scholarly journals Juvenile Idiopathic Arthritis

2021 ◽  
Author(s):  
Vadood Javadi Parvaneh ◽  
Khosro Rahmani

Juvenile idiopathic arthritis (JIA) is the most common form of chronic synovial joint inflammation in children. It potentially leads to disability and psychosocial outcomes for children and their families. In the absence of appropriate treatment, this can lead to joint destruction and disability. Thus, early diagnosis and aggressive treatment are essential. With the presentation of new biologic DMARDs, based on understanding the disease pathophysiology and molecular pathogenesis, the course of the disease and its outcome have been changed profoundly. In this chapter, the early diagnosis, appropriate treatment, and outcomes approaches are described. These include the latest diagnosis and management options.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1060.2-1060
Author(s):  
T. Suto ◽  
K. Von Dalwigk ◽  
A. Platzer ◽  
B. Niederreiter ◽  
T. M. Karonitsch

Background:TNF-mediated fibroblast-like synoviocyte (FLS) activation is important for inflammation and joint destruction in rheumatoid arthritis (RA). The role of TNF-receptor 1 (TNFR1) in FLS activation has thoroughly been characterized. The functions of TNFR2 are, however, largely unknown.Objectives:To investigate the contribution of TNFR2 to the TNF-mediated activation of FLS.Methods:RA-FLS were transfected with TNFR2-targeting siRNA pools and transcriptional changes were determined by RNA-seq. QPCR, ELISA and immunoblotting were used to confirm the RNA-seq results and to gain insights into the pathways that regulate TNFR2-mediated changes in FLS.Results:TNF stimulation of FLS resulted in a strong upregulation of proinflammatory cytokines, chemokines, tissue-degrading enzymes and other genes that are associated with synovial inflammation in RA. Silencing of TNFR2 markedly diminished the TNF-response of RA-FLS. Especially, “interferon”-stimulated-genes (ISGs) including putative master regulators of joint inflammation, such as the CXCR3 chemokines CXCL9, CXCL10 and CXCL11 were affected by the knockdown of TNFR2. Consistently, immunoblots showed that TNFR2 was required for the TNF-induced phosphorylation of the transcription factor STAT1, which is known to mediate the transcription of ISGs, such as CXCR3 chemokines.Conclusion:TNFR2 regulates proinflammatory gene expression in RA-FLS via STAT1 and thereby contributes to the detrimental effects of TNF in synovial joint inflammation.Disclosure of Interests:None declared


2021 ◽  
pp. 148-153
Author(s):  
Tetsuko Sato ◽  
Takenobu Yamamoto ◽  
Yumi Aoyama

Varicella zoster virus (VZV)-associated meningitis is usually progressive and can be fatal, and early diagnosis and aggressive treatment with intravenous antivirals such as acyclovir (ACV) are required in immunocompromised patients. Patients receiving corticosteroids and immunosuppressive therapy have a significantly higher risk of VZV-associated meningitis. In this report, we describe an unusual case of herpes zoster (HZ) in a young woman who was first diagnosed during tapering of prednisone for dermatomyositis. The skin lesions affected the left L2 and L3 dermatomes, which is unusual in VZV-associated meningitis. Despite showing a good rapid response to antivirals, she developed VZV-associated meningitis immediately after discontinuation of ACV. This phenomenon is often called rebound VZV reactivation disease and occurs after discontinuation of antivirals. This case was notable in that the affected dermatomes were distant from the cranial nerves. Thus, progression of HZ to VZV reactivation-associated meningitis can occur even in appropriately treated HZ patients. Continuation of antivirals beyond 1 week in patients on immunosuppressive therapy may be associated with a decreased risk of severe rebound VZV disease, such as VZV-associated meningitis.


2021 ◽  
Author(s):  
Søren Lomholt ◽  
Morten A. Nielsen ◽  
Maithri P. Aspari ◽  
Peter B. Jørgensen ◽  
Adam P. Croft ◽  
...  

