Intraarticular steroids as DMARD-sparing agents for juvenile idiopathic arthritis flares: Analysis of the Childhood Arthritis and Rheumatology Research Alliance Registry

BACKGROUND: Children with juvenile idiopathic arthritis (JIA) who achieve a drug free remission often experience a flare of their disease requiring either intraarticular steroids (IAS) or systemic treatment with disease modifying anti-rheumatic drugs (DMARDs). IAS offer an opportunity to recapture disease control and avoid exposure to side effects from systemic immunosuppression. We examined a cohort of patients treated with IAS after drug free remission and report the probability of restarting systemic treatment within 12 months. METHODS: We analyzed a cohort of patients from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry who received IAS for a flare after a period of drug free remission. Historical factors and clinical characteristics and of the patients including data obtained at the time of treatment were analyzed. RESULTS: We identified 46 patients who met the inclusion criteria. Of those with follow up data available 49% had restarted systemic treatment 6 months after IAS injection and 70% had restarted systemic treatment at 12 months. The proportion of patients with prior use of a biologic DMARD was the only factor that differed between patients who restarted systemic treatment those who did not, both at 6 months (79% vs 35%, p < 0.01) and 12 months (81% vs 33%, p < 0.05). CONCLUSION: While IAS are an option for all patients who flare after drug free remission, it may not prevent the need to restart systemic treatment. Prior use of a biologic DMARD may predict lack of success for IAS. Those who previously received methotrexate only, on the other hand, are excellent candidates for IAS.

Intraarticular Glucocorticoid Injection as Second-line Treatment for Lyme Arthritis in Children.

OBJECTIVE: To determine whether second-line intraarticular glucocorticoid (IAGC) injection improves outcomes in children with persistently active Lyme arthritis after initial antibiotics. METHODS: We conducted an observational comparative effectiveness study through chart review within 3 pediatric rheumatology centers with distinct clinical approaches to second-line treatment of Lyme arthritis. We primarily compared children receiving second-line IAGC to children receiving a second course of antibiotics alone. We evaluated the risk of developing antibiotic-refractory Lyme arthritis (ARLA) using logistic regression and the time to clinical resolution of Lyme arthritis using Cox regression. RESULTS: Of 112 children with persistently active Lyme arthritis after first-line antibiotics, 18 children received second-line IAGC (13 with concomitant oral antibiotics). Compared to children receiving second-line oral antibiotics alone, children treated with IAGC had similar baseline characteristics but lower rates of ARLA (17% vs 44%; OR 0.3, 95% CI 0.1-0.95; p = 0.04) and faster rates of clinical resolution (HR 2.2, 95% CI 1.2-3.9; p = 0.01). Children in IAGC and oral antibiotic cohorts did not differ in treatment-associated adverse events. Among children receiving second-line IAGC, outcomes appeared similar irrespective of use of concomitant antibiotics. Outcomes were also similar between intravenous (IV) and oral antibiotic-treated cohorts, but older children seemed to respond more favorably to IV therapy. IV antibiotics were also associated with higher rates of toxicity. CONCLUSION: IAGC injection appears to be an effective and safe second-line strategy for persistent Lyme arthritis in children, associated with rapid clinical resolution and reduced need for additional treatment.

Pediatric Antibiotic-refractory Lyme Arthritis: A Multicenter Case-control Study.

OBJECTIVE: Few factors have consistently been linked to antibiotic-refractory Lyme arthritis (ARLA). We sought to identify clinical and treatment factors associated with pediatric ARLA. METHODS: We performed a case-control study in 3 pediatric rheumatology clinics in a Lyme-endemic region (2000-2013). Eligible children were aged ≤ 18 years with arthritis and had positive testing for Lyme disease by Western blot. Cases were 49 children with persistently active arthritis despite ≥ 8 weeks of oral antibiotics or ≥ 2 weeks of parenteral antibiotics; controls were 188 children whose arthritis resolved within 3 months of starting antibiotics. We compared preselected demographic, clinical, and treatment factors between groups using logistic regression. RESULTS: Characteristics positively associated with ARLA were age ≥ 10 years, prolonged arthritis at diagnosis, knee-only arthritis, and worsening after starting antibiotics. In contrast, children with fever, severe pain, or other signs of systemic inflammation were more likely to respond quickly to treatment. Secondarily, low-dose amoxicillin and treatment nonadherence were also linked to higher risk of ARLA. Greater antibiotic use for children with ARLA was accompanied by higher rates of treatment-associated adverse events (37% vs 15%) and resultant hospitalization (6% vs 1%). CONCLUSION: Older children and those with prolonged arthritis, arthritis limited to the knees, or poor initial response to antibiotics are more likely to have antibiotic-refractory disease and treatment-associated toxicity. Children with severe symptoms of systemic inflammation have more favorable outcomes. For children with persistently active Lyme arthritis after 2 antibiotic courses, pediatricians should consider starting antiinflammatory treatment and referring to a pediatric rheumatologist.

Epstein Barr virus induced lymphoma in a child with IPEX syndrome.

IPEX syndrome (immune deficiency, polyendocrinopathy, enteropathy, X-linked) is a disorder or regulatory T cell (Treg) function which can result in early death due to infection or complications related to autoimmunity. Therapeutic options for these patients can include allogeneic stem cell transplantation (SCT) or the use of immunosuppressive regimens to control the manifestations of autoimmunity. We report a patient with IPEX syndrome who was managed with rapamycin and subsequently developed EBV induced lymphoma.

An assessment of variables affecting transition readiness in pediatric rheumatology patients.

