Systemic Onset Juvenile Rheumatoid Arthritis Research Articles

Adult-onset Still's Disease: A Case Report

Adult-onset Still's Disease is a rare auto inflammatory disorder of unknown etiology characterized mainly by high spiking fever, arthritis, evanescent rash and lymphadenopathy. It is a form of systemic onset juvenile rheumatoid arthritis that is encountered in adults, typically between 15-25 years and 36-45years. We here describe a 28 years lady with fever, arthritis of multiple large joints, lymphadenopathy and rash, with negative Rheumatoid factor and evidence of past infection with Ebstein-Barr virus and Parvovirus B19. History, examination findings and investigations showed several features consistent with adult-onset Still's disease along with high ferritin level. After exclusion of probable other diagnosis and use of Yamaguchi criteria, she was diagnosed with adult-onset Still's disease. All the major and minor criteria of Yamaguchi for diagnosis were met. Her disease responded well with steroid, she achieved remission and is currently under maintenance therapy. Keywords: Adult-onset stills disease; arthritis; ferritin; fever.

Systemic-onset juvenile rheumatoid arthritis at primary health care: Case report

Introduction: Systemic-onset juvenile rheumatoid arthritis is a chronic, autoimmune disease that occurs at an early age, i.e., during the first four years of life. Symptoms may include: fever, malaise, weakness, faint salmon-colored skin rash, whereas the symmetrical polyarticular arthritis occurs in the advanced phases of the disease. Case report: This paper presents a case of three year-old patient with fever, rash, and swollen lymph nodes in the neck, but without signs of arthritis. During six months of the diagnostic period child repeatedly had fever, but laboratory values were normal, and consultations with infectious disease specialist, pulmonologist and hematologist did not reveal anything useful. As there are no specific parameters when it comes to this disease, final diagnosis was based on the clinical features. After only seven days of therapy that included administration of glucocorticoids, fever and subjective symptoms were no longer reported.

Functional analysis of natural killer cells in children with macrophage activation syndrome

Objective To analyze the functional alteration of natural killer (NK) cells from patients with macrophage activation syndrome (MAS) in active phase and after treatment.Methods Peripheral blood samples were collected from 12 healthy subjects,12 patients with systemic onset juvenile rheumatoid arthritis (SoJIA) but without an episode of MAS and 12 patients with MAS.Flow cytometry analysis was performed to detect NK cells and their expression of perforin,granzyme B,interferon (IFN)-γand tumour necrosis factor (TNF)-α.The cytotoxicity of NK cells to K562 cell was also analyzed.All of the patients with MAS were diagnozed by clinical features and the pathologic examination of hemophagocytosis in bone marrow.The function of NK cells were analyzed before any treatment and on the fifth day as well as in third month after treatment with glucocorticoid,intravenous immunoglobulin and/or cyclosporin A.Results Compared with healthy subjects and patients with SoJIA,patients with MAS had lower NK cell counts,reduced cytotoxicity and decreased expression of perforin and granzyme B before or on the fifth day after treatment (P＜0.05).However,increased production of IFN-γ and TNF-α by NK cells were observed (P＜ 0.05).In the third month after treatment,the cytotoxicity of NK cells and the expression of perforin and granzyme B in patients with MAS were lower than those in healthy subjects and patients with SoJIA (P＜ 0.05),but no statistically significant differences with NK cell counts and production of IFN-γand TNF-α were observed beween the patients with MAS and healthy subjects (P＞0.05).Conclusion NK cells from patients with active MAS were characterized by reduced cytotoxicity and enhanced production of IFN-γ and TNF-α.Upon medical treatment,the number of NK cells in patients with MAS were up-regulated and their production of IFN-γand TNF-α were down-regulated.However,the cytotoxicity of NK cells and the expression of perforin and granzyme B were not affected.Reduced cytotoxicity and decreased production of perforin and granzyme B with NK cells might be the durative features for the patients with MAS. Key words: Macrophage activation syndrome; Natural killer cell; Cytotoxicity ; Cytokine

AB0695 Cyclosporine usage in resistant systemic jia-an experience from india

BackgroundThe mainstay of treatment of Systemic JIA (sJIA) are corticosteroids(1,2), with majority being well responsive to steroids. But stopping steroids is really challenging as many relapse on tapering off or...