Fibroblasts like synoviocytes (FLS) play several significant roles in rheumatoid arthritis (RA) pathophysiology. This chapter will describe known roles of FLS in disease initiation, joint inflammation, disease persistence and joint destruction. It will describe the newly characterized subsets of FLS based on single cell RNA sequencing studies, and their association to specific aspects of the disease. Finally, we will discuss the future of targeting FLS in the treatment of RA. The FLS in the synovial lining layer are identified by surface complement decay-accelerating factor (CD55) along with lubricin and metallopeptidase expression. Pathological activation of this lining layer subset result in bone and cartilage damage in mice. FLS of the sublining layer are often characterized by THY1 expression, but recent studies have highlighted a heterogeneity where several distinct subsets are identified by additional markers. Sublining FLS expressing human leukocyte antigen-DRA (HLA-DRA) produce C-X-C motif chemokine 12 (CXCL12) and receptor activator of nuclear factor-κB ligand (RANKL) and seems to constitute a pro-inflammatory subset that is associated with inflammation and tertiary lymphoid structures. Another subset of FLS characterized by CD34 expression may discriminate a common progenitor fibroblast subset. Taken together, studies isolating and characterizing gene expression in synovial FLS report both associations of unknown importance and markers that may impose protective or destructive features. This supports evidence of FLS as active players in RA pathology capable of cellular recruitment, local cellular crosstalk and promotion of joint destruction. These discoveries may serve as an atlas for synovial activation in RA and have identified several potential fibroblast markers for the development of targeted treatment.


2021 ◽  
Vol 12 ◽  
Author(s):  
Samuel Kemble ◽  
Adam P. Croft

Rheumatoid arthritis (RA) is a chronic prototypic immune-mediated inflammatory disease which is characterized by persistent synovial inflammation, leading to progressive joint destruction. Whilst the introduction of targeted biological drugs has led to a step change in the management of RA, 30-40% of patients do not respond adequately to these treatments, regardless of the mechanism of action of the drug used (ceiling of therapeutic response). In addition, many patients who acheive clinical remission, quickly relapse following the withdrawal of treatment. These observations suggest the existence of additional pathways of disease persistence that remain to be identified and targeted therapeutically. A major barrier for the identification of therapeutic targets and successful clinical translation is the limited understanding of the cellular mechanisms that operate within the synovial microenvironment to sustain joint inflammation. Recent insights into the heterogeneity of tissue resident synovial cells, including macropahges and fibroblasts has revealed distinct subsets of these cells that differentially regulate specific aspects of inflammatory joint pathology, paving the way for targeted interventions to specifically modulate the behaviour of these cells. In this review, we will discuss the phenotypic and functional heterogeneity of tissue resident synovial cells and how this cellular diversity contributes to joint inflammation. We discuss how critical interactions between tissue resident cell types regulate the disease state by establishing critical cellular checkpoints within the synovium designed to suppress inflammation and restore joint homeostasis. We propose that failure of these cellular checkpoints leads to the emergence of imprinted pathogenic fibroblast cell states that drive the persistence of joint inflammation. Finally, we discuss therapeutic strategies that could be employed to specifically target pathogenic subsets of fibroblasts in RA.


2018 ◽  
Vol 132 (9) ◽  
pp. 827-831 ◽  
Author(s):  
K Mahawerawat ◽  
P Kasemsiri

AbstractBackgroundAlthough melioidosis in the head and neck region is uncommon, it is a potentially life-threatening infection. Thus, early diagnosis and proper management are very important.ObjectivesTo report the clinical presentation and management of melioidosis in the head and neck.MethodA retrospective study was conducted from 1 January 2013 to 31 October 2016 in Mukdahan Hospital, Thailand. Case records of patients who had presented with culture-positive melioidosis were analysed.ResultsMedical records of 49 patients (23 males and 26 females) were analysed. Patients ranged in age from 1 to 75 years. Clinical presentations included 22 parotid abscesses, 16 neck abscesses and 11 suppurative lymphadenitis cases. Only 35 patients (71 per cent) had high indirect haemagglutination assay titres of ≥ 1:160 (95 per cent confidence interval = 45.35–88.28). Almost half of the patients received intravenous ceftazidime and subsequently oral co-trimoxazole. Oral antibiotic regimens were prescribed for mild localised melioidosis. Overall, 95.65 per cent of patients were in remission and no relapses were observed (95 per cent confidence interval = 85.47–98.80).ConclusionCareful clinical correlation and proper investigation are required to establish an early diagnosis of melioidosis and to initiate appropriate treatment.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_5) ◽  
Author(s):  
A Hamami ◽  
A Babakhouya ◽  
A El Ouali ◽  
A Ghannam ◽  
M Rkain ◽  
...  

