2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis­Associated Uveitis

To develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA).Methods. Pediatric rheumatologists, ophthalmologists with expertise in uveitis, patient representatives, and methodologists generated key clinical questions to be addressed by this guideline. This was followed by a system-atic literature review and rating of the available evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation). A group consensus process was used to compose the nal recommendations and grade their strength as conditional or strong. Due to a lack of literature with good quality of evidence, recommendations were formulated on the basis of available evidence and a consensus expert opinion. Regular ophthalmic screening of children with JIA is recom-mended because of the risk of uveitis, and the frequency of screening should be based on individual risk factors.

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non- Systemic Polyarthritis, Sacroiliitis, and Enthesitis

To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non- systemic polyarthritis, sacroiliitis, or enthesitis.Methods. The Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and recined by members of the guideline development teams. A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of evidence. A group consensus process was conducted among the Voting Panel to generate the nal recommendations and grade their strength. A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions. Thirty- nine recommendations were developed (8 strong and 31 conditional). The quality of supporting evidence was very low or low for 90% of the recommendations. Recommendations are provided for the use of nonsteroidal antiinflammatory drugs, disease- modifying antirheumatic drugs, biologics, and intraarticular and oral glucocorticoids. Recommendations for the use of physical and occupational therapy are also provided. Specific recommendations for polyarthritis address general medication use, initial and subsequent treatment, and adjunctive therapies. Good disease control, with therapeutic escalation to achieve low disease activity, was recommended. The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies. This guideline provides direction for clinicians, caregivers, and patients making treatment decisions. Clinicians, caregivers, and patients should use a shared decision- making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Long-term breastfeeding influences disease activity in a low-income juvenile idiopathic arthritis cohort.

To determine the influence of breastfeeding duration in the clinical activity of low-income juvenile idiopathic arthritis (JIA). Ninety-one JIA patients followed in Fortaleza-CE, Brazil, were cross-sectionally evaluated from May 2015 to April 2016. Breastfeeding duration was obtained by interviewing mothers. Mean age was 14.6 ± 5.2 years with 10.31 ± 3.7 years of disease duration. Polyarticular category predominated, with 39 (42.8%) patients, followed by 23 (25.3%) oligoarticular and 17 (18.7%) enthesitis-related. Forty-seven (61.8%) were receiving methotrexate isolated or combined to leflunomide, which was used by 12 (15.4%); 30 (32.9%) were on biologic DMARD with 16 (53.3%) etanercept, 8 (26.7%) adalimumab, 3 (10%) tocilizumab, and 1 (3.3%) each on infliximab, abatacept, and canakinumab. Mean(SD) CHAQ and JADAS27 were 0.37 ± 0.36 and 5.03 ± 6.1, respectively and 22 (24%) had permanent joint deformities. No family declared monthly income over US$900.00 and 32 (37.2%) earned less than US$300.00. Eighty-three (91%) were ever breastfed; over two-thirds were breastfed for more than 3 months. Those breastfed for more than 6 months had less joint deformities and a tendency to lower JADAS27 and CHAQ scores using minimally adjusted general linear or logistic models, as appropriate. Parental smoking or literacy and family income did not differ regarding breastfeeding time. This is a low-income JIA cohort with the highest breastfeeding prevalence ever reported. Breastfeeding over 6 months was associated with less disease activity.Key Point• Long-term breastfeeding benefits juvenile idiopathic arthritis.

Inmunizaciones en pacientes con artritis idiopática juvenil / Immunizations in patients with juvenile idiopathic arthritis

Los pacientes con AIJ/ARJ presentan un riesgo mayor de infecciones inmunopreveni-bles, debido a su disfunción inmune, exacerbada por la actividad de su enfermedad y la terapia inmunosupresora. Las vacunas inactivadas han demostrado un perfil de seguridad adecuado en estos pacientes, por lo que no están contraindicadas, aunque su respuesta inmune puede ser inadecuada. Las vacunas vivas atenuadas, formal-mente contraindicadas, poseen una información creciente que permite evaluar su riesgo beneficio de manera individual. Por este motivo, debemos procurar mantener el calendario de vacunas actualizado y complementado, evitando el retraso en esque-mas de vacunación y poniéndolo al día lo antes posible, con estrategias basadas en el individuo, idealmente antes de iniciar la terapia inmunosupresora o de lo contrario durante ella. Para llevar a cabo esto debemos conocer y considerar los intervalos entre las vacunas, los esquemas acelerados, la solicitud de vacunas especiales, las aprobaciones vigentes y, finalmente, sus contraindicaciones.

