Peripheral Disease Manifestations Research Articles

Do the provisional PRINTO Enthesitis/Spondylitis-Related JIA criteria capture youth with axial spondyloarthritis?

The Paediatric Rheumatology International Trials Organisation (PRINTO) recently undertook an effort to better harmonize the pediatric and adult arthritis criteria. These provisional criteria are being refined for optimal performance. We aimed to investigate differences between patients who did and did not fulfill these PRINTO criteria amongst youth diagnosed with juvenile spondyloarthritis (SpA) that met axial juvenile SpA (axJSpA) classification criteria. This was a retrospective cross-sectional sample of youth diagnosed with juvenile SpA who met the axJSpA classification criteria. Demographics, clinical manifestations, and physician and patient-reported outcomes were abstracted from medical records. MRI scans underwent central imaging review by at least 2 central raters. Differences between groups were compared using Wilcoxon signed-rank test or chi-square, as appropriate. Of 158 patients that met axJSpA criteria, 107 (68%) met the PRINTO provisional criteria for enthesitis/spondylitis-related arthritis. Forty-one (26%) did not fulfill any of the 3 major PRINTO criteria due to lack of peripheral disease manifestations. Demographics, prevalence of inflammatory or structural lesions on MRI, family history of SpA, and duration of pain were not statistically different between those who did and did not meet PRINTO criteria. Those who fulfilled the PRINTO criteria had significantly more peripheral arthritis, enthesitis, and HLA-B27 positivity but reported less sacral/buttock pain. Phenotypic differences of children with axJSpA between those who were and were not classified by the PRINTO criteria were primarily due to peripheral disease manifestations and HLA-B27 positivity. Modification of the PRINTO provisional criteria may facilitate capture of youth with primarily axial disease.

Children With Enthesitis-Related Arthritis and Possible Benefits From Treatments for Adults With Spondyloarthritis.

This review will summarize clinical, genetic, and pathophysiologic characteristics that are shared between children with enthesitis-related arthritis (ERA) with axial involvement and adults with nonradiographic (and in some cases radiographic) axial spondyloarthritis (SpA), as well as between children with ERA and primarily peripheral disease manifestations and adults with peripheral SpA. Due to the differences in classification criteria for children with ERA and adults with axial and peripheral SpA, the US Food and Drug Administration (FDA) granted automatic full waivers of studies in children for new medications for "axial spondyloarthropathies including ankylosing spondylitis" up until July 2020. Thus, although current juvenile idiopathic arthritis treatment guidelines recommend the use of biologic disease-modifying antirheumatic drugs as part of the early treatment for patients with ERA, none of the FDA-approved therapies for peripheral SpA or nonradiographic axial SpA (certolizumab pegol, ixekizumab, and secukinumab) have been studied or are labeled for use in children with ERA. Considering the similarities between adult SpA and ERA in terms of etiology, genetics, pathogenesis, and clinical manifestations summarized in this review, medications approved for axial SpA or peripheral SpA should also be studied in children with active ERA involving axial or peripheral joints, respectively, with the intent to achieve labeling for use in children. Considering the current lack of effective FDA-approved therapies for ERA, the FDA should also consider requiring pediatric studies for medications that have already been approved for the treatment of adults with SpA.

Peripheral disease contributes significantly to the level of disease activity in axial spondyloarthritis

ObjectiveSpondyloarthritis (SpA) can encompass axial, peripheral and extra-articular disease manifestations. Patients are classified as axial or peripheral SpA depending on the presence or absence of current back pain, independently of...

Liver function in Huntington's disease assessed by blood biochemical analyses in a clinical setting

Huntington's disease (HD) is a dominantly inherited, progressive neurological disorder caused by a CAG repeat elongation in the huntingtin gene. In addition to motor-, psychiatric- and cognitive dysfunction, peripheral disease manifestations in the form of metabolic changes and cellular dysfunction are seen. Blood levels of a wide range of hormones, metabolites and proteins have been analyzed in HD patients, identifying several changes associated with the disease. However, a comprehensive panel of liver function tests (LFT) has not been performed. We investigated a cohort of manifest and premanifest HD gene-expansion carriers and controls, using a clinically applied panel of LFTs. Here, we demonstrate that the level of alkaline phosphatase is increased in manifest HD gene-expansion carriers compared to premanifest HD gene-expansion carriers and correlate with increased disease severity indicated by the Unified Huntington's disease rating scale-Total Functional Capacity Score (UHDRS-TFC). For gamma-glutamyl transferase, elevated levels were more frequent in the manifest groups than in both the HD gene-expansion negative controls and premanifest HD gene-expansion carriers. Finally, the manifest HD gene-expansion carriers displayed moderate increases in total cholesterol and blood glucose relative to the premanifest HD gene-expansion carriers, as well as increased C-reactive protein relative to HD gene-expansion negative controls. Our results show that LFT values are elevated more frequently in manifest compared to premanifest HD gene-expansion carriers and controls. The majority of the manifest HD gene-expansion carriers receive medication, and it is possible that this can influence the liver function tests performed in this study.

