Donald P. Goldsmith

Pain Intensity, Psychological Inflexibility, and Acceptance of Pain as Predictors of Functioning in Adolescents with Juvenile Idiopathic Arthritis: A Preliminary Investigation

Juvenile Idiopathic Arthritis (JIA) is a chronic rheumatic disease associated with pain and maladjustment. This study investigated whether pain, acceptance of pain, and psychological inflexibility uniquely predicted functional disability, anxiety, general quality of life (QOL), and health-related quality of life (HQOL) among adolescents with JIA. Twenty-three adolescents with JIA and pain were recruited from a pediatric rheumatology clinic. Participants completed self-report measures pertaining to the key study variables. A series of multiple regression analyses demonstrated that higher pain uniquely predicted higher functional disability. Greater psychological inflexibility uniquely predicted higher anxiety, lower general QOL, and lower HQOL. Increases in acceptance of pain were found to be uniquely related to increases in general QOL. These data confirm prior findings that pain impacts functioning, and provide preliminary findings that psychological inflexibility and acceptance may be important targets of psychological intervention for youth with JIA and pain to improve functioning and QOL.

Development of autoimmune hepatitis in a child with systemic-onset juvenile idiopathic arthritis during therapy with etanercept.

Autoimmune hepatitis is a progressive chronic inflammatory liver disease of unknown etiology. The diagnosis and classification is based on histologic abnormalities and the presence of abnormal serum autoantibodies and globulins. We report the case of a patient with systemic-onset juvenile idiopathic arthritis (JIA) who developed type 1-autoimmune hepatitis while receiving etanercept, a tumor necrosis factor (TNF)-blocker.

Safety of celecoxib and nonselective nonsteroidal anti-inflammatory drugs in juvenile idiopathic arthritis: results of the phase 4 registry

BackgroundThis study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs).MethodsChildren aged ≥2 to <18xa0years with rheumatoid-factor–positive or –negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (≤6xa0months) an nsNSAID or celecoxib. Enrolled patients were followed to the end of the study, whether they remained on the original NSAID, switched, or discontinued therapy altogether. All adverse events (AEs) regardless of severity were captured in the database.ResultsA total of 274 patients (nsNSAID, nu2009=u2009219; celecoxib, nu2009=u200955) were observed for 410 patient-years of observation. Naproxen, meloxicam, and nabumetone were the most frequently used nsNSAIDs. At baseline, the celecoxib group was older, had a numerically longer median time since diagnosis, and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance. AEs reported were those frequently observed with NSAID treatment and were similar across groups (nsNSAIDs: 52.0%; celecoxib: 52.9%). Twelve unique patients experienced a total of 18 serious AEs; the most frequent were infections, and none was attributed to NSAID use.ConclusionsThe safety profile of celecoxib and nsNSAIDs appears similar overall. The results from this registry, ongoing pharmacovigilance, and the phase 3 trial that led to the approval of celecoxib for children with JIA provide evidence that the benefit-risk for celecoxib treatment in JIA remains positive.Trial registrationClinicalTrials.gov identifier NCT00688545.

Pilot study comparing the Childhood Arthritis & Rheumatology Research Alliance (CARRA) systemic Juvenile Idiopathic Arthritis Consensus Treatment Plans

ObjectivesTo assess the feasibility of studying the comparative effectiveness of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans (CTPs) for systemic Juvenile Idiopathic Arthritis (JIA) using an observational registry.MethodsUntreated systemic JIA patients enrolled in the CARRA Registry were begun on one of 4 CTPs chosen by the treating physician and patient/family (glucocorticoid [GC] alone; methotrexate [MTX]u2009±u2009GC; IL1 inhibitor [IL1i]u2009±u2009GC; IL6 inhibitor [IL6i]u2009±u2009GC). The primary outcome of clinical inactive disease (CID) without current GC use was assessed at 9xa0months. Trial registration: clinicaltrials.gov NCT01697254; first registered 9/28/12 (retrospectively enrolled).ResultsThirty patients were enrolled at 13 sites; eight patients were started on a non-biologic CTP (2 GC, 6 MTX) and 22 patients on a biologic CTP (12 IL1i, 10 IL6i) at disease onset. Demographic and disease features were similar between CTP groups. CTP choice appeared to segregate by site preference. CID off GC was achieved by 37% (11 of 30) including 11/22 (50%) starting a biologic CTP compared to 0/8 starting a non-biologic CTP (pu2009=u20090.014). There were four serious adverse events: two infections, one appendicitis and one macrophage activation syndrome.ConclusionsThe CARRA systemic JIA CTP pilot study demonstrated successful implementation of CTPs using the CARRA registry infrastructure. Having demonstrated feasibility, a larger study using CTP response to better determine the relative effectiveness of treatments for new-onset systemic JIA is now underway.