Patients with JIA/JRA present a higher risk of vaccine-preventable infections, due to their immune dysfunction, exacerbated by the activity of their disease and immu-nosuppressive therapy. Inactivated vaccines have shown an adequate safety profile in these patients, so they are not contraindicated, although their immune response may be impaired. Live attenuated vaccines, formally contraindicated, have a growing information that allows to evaluate their risk benefit case by case. For this reason we must try to keep the vaccination schedule updated and supplemented, avoiding the delay in vaccination schemes and updating it as soon as possible, with taylor-based strategies, ideally before starting immunosuppressive therapy or otherwise during it. To carry out this we must manage and consider the intervals between the vaccines, the accelerated schemes, the request for special vaccines, the current approvals and, finally, their contraindications.

[Current therapy of polyarticular forms of juvenile idiopathic arthritis]. / Aktuelle Therapie der polyartikulären Verlaufsform der juvenilen idiopathischen Arthritis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in infancy and childhood. Approximately 20 % of patients with JIA suffer from the polyarticular form of the disease, which causes a substantial disease burden and long-term sequelae. Therapeutic approaches have used steroids and conventional disease modifying antirheumatic drugs (DMARD) but over the last decade new drugs have become available for the treatment of JIA, in particular biologic DMARD. This article summarizes the current therapy options for polyarticular JIA.

Sibling Exposure and Risk of Juvenile Idiopathic Arthritis.

OBJECTIVE: Susceptibility to juvenile idiopathic arthritis (JIA) is presumed to be determined by both genes and environment. However, the environmental factors remain largely unknown. The hygiene hypothesis suggests that exposure to siblings, as a marker of exposure to microbes in early life, may protect against the development of later immune disorders. Some prior evidence suggests this may also be true for JIA. The present study was undertaken to test this hypothesis in detail. METHODS: We conducted a comprehensive analysis of the role of sibling exposure in JIA risk within the Childhood Arthritis Risk Factor Identification Study JIA case-hospital control sample (302 cases and 676 controls) from Victoria, Australia. RESULTS: We found that, compared to being an only child, having any siblings was protective against JIA, with an adjusted odds ratio (OR) of 0.46 (95% confidence interval [95% CI] 0.28-0.74) (P = 0.001). The protective association appeared to increase with increasing number of siblings (e.g., for ≥3 siblings, adjusted OR 0.25 [95% CI 0.13-0.48], P < 0.001). A protective association of siblings was also observed when we considered cumulative sibling years by age 6 (e.g., for ≥3 years of exposure versus no exposure, adjusted OR 0.49 [95% CI 0.30-0.79], P = 0.003). We also compared cases to a second control sample (n = 341) collected from the community and weighted to represent the child population of Victoria. Data remained supportive of an association between sibling exposure and protection against JIA, particularly for exposure to younger siblings. CONCLUSION: Increased exposure to siblings is associated with a reduced risk of disease in our sample. This suggests that increased microbial exposure in childhood may confer protection against the development of JIA.

Helminth infection does not reduce risk for chronic inflammatory disease in a population-based cohort study.

BACKGROUND & AIMS: Parasitic helminth infections can suppress symptoms of allergy, type 1 diabetes, arthritis, and inflammatory bowel disease in animal models. We analyzed data from a large, population-based cohort study to determine whether common childhood enterobiasis protects against these diseases. METHODS: We collected information on individual prescriptions filled for the drug mebendazole against Enterobius vermicularis for all children born in Denmark 1995-2008 from the National Register of Medicinal Product Statistics (n = 924,749; age 0-14 years); 132,383 of these children (14%) filled a prescription for mebendazole, 102,482 of the children (11%) had a household peer who was registered with a filled mebendazole prescription, and the remaining 689,884 children (75%) comprised the reference group. Children diagnosed with asthma, type 1 diabetes, juvenile arthritis, ulcerative colitis, or Crohn's disease were identified from the National Patient Registry. We used Poisson regression to estimate confounder-adjusted incidence rate ratios for first in- or outpatient hospital diagnosis of chronic inflammatory disease according to history of mebendazole treatment prescribed to children in the study. RESULTS: Chronic inflammatory disease was diagnosed in 10,352 children during 6.4 million person-years of follow-up. The incidence rate ratios was 1.07 for asthma (95% confidence interval [CI]: 1.00-1.13), 1.05 for type 1 diabetes (95% CI: 0.79-1.12), 1.13 for juvenile arthritis (95% CI: 0.94-1.37), 0.77 for ulcerative colitis (95% CI: 0.41-1.46), and 1.44 for Crohn's disease (95% CI: 0.82-2.53). Results were not modified by number of treatments or age at treatment. CONCLUSIONS: Based on a population-based analysis, enterobiasis does not reduce risk for asthma, type 1 diabetes, arthritis, or inflammatory bowel disease.

