Matthew L. Stoll

Consensus treatment plans for new-onset systemic juvenile idiopathic arthritis.

There is wide variation in therapeutic approaches to systemic juvenile idiopathic arthritis (JIA) among North American rheumatologists. Understanding the comparative effectiveness of the diverse therapeutic options available for treatment of systemic JIA can result in better health outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans and standardized assessment schedules for use in clinical practice to facilitate such studies.

Altered microbiota associated with abnormal humoral immune responses to commensal organisms in enthesitis-related arthritis.

IntroductionPrior studies have established altered microbiota and immunologic reactivity to enteric commensal organisms in inflammatory bowel disease (IBD). Since intestinal inflammation is present in a subset of patients with both pediatric and adult spondyloarthritis (SpA), we hypothesized that SpA patients may also have altered microbiota and immune responsiveness to enteric organisms.MethodsStool and blood specimens were collected from children with enthesitis-related arthritis (ERA) and non-inflammatory controls. DNA purified from stool was subject to PCR amplification and sequencing of the variable IV region from the 16S rDNA gene. IgA and IgG Enzyme-linked Immunosorbent Assays (ELISAs) were performed on select species of bacteria in most subjects.ResultsTwenty-five children with ERA and 13 controls were included. The ERA patients had less Faecalibacterium prausnitzii (3.8% versus 10%, P = 0.008) and lachnospiraceae family (12 versus 7.0%, P = 0.020), a statistically significant increase in bifidobacterium (1.8% versus 0%, P = 0.032) and a non-statistically significant increase in Bacteroides (21% versus 11%, P = 0.150). Akkermansia muciniphila was abundant (>2%) in 7/27 ERA patients but none of the controls (P = 0.072.) Cluster analysis revealed two clusters of ERA patients: Cluster one (n = 8) was characterized by high levels of Bacteroides genus, while a second (n = 15) cluster had similar levels as the controls. Seven of 17 (41%) of the ERA subjects in Cluster 2 compared to 0/8 of the subjects in Cluster 1 had abundant Akkermansia muciniphila (P = 0.057). Serum IgA and IgG antibody levels against F. prausnitzii and B. fragilis were similar between patients and controls, whereas the two groups showed divergent responses when the fecal relative abundances of F. prausnitzii and Bacteroides were compared individually against IgA antibody levels recognizing F. prausnitzii and B. fragilis, respectively.ConclusionThe abundance of F. prausnitzii in the stool among patients with ERA is reduced compared to controls, and Bacteroides and A. muciniphila are identified as associative agents in subsets of ERA patients. Differences in the humoral responses to these bacteria may contribute to disease.

Risk Factors for Temporomandibular Joint Arthritis in Children with Juvenile Idiopathic Arthritis

Objective. To determine the prevalence and features of temporomandibular joint (TMJ) arthritis by magnetic resonance imaging (MRI) among children with juvenile idiopathic arthritis (JIA), and to identify risk factors for TMJ arthritis. Methods. A retrospective chart review was performed on 187 patients with JIA who underwent a TMJ MRI at Children’s Hospital of Alabama between September 2007 and June 2010. Demographic and clinical information was abstracted from the charts. Univariate and multivariate analyses were performed to identify risk factors for TMJ arthritis identified by MRI. Results. MRI evidence of TMJ arthritis was detected in 43% of patients, with no significant difference among JIA categories. The number of joints with active arthritis (exclusive of the TMJ) and the use of systemic immunomodulatory therapies were not associated with TMJ arthritis. Multivariable analysis revealed a strong association between mouth-opening deviation and TMJ arthritis (OR 6.21, 95% CI 2.87–13.4). A smaller maximal incisal opening and shorter disease duration were also associated with an increased risk of TMJ arthritis. Conclusion. TMJ arthritis was identified in a substantial proportion of children with JIA (43%) and affects all JIA categories. TMJ arthritis was present in some patients despite limited or otherwise quiescent disease and in the presence of concurrent systemic immunomodulatory therapy. Routine evaluation for TMJ arthritis by MRI is warranted for all children with JIA.

