthritis acrjournals.onlinelibrary.wiley.com/doi/epdf/10....

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ACR Journals@acr-journals· Jul 3

Calcium pyrophosphate deposition (CPPD) disease is a common crystalline arthritis in older adults, yet few data are available to guide management. Expert Perspective in Arthritis & Rheumatology discusses the spectrum of CPPD manifestations & recommended treatment approaches. doi.org/10.1002/art....