Sexual maturation in Egyptian boys and girls with juvenile rheumatoid arthritis

Children with juvenile rheumatoid arthritis (JRA) exhibit a compromised growth status while information concerning the pattern of their sexual maturity is scant. The aim of the current work was to study sexual maturity in boys and girls with JRA. The study included eighty JRA patients they were 45 male and 35 female and eighty age- and sex-matched normal children served as controls. Development of genitalia was evaluated as per sexual maturity rating criteria given by Tanner score. Development of hair (pubic, axillary and facial) and age of monarch to JRA females were noted The mean (±SD) age of appearance of genitalia stage G-2 in boys with systemic onset JRA (12.0 ± 0.3 years) was earlier when compared with pauciarticular (12.60 ± 0.93 years) and polyarticular (13.39 ± 0.93 years) JRA but delayed for all types of JRA when compared with controls (10.06 ± 0.63 years). In comparison with female groups, the mean (±SD) age of appearance of genitalia stage G-2 with systemic onset JRA (12.0 ± 0.4 years) was also earlier when compared with pauciarticular (12.68 ± 1.09 years) and polyarticular (13.72 ± 0.39 years). Age of menarche delayed in all JRA female patients. None of the study group reach stage G-5 of genitalia development. The timing of initiation of sexual maturity in boys and girls with JRA delayed and this delay variable according to disease subtype.

Subglottic stenosis in juvenile rheumatoid arthritis

Juvenile rheumatoid arthritis (JRA), now termed juvenile idiopathic arthritis (JIA), is a well-described group of arthritides in the pediatric population with known associations with airway compromise. Subclasses are based on associated symptoms and number of joints involved, namely pauciarticular, polyarticular, and systemic onset JRA. Cricoarytenoid arthritis (CA), as a cause of airway compromise, is rarely associated with JRA as compared to adult onset rheumatoid arthritis, however, there are reports of CA with JRA. Additionally, JRA is associated with other rheumatologic diseases, which include a reported case of Wegener's granulomatosis. Wegener's granulomatosis has a well-established association with subglottic stenosis. Described below is the case study of an 18 year-old African American female with a 5-year history of pauciarticular juvenile rheumatoid arthritis developed worsening shortness of breath, orthopnea, and stridor over a 1-month period. The patient had a firm circumferential subglottic mass obstructing approximately 80% of the lumen and requiring tracheostomy tube placement. Biopsies of the mass revealed only acute and chronic inflammation. There was no evidence of rheumatoid nodules, granulomas, acid fast, or fungal organisms. To our knowledge, this is the first case history reported of a patient with JRA and idiopathic subglottic stenosis; this potentially establishes an association between the two disease processes.

A Case of Macropharge Activation Syndrome Successfully Treated with Combination Therapy Including Etanercept

Macrophage activation syndrome (MAS) is a severe, potentially life-threatening complication of childhood systemic inflammatory disorder, primarily systemic onset juvenile rheumatoid arthritis (SoJRA). It is characterized by pancytopenia, liver insufficiency, coagulopathy, and neurologic symptoms. The clinical manifestations are caused by the activation and uncontrolled proliferation of T lymphocytes and macrophages, leading to cytokine overproduction including tumor necrosis factor-α (TNF-α). Methylprednisolone pulse therapy and cyclosporine A have made a considerable progress in the treatment of MAS. However, the mortality rate remains high suggesting the need of another therapeutic agent. Several cases of MAS successfully treated with TNF-α inhibitor (etanercept) have been reported. We report the first Korean case of MAS successfully treated with combination therapy of corticosteroid, cyclosporine A and etanercept.

