Current Medication Practices and Preferences Among Patients With Psoriatic Arthritis.

OBJECTIVE: The aim of this study was to evaluate real-world psoriatic arthritis (PsA) medication use and patient medication preferences. METHODS: This is a cross-sectional survey of Classification for Psoriatic Arthritis criteria defined PsA patients recruited from a single-center PsA registry from June to September 2020. Preferences were ranked on a 5-point Likert scale ranging from "not at all important" to "extremely important." RESULTS: One hundred thirty-seven patients (29%) responded. The median duration (years) of PsA skin and joint symptoms was 19 (interquartile range, 10-34) and 12 (interquartile range, 8-21), respectively. The most common initial immunomodulatory medications were anti-tumor necrosis factor α (35%), methotrexate (19%), and anti-phosphodiesterase 4 (anti-PDE4) (12.4%). At survey administration, the most common immunomodulatory therapies were anti-tumor necrosis factor α (30%), anti-interleukin 17 (IL-17) (20.4%), and methotrexate (10.2%). After 2018, when updated guidelines from the American College of Rheumatology/National Psoriasis Foundation were published, a significantly higher percentage of patients' first medication was an anti-IL-17 compared with 2018 or earlier (30% vs 3.5%, p < 0.001), a pattern also seen with anti-PDE4 (40% vs 11.5%, p < 0.012). Medication preferences most ranked as "extremely" important were prevention of joint damage (80%), ability to perform daily activities (71%), prevention of pain (70.1%), rheumatologist recommendation (63%), and medication adverse effects (62%). CONCLUSIONS: The significant increase of anti-IL-17 and anti-PDE4 medications as initial treatment after 2018 may reflect their inclusion as potential initial therapy in updated guidelines, along with the importance placed by patients on medication adverse effects. Given the expanding armamentarium of PsA medications, it is increasingly important to align patient preferences and therapeutic options to ensure durable use of effective therapy.

Podocyte-Specific Deletion of Yes-Associated Protein Causes FSGS and Progressive Renal Failure.

FSGS is the most common primary glomerular disease underlying ESRD in the United States and is increasing in incidence globally. FSGS results from podocyte injury, yet the mechanistic details of disease pathogenesis remain unclear. This has resulted in an unmet clinical need for cell-specific therapy in the treatment of FSGS and other proteinuric kidney diseases. We previously identified Yes-associated protein (YAP) as a prosurvival signaling molecule, the in vitro silencing of which increases podocyte susceptibility to apoptotic stimulus. YAP is a potent oncogene that is a prominent target for chemotherapeutic drug development. In this study, we tested the hypothesis that podocyte-specific deletion of Yap leads to proteinuric kidney disease through increased podocyte apoptosis. Yap was selectively silenced in podocytes using Cre-mediated recombination controlled by the podocin promoter. Yap silencing in podocytes resulted in podocyte apoptosis, podocyte depletion, proteinuria, and an increase in serum creatinine. Histologically, features characteristic of FSGS, including mesangial sclerosis, podocyte foot process effacement, tubular atrophy, interstitial fibrosis, and casts, were observed. In human primary FSGS, we noted reduced glomerular expression of YAP. Taken together, these results suggest a role for YAP as a physiologic antagonist of podocyte apoptosis, the signaling of which is essential for maintaining the integrity of the glomerular filtration barrier. These data suggest potential nephrotoxicity with strategies directed toward inhibition of YAP function. Further studies should evaluate the role of YAP in proteinuric glomerular disease pathogenesis and its potential utility as a therapeutic target.

Dendrin ablation prolongs life span by delaying kidney failure.

Podocyte loss is central to the progression of proteinuric kidney diseases leading to end-stage kidney disease (ESKD), requiring renal replacement therapy, such as dialysis. Despite modern tools and techniques, the 5-year mortality of some patients requiring dialysis remains at about 70% to 80%. Thus, there is a great unmet need for podocyte-specific treatments aimed at preventing podocyte loss and the ensuing development of ESKD. Here, we show that ablation of the podocyte death-promoting protein dendrin delays the onset of ESKD, thereby expanding the life span of mice lacking the adapter protein CD2AP. Ablation of dendrin delays onset and severity of proteinuria and podocyte loss. In addition, dendrin ablation ameliorates mesangial volume expansion and up-regulation of mesangial fibronectin expression, which is mediated by a podocyte-secreted factor. In conclusion, onset of ESKD and death can be markedly delayed by blocking the function of dendrin.