Spinal muscular atrophy: from tissue specificity to therapeutic strategies.

Spinal muscular atrophy (SMA) is the most frequent genetic cause of death in infants and toddlers. All cases of spinal muscular atrophy result from reductions in levels of the survival motor neuron (SMN) protein, and so SMN upregulation is a focus of many preclinical and clinical studies. We examine four issues that may be important in planning for therapeutic success. First, neuromuscular phenotypes in the SMNΔ7 mouse model closely match those in human patients but peripheral disease manifestations differ, suggesting that endpoints other than mouse lifespan may be more useful in predicting clinical outcome. Second, SMN plays important roles in multiple central and peripheral cell types, not just motor neurons, and it remains unclear which of these cell types need to be targeted therapeutically. Third, should SMN-restoration therapy not be effective in all patients, blocking molecular changes downstream of SMN reduction may confer significant benefit, making it important to evaluate therapeutic targets other than SMN. Lastly, for patients whose disease progression is slowed, but who retain significant motor dysfunction, additional approaches used to enhance regeneration of the neuromuscular system may be of value.

FRI0459 Hla-b27 positive versus hla-b27 negative spondyloarthritis: different phenotypes but similar disease burden

BackgroundHLA-B27 has become increasingly important in the classification of both axial and peripheral spondyloarthritis (SpA) as this genetic factor is a major criterium in the new Assessment in SpondyloArthritis international...

Recent Advances in Imaging in Psoriatic Arthritis

The recent introduction of effective therapies in psoriatic arthritis (PsA) has increased the demand for efficient tools for diagnosis, monitoring and prognostication of PsA, and has caused an increased research effort within imaging in this disease. The clinical appearance of PsA is very diverse, involving the spine, sacroiliac joints, peripheral joints and/or entheses, and accordingly imaging findings vary. In the present paper, we present a review of the recent advances in imaging in PsA, focusing primarily on ultrasonography and magnetic resonance imaging of peripheral disease manifestations.

Viral Exploitation of Host SOCS Protein Functions

Over the past decade, a family of host proteins known as suppressors of cytokine signaling (SOCS) have emerged as frequent targets of viral exploitation. Under physiologic circumstances, SOCS proteins negatively regulate inflammatory signaling pathways by facilitating ubiquitination and proteosomal degradation of pathway machinery. Their expression is tightly regulated to prevent excessive inflammation while maintaining protective antipathogenic responses. Numerous viruses, however, have developed mechanisms to induce robust host SOCS protein expression following infection, essentially "hijacking" SOCS function to promote virus survival. To date, SOCS proteins have been shown to inhibit protective antiviral signaling pathways, allowing viruses to evade the host immune response, and to ubiquitinate viral proteins, facilitating intracellular viral trafficking and progeny virus assembly. Importantly, manipulation of SOCS proteins not only facilitates progression of the viral life cycle but also powerfully shapes the presentation of viral disease. SOCS proteins can define host susceptibility to infection, contribute to peripheral disease manifestations such as immune dysfunction and cancer, and even modify the efficacy of therapeutic interventions. Looking toward the future, it is clear that a better understanding of the role of SOCS proteins in viral diseases will be essential in our struggle to modulate and even eliminate the pathogenic effects of viruses on the host.

Immunosuppressive therapy in the treatment of immune-mediated disease.

Immune-mediated diseases represent some of the most frustrating types of disorders that are diagnosed and treated in veterinary medicine. Drug-induced immunosuppression is an attempt to control the aberrant immune response against self antigens but the immunosuppression can result in sepsis or other unacceptable adverse effects. If the pathophysiology of immune-mediated and autoimmune disease is considered, the immune response can be divided into several components and attempts can be made to selectively deal with each component separately. The components of the immune response that can be manipulated by therapy include antibodies, effector cells, the mononuclear phagocytic system, and the peripheral manifestations of disease. This article reviews the therapy of immune-mediated and autoimmune diseases based on a pathophysiologic approach and discusses conventional as well as current therapies in the treatment of these devastating diseases.