Systemic Sarcoidosis With Neurosarcoidosis Features as a Risk Factor for Multifocal Osteonecrosis.

Sarcoidosis is a systemic inflammatory disease that affects diverse organs such as the lungs, skin, eyes, and brain. Osseous involvement in sarcoidosis usually affects bones of the appendages with direct infiltration of non-caseating granulomas without bony infarcts. Symptoms of sarcoid bone lesions respond well to corticosteroid therapy. In contrast, corticosteroids act as a risk factor for the development of osteonecrosis resulting in pain and disability. Osteonecrosis that involves three or more different anatomic sites, defined as multifocal osteonecrosis (MFON), is rare. MFON has not been documented in the setting of sarcoidosis. We report a systemic sarcoidosis patient with predominant neuropsychiatric manifestations, who progressively developed MFON. Despite the limited use of corticosteroid treatment, the high burden of systemic sarcoidosis and its related neuropsychiatric involvementmay have collectively contributed to the development of MFON. This case highlights the rare association of MFON with systemic sarcoidosis and the need for further investigation into the underlying pathogenesis of MFON to prevent disability and morbidity.

Double-negative T cells in pediatric rheumatic diseases.

Double-negative (CD4-CD8-) T (DNT) cells have been implicated in Autoimmune Lymphoproliferative Syndrome (ALPS), where their expansion inside the circulating pool of T cells represents a diagnostic criterion. Recent experimental evidence has supported the immunomodulatory roles of DNT cells, and studies in adult patients have suggested that they may be altered in some immune-mediated conditions. This study aimed to retrieve available data on circulating DNT cells in pediatric rheumatic disorders that do not arise in the context of ALPS through a systematic literature review of three scientific databases (PubMed, Scopus, and Web of Science). The final output of the systematic literature search consisted of eight manuscripts, including cross-sectional (n=6) and longitudinal (n=2) studies. Overall, the pooled population of patients includes children affected with pediatric Systemic Lupus Erythematosus (n=104), Juvenile Idiopathic Arthritis (n=92), Behçet's disease (n=15), mixed connective tissue disease (n=8), Juvenile Dermatomyositis (n=6), and Kawasaki disease/multisystem inflammatory disease in children (n=1 and n=14, respectively); moreover, one study also included 11 children with a high titer of antinuclear antibody but no diagnosis of rheumatic disease. All studies except one included a control group. The number of DNT cells were increased in most studies of children with rheumatic diseases. Even if such a limited number of studies and their great heterogeneity in several methodological aspects do not allow for reliable conclusions about the relevance of DNT cells in specific rheumatic conditions in children, this cell population deserves further investigation in this pathological setting through well-designed clinical studies.

Optical coherence tomography angiography as a potential tool in differential diagnosis of multiple sclerosis and rheumatic disorders with central nervous system involvement.

PURPOSE: The aim of this study is to analyse whether optical coherence tomography angiography (angio-OCT, OCTA) measurements can be a useful tool to differentiate central nervous system (CNS) involvement in rheumatic disorders (RD) from multiple sclerosis (MS). METHODS: A total of 85 patients- 41 with MS, 21 with RD with CNS involvement and 23 healthy controls were included in the study. All individuals underwent OCTA and the following parameters were measured in each eye separately: average foveal and parafoveal vessel density (VD), average foveal and parafoveal vessel length (VL) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), as well as area, perimeter, and circularity of the foveal avascular zone. RESULTS: OCTA showed a VD reduction in the foveal region of the SCP in eyes of RD patients when compared to MS patients (21.96 ± 3.39 vs.23.88 ± 3.05 (p = 0.003)). There have been no significant differences in any of the assessed parameters that is average VD and total average VL in the foveal area of the SCP as well as of the DCP in the general population comprising healthy controls, MS and RD groups (p > 0.05 for all). CONCLUSIONS: Our results suggest that an OCTA finding of decreased VD in the foveal region of the SCP may be considered as a potentially useful biomarker of RD in comparison with MS patients.

Knowledge About and the Use of Oral Nonsteroidal Anti-inflammatory Drugs Among Patients With Rheumatic Disorders in Saudi Arabia: A Cross-Sectional Study.