Possible environmental determinants of juvenile idiopathic arthritis.

Like other autoimmune diseases, including adult RA, risk of developing juvenile idiopathic arthritis (JIA) is thought to be determined by a complex combination of genetic and environmental factors. Although some predisposing JIA genes are now being identified, research aimed at identifying environmental influences lags behind most other autoimmune conditions. Here we review research to date, from which some evidence has been generated to support a role for breastfeeding, infection and maternal smoking in determining JIA risk. We also propose further hypotheses worthy of testing, based on knowledge acquired for other autoimmune diseases. These include the role of vitamin D and sun exposure, and the role of early-life infection ('the hygiene hypothesis') in determining risk. Finally, we discuss future directions including practical study designs to more comprehensively test hypotheses and provide new insight into this important area of research.

A gender perspective on the extent to which mothers and fathers each take responsibility for care of a child with high and intermediate imperforate anus.

Imperforate anus is a malformation of the child's anus. Parents' experiences of responsibility for care of the child may differ. The aim of this study was to evaluate a gender perspective on the extent to which mothers and fathers each take responsibility for the care of a child with high and intermediate imperforate anus. Parents of children with imperforate anus and two control groups of children and parents participated. Data collection with questionnaires focusing on responsibility was performed. In conclusion, our study revealed additional evidence of unevenly divided parental responsibility for care of a child with a chronic condition. The mothers in this study were shown to be the primary caregiver.

The child with arthritis in the school setting.

Arthritis is a condition often associated with the elderly. However, arthritis affects approximately 275,000 children nationwide. Symptoms may vary from one swollen joint to multiply affected joints coupled with fatigue, fever, and rash. Its effect on the school-age child can range from missing a few days of school per year to hospitalizations requiring tutoring to keep up with missed schoolwork. Other issues include the social impact of medications and their side effects, noncompliance, frequent doctor's visits interfering with school and afterschool activities, and not being able to keep up with peers. The financial impact of multiple copayments for office visits and medications and the stress associated with work absence puts a strain on parents. The school nurse recognizes how these factors can affect the academic success of children with a chronic disease and can provide care that will assist students and families address and cope with these concerns.

How do parents of children with juvenile idiopathic arthritis (JIA) perceive their therapies?

BACKGROUND: Complementary and alternative medical (CAM) therapies are commonly used by pediatric patients with chronic medical conditions. Little is known about parents' perceptions of these therapies. This study describes the views of parents of patients with juvenile idiopathic arthritis (JIA) regarding conventional and CAM therapies. METHODS: Parents of children with JIA seen at a pediatric rheumatology clinic were surveyed between June 1 and July 31, 2007. Questionnaires asked about patients' use of over 75 therapies in the past 30 days, their perceived helpfulness (0 = not helpful; 3 = very helpful), perceived side effects (0 = none; 3 = severe), and whether each therapy would be recommended to other patients with JIA (Yes, No, Not sure). RESULTS: Questionnaires were returned by 52/76 (68%) parents; patients' average age was 10.9 years and 87% were Caucasian. Medications were used by 45 (88%) patients; heat (67%) and extra rest (54%) were also commonly used. CAM therapies were used by 48 (92%), e.g., massage (54%), vitamins and other supplements (54%), avoiding foods that worsened pain (35%) and stress management techniques (33%). Among the therapies rated by 3 or more parents, those that scored 2.5 or higher on helpfulness were: biologic medications, methotrexate, naproxen, wheelchairs, orthotics, heat, vitamins C and D, music, support groups and prayer. CAM therapies had 0 median side effects and parents would recommend many of them to other families. CONCLUSION: JIA patients use diverse therapies. Parents report that many CAM therapies are helpful and would recommend them to other parents. These data can be used in counseling patients and guiding future research.

Self-investigation to explore the impact of juvenile arthritis on adolescent life: a case-study.