Abstract Background Vasculitis in children constitute a heterogeneous group of pathologies considered as a rarity in our context and therefore deserves to be better known. Despite their individualization for more than forty years throughout the world, they continue to be a challenging condition both in terms of diagnosis and treatment. The objective of our study is to report the epidemiological profiles of vasculitis and to assess the clinical and Para clinical profile of our patients, in order to contribute to a better knowledge of these conditions in our context, whose early diagnosis allows the starting of an appropriate treatment and the improvement of the prognosis. Material and methods This is a retrospective study, in which we collected data of all children in whom the diagnosis of vasculitis was confirmed, and who were hospitalized in the pediatric department of the University Hospital Center (CHU) Mohamed VI of Oujda over a period of 3 years from July 2014 to July 2017. Results Thirty-three patients were selected; 25 boys (76%) and 8 girls (24%), including 16 patients with Kawasaki disease; 14 patients with Henoch-Schonlein purpura (HSP); 2 patients with Polyarteritis nodosa (PAN); and 1 patient with Takayasu. A male predominance was noted with a sex ratio of 3.16. HSP represented 42.42% of the cases, the most affected age group was between 5 and 9 years in 45% of cases. Purpura was the most frequent symptom (100%) with petechial appearance in 77% of cases and localized in the lower limbs in all cases (100%). Joints were affected in 13 cases (93%), abdominal symptoms were found in 81.82% of cases, with one case of melena and 3 cases of rectal bleeding. The renal symptoms were mainly biological and were dominated by urinary proteinuria (45%), microscopic hematuria in one case, macroscopic hematuria in 3 cases, hypertension in one case and nephrotic syndrome in one case. Five patients developed renal insufficiency, two children had moderate renal insufficiency and three had severe renal insufficiency. Kawasaki disease represented the majority of cases: 16 cases (48.48%), affecting children between 4 and 41 months of age with an average age of 22 months, with most affected age group was between 12 and 24 months in 55%. The appeal signs were multiple dominated by fever which represents 100% of cases, skin rash in 82%, ocular redness in 45%, enanthema in 45%, oedema of the extremities in 45%, and adenopathy in 6% (one case). The inflammatory syndrome was present in all patients. Cardiac Doppler ultrasound was performed in 14 patients. It was abnormal in 22% of cases. 11 patients received a course of IGIV (54.54%), at a dose of 2 g/Kg in a single 12-h infusion. Aspirin was administered in all patients. The evolution was favorable in 15 patients, only one case was complicated by giant aneurysms of both coronaries, which evolved to a slight decrease in size and disappearance of the pericardial effusion. Valvular abnormality was noted in one case and minimal pericardial effusion in one case. Conclusion This study confirmed that incidence of vasculitis in children in our context is average, this can be seen on the non-negligible number of cases (33 cases) collected over a period of 3 years. Early diagnosis of this condition key to allow an initiation of an appropriate treatment and improvement of the prognosis.


Author(s):  
Andrew Filer ◽  
Maria Juarez ◽  
Christopher Buckley

In order to understand and explore the function and roles of fibroblasts, it is necessary to understand their lineage relationships to other mesenchymal cells. Fibroblasts are ubiquitous non-epithelial, non-endothelial, and non-haematopoietic adherent cells that have the capacity to produce and remodel extracellular matrix. In addition to their well-known ’landscaping’ function which determines the unique structure and function of different organs, they play an important role in wound healing, immune tolerance, and disease. In cancer, epithelial-stromal interactions have been implicated in disease initiation and progression. In rheumatoid arthritis, synovial fibroblasts at diseased sites become persistently activated and behave abnormally, orchestrating joint inflammation and contributing to joint destruction. Recent evidence suggests that the activated phenotype of fibroblasts in pathology may result from epigenetic programming, which is becoming a major focus for development of new therapeutics.


2020 ◽  
Vol 13 (9) ◽  
pp. e236431
Author(s):  
Kelli Stager ◽  
Leanna Wise

Antimelanoma differentiation-associated gene 5 (MDA-5) dermatomyositis is a subtype of dermatomyositis that is associated with rapidly progressive interstitial lung disease (RP-ILD), as well as with a variety of cutaneous manifestations. Patients with MDA-5 dermatomyositis tend to have a poor prognosis that is often attributed to the high rates of concurrent RP-ILD. Given the severity of disease, early diagnosis and aggressive management is pivotal. We present a case of a 40-year-old woman diagnosed with MDA-5 dermatomyositis who presented with weakness, painful cutaneous ulcerations and interstitial lung disease. She was treated with monthly intravenous Ig (IVIg), weight-based prednisone and mycophenolate mofetil (MMF). After approximately 2 years of treatment, her interstitial lung disease remains stable and she has had significant improvement in weakness and cutaneous ulcerations. Our case provides evidence for early and aggressive treatment of MDA-5 dermatomyositis with a combination of weight-based prednisone, MMF and IVIg.


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