AIMS: The aims were to evaluate rheumatic disorder patients' knowledge of the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs), dosage (from where the knowledge is acquired), contraindications (in pregnancy), and drug interactions (such as drug-related disorders), to improve their knowledge about taking NSAIDs in Saudi Arabia. STUDY DESIGN: It is a descriptive cross-sectional study. PLACE AND DURATION OF STUDY: The study was conducted among patients with rheumatic disorder (RD) in Saudi Arabia who were invited to join by completing an online questionnaire, from August to November 2022. METHODOLOGY: Patients with RD who were 16 years and older, received oral NSAIDs, and agreed to participate were included in the study. The data was collected using an Internet-based questionnaire. The Internet-based questionnaire was designed using the Google Forms (Google LLC, Mountain View, California, United States) online survey platform. A consent form accompanied the questionnaire in a cover letter briefly describing the investigation. RESULTS: A total of 756 participants answered the questionnaire and participated in the final analysis. Most of the participants (75.93%) were female. The type of NSAID used by the participants was Ibuprofen. The majority (83.41%) reported that they responded to the medication. When asked about the primary source of information about the correct dose of these medications, more than two-thirds (69.32%) reported that physicians are the main source of information. The majority of the participants (83.39%) denied using NSAIDs during pregnancy. Half of the participants (49.22%) said they had discussed these medications' harmful effects with their doctors or pharmacists. The female participants were more knowledgeable about NSAIDs and their side effects than the males. CONCLUSION: The patient's knowledge related to the use of oral NSAIDs was not that satisfactory. There is an urgent need to educate the public regarding the appropriate use of NSAIDs by healthcare providers, particularly in relation to their proper use, potential side effects, and risks associated with long-term use.

Immunological Pathways in Sarcoidosis and Autoimmune Rheumatic Disorders-Similarities and Differences in an Italian Prospective Real-Life Preliminary Study.

BACKGROUND: The pathogenesis of sarcoidosis involves T cells and B lymphocytes that produce autoantibodies. We compared the expression of different T and B cell subsets in sarcoidosis and three B-mediated rheumatic diseases that can affect the lungs in an attempt to identify similarities and differences that distinguish these diseases. METHODS: The study included patients referred to Siena University Hospital's respiratory disease and rheumatology units. Patients were enrolled prospectively and consecutively. Healthy volunteers were also included. Multicolor flow cytometry was performed on phenotype T and B cell subsets. Multivariate analysis was carried out to reduce the dimensionality of the data. RESULTS: Fifteen patients had a diagnosis of sarcoidosis, fourteen idiopathic inflammatory myopathies (IIM), five granulomatosis with polyangiitis (GPA), ten microscopic polyangiitis (MPA), and seven were controls. Thirty-five T and B cell subsets were phenotyped, 15 of which were significantly different in sarcoidosis, B-mediated rheumatic disorders, and controls. Principal components analysis distinguished the four groups of patients with a total explained variance of 54.7%. A decision tree was constructed to determine which clustering variables would be most useful for distinguishing sarcoidosis, IIM, MPA, and GPA. The model showed regulatory T helper cells (Th-reg) > 5.70% in 91% of sarcoidosis patients as well as Th-reg ≤ 5.70 and Th17 > 43.27 in 100% of MPA. It also showed Th-reg ≤ 5.70, Th17 ≤ 43.27 and Tfh-reg ≥ 7.81 in 100% of GPA patients, and Th-reg ≤ 5.70, Th17 ≤ 43.27 and Tfh-reg ≤ 7.81 in 100% of IIM patients. CONCLUSION: The immune cell profile sheds light on similarities and differences between sarcoidosis and B-mediated rheumatic diseases. Sarcoidosis and autoimmune diseases show similar patterns of cellular immune dysregulation, suggesting a common pathogenic pathway that may provide an opportunity for further understanding autoimmunity and exploring biological therapies to treat sarcoidosis.

Monocyte subpopulations display disease-specific miRNA signatures depending on the subform of Spondyloarthropathy.