The diagnostic and monitoring value of serum anti-mutated citrullinated vimentin antibodies (anti-MCV) in juvenile rheumatoid arthritis

Background: JRA is currently diagnosed using the American College of Rheumatology (ACR) 1987 revised criteria that are primarily based on clinical parameters. The criteria may be insufficient for the diagnosis of early RA as they are based upon measurements of disease classification predominately featuring manifestations typical of later-stage disease. Measurement of serum anti-mutated citrullinated vimentin antibodies (MCV) has been shown to be a better marker for early adult RA, and it correlates well with the disease activity score (DAS). Objectives: The aim of this work is to evaluate the role of antimutated citrullinated vimentin antibodies (anti-MCV) in the diagnosis, and in monitoring disease activity in juvenile rheumatoid arthritis. Methods: The study included 40 children with JRA fulfilling the American College of Rheumatology criteria for diagnosis of JRA: 4 children with oligoarticular JRA, 12 with polyarticular JRA and 24 children with systemic onset JRA. Fifty healthy children, matching the patients in age and sex served as a control group. The studied children with JRA were subjected to laboratory tests including CBC, ESR, CRP, ANA and rheumatoid factor (RF). Serum samples from both patients and controls were assayed for anti-MCV levels using an ELISA technique. Results: The study showed high mean serum anti-MCV antibodies level in JRA patients when compared to controls (P= 0.00). In addition, there were no significant correlations between anti-MCV antibody levels and parameters of disease activity, namely, number of swollen joints, number of tender joints, ESR and CRP. The receiver operating characteristic (ROC) curve was drawn and it showed that the area under the curve (AUC) was (0.896). At a cutoff level > 17 u/mL, anti-MCV antibodies had diagnostic specificity of 88%, diagnostic sensitivity of 87.5%, negative and positive predictive values of 89.8% and 85.4%, respectively and diagnostic efficacy of 87.8%. We also reported 3/40 of JRA patients to be positive for RF and 2/40 of JRA patients to be positive for ANA. Conclusion: Measurement of serum anti MCV antibody level holds promise as a diagnostic tool in JRA. However, they failed to show a significant efficacy in determining disease activity. Keywords: Juvenile rheumatoid arthritis, MCV Egypt J Pediatr Allergy Immunol 2012;10(2):75-80

The difficult management of systemic-onset juvenile rheumatoid arthritis. Level of serum ferritin as aspecific diagnostic finding

Systemic-onset JRA is characterized by spiking fevers lasting more than two weeks, typically occurring once, twice each day, with temperature returning to the normal or below normal. There are no specific diagnostic tests for systemic JRA. High level of serum ferritin is the most important, no specific, diagnostic finding associated.

Follistatin‐like protein 1 is a mesenchyme‐derived inflammatory protein and may represent a biomarker for systemic‐onset juvenile rheumatoid arthritis

To examine both the source of follistatin-like protein 1 (FSTL-1) and the factors that induce its expression in arthritis, and to determine whether juvenile rheumatoid arthritis (JRA) is characterized by overexpression of FSTL-1. FSTL-1 expression patterns were analyzed by immunohistochemical staining of joint tissue derived from mice with collagen-induced arthritis. Induction of FSTL-1 secretion was assessed in osteoblasts, adipocytes, and human fibroblast-like synoviocytes in response to transforming growth factor beta (TGFbeta), interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), and IL-6. In addition, sera and synovial fluid from children with oligoarticular, polyarticular, or systemic-onset JRA were assayed for FSTL-1 using a custom enzyme-linked immunosorbent assay. FSTL-1 concentrations in these patients were assessed for correlations with the erythrocyte sedimentation rate (ESR) and platelet count. Immunohistochemical staining of murine joint sections demonstrated expression of FSTL-1 in all cell types of the mesenchymal lineage, including osteocytes, chondrocytes, adipocytes, and fibroblasts. FSTL-1 could be induced in osteoblasts, adipocytes, and human fibroblast-like synoviocytes by TGFbeta, IL-1beta, TNFalpha, and IL-6. The IL-1beta response was significantly greater than the TNFalpha response (P < 0.05). In human serum and synovial fluid, only those samples from children with the systemic-onset JRA subtype had elevated concentrations of FSTL-1. The synovial fluid concentrations of FSTL-1 were 2-3-fold higher than the serum concentrations. The elevation in serum FSTL-1 concentrations seen in children with systemic-onset JRA correlated closely with elevations in the ESR and platelet count. These findings demonstrate that the arthritic joint matrix is a major source of FSTL-1 and that IL-1beta is a central mediator of FSTL-1 secretion. Furthermore, FSTL-1 may represent a useful biomarker of disease activity in systemic-onset JRA.