BACKGROUND: We sought to identify which adolescent patient characteristics might lead to subjective reported independence in accessing medical care when patients transition from pediatric to adult medicine. METHODS: Pediatric and adult rheumatologists were asked which pediatric patient characteristics they believed would improve transition to adult medical care. Based on these responses, a questionnaire was created and administered to 76 teenage/young adult patients in a pediatric rheumatology clinic. The first set of questions included demographic, disease features, and life skills questions. The second set of questions pertained to self-reported independence in managing medical care. Data was analyzed to see if there were any significant associations between an individual's response to demographic, disease feature, or life skills questions and the independence outcome questions. RESULTS: In our study, older age correlated with self-reported independence in almost all questions asked regarding accessing medical care. Other patient characteristics that were associated with increased self-perceived autonomy included having a younger parent, having a family member with a similar disease, longer disease duration, having a comorbid non-rheumatic diagnosis, and having had a summer job. CONCLUSIONS: The patient characteristics that we found associated with self-reported independence in obtaining medical care should be considered when determining which patients might be more likely to make a successful transition.

Lyme arthritis of the pediatric lower extremity in the setting of polyarticular disease.

BACKGROUND: Lyme arthritis can be readily treated with use of oral antibiotics without any need for surgery. In Lyme-endemic areas, differentiating between Lyme arthritis and septic arthritis can be difficult. Laboratory testing for Lyme disease often results in a delay in diagnosis because many labs batch-test Lyme specimens only two times per week due to lack of equipment or increased expense. Delayed diagnosis can lead to unneeded surgery in cases in which the surgeon indicates the patient for a joint irrigation and debridement (I & D) for possible septic arthritis while waiting for Lyme serology results. The purpose of this study was to develop an algorithm for the treatment of patients with possible Lyme arthritis, with particular attention to poly-articular involvement. METHODS: Thirty-nine patients with poly-articular Lyme arthritis, including ankle involvement, were reviewed retrospectively. Patients were included if the ankle was involved, if they were less than 18 years of age, and had available laboratory information and a serologic diagnosis of Lyme disease. RESULTS: Only two patients had isolated ankle involvement; of those with poly-articular involvement, 34 patients had ankle/knee involvement. Nine patients presented with pain in the ankle with passive range of motion (PROM) (22 %); two (4.8 %) had refusal to bear weight, and 10 (24 %) had an antalgic gait. All patients had a positive Western blot. Ten patients had a peripheral white blood cell (WBC) count >12,500/mm(3) , and 16 patients had an erythrocyte sedimentation rate (ESR) >40 mm/h. CONCLUSION: Without immediate availability of Lyme serology, the decision to perform surgical drainage of a swollen joint in the setting of possible Lyme arthritis versus septic bacterial arthritis remains a clinical dilemma. Our data suggests that patients presenting with one or fewer Kocher criteria symptoms, poly-articular disease, and minimal pain with PROM have Lyme, rather than septic, arthritis. These patients can be treated with joint aspiration for cultures, appropriate antibiotics for Lyme disease, and careful serial exams while waiting for results of Lyme serology rather than immediate surgical I & D.

Papular xanthomas and erosive arthritis in a 3 year old girl, is this a new MRH variant?

Xanthomatous skin lesions and arthritis in children are not a common association. We present the case of a 3 year old girl who presented with xanthomatous lesions in the periungual region of both hands, around the nares and on her forehead, associated with significant arthritis that was clinically compatible with multicentric reticulohistiocytosis. However, pathology of the xanthomatous lesions was more suggestive of papular xanthoma, a disease that is not associated with arthritis. Based on her presentation and the negative lipid workup, she was treated for presumed multicentric reticulohistiocytosis. Multiple treatment strategies were utilized, with improvement on a combination of infliximab, methotrexate, and prednisone. We review the different diagnoses that should be considered in children with xanthomas and arthritis as well as the different pharmacologic therapies used in children with multicentric reticulohistiocytosis.

Evaluation of the presentation of systemic onset juvenile rheumatoid arthritis: data from the Pennsylvania Systemic Onset Juvenile Arthritis Registry (PASOJAR).

OBJECTIVE: To characterize the initial clinical and laboratory features of patients with systemic onset juvenile rheumatoid arthritis (soJRA) through a Web-based registry. METHODS: Patients diagnosed with soJRA in the last 15 years at 3 medical centers in Pennsylvania were identified. Data were collected retrospectively using a Web-based interface in compliance with patient privacy standards. Inferential statistics were used to compare features of patients with and without macrophage activation syndrome. RESULTS: We identified 136 patients; 88% of patients presented with arthritis (8% mono-, 45% oligo-, 47% polyarticular). The most common joints involved were the knee (68% of patients with arthritis), wrist (68%), and ankle (57%). The International League of Associations for Rheumatology criteria for systemic juvenile idiopathic arthritis (SJIA) identified only 30% of patients at presentation. CONCLUSION: We successfully characterized the presenting features of a relatively rare disease, soJRA, through the use of a Web-based registry. Current classification criteria for SJIA may not be particularly sensitive for diagnosis at presentation.

Lyme disease presenting as popliteal cyst in children.

Lyme disease is the most common tick-borne disease in North America. Our review of the literature found few reports of Lyme disease presented in the orthopaedic literature. However, Lyme disease presenting as a popliteal cyst, with or without rupture, is rarely reported. We present 4 cases of Lyme disease that initially presented to our pediatric orthopaedic clinic for treatment of a popliteal cyst. The early diagnosis and treatment of Lyme disease may help prevent the often-devastating long-term sequelae of Lyme disease. The goal of this article is to increase the awareness of Lyme disease presenting in children as a popliteal cyst.