Spondyloarthropathies (SpA) are a family of rheumatic disorders that could be divided into axial (axSpA) and peripheral (perSpA) sub-forms depending on the disease clinical presentation. The chronic inflammation is believed to be driven by innate immune cells such as monocytes, rather than self-reactive cells of adaptive immune system. The aim of the study was to investigate the micro-RNA (miRNA) profiles in monocyte subpopulations (classical, intermediate and non-classical subpopulations) acquired from SpA patients or healthy individuals in search for prospective disease specific and/or disease subtype differentiating miRNA markers. Several SpA-specific and axSpA/perSpA differentiating miRNAs have been identified that appear to be characteristic for specific monocyte subpopulation. For classical monocytes, upregulation of miR-567 and miR-943 was found to be SpA-specific, whereas downregulation of miR-1262 could serve as axSpA-differentiating, and the expression pattern of miR-23a, miR-34c, mi-591 and miR-630 as perSpA-differentiating markers. For intermediate monocytes, expression levels of miR-103, miR-125b, miR-140, miR-374, miR-376c and miR-1249 could be used to distinguish SpA patients from healthy donors, whereas the expression pattern of miR-155 was identified as characteristic for perSpA. For non-classical monocytes, differential expression of miR-195 was recognized as general SpA indicator, while upregulation of miR-454 and miR-487b could serve as axSpA-differentiating, and miR-1291 as perSpA-differentiating markers. Our data indicate for the first time that in different SpA subtypes, monocyte subpopulations bear disease-specific miRNA signatures that could be relevant for SpA diagnosis/differentiation process and may help to understand SpA etiopathology in the context of already known functions of monocyte subpopulations.

Very low calorie ketogenic diet and common rheumatic disorders: A case report.

BACKGROUND: The scientific literature provides evidence that nutritional ketosis can be an important support in the treatment of pathologies in which inflammation is present, as recent studies have shown that ketone bodies have anti-inflammatory activity in numerous diseases, including rheumatic diseases. We report the case of a 22-year-old woman with class I obesity and juvenile idiopathic arthritis who started treatment with a very low calorie ketogenic diet (VLCKD). CASE SUMMARY: The patient was a 22-year-old woman diagnosed with juvenile idiopathic arthritis at age 4 years and with a body mass index (BMI) of 30.8 kg/m2, waist circumference (WC) 80 cm, fat mass (FM) 28.1 kg, free FM 45.7 kg, and visceral adipose tissue (VAT) 3.5 kg, assessed on bioimpedance analysis. She was treated using a commercial VLCKD weight-loss program (PNK® method); this program provides high-biological-value protein preparations and natural foods. Each protein preparation contains 15 g protein, 4 g carbohydrate, 3 g fat, and 50 mg omega-3 docosahexaenoic acid, with an energy content of 90-120 kcal. After four months on the program, the BMI was 28.6 kg/m2, WC 73 cm, FM 23.2 kg, free FM 41.9 kg, and VAT 2.9 kg. CONCLUSION: VLCKD enabled the patient to reach her target weight and to reduce her joint pain and headaches. Laboratory inflammatory indices also normalized.

Potential Phytoconstituents of Genus Vitex for the Management of Rheumatoid Arthritis: A Review.

Rheumatoid arthritis is one of the most predominant conditions which have utmost influence on the society. The disease is an inflammatory disorder which affects joints, connective tissues, muscles, tendons and fibrous tissues. Approximately 270 known species of vitex genus are known, extending from shrubs to trees in the tropical, sub-tropical regions and temperate zones. Several species of vitex have been used traditionally over world-wide. The main focus of the present study is to review various phytoconstituents isolated from the genus vitex which can be used for the treatment of rheumatic disorders. The study also covers the underlying targets of the phytoconstituents which can be possible potential hits for the management of Rheumatic disorders.

MicroRNAs-mediated regulation pathways in rheumatic diseases.

