Abatacept and sodium thiosulfate for treatment of recalcitrant juvenile dermatomyositis complicated by ulceration and calcinosis.

We report the successful use of abatacept and sodium thiosulfate in a patient with severe recalcitrant juvenile dermatomyositis complicated by ulcerative skin disease and progressive calcinosis. This combination therapy resulted in significant reductions in muscle and skin inflammation, decreased corticosteroid dependence, and halted the progression of calcinosis.

Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases.

BACKGROUNDUndifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify diseases with available targeted treatments.METHODSSixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing.RESULTSThirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator [NEMO]), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome-like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody-positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS.CONCLUSIONSIn patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18-mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5-autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression.TRIAL REGISTRATIONClinicalTrials.gov NCT02974595.FUNDINGThe Intramural Research Program of the NIH, NIAID, NIAMS, and the Clinical Center.

CT-guided percutaneous steroid injection for management of inflammatory arthropathy of the temporomandibular joint in children.

OBJECTIVE: The purposes of this study were to retrospectively review an injection technique, to develop a grading system for evaluation of imaging findings, and to report preliminary outcome related to percutaneous CT-guided steroid injection into the temporomandibular joints of children with inflammatory arthropathy. CONCLUSION: CT-guided steroid injection into the temporomandibular joint of children with inflammatory arthropathy results in clinical and imaging improvement in a substantial proportion of children treated.

Phenotypic and Genotypic Characterization and Treatment of a Cohort With Familial Tumoral Calcinosis/Hyperostosis-Hyperphosphatemia Syndrome.

Familial tumoral calcinosis (FTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is a rare disorder caused by mutations in the genes encoding fibroblast growth factor-23 (FGF23), N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO. The result is functional deficiency of, or resistance to, intact FGF23 (iFGF23), causing hyperphosphatemia, increased renal tubular reabsorption of phosphorus (TRP), elevated or inappropriately normal 1,25-dihydroxyvitamin D3 (1,25D), ectopic calcifications, and/or diaphyseal hyperostosis. Eight subjects with FTC/HHS were studied and treated. Clinical manifestations varied, even within families, ranging from asymptomatic to large, disabling calcifications. All subjects had hyperphosphatemia, increased TRP, and elevated or inappropriately normal 1,25D. C-terminal FGF23 was markedly elevated whereas iFGF23 was comparatively low, consistent with increased FGF23 cleavage. Radiographs ranged from diaphyseal hyperostosis to massive calcification. Two subjects with severe calcifications also had overwhelming systemic inflammation and elevated C-reactive protein (CRP). GALNT3 mutations were identified in seven subjects; no causative mutation was found in the eighth. Biopsies from four subjects showed ectopic calcification and chronic inflammation, with areas of heterotopic ossification observed in one subject. Treatment with low phosphate diet, phosphate binders, and phosphaturia-inducing therapies was prescribed with variable response. One subject experienced complete resolution of a calcific mass after 13 months of medical treatment. In the two subjects with systemic inflammation, interleukin-1 (IL-1) antagonists significantly decreased CRP levels with resolution of calcinosis cutis and perilesional inflammation in one subject and improvement of overall well-being in both subjects. This cohort expands the phenotype and genotype of FTC/HHS and demonstrates the range of clinical manifestations despite similar biochemical profiles and genetic mutations. Overwhelming systemic inflammation has not been described previously in FTC/HHS; the response to IL-1 antagonists suggests that anti-inflammatory drugs may be useful adjuvants. In addition, this is the first description of heterotopic ossification reported in FTC/HHS, possibly mediated by the adjacent inflammation. © 2016 American Society for Bone and Mineral Research.

High prevalence of temporomandibular joint arthritis at disease onset in children with juvenile idiopathic arthritis, as detected by magnetic resonance imaging but not by ultrasound.

OBJECTIVE: To determine the prevalence of temporomandibular joint (TMJ) disease in a cohort of children with new-onset juvenile idiopathic arthritis (JIA), and to compare magnetic resonance imaging (MRI) with ultrasound (US) for the detection of acute and chronic changes of TMJ arthritis. METHODS: Between January 2005 and April 2007, children with newly diagnosed JIA were prospectively evaluated for TMJ arthritis. Prior to imaging, jaw pain and disability were assessed with questionnaires and physical examination. The TMJs of all patients were imaged with MRI and US within 8 weeks of diagnosis. RESULTS: Of the 32 patients enrolled, 78% were female, and the median age was 8.6 years (range 1.5-17.2 years). Acute TMJ arthritis was diagnosed in 75% of the children by MRI and in none by US; chronic arthritis was diagnosed in 69% by MRI and in 28% by US. Findings of both acute and chronic TMJ disease were detected by MRI in 53% of the patients. Of those with acute TMJ arthritis, 71% were asymptomatic, and 63% had normal findings on jaw examination. Fifty-six percent of patients with acute disease had an improved maximal incisal opening after corticosteroid injection. Among these responders, 56% had been asymptomatic and had normal jaw examination findings. CONCLUSION: TMJ arthritis was present in the majority of patients with new-onset JIA. Findings on MRI along with responses to treatment among asymptomatic patients with normal jaw examination findings suggest that a history review and physical examination are not sufficient to screen for TMJ disease. Our results also suggest that MRI and US findings are not well correlated, and that MRI is preferable for the detection of TMJ disease in new-onset JIA.

Reactive arthritis of the temporomandibular joints and cervical spine in a child.