Pyogenic arthritis caused by capnocytophaga gingivalis in an immunocompetent three-year-old male.

Capnocytophaga gingivalis is most often isolated as normal oral flora or with periodontal disease. This organism is also associated with sepsis usually in immunocompromised hosts. We identified pyogenic arthritis caused by C. gingivalis in a 3-year-old immunocompetent male, whose clinical course closely resembled monoarticular onset pauciarticular juvenile rheumatoid arthritis. This is the first report of C. gingivalis septic arthritis in the world literature, but there are increasing reports of infections with this carbon dioxide-loving organism at other sites in non-immunocompromised individuals. The subacute presentation of the monoarthritis with this organism of low virulence led to a long delay in diagnosis and treatment. Any monoarthritis must continue to raise concern about infection.

Physicians’ perspectives on the diagnosis and management of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome

To assess the practice patterns of pediatric rheumatology and infectious diseases subspecialists in the diagnosis and treatment of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. An online survey assessing diagnostic and treatment approaches was sent to 424 members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) and 980 members of the Pediatric Infectious Disease Society (PIDS). 277 physicians (123 from CARRA and 154 from PIDS representing 21% of the total membership) completed the survey. To diagnose PFAPA, most respondents agreed that patients must have the following features of the diagnostic criteria: stereotypical fever episodes (95%), asymptomatic intervals between episodes (93%), and normal growth and development (81%). However, 71% of the respondents did not require age of onsetu2009<5 years, 33% did not require regular intervals between episodes, and 79% did not require the concomitant signs of aphthous stomatitis, adenitis, or pharyngitis during episodes as long as episodes were regular. Over half (58%) considered episode resolution with steroids to be diagnostic of PFAPA. Corticosteroids, antipyretics, tonsillectomy, and cimetidine were the most commonly prescribed treatments, while steroids and tonsillectomy were most effective. Subspecialists in pediatric rheumatology and infectious diseases showed limited adherence to the complete published criteria for diagnosing PFAPA suggesting heterogeneity in the characteristics of patients diagnosed with the disorder. These findings emphasize the need to develop consensus diagnostic and treatment guidelines in well-characterized patient populations.

Poststreptococcal rheumatic manifestations: an ongoing tale.