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are two common rheumatic disorders marked by persistent inflammatory joint disease. Patients with RA have osteodestructive symptoms, but those with AS have osteoproliferative manifestations. Ligaments, joints, tendons, bones, and muscles are all affected by rheumatic disorders. In recent years, many epigenetic factors contributing to the pathogenesis of rheumatoid disorders have been studied. MicroRNAs (miRNAs) are small, non-coding RNA molecules implicated as potential therapeutic targets or biomarkers in rheumatic diseases. MiRNAs play a critical role in the modulation of bone homeostasis and joint remodeling by controlling fibroblast-like synoviocytes (FLSs), chondrocytes, and osteocytes. Several miRNAs have been shown to be dysregulated in rheumatic diseases, including miR-10a, 16, 17, 18a, 19, 20a, 21, 27a, 29a, 34a, 103a, 125b, 132, 137, 143, 145, 146a, 155, 192, 203, 221, 222, 301a, 346, and 548a.The major molecular pathways governed by miRNAs in these cells are Wnt, bone-morphogenic protein (BMP), nuclear factor (NF)-κB, receptor activator of NF-κB (RANK)-RANK ligand (RANKL), and macrophage colony-stimulating factor (M-CSF) receptor pathway. This review aimed to provide an overview of the most important signaling pathways controlled by miRNAs in rheumatic diseases.

Treatment of Sexual Dysfunction in Women with Systemic Autoimmune Rheumatic Disorders: A Systematic Review.

INTRODUCTION: Female sexual dysfunction (SD) is an under-recognized and undertreated problem in patients with systemic autoimmune rheumatic disorders (SARDs). OBJECTIVES: To summarize and evaluate the existing treatment modalities for SD in females with SARDs. METHODS: A systematic review was conducted following the PRISMA guidelines. Electronic databases were searched up to April 2022 for studies that assessed the use of pharmacological and non-pharmacological treatment modalities for the management of SD in females with SARDs. Randomized and observational studies were included. (PROSPERO: CRD42022296381). RESULTS: Seven studies with 426 females with SD were included. Seven different treatment modalities belonging to 5 different classes (androgen therapy, phosphodiesterase-5 inhibitors, exercise, education and local creams) were evaluated in patients with systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis. The majority of the studies were of low methodological quality. Standardized patient education and 8-week aerobic walking programs were successful in improving female SD. Local creams improved dyspareunia in females with systemic sclerosis. Testosterone did not significantly improve SD in patients with systemic lupus erythematosus. Accordingly, tadalafil did not result in a significant improvement of SD in females with systemic sclerosis, based on the Female Sexual Function Index. CONCLUSION: There is a lack of sufficient evidence to recommend a certain management strategy for SD in females with SARDs. Nonpharmacological therapy and lubricant creams may be beneficial in females with SARDs. No benefit was demonstrated after androgen therapy or tadalafil. Still, no definite conclusions can be drawn due to the important limitations of the available literature. Overall, our results may be considered preliminary and further research in the field is mandatory. Baniotopoulos P, Pyrgidis N, Minopoulou I, et al. Treatment of Sexual Dysfunction in Women with Systemic Autoimmune Rheumatic Disorders: A Systematic Review. Sex Med Rev 2022;10:520-528.

A systematic review on mucocutaneous presentations after COVID-19 vaccination and expert recommendations about vaccination of important immune-mediated dermatologic disorders.

With dermatologic side effects being fairly prevalent following vaccination against COVID-19, and the multitude of studies aiming to report and analyze these adverse events, the need for an extensive investigation on previous studies seemed urgent, in order to provide a thorough body of information about these post-COVID-19 immunization mucocutaneous reactions. To achieve this goal, a comprehensive electronic search was performed through the international databases including Medline (PubMed), Scopus, Cochrane, Web of science, and Google scholar on July 12, 2021, and all articles regarding mucocutaneous manifestations and considerations after COVID-19 vaccine administration were retrieved using the following keywords: COVID-19 vaccine, dermatology considerations and mucocutaneous manifestations. A total of 917 records were retrieved and a final number of 180 articles were included in data extraction. Mild, moderate, severe and potentially life-threatening adverse events have been reported following immunization with COVID vaccines, through case reports, case series, observational studies, randomized clinical trials, and further recommendations and consensus position papers regarding vaccination. In this systematic review, we categorized these results in detail into five elaborate tables, making what we believe to be an extensively informative, unprecedented set of data on this topic. Based on our findings, in the viewpoint of the pros and cons of vaccination, mucocutaneous adverse events were mostly non-significant, self-limiting reactions, and for the more uncommon moderate to severe reactions, guidelines and consensus position papers could be of great importance to provide those at higher risks and those with specific worries of flare-ups or inefficient immunization, with sufficient recommendations to safely schedule their vaccine doses, or avoid vaccination if they have the discussed contra-indications.