BACKGROUND: Temporomandibular joint (TMJ) arthritis is frequently seen in children with chronic arthritis. It has rarely been described in a non-infectious acute setting. We report a case of reactive arthritis isolated to the TMJs and cervical spine. CASE PRESENTATION: A 6-year-old Native American boy hospitalized for treatment of lymphadenitis and aseptic meningitis had an incidental brain magnetic resonance imaging (MRI) finding of effusions in the TMJs, as well as the atlanto-occipital and C1-C2 articulations. Repeat TMJ and cervical spine MRI four weeks later showed resolution of effusions. Reactive TMJ arthritis has been previously reported in adults but not in children. CONCLUSION: This report represents the first pediatric case of reactive arthritis isolated to the cervical spine and TMJs. Arthritis of the TMJ should be considered in the differential diagnosis of children with reactive arthritides.

Temporomandibular joint arthritis in juvenile idiopathic arthritis: the forgotten joint.

PURPOSE OF REVIEW: This review explores the prevalence, clinical and radiographic signs, and treatment of temporomandibular joint arthritis in children with juvenile idiopathic arthritis. RECENT FINDINGS: Temporomandibular joint arthritis seems to be a more frequent manifestation in patients with juvenile idiopathic arthritis than previously believed, in part due to the paucity of clinical symptoms and poor sensitivity of conventional radiographs used for diagnosis. Antinuclear antibody positivity, early onset of disease, and presence of systemic or polyarticular disease are all risk factors for temporomandibular joint arthritis but may underpredict temporomandibular joint involvement in juvenile idiopathic arthritis. Magnetic resonance imaging enhanced with gadolinium is currently the gold standard in detection of temporomandibular joint arthritis, and treatment with intra-articular corticosteroids has been shown to be effective and safe, with minimal side effects. SUMMARY: Given the paucity of clinical symptoms in temporomandibular joint arthritis, detection of temporomandibular joint inflammation using contrast-enhanced magnetic resonance imaging is essential for instituting appropriate therapy in a timely fashion. The use of intra-articular corticosteroids holds promise for control of temporomandibular joint inflammation and prevention of associated morbidities.

Benefit of intraarticular corticosteroid injection under fluoroscopic guidance for subtalar arthritis in juvenile idiopathic arthritis.

OBJECTIVE: To determine the demographics of subtalar arthritis, the response to intraarticular corticosteroid injection, and the injection complication rate in a clinic sample of children with juvenile idiopathic arthritis (JIA). METHODS: A chart review was performed of all patients at a tertiary medical center who underwent subtalar corticosteroid injection during the past 5 years. Injection of 1 ml of triamcinolone hexacetonide or acetonide into the midsubtalar joint was performed using a lateral oblique approach under fluoroscopic guidance. Improvement was defined by enhanced foot inversion and eversion at the following office visit. RESULTS: Thirty-eight patients underwent 55 subtalar injections during the study period. All 7 JIA subtypes were represented. Thirty-one patients (82%) had subtalar arthritis at time of JIA diagnosis and 32 (84%) had concomitant tibiotalar ankle arthritis. Improvement was observed following 34 (89%) of the initial 38 injections. The mean duration of improvement was 1.2 years (SD +/- 0.9). Twenty patients (53%) developed hypopigmentation or subcutaneous atrophy. This complication was associated with a higher volume of injected corticosteroid per patient weight (p = 0.02) and with less efficacious injections (p = 0.04). CONCLUSION: Subtalar arthritis in children with JIA is common. Similar to other joints, subtalar arthritis responds to corticosteroid injection in approximately 90% of cases and often remains improved for greater than one year. Hypopigmentation and subcutaneous atrophy are frequent complications and are likely related to the dose of injected corticosteroid and possibly the accuracy of needle placement.

Utility of corticosteroid injection for temporomandibular arthritis in children with juvenile idiopathic arthritis.

OBJECTIVE: To assess the effects of computed tomography (CT)-guided injection of corticosteroid into the temporomandibular joint (TMJ) in children with juvenile idiopathic arthritis (JIA) and clinical and magnetic resonance imaging (MRI) evidence of TMJ inflammation. METHODS: Twenty-three children ages 4-16 years with JIA and MRI evidence of TMJ inflammation received CT-guided TMJ injections of corticosteroid (triamcinolone acetonide [n = 16] or triamcinolone hexacetonide [n = 7]). Jaw pain or dysfunction and maximal incisal opening (MIO) distance were assessed before and after injection. Fourteen patients had followup MRI studies of the TMJ 6-12 months after injection. RESULTS: Of the 13 patients with symptoms of jaw pain prior to corticosteroid treatment, 10 (77%) had complete resolution of pain (P < 0.05). Prior to corticosteroid injection, MIO in all 23 patients was below age-matched normal values. After injection, the MIO was improved by at least 0.5 cm in 10 patients (43%) (P = 0.0017). Patients under 6 years of age at the time of injection showed the best response, with a postinjection MIO similar to that in age-matched controls (P = 0.2267). There was involvement of 23 TMJs in the 14 patients who had followup MRI studies; resolution of effusions was observed in 11 (48%) of the TMJs. Other than short-term facial swelling in 2 patients, there were no side effects. CONCLUSION: The majority of children with symptomatic TMJ arthritis improved after intraarticular corticosteroid injection. Approximately half the patients experienced significant improvement in MIO and TMJ effusion. These data suggest that corticosteroid injection may be a useful procedure for the prevention and treatment of morbidities associated with TMJ arthritis in JIA.