Introduction: Prior 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. Methods: Stool 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. Results: Twenty-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. Conclusion: The 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.

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.

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.

Arthritis involving the temporomandibular joint (TMJ) complicates 40 - 96% of cases of juvenile idiopathic arthritis (JIA), potentially leading to devastating changes to form and function. Optimal evaluation and management of this joint remains a matter of ongoing discussion. We performed a PubMed search for all articles with keywords “temporomandibular” and “arthritis”, covering the dates 2002 through February 28, 2018. A separate PubMed search was performed for all articles with keywords “temporomandibular joint”, “arthritis”, and “treatment” covering the same dates. The TMJ is a particularly challenging joint to assess, both clinically and with imaging studies. Clinical assessment of the TMJ is hampered by the low sensitivity of joint pain as well as the absence of physical exam findings early in the disease process. As with all joints, plain radiography and computed tomography only detect arthritic sequelae. Additionally, there is mixed data on the sensitivity of ultrasound, leaving magnetic resonance imaging (MRI) as the optimal diagnostic modality. However, several recent studies have shown that non-arthritic children can have subtle findings on MRI consistent with TMJ arthritis, such as joint effusion and contrast enhancement. Consequently, there has been an intense effort to identify features that can be used to differentiate mild TMJ arthritis from normal TMJs, such as the ratio of the enhancement within the TMJ itself compared to the enhancement in surrounding musculature. With respect to treatment of TMJ arthritis, there is minimal prospective data on medical therapy of this complicated joint. Retrospective studies have suggested that the response to medical therapy of the TMJ may lag behind that of other joints, prompting use of intraarticular (IA) therapy. Although most studies have shown short-term effectiveness of corticosteroids, the long-term safety of this therapy on local growth as well as on the development of IA heterotopic bone have prompted recommendations to limit use of IA corticosteroids. Severe TMJ disease from JIA can also be managed non-operatively with splints in a growing child, as well as with surgery. In this review, we summarize literature on the diagnosis and management of TMJ arthritis in JIA and suggest a diagnostic and therapeutic algorithm for children with refractory TMJ arthritis.

We have previously shown alterations in the composition of the gut microbiota in children with enthesitis-related arthritis (ERA). To explore the mechanisms by which an altered microbiota might predispose to arthritis, we performed metabolomic profiling of fecal samples of children with ERA. Fecal samples were collected from two cohorts of children with ERA and healthy control subjects. Nano-liquid chromatography—mass spectroscopy (LC-MS) was performed on the fecal water homogenates with identification based upon mass: charge ratios. Sequencing of the 16S ribosomal DNA (rDNA) on the same stool specimens was performed. In both sets of subjects, patients demonstrated lower diversity of ions and under-representation of multiple metabolic pathways, including the tryptophan metabolism pathway. For example, in the first cohort, out of 1500 negatively charged ions, 154 were lower in ERA patients, compared with only one that was higher. Imputed functional annotation of the 16S ribosomal DNA sequence data demonstrated significantly fewer microbial genes associated with metabolic processes in the patients compared with the controls (77 million versus 58 million, P=0.050). Diminished metabolic diversity and alterations in the tryptophan metabolism pathway may be a feature of ERA.