Thoracic Involvement in Systemic Autoimmune Rheumatic Diseases: Pathogenesis and Management.

Thoracic involvement is one of the main determinants of morbidity and mortality in patients with autoimmune rheumatic diseases (ARDs), with different prevalence and manifestations according to the underlying disease. Interstitial lung disease (ILD) is the most common pulmonary complication, particularly in patients with systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs) and rheumatoid arthritis (RA). Other thoracic manifestations include pulmonary arterial hypertension (PAH), mostly in patients with SSc, airway disease, mainly in RA, and pleural involvement, which is common in systemic lupus erythematosus and RA, but rare in other ARDs.In this review, we summarize and critically discuss the current knowledge on thoracic involvement in ARDs, with emphasis on disease pathogenesis and management. Immunosuppression is the mainstay of therapy, particularly for ARDs-ILD, but it should be reserved to patients with clinically significant disease or at risk of progressive disease. Therefore, a thorough, multidisciplinary assessment to determine disease activity and degree of impairment is required to optimize patient management. Nevertheless, the management of thoracic involvement-particularly ILD-is challenging due to the heterogeneity of disease pathogenesis, the variety of patterns of interstitial pneumonia and the paucity of randomized controlled clinical trials of pharmacological intervention. Further studies are needed to better understand the pathogenesis of these conditions, which in turn is instrumental to the development of more efficacious therapies.

Immunogenicity of Rituximab biosimilar GP2013 in chronic inflammatory rheumatic disorders in daily clinical practice.

OBJECTIVE: To study in daily practice the risk of immunogenicity of patients treated with the biosimilar rituximab (RTX) GP2013 used for chronic inflammatory rheumatic disorders. METHODS: A prospective monocentric routine care study was carried out between September 2018 and May 2021, including consecutive patients treated with the biosimilar RTX GP2013. Biosamples were taken before each infusion to quantify anti-RTX antibodies (ADAbs) and serum RTX trough levels by ELISA (Lisa Tracker Duo Rituximab, LTR005, Theradiag). RESULTS: 168 GP2013-treated patients were included (129 who switched from originator RTX and 39 originator RTX naïve). The analysis of 602 samples identified 15 patients (8%) with positive ADAbs including 6 and 9 with transient and persistent ADAbs, respectively. The switch from originator RTX to GP2013 did not increase the risk of immunogenicity, with an incidence rate of 0.8 for 100 patient years. The frequency of persistent ADAs was higher in non-RA patients (5/56, 9% vs. 4/112, 3.5%). Patients with positive persistent ADAbs were more frequently non-caucasian (7/9, 78%, vs. 56/159, 35%, p<0.01) and all had detectable circulating B cells (vs. 40% in ADAb-negative patients, P<0.001). ADAb positivity was not associated with disease activity or RTX discontinuation but patients with ADAb titers >100 ng/mL experienced reduced treatment efficacy or severe infusion-related reaction. CONCLUSION: Within the study duration, the immunogenicity of GP2013 is a rare event affecting the pharmacodynamics of RTX. Although development of ADAbs had no impact on treatment discontinuation, possible harmful consequences may be observed in patients with high antibody levels.

Treatment of Sexual Dysfunction in Women with Systemic Autoimmune Rheumatic Disorders: A Systematic Review.

INTRODUCTION: Female sexual dysfunction (SD) is an under-recognized and undertreated problem in patients with systemic autoimmune rheumatic disorders (SARDs). OBJECTIVES: To summarize and evaluate the existing treatment modalities for SD in females with SARDs. METHODS: A systematic review was conducted following the PRISMA guidelines. Electronic databases were searched up to April 2022 for studies that assessed the use of pharmacological and non-pharmacological treatment modalities for the management of SD in females with SARDs. Randomized and observational studies were included. (PROSPERO: CRD42022296381). RESULTS: Seven studies with 426 females with SD were included. Seven different treatment modalities belonging to 5 different classes (androgen therapy, phosphodiesterase-5 inhibitors, exercise, education and local creams) were evaluated in patients with systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis. The majority of the studies were of low methodological quality. Standardized patient education and 8-week aerobic walking programs were successful in improving female SD. Local creams improved dyspareunia in females with systemic sclerosis. Testosterone did not significantly improve SD in patients with systemic lupus erythematosus. Accordingly, tadalafil did not result in a significant improvement of SD in females with systemic sclerosis, based on the Female Sexual Function Index. CONCLUSION: There is a lack of sufficient evidence to recommend a certain management strategy for SD in females with SARDs. Nonpharmacological therapy and lubricant creams may be beneficial in females with SARDs. No benefit was demonstrated after androgen therapy or tadalafil. Still, no definite conclusions can be drawn due to the important limitations of the available literature. Overall, our results may be considered preliminary and further research in the field is mandatory.