Treatment of juvenile idiopathic arthritis: a revolution in care

A generation ago, children with arthritis faced a lifetime of pain and disability. Today, there are a multitude of treatment options, including a variety of biologics targeting key cytokines and other inflammatory mediators. While non-steroidal anti-inflammatory drugs and corticosteroids were once the mainstay of therapy, they are now largely used as bridge or adjunctive therapies. Among the conventional disease-modifying anti-rheumatic drugs, methotrexate remains first-line therapy for most children with juvenile idiopathic arthritis (JIA) due to its long track record of safety and effectiveness in the management of peripheral arthritis. Sulfasalazine and leflunomide may also have a secondary role. The tumor necrosis factor inhibitors (TNFi) have shown tremendous benefit in children with polyarticular JIA and likely in enthesitis-related arthritis and psoriatic JIA as well. There may be additional benefit in combining TNFi with methotrexate. Abatacept and tocilizumab also appear to benefit polyarticular JIA; the role of rituximab remains unclear. For the treatment of systemic JIA, while the TNFi are of less benefit, blockade of interleukin-1 or interleukin-6 is highly effective. Additionally, interleukin-1 blockade appears to be effective treatment of macrophage activation syndrome, one of the most dangerous complications of JIA; specifically, anakinra in combination with cyclosporine and corticosteroids may obviate the need for cytotoxic approaches. In contrast, methotrexate along with the TNFi and abatacept are effective agents for the management of uveitis, another complication of JIA. Overall, the biologics have demonstrated an impressive safety record in children with JIA, although children do need to be monitored for rare but potentially dangerous adverse events, such as tuberculosis and other infections; paradoxical development of additional autoimmune diseases; and possibly an increased risk of malignancy. Finally, there may be a window of opportunity during which children with JIA will demonstrate most optimal responses to aggressive therapy, underscoring the need for rapid diagnosis and initiation of treatment.

Comparison of Vancouver and International League of Associations for rheumatology classification criteria for juvenile psoriatic arthritis

OBJECTIVE The International League of Associations for Rheumatology (ILAR) criteria constitute the current international diagnostic standard for juvenile psoriatic arthritis (PsA), replacing the less-restrictive Vancouver criteria. The impact of this change on the population diagnosed with juvenile PsA is unknown. METHODS We reviewed the records of patients seen in a pediatric rheumatology clinic with International Classification of Diseases, Ninth Revision diagnosis codes for psoriasis, PsA, or spondylarthritis. Characteristics of children who met the Vancouver and ILAR criteria were compared. RESULTS Of 139 children meeting the Vancouver criteria for juvenile PsA, ILAR criteria excluded 80 (58%). Grounds for exclusion were insufficiently definitive rash (44%), a competing diagnosis of enthesitis-related arthritis (23%), family history of psoriasis limited to second-degree relatives (16%), fulfillment of criteria for >1 subtype of juvenile idiopathic arthritis (JIA) (5%), and HLA-B27 in a male with arthritis onset after age 6 (2%). Remaining patients were not homogeneous but could be divided into younger and older subpopulations differing in clinical features as described previously among patients identified under the Vancouver standard. Of excluded patients, 76% were reclassified as having other forms of JIA yet were phenotypically comparable with those retained. CONCLUSION Despite apparently modest changes from previous criteria, ILAR definitions strikingly restrict the diagnosis of PsA in childhood. Similarity between excluded and included patients suggests that these restrictions may not reflect substantive clinical differences. To the extent that excluded patients become reclassified within JIA, current criteria risk compromising other ILAR categories while reducing the number of patients available for the study of juvenile PsA.

Spondyloarthritis in a Pediatric Population: Risk Factors for Sacroiliitis

Objective. Pediatric rheumatologists may have an opportunity to diagnose sacroiliitis in its early stages, prior to the development of irreversible radiographic changes. Early diagnosis frequently requires magnetic resonance imaging (MRI), the use of which is limited by expense and requirement for sedation. We set out to identify features of juvenile spondyloarthritis (SpA) associated with the highest risk of sacroiliitis, to identify patients who may be candidates for routine MRI-based screening. Methods. We reviewed the charts of 143 children seen at Texas Scottish Rite Hospital for Children diagnosed with SpA based on the International League of Associations for Rheumatology criteria for enthesitis-related arthritis or the Amor criteria for SpA. We performed logistic regression analysis to identify risk factors for sacroiliitis. Results. A group of 143 children were diagnosed with SpA. Consistent with the diagnosis of SpA, 16% had psoriasis, 43% had enthesitis, 9.8% had acute anterior uveitis, and 70% were HLA-B27+. Fifty-three children had sacroiliitis, of which 11 cases were identified by imaging studies in the absence of suggestive symptoms or physical examination findings. Logistic regression analysis revealed that hip arthritis was a positive predictor of sacroiliitis, while dactylitis was a negative predictor. Conclusion. Children with SpA are at risk for sacroiliitis, which may be present in the absence of suggestive symptoms or physical examination findings. The major risk factor for sacroiliitis is hip arthritis, while dactylitis may be protective. Routine screening by MRI should be considered in patients at high risk of developing sacroiliitis.