Spondyloarthritis in inflammatory bowel disease cohorts: systematic literature review and critical appraisal of study designs.

To critically appraise study designs evaluating spondyloarthritis (SpA) phenotypes in patients with inflammatory bowel disease (IBD). A systematic literature review of PubMed, Ovid, Scopus, Cinahl, Medline, Web of Science, and Cochrane databases was performed. Articles published from January 2000 - March 2020 were included if they evaluated the prevalence/incidence of musculoskeletal disease in cohorts of IBD patients. Most of the 69 included studies were clinic based (54/69, 78%), single center (47/69, 68%) and cross-sectional (60/69, 87%). The median prevalence of axial and peripheral SpA in IBD was 5% (range 1 - 46%) and 16% (range 1 - 43%), respectively. In 38 studies that evaluated axial disease in prospectively enrolled patients, inflammatory back pain was analyzed in 53%. SpA classification criteria were used in 68% and imaging was performed in 76%. In 35 studies that evaluated peripheral disease in prospectively enrolled patients, SpA classification criteria were used in 46%. A physical exam was performed in 74%, and it was performed by a rheumatologist in 54% of studies with a physical exam. Sub-phenotypes of peripheral SpA (mono- or oligo-arthritis, polyarthritis, enthesitis, dactylitis) were variably reported. Seventy-four percent of studies did not mention whether osteoarthritis and fibromyalgia had been assessed or excluded. The spectrum of SpA phenotypes in IBD patients remains incompletely characterized. Future studies should focus on standardizing the variables collected in IBD-SpA cohorts and defining musculoskeletal phenotypes in IBD-SpA in order to better characterize this disease entity and advance the field for clinical and research purposes.

Defining the phenotype, pathogenesis and treatment of Crohn's disease associated spondyloarthritis.

Peripheral and axial spondyloarthritis are the most common extra-intestinal manifestations reported in patients with Crohn's disease. Despite the frequency of Crohn's disease associated spondyloarthritis, clinical diagnostic tools are variably applied in these cohorts and further characterization with validated spondyloarthritis disease activity indexes are needed. In addition, the pathogenesis of Crohn's disease associated spondyloarthritis is not well understood. Evidence of shared genetic, cellular, and microbial mechanisms underlying both Crohn's disease and spondyloarthritis highlight the potential for a distinct clinicopathologic entity. Existing treatment paradigms for Crohn's disease associated spondyloarthritis focus on symptom control and management of luminal inflammation. A better understanding of the underlying pathogenic mechanisms in Crohn's disease associated spondyloarthritis and the link between the gut microbiome and systemic immunity will help pave the way for more targeted and effective therapies. This review highlights recent work that has provided a framework for clinical characterization and pathogenesis of Crohn's disease associated spondyloarthritis and helps identify critical gaps that will help shape treatment paradigms.

Is There a Role for MRI to Establish Treatment Indications and Effectively Monitor Response in Patients with Axial Spondyloarthritis?

MRI has an important role in the assessment of axial spondyloarthritis (axSpA), particularly early in the disease course, before radiographic damage is apparent. For this reason, MRI was incorporated into the 2009 ASAS/OMERACT classification criteria for spondyloarthritis. However, there are current controversies regarding its use. Important questions include whether the spine should be used in the routine diagnosis and classification of axSpA, whether MRI should replace radiographs as the imaging modality of choice in axSpA, and whether MRI findings in axSpA have prognostic significance.

Who Is Ordering MRIs in Newly Diagnosed Breast Cancer Patients?