OBJECTIVE: To gain insight into the personal experience and feelings of an adolescent with a chronic disease. METHODS: We report on the application of the self-confrontation method (SCM), illustrated by a case-example of an adolescent with juvenile idiopathic arthritis. RESULTS: Although taken at face value she was not impeded by the arthritis, through self-assessment with the SCM this adolescent acknowledged and addressed the emotional struggle to keep the arthritis secret and to constantly test the physical limits of her body. After the process of self-reflection, the adolescent showed a better integration of her arthritis experiences into her life story. CONCLUSION: With the SCM the adolescent could explore her own functioning and well-being on a manifest, as well as on an emotional and motivational level. PRACTICE IMPLICATIONS: In future research, by studying the self-investigations of a group of adolescents with chronic diseases, common risk factors for the development of a stable identity during adolescence might be identified. In clinical care, the SCM promotes self-knowledge, allowing for an intrinsic motivation to deal with the emotional impact of the disease.

Quantitative histological changes of repeated antigen-induced arthritis in the temporomandibular joints of rabbits treated with intra-articular corticosteroid.

BACKGROUND: To compare the inflammatory changes of antigen-induced temporomandibular joint (TMJ) arthritis in rabbits by different histological methods and to evaluate the immunomodulatory effect of intra-articular corticosteroid injections histologically. METHODS: 35 rabbits (10 weeks old) pre-sensibilized with ovalbumin were divided into three groups: a placebo group of five (saline), an arthritis group of 15 (ovalbumin) and a steroid-treated group of 15 (ovalbumin + corticosteroid). Additionally, a group of seven rabbits receiving no sensibilization with ovalbumin and no intra-articular injections served as controls. Histomorphometry of the inflammatory changes in the subsynovial connective tissue (SSCT) of the TMJ included: (i) semi-quantitative (S-Q) scoring of inflammation and synovial proliferation, (ii) thickness measurements and fractional surface and (iii) stereological quantitative assessment of volume and plasma cells in thick sections of the SSCT by an optical fractionator. RESULTS: The histomorphometry showed synovial proliferation in both the arthritis and the steroid groups. The plasma cell count obtained by the optical fractionator was significantly reduced when treating the TMJ with corticosteroids. However, the thickness of the synovial lining and volume of the SSCT as well as S-Q scoring of inflammation showed no difference between the arthritis and the steroid-treated groups. The optical fractionator proved a superior tool compared to S-Q assessments. CONCLUSION: Counting of plasma cells in the SSCT showed that corticosteroids reduced the inflammation, but did not eliminate it. Semiquantitative scoring of synovial proliferation and inflammation demonstrated low sensitivity regarding changes in immunomodulation in antigen-induced arthritis compared to stereological quantitative estimations using an optical fractionator.

Safety and efficacy of meningococcal c vaccination in juvenile idiopathic arthritis.

OBJECTIVE: To determine whether vaccinations aggravate the course of autoimmune diseases such as juvenile idiopathic arthritis (JIA) and whether the immune response to vaccinations may be hampered by immunosuppressive therapy for the underlying disease. METHODS: In this multicenter cohort study, 234 patients with JIA (ages 1-19 years) were vaccinated with meningococcal serogroup C (MenC) conjugate to protect against serogroup C disease (caused by Neisseria meningitidis). Patients were followed up for disease activity for 1 year, from 6 months before until 6 months after vaccination. IgG antibody titers against MenC polysaccharide and the tetanus carrier protein were determined by enzyme-linked immunosorbent assay and toxin binding inhibition assay, respectively. A serum bactericidal assay was performed to determine the function of the anti-MenC antibodies. RESULTS: No change in values for any of the 6 components of the core set criteria for juvenile arthritis disease activity was seen after MenC vaccination. Moreover, no increase in the frequency of disease relapse was detected. Mean anti-MenC IgG concentrations in JIA patients rose significantly within 6-12 weeks after vaccination. Of 157 patients tested, 153 were able to mount anti-MenC IgG serum levels >2 micro g/ml, including patients receiving highly immunosuppressive medication. The 4 patients with a lower anti-MenC antibody response displayed sufficient bactericidal activity despite receiving highly immunosuppressive medication. CONCLUSION: The MenC conjugate vaccine does not aggravate JIA disease activity or increase relapse frequency and results in adequate antibody levels, even in patients receiving highly immunosuppressive medication. Therefore, patients with JIA can be vaccinated safely and effectively with the MenC conjugate.

Prevention of osteoporosis: a randomized clinical trial to increase calcium intake in children with juvenile rheumatoid arthritis.