Persistent pruritic papules and plaques: a characteristic histopathologic presentation seen in a subset of patients with adult‐onset and juvenile Still's disease

'Persistent pruritic papules and plaques' of Still's disease represents a recently described eruption seen in a subset of patients. Most cases reported in the literature to date have been associated with adult-onset Still's disease. We present the clinical and histopathologic examinations of three female patients ranging in age from 15 to 54 years. Our three patients each presented with clinical findings consistent with Still's disease. The youngest patient suffered from the juvenile form of Still's disease (systemic-onset juvenile rheumatoid arthritis). Each patient had a persistent, pruritic eruption with histopathologic findings of dyskeratosis confined to the upper layers of the epidermis as well as a sparse superficial dermal infiltrate containing scattered neutrophils. These cases confirm the characteristic clinical and histopathologic findings of 'persistent papules and plaques of Still's disease' and show the potential for this eruption in both the adult and juvenile age groups.

Sexual maturation in boys with juvenile rheumatoid arthritis

This paper aimed to study sexual maturation of boys with juvenile rheumatoid arthritis (JRA) during adolescence. This study was carried out in the Department of Pediatrics, Advanced Pediatrics Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India. A total of 70 boys (between 9 and 17 years of age) diagnosed as cases of JRA comprised the sample for this study. Every child was examined for the development of genitalia as per criteria given by Tanner (Growth at adolescence, 2nd edn, Blackwell, Oxford, 1962) at half-yearly age intervals. However, with regard to development of hair (pubic, axillary and facial) mere presence or absence was noted. Mean (±SD) age of attainment of different stages of genitalia development as well as for eruption of hair was ascertained amongst boys who entered puberty using conventional statistics. Initiation of genitalia development (i.e. appearance of G-2 stage) was earliest among boys with systemic onset JRA (10.8 ± 1.3 years). None of the boys with JRA could attain final stage (G-5) of genitalia development by the age of 17 years, as compared with normal Chandigarh boys who had attained this by 15.2 years. Age of appearance of axillary, pubic, and facial hair was also earlier in systemic onset type of disease as compared with those with pauciarticular and polyarticular JRA. The timing of initiation of sexual maturity in boys with different types of JRA remains variably affected, and appears to experience substantial delay in completion of puberty.

Immunologic rheumatic disorders

We provide the basics for clinicians who might be called on to consider the diagnosis of diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) in their practice. We will emphasize clinical recognition and first-line laboratory testing. Only characteristics of the classic rheumatic inflammatory diseases (ie, RA, seronegative spondyloarthropathy, SLE, antiphospholipid syndrome, Sjögren syndrome, scleroderma, and polymyositis/dermatomyositis) will be covered. In the past decade, treatment for RA and seronegative spondyloarthropathy has substantially improved. Their treatment has been revolutionized by the use of methotrexate and, more recently, TNF inhibitors, T-cell costimulation modulators, and B-cell depletion. The goal of RA treatment today is to induce a complete remission as early as possible in the disease process, with the mantra being "elimination of synovitis equals elimination of joint destruction." The hope is that if the major mediators of Sjögren syndrome, SLE, or scleroderma can be identified and then blocked, as in the example of TNF inhibitors in patients with RA, more specific treatments will become available. Thus RA has become an excellent model of this evolving paradigm. Through the identification of major mediators in its pathogenesis, novel and highly efficacious therapeutic agents have been developed.