The role of MRI in the workup of newly diagnosed breast cancer patients remains controversial. Breast MRI detects additional disease, but this has not translated into improved outcomes. In light of a dramatic rise in MRI use, we investigated patterns of MRI ordering for newly diagnosed breast cancer. All newly diagnosed breast cancer cases presenting for surgical management to a specialized breast center from 2011 to 2013 were reviewed. Patients who had an MRI ordered by their operating surgeon were compared with those who had an MRI completed previously. Of 1037 patients, 504 (49%) with newly diagnosed breast cancer underwent MRI as part of their preoperative evaluation. Variables associated with MRI use included commercial insurance, increased breast density, genetic testing, mamographically occult disease, and lobular pathology. Of women who presented to our center with an MRI already completed, 63 per cent were ordered by a primary care provider. Of the 504 patients, 233 (44%) who had an MRI underwent an additional biopsy, and 166 (33%) had a resultant change in management. There was no significant difference in MRI-directed change in patient care depending on ordering provider. Further research is needed to develop evidence-based guidelines for preoperative MRI evaluation to optimize patient outcomes.

The Use of Biologic Therapies in Uveitis.

Therapy for autoimmune ophthalmic disease is currently evolving. The improved understanding of the abnormal immune response in the various forms of uveitis has resulted in targeted therapy. The aberrations of the immune system have been characterized by atypical cell populations, cytokine expression, and cell-cell interactions. Different patterns of cytokine expression have now been delineated in the abnormal uveal tract with exaggerated and/or abnormal expression of TNF, IL-1, IL-2, IL-6, and IL-17. The development of therapies for other conditions in which these cytokines play an important role has resulted in the availability of biological agents that have been adopted for use in the therapy for uveitis. Adalimumab and infliximab have been the best studied anti-TNF agents and indeed have now been recommended by an expert panel as first-line treatment of ocular manifestations of Behçet's disease and second-line treatment for other forms of uveitis (Levy-Clarke et al. (Ophthalmology, 2013). Other anti-TNF agents have been studied as well. Daclizumab, a monoclonal antibody directed against the IL-2 receptor, has also demonstrated utility in treating uveitis as have some of the anti-IL1 agents. Gevokizumab has been granted orphan drug designation for the treatment of resistant forms of uveitis. Therapies affecting IL-6, including tocilizumab are being studied, and available medications that block antigen presenting cell and T cell interaction such as abatacept have been reported to be effective in uveitis. Interferons as well as rituximab have also been evaluated in small studies. Although these biologic therapies have provided a larger armamentarium to treat uveitis, challenges remain. Uveitis is not a single illness; rather, it is a manifestation of many potential systemic diseases that may have very specific individual therapeutic targets. Identifying and characterizing these underlying diseases is not always achieved, and more importantly, the most effective therapies for each entity have not been defined.

The Impact of Histologic Variants on FSGS Outcomes.

Focal segmental glomerulosclerosis (FSGS) is the most common glomerular disease leading to end-stage renal disease. The clinical course is highly variable with disparate responses to therapeutic intervention and rates of progression. Histologic variant subtype has been commonly used as a prognostic and therapeutic guide in the clinical management of FSGS. The tip lesion is widely considered to portend the most favorable prognosis and to be the most responsive to steroid therapy. Conversely, the collapsing lesion, more prevalent in patients of African descent, is associated with steroid resistance and higher risk of disease progression. In the 10 years since the Columbia classification system for FSGS was published, some retrospective and one prospective study explored the impact of histologic variants at the time of biopsy on FSGS outcomes. The results largely validate its clinical predictive value with respect to treatment response, though its utility in cases recurring after kidney transplantation is still unknown. Sampling and interpretation errors are additional sources of caution. More research is needed to fully define reproducible prognostic and therapeutic markers for this polymorphic disorder.

Whipple's disease.

This article reviews the microbiology, pathophysiology, epidemiology, clinical manifestations, diagnostic testing, and treatment of Whipple's disease, an illness caused by Tropheryma whipplei and characterized by multivariate clinical manifestations including an inflammatory arthropathy. Diagnosis is confirmed by tissue sampling with periodic acid-Schiff staining and/or polymerase chain reaction. Clinical manifestations most frequently manifest in the gastrointestinal tract, musculoskeletal system, neurologic system, heart, and eyes, but can affect any site. Successful therapy with appropriate antibiotics is potentially curable, but recurrences may occur.