In this month’s Journal of Clinical Rheumatology, Sarakbi et al present a retrospective review of 26 patients with poststreptococcal inflammatory articular disease, 5 of whom solely experienced tendonitis, enthesitis, or tenosynovitis. Four additional individuals exhibited the more typically described findings of poststreptococcal reactive arthritis (PSRA) plus the above periarticular findings. Although prior reports of PSRA have included small number of patients with tenosynovitis, these findings have not been emphasized as being part of the usual clinical PSRA spectrum. None of the patients in Sarakbi’s report were tested for the presence of the HLA-B27 antigen. Although none demonstrated clinical characteristics suggestive of spondyloarthropathy, it remains possible that streptococcal infection may have induced reactive arthritis at least in some of their patients who may have been HLA-B27 positive. There are additional likely streptococcal triggered rheumatic disorders. Barash and Goldzweig recently reported on the possible role of streptococcal infection inciting flares in children with juvenile idiopathic arthritis both during established disease and at onset. Streptococcal infection has also been linked to exacerbations/induction of childhood cutaneous polyarteritis and uveitis. Since the earliest descriptions of PSRA by Crea and Mortimer in 1959 and Goldsmith and Long in 1982, the differentiation of PSRA from acute rheumatic fever (ARF) has remained unsettled. The primary reasons for this uncertainty is that most of the differences between PSRA and ARF are arthritis descriptors such as the time of onset after streptococcal infection, pattern and distribution of involved joints, duration of active arthritis, and the time needed to achieve a therapeutic response. Individuals with arthritis and none of the other major clinical manifestations of ARF have always offered the greatest diagnostic challenges. Compared with ARF the arthritis of PSRA is more likely to occur within 10 days after infection, be symmetrical and nonmigratory, last longer than 3 weeks, and be poorly responsive to aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs). Periarticular findings, such as tenosynovitis, have not been considered to be part of the clinical spectrum of ARF. Other authors such as Pileggi and Hicks, however, have reported that an additive and prolonged pattern of arthritis as well as aspirin unresponsivity may be seen in from 19.5% to 36% of patients with ARF. Tutar et al also concluded that there was considerable overlap between the articular findings of PSRA and ARF. Most recently Barash et al retrospectively assessed the records of 68 children with ARF and 159 with PSRA, and determined that 4 variables as follows: erythrocyte sedimentation rate, C-reactive protein, duration of joint symptoms after starting NSAID’s, and relapse of synovitis after cessation of NSAID’s provided enough discriminative data to acceptably differentiate these patients with a 79% sensitivity and 87.5% specificity rate. Those with higher erythrocyte sedimentation rate, C-reactive protein, shorter duration of joint symptoms post-NSAID therapy, and without relapse when NSAID’s were stopped, were diagnosed as having ARF rather than PSRA. Widespread present-day management of PSRA is antibiotic prophylaxis for 1 year as recommended by the American Heart Association. Small numbers of individuals, primarily children, have been reported to develop cardiac valvular disease. Some clinicians, however, alter this proposed treatment regimen and extend antibiotic treatment for as long as 2 years or simply choose to manage these individuals as typical patients with ARF without carditis. In 2009, van Bemmel et al prospectively analyzed 75 adults with PSRA not given antibiotic prophylaxis compared with a control population. There was no increased risk of valvular heart disease in those with PSRA. Any proposed recommendations for therapy for PSRA must be linked to a reliable diagnosis. At this time, there is no validated definition of PSRA. Barash et al and her group’s effort to differentiate ARF from PSRA comes the closest yet. A weakness of their study, however, is that the same population was used to both test and generate the outcome equation. They also concluded that their results need validation in a prospective study. So what’s the clinician to do with this suggestive but inconclusive information? What the diagnostician has always done: assemble the available facts as reliably as possible, follow the patient

Pachydermatodactyly Mimics Polyarticular Juvenile Idiopathic Arthritis

Pachydermatodactyly is an infrequently recognized disorder characterized by painless swelling of the soft tissues around the proximal interphalangeal joints. We report 2 cases erroneously diagnosed as polyarticular juvenile idiopathic arthritis, then referred to pediatric rheumatology for further assessment because of lack of improvement after initial treatment.

Neurological Complications of Rheumatic Disease

Rheumatic disease represents a broad spectrum of systemic conditions manifested by multisystem involvement and mediated by autoimmunity and inflammation. Their neurological complications may occur at any point in the disease process and are diagnostically challenging. For years central nervous system (CNS) was considered as a system uniquely protected from effects of the immune system because of the blood-brain barrier. Indeed, under physiological conditions immune access to CNS is tightly regulated. Over the past decade, new scientific discoveries highlighted pathways by which immune and neurological systems interact, including a variety of mechanisms controlling permeability of blood-brain barrier, and specific roles that CD4+ and CD8+ T-lymphocytes play in initiation of specific adaptive immune response to neural specific antigens. This leads to release of proinflammatory cytokines (interleukin 1, interleukin 6, and tumor necrosis factor alpha). In addition, B-cells involved in CNS inflammation produce antibodies against membrane bound and soluble antigens. This article describes specific neurological manifestations of the most common autoimmune rheumatic disorders.

PW02-002 - Single MVK mutation and recurrent fevers

HyperIgD syndrome is an autoinflammatory disorder caused by mutations in the MVK gene. While mutations in most patients follow autosomal recessive inheritance, we have identified a cohort of patients with recurrent fevers and only 1 mutation in the MVK gene.