OBJECTIVE: To test the efficacy of a behavioral intervention (BI) compared to an enhanced standard of care (ESC) dietary counseling on increasing dietary calcium (Ca) intake in children with juvenile rheumatoid arthritis (JRA). METHODS: Three-day food diaries collected at baseline and posttreatment were analyzed for Ca intake in 49 children with JRA randomly assigned to either BI or an ESC treatment. RESULTS: Children in the BI (N = 25) demonstrated a significantly greater increase in average dietary Ca intake (M = 839) than children in the ESC (N = 24; M = 420) (F = 14.39; p < .001). Post hoc analysis revealed that children in both groups demonstrated significant gains in dietary Ca intake baseline to posttreatment. A significantly greater percentage of children in the BI (92%) attained the goal of 1500 mg/Ca at posttreatment compared to the ESC (17%), X2= 28.09; p < .001. CONCLUSIONS: Behavioral intervention can have a positive impact on increasing dietary Ca intake. Future research will need to evaluate the maintenance of gains in dietary Ca intake following treatment cessation and the impact of increased Ca intake on bone mineral density.

[Physical exercise and bone development in chronically ill children]. / Exercice physique et développement osseux de l'enfant malade chronique.

Children with chronic diseases are at increased risk of sub-optimal bone mineral acquisition and osteoporosis, especially those who have a growth and pubertal delay, reduced physical activity, inadequate nutrition, malabsorption or take medications which may influence bone development. Weight-bearing physical activity has a beneficial effect on bone development of healthy children but little is known in children with chronic diseases. Preliminary results of our cross-sectional study in children with juvenile idiopathic arthritis (JIA) suggest that hip bone mineral density is positively related with physical fitness and muscle strength and is reduced at the more affected side. We have initiated two randomized controlled trials to determine the effects of a moderate impact exercise training program on bone mineral density of children with JIA and type 1 diabetes mellitus.

Motivation as a crucial predictor of good compliance in adolescents with rheumatoid arthritis.

The purpose of this study was to identify the predictors of compliance shown by adolescents with juvenile rheumatoid arthritis (JRA). Three hundred individuals aged 13-17 years were randomly selected from the Finnish Social Insurance Institution's register. The questionnaires were sent to the adolescents selected from the register to be returned directly to the researcher in a self-addressed envelope. Ninety-one per cent (n = 274) returned the questionnaire. Logistic regression was used to find the factors that predicted compliance with health regimens. The compliance of adolescents with JRA was predicted on the basis of motivation, fear of acute problems, support from nurses, energy and willpower, and threat to social well-being. The most powerful predictor was motivation. The likelihood of the adolescents who had good motivation to comply with health regimens was 29.13-fold compared to the adolescents who did not have good motivation. The next powerful predictor was fear of acute problems. The adolescents who felt fear of acute problems complied with health regimens with a 20.35-fold likelihood compared to the adolescents who did not have fears. The third powerful predictor was support from nurses. The likelihood of adolescents supported by nurse to comply with health regimens was 17.03-fold compared to the adolescents who did not receive support from nurses. The likelihood of adolescents who had energy and willpower to comply with health regimens was 7.56-fold compared to the adolescents who did not have energy and willpower. Also, the threat to social well-being predicted good compliance.

Support as a crucial predictor of good compliance of adolescents with a chronic disease.

The purpose of this study was to describe the factors that predict compliance among adolescents with a chronic illness. The data were collected by questionnaires from adolescents with asthma, epilepsy, juvenile rheumatoid arthritis (JRA) and insulin-dependent diabetes mellitus (IDDM). Groups of 300 adolescents with these illnesses were selected from the Finnish Social Insurance Institution's register, giving a total study series of 1200 individuals. The final response percentage was 88% (n = 1061). The data were analysed with the SPSS software. Logistic regression was used to indicate the predictors of good compliance. The compliance of adolescents with a chronic disease was predicted on the basis of support from parents, nurses, physicians and friends, as well as motivation, energy and willpower. The most powerful predictor was support from nurses. The likelihood of adolescents supported by nurses complying with health regimens was 7.28-fold compared to the adolescents who did not receive support from nurses. The next powerful predictor was energy and willpower. Adolescents who had the energy and willpower to take care of themselves complied with health regimens with a 6.69-fold likelihood compared to the adolescents who did not have energy and willpower. Adolescents who had good motivation were 5.28 times more likely to comply than the adolescents who did not have motivation. Support from parents, physicians and friends similarly predicted good compliance with health regimens.