Longitudinal growth attainments of Indian boys with Juvenile Rheumatoid Arthritis

The objective is to study the pattern of distance and velocity growth in terms of weight and height in adolescent boys with Juvenile Rheumatoid Arthritis (JRA). This study was conducted on children diagnosed to have JRA (Cassidy and Petty in Juvenile Rheumatoid Arthritis, WB Saunders Co., Philadelphia, 2005) at the Pediatric Rheumatology and Immunology Clinic of Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh. A total of 203 observations made on 70 boys with JRA, between 9 and 17 years of age, comprised the sample for this prospective mixed-longitudinal growth study. Each subject was measured for body weight and standing height using standardized anthropometric techniques (Eveleth and Tanner in Worldwide variation in human growth, Cambridge University Press, New York, 1990) at half yearly age intervals. All anthropometric measurements were carried out in the Growth Laboratory of Advanced Pediatrics Centre. Boys with polyarticular and systemic onset types of JRA in general measured lighter than their pauciarticular counterparts throughout the period of study. Height attainments in boys with polyarticular and systemic onset JRA measured shorter than their pauciarticular counterparts till 15 years and 12 years, respectively, where-after they became comparable to boys with pauciarticular JRA. As compared to normal Indian (Bhalla and Kumar in Int J Anthropol 18:113-125, 2003; Aggarwal et al. in Indian Pediatr 29:1203-1282, 1992) and American (Ogden et al. in Pediatrics 109:45-60, 2002) counterparts boys representing all categories of JRA remained lighter and shorter. Onset of Peak Height Velocity (PHV) in boys with polyarticular JRA (i.e. 12.5 years) was delayed by 1 year as compared to boys with pauciarticular JRA (i.e. 11.5 years). Attainment of Peak Weight Velocity (PWV) in boys with polyarticular JRA (i.e. 13.5 years) was also delayed by 1 year when compared to those with pauciarticular type (i.e. 12.5 years). In conclusion, weight and height growth attainments in Indian adolescent boys afflicted with different categories of JRA in general remained impaired as compared to their normal counterparts. However, the magnitude of growth deficit experienced by them appears to be a disease severity related phenomenon. This is the first study of its kind from a developing country.

A 21-Year-Old Man with Systemic-Onset Juvenile Rheumatoid Arthritis, Cough and Progressive Dyspnea

Primary or nonobstructive, endogenous lipoid pneumonia is a rare clinical entity usually associated with an underlying systemic disease. The present report describes a case involving a 21-year-old man with systemic-onset juvenile rheumatoid arthritis who developed primary endogenous lipoid pneumonia. Multiple treatment regimens were attempted; however, definitive management was only achieved through double-lung transplantation.

Systemic juvenile rheumatoid arthritis in an 11 year old boy: a case report

Juvenile rheumatoid arthritis (JRA) is the mostcommon rheumatic condition in childrenand a major cause of chronic disability. 1 JRAis defined as persistent arthritis in one oro e joints for at least six weeks, when certainexclusionary conditions have been eliminated.2·3The three major subtypes of JRA are based onthe symptoms at disease onset and are designatedas systemic onset, pauciarticular onset, andpolyarticular onset.2 Systemic onset juvenilerheumatoid arthritis (SoJRA) represents about10-20% of all forms of JRA.4The incidence of ]RA is approximately 13.9/100,000 per year among children 15 years old oryounger.1 In Finland, the incidence was 19.5/100,000of the population under 16 years of age. The incidencewas significantly higher than in earlier years (1980,1985, and 1990) in the same district.5 Different racialand ethnic groups appear to have varying frequenciesof the subtype of JRA.1The treatment of JRA is achieved usingcombinations of anti-inflammatory and immunomodulatorymedications in combination withphysical and occupational therapy, occasionalsurgery, nutritional support, and psychosocial andeducational partnerships with patients and parents.3,6It is widely thought that a comprehensive teamapproach is associated with a superior outcome. 7This paper reports a case of systemic JRA in an 11-year old boy.