Imaging of the Temporomandibular Joint in Juvenile Idiopathic Arthritis

Temporomandibular joint (TMJ) arthritis in children with juvenile idiopathic arthritis (JIA) is extremely common but frequently asymptomatic. Magnetic resonance imaging (MRI) with contrast remains the gold standard for identifying TMJ arthritis in JIA. A reliable scoring system with published MRI examples of typical acute and chronic TMJ arthritis changes will be invaluable for future prospective treatment trials of TMJ arthritis in JIA.

High Doses of Infliximab in the Management of Juvenile Idiopathic Arthritis

Objective. To review our experiences with high-dose infliximab (IFX) to treat juvenile idiopathic arthritis (JIA). We routinely use high doses of IFX (10–20 mg/kg) in children with recalcitrant or highly active JIA. Although biologics have revolutionized treatment of JIA, many patients have active disease despite therapy. Studies have shown benefits of high-dose IFX in several conditions, including inflammatory bowel disease, psoriasis, and idiopathic uveitis. The safety and effectiveness of high-dose IFX have not been evaluated in JIA. Methods. We performed a retrospective review of children with JIA who received IFX ≥ 10 mg/kg. We recorded all serious adverse events (SAE), medically important infections, and infusion reactions. We also recorded the physician global assessment of disease activity (MD global) and active joint count (AJC) at initiation of high-dose IFX and 3, 6, and 12 months thereafter. Results. Fifty-eight subjects received a total of 1064 infusions over 95 person-years. There were a total of 9 SAE (9.5/100 person-yrs), 7 of which were potentially related to therapy, and 6 infusion reactions (0.5%), none constituting anaphylaxis. Statistically significant improvements were observed in the AJC (median 0, range 0–31, vs 2, 0–39) and MD global (12, 2–31, vs 22, 5–80) over the first year. Conclusion. High-dose IFX appears safe in the management of JIA. Future prospective controlled studies are necessary to evaluate its safety and efficacy.

Psoriatic juvenile idiopathic arthritis: a tale of two subgroups.

Purpose of reviewThe International League of Associations for Rheumatology criteria parse out juvenile idiopathic arthritis (JIA) into seven groups, with the aim of creating homogeneous subgroups suitable for clinical and research evaluation. However, prior studies have shown that psoriatic JIA (psJIA) may be a heterogeneous entity. Recent findingsPsJIA is composed of two subgroups, differentiated by age at onset. Older children with psJIA have features of spondyloarthritis, including relative male preponderance, increased risk of axial involvement, and enthesitis. Extrapolating from studies on adults with psoriatic arthritis, the mechanism of older-onset PsJIA appears to involve autoinflammatory dysregulation centered at the synovial-entheseal complex; there may also be a role for gut inflammation in a subset of patients. In contrast, patients with early-onset PsJIA bear similarities to early-onset oligoarticular and polyarticular JIA patients, including female preponderance, antinuclear antibody (ANA) positivity, and certain human leukocyte antigen types, suggesting a possible role for traditional autoimmune mechanisms. Both groups, however, share a high frequency of dactylitis. SummaryThis review demonstrates that PsJIA is a heterogeneous entity, with different clinical, genetic, and possibly pathophysiological features. Future studies are needed to explore the mechanisms of arthritis in both subgroups, particularly in the early-onset children.

Fecal Calprotectin in Children with the Enthesitis-related Arthritis Subtype of Juvenile Idiopathic Arthritis

To the Editor: Subclinical gut inflammation is present in two-thirds of adult and pediatric patients with spondyloarthritis (SpA)1,2 and predicts a chronic course of arthritis2,3. Thus, there may be value in evaluating the gut in patients with SpA. However, commonly used tests, such as colonoscopy, barium studies, and computed tomography, are limited by expense, invasiveness, or radiation exposure4, prompting a need for noninvasive surrogate markers. Serologic markers revealed a large number of false-positive tests5. Fecal calprotectin is a sensitive and specific marker for the presence of inflammatory bowel disease or other intestinal illnesses6. This test has not heretofore been used to assess for subclinical gut inflammation in patients with arthritis. In this study, we measured fecal calprotectin levels in children with enthesitis-related arthritis (ERA), comparing them to children with non-SpA subtypes of juvenile idiopathic arthritis (JIA), as well as children with unrelated connective tissue diseases (CTD) and noninflammatory control subjects. We enrolled 4 groups of children: (1) 9 with the ERA subtype of JIA; (2) 17 with other subtypes of JIA [persistent oligoarticular, n = 6; extended oligoarticular, n = 1; rheumatoid factor-negative (RF–) polyarticular, n = 8; RF+ polyarticular, n = 2]; (3) 9 with unrelated CTD (dermatomyositis, n = 3; localized scleroderma, n = … Address correspondence to Dr. Punaro; E-mail: Marilynn.Punaro{at}TSRH.org.