Experimental evidence for proarrhythmic effects of nonsteroidal anti-inflammatory drugs in a sensitive whole-heart model.

BACKGROUND: Previous studies have raised serious concerns on cardiovascular safety of widely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, the aim of this study was to characterize the electrophysiological effects of certain NSAIDs in an established whole heart model of proarrhythmia. METHODS AND RESULTS: Thirty-eight hearts of New Zealand White rabbits were harvested and retrogradely perfused employing a Langendorff setup, and electrophysiology studies were performed to investigate action potential duration at 90% of repolarization (APD90 ), QT intervals, and effective refractory period (ERP). After generating baseline data, hearts were perfused with ibuprofen (Group 1, n = 12; 10 and 30 µM), indomethacin (Group 2, n = 13; 10 and 20 µM) and diclofenac (Group 3, n = 13; 10 and 20 µM), respectively, and the pacing protocols were repeated for each concentration. In all groups, perfusion with the NSAIDs resulted in a significant and reproducible shortening of APD90 and QT interval. In all groups, the arrhythmia susceptibility was significantly raised as occurrence of monomorphic ventricular tachycardia under programmed ventricular stimulation was significantly increased under perfusion with ibuprofen, indomethacin and diclofenac in all concentrations. CONCLUSION: The perfusion with ibuprofen, indomethacin and diclofenac in commonly used doses raised the arrhythmia susceptibility in an established rabbit whole-heart model while APD shortening and shortened ERP seem to be crucial for arrhythmogenesis.

Rheumatological Adverse Events of Cancer Therapy with Immune Checkpoint Inhibitors.

Latin America is experiencing a demographic and epidemiological transition, with an increase in non-communicable diseases such as cancer. One of the greatest advances in the therapeutic approach to cancer has been the discovery of immunotherapy, and specifically of checkpoint inhibitors (CPIs). Since inhibition of CTLA-4 and PD-1/PD-L1 enhances the immune response, cancer immunotherapies are associated with a new class of toxicities of autoimmune and/or autoinflammatory origin. These immune-related adverse events (irAEs) result in a broad spectrum of clinical events including rheumatic clinical syndromes, which may resemble classic rheumatic diseases. The most common rheumatic manifestations include inflammatory arthritis, myositis, vasculitis, and sicca syndrome. Recognizing rheumatologic irAEs is challenging due to the wide spectrum of clinical presentations that often do not fulfill traditional classification criteria of rheumatic diseases. A delayed diagnosis and treatment can lead to long-term disability, and disorders may become chronic and require ongoing immunosuppressive therapy. The management of irAEs includes the prompt detection and appropriate grading since their management is dictated by their severity. The growing use of CPIs, and the ensuing increase in irAEs, warrants an increasing collaboration between rheumatologists and oncologists. Understanding the pathophysiology, diagnosis, grading, and therapeutic implications of irAEs in patients with cancer is thus a requirement for Latin American oncologists and rheumatologists alike.

Role of autoantibodies in the diagnosis and prognosis of interstitial lung disease in autoimmune rheumatic disorders.