Bone Marrow Findings, and TNF-α, IL-18 Expression in Bone Marrow of Adult Onset Still's Disease Patients

Objective: Inflammatory cytokines may play important roles in the pathogenesis of adult onset Still's disease. The enhanced expression of IL-18 was reported in the bone marrow of a Japanese systemic onset juvenile rheumatoid arthritis patient but not in the other organs. To date, there are very few studies relating the bone marrow and AOSD. This study examined the bone marrow findings as well as TNF-α and IL-18 expression in the bone marrow of AOSD patients. Methods: A retrospective study was performed on 15 AOSD patients who had undergone a bone marrow examination at a university hospital. The clinical and laboratory findings, as well as the bone marrow findings, were analyzed. Immunohistochemistry of IL-18 and TNF-α in bone marrow was performed. Results: The bone marrow cellularity and myeloid/erythroid cell ratio showed no correlation with the clinical and laboratory findings. TNF-α was expressed at 0.8∼9.8% and IL-18 was expressed at 0.4∼9.8% of bone marrow cells. Cytokine expression was not associated with the clinical patterns of AOSD. The platelet count correlated with the bone marrow TNF-α expression but TNF-α did not correlate with IL-18 expression.

Systemic-onset juvenile rheumatoid arthritis and ANCA-associated glomerulonephritis

Systemic-onset juvenile rheumatoid arthritis (SoJRA) associated renal lesions are unusual, except for amyloidosis or side effects of antirheumatic drugs. We report on 3 children with SoJRA diagnosed in the first years of life, who presented a perinuclear antineutrophil cytoplasmic antibodies (pANCA) associated glomerulonephritis during the disease course. ANCA glomerulonephritis was diagnosed after 5, 6 and 1 year follow-up for SoJRA in Patients 1, 2 and 3 respectively. Treatment and outcome of the kidney lesions were as follows: Pt1 was treated with steroids bolus associated to rituximab then switched for mycophenolate mofetyl (MMF). At the age of 7, he benefited from anakinra for the still ongoing systemic symptoms of the SoJRA with excellent results on both inflammation baseline and proteinuria. Despite steroids bolus and azathioprine in Pt2, renal lesions led gradually to end stage renal disease (ESRD) when she was 17. She benefited from kidney transplantation and interestingly both systemic symptoms and renal function are well under triple immunosuppressant (MMF, tacrolimus and steroids) with a follow up of 3 years after transplantation. Pt3 evolved to ESRD despite the use of steroids bolus, cyclophosphamide, cyclosporine and immunoglobulin. She died when she was 16 years, after 4 years of dialysis, from a severe sepsis with digestive occlusion. ANCA vasculitis is exceptional in the JRA. Outcome is poor and can lead to ESRD and death. ANCA-associated glomerulonephritis were related to SoJRA with uncontrolled inflammation baseline. These data suggest a common pathogenesis between SoJRA and ANCA glomerulonephritis and underline overlapping syndrome in the pediatric practice.

Presenting Features of Systemic Onset JRA

Presenting Features of Systemic Onset JRA

Do children with lupus have fewer male siblings?

It is widely acknowledged that genetic factors play a significant role in the pathogenesis of systemic lupus erythematosus (SLE). However, the female preponderance remains unexplained. We hypothesized that the female preponderance in childhood SLE results from selection early in the course of conception against male fetuses bearing genetic material predisposing to SLE. If this hypothesis is accurate, there should be a decreased number of male children in families with a child with SLE. Alternatively, children with SLE would have fewer male siblings. Further, this hypothesis may apply to other diseases with a female predominance such as pauciarticular onset juvenile rheumatoid arthritis (PaJRA), and not apply to diseases without female preponderance such as systemic onset juvenile rheumatoid arthritis (SoJRA). Chart review of patients with childhood onset SLE and PaJRA revealed a greater number of female children in these families compared with families of patients with SoJRA. Large-scale epidemiologic studies with precise counting of miscarriages and abortions could help to confirm these findings. Detailed studies of genetic and maternal intrauterine factors are required to conclusively prove this hypothesis.