Interstitial lung disease (ILD) has been recognized as a frequent manifestation associated with a substantial morbidity and mortality burden in patients with autoimmune rheumatic disorders. Serum autoantibodies are considered good biomarkers for identifying several subsets or specific phenotypes of ILD involvement in these patients. This review features the role of several autoantibodies as a diagnostic and prognostic biomarker linked to the presence ILD and specific ILD phenotypes in autoimmune rheumatic disorders. The case of the diverse antisynthetase antibodies in the antisynthease syndrome or the anti-melanoma differentiation-associated 5 protein (MDA5) antibodies as a marker of a severe condition such as rapidly progressive ILD in patients with clinically amyopathic dermatomyositis are some of the associations herein reported in the group of myositis spectrum disorders. Specific autoantibodies such as the well-known anti-topoisomerase I (anti-Scl70) or the anti-Th/To, anti-U11/U12 ribonucleoprotein, and anti-eukaryotic initiation factor 2B (eIF2B) antibodies seems to be specifically linked to ILD in patients with systemic sclerosis. Overlap syndromes between systemic sclerosis and myositis, also have good ILD biomarkers, which are the anti-PM/Scl and anti-Ku autoantibodies. Lastly, other not so often reported disorders as being associated with ILD but recently most recognized as is the case of rheumatoid arthritis associated ILD or entities herein included in the miscellaneous disorders section, which include anti-neutrophil cytoplasmic antibody-associated interstitial lung disease, Sjögren's syndrome or the mixed connective tissue disease, are also discussed.

Osteoporotic Fractures and Vertebral Body Reshaping in Children With Glucocorticoid-treated Rheumatic Disorders.

CONTEXT: Osteoporotic fractures are an important cause of morbidity in children with glucocorticoid-treated rheumatic disorders. OBJECTIVE: This work aims to evaluate the incidence and predictors of osteoporotic fractures and potential for recovery over six years following glucocorticoid (GC) initiation in children with rheumatic disorders. METHODS: Children with GC-treated rheumatic disorders were evaluated through a prospective inception cohort study led by the Canadian STeroid-induced Osteoporosis in the Pediatric Population (STOPP) Consortium. Clinical outcomes included lumbar spine bone mineral density (LS BMD), vertebral fractures (VF), non-VF, and vertebral body reshaping. RESULTS: A total of 136 children with GC-treated rheumatic disorders were enrolled (mean age 9.9 years, SD 4.4). The 6-year cumulative fracture incidence was 16.3% for VF, and 10.1% for non-VF. GC exposure was highest in the first 6 months, and 24 of 38 VF (63%) occurred in the first 2 years. Following VF, 16 of 19 children (84%) had complete vertebral body reshaping. Increases in disease activity and body mass index z scores in the first year and declines in LS BMD z scores in the first 6 months predicted incident VF over the 6 years, while higher average daily GC doses predicted both incident VF and non-VF. LS BMD z scores were lowest at 6 months (mean -0.9, SD 1.2) and remained low by 6 years even when adjusted for height z scores (-0.6, SD 0.9). CONCLUSION: VF occurred early and were more common than non-VF in children with GC-treated rheumatic disorders. Eighty-four percent of children with VF underwent complete vertebral body reshaping, whereas vertebral deformity persisted in the remainder of children. On average, LS BMD z scores remained low at 6 years, consistent with incomplete recovery.

The Emerging Roles of Endocrine Hormones in Different Arthritic Disorders.

The relationship between endocrine hormones and the spectrum of rheumatic conditions has long been discussed in the literature, focusing primarily on sexual hormones, such as estrogens, androgens, prolactin (PRL). Estrogens are indeed involved in the pathogenesis of the main inflammatory arthritis thanks to their effects on the immune system, both stimulatory and inhibitory. The PRL system has been discovered in synovial tissue of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), patients and has been propose as a new potential therapeutic target. Besides sexual hormones, in the last years scientific interest about the crosstalk of immune system with other class of hormones has grown. Hormones acting on the bone tissue (i.e. parathyroid hormone, vitamin D) and modulators of the Wnt pathway (i.e. Dickkopf-1) have been demonstrated to play active role in inflammatory arthritis course, defining a new field of research named osteoimmunology. PTH, which is one of the main determinants of Dkkopf-1, plays a crucial role in bone erosions in RA and a correlation between PTH, Trabecular Bone Score (TBS) and disease activity has been found in ankylosing spondylitis (AS). In PSA is under studying the interaction among IL-17 and bone metabolism. The purpose of this review is to discuss and summarize the recent data about the interaction between endocrine hormone and immune system in the main rheumatic disorders, covering in particular the role of bone-related hormones and cytokines. We will describe this relationship from a biochemical, diagnostic and therapeutic perspective, with a particular focus on RA, PsA and AS.