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.

Childhood primary angiitis of the central nervous system with metachronous hemorrhagic infarcts: a postmortem study with clinicopathologic correlation.

This neuropathologic case study illustrates the discovery of metachronous hemorrhagic infarcts insinuating round mass-like lesions by magnetic resonance imaging in the setting of childhood primary angiitis of the central nervous system (cPACNS) raising diagnostic awareness of this unusual presentation in a clinical and neuroimaging context. The report underscores the importance of recurrent vasculitis-induced ischemic brain damage as a pathologic correlate of relapsing cPACNS and offers a critical reappraisal of common imitators as well as a clinicopathologic approach to differential diagnosis. Attention is drawn to the caveat that although magnetic resonance imaging findings at initial presentation may not be typical for stroke, they later exhibit attributes of cerebral infarction at both the subacute and chronic stages. A pattern of cPACNS characterized predominantly by multiple petechial-like cortical hemorrhages with pathologic features of hemorrhagic infarcts is recognized. The present study lends credence to the practice of a rigorous autopsy-based approach aimed at a better understanding of the anatomic pathology and biology of cPACNS and at facilitating prospective neuroimaging and biopsy-based surgical pathology correlations, ultimately enhancing diagnostic accuracy in clinical settings. Although PACNS is, by definition, a diagnosis of exclusion, it should be considered from the outset in the differential diagnosis of ischemic stroke or hemorrhagic stroke or of unusual and relapsing intra-axial mass-like CNS lesions in children, necessitating appropriate pathologic evaluation of brain biopsy specimens.

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

BACKGROUND: This 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). METHODS: Children aged ≥2 to <18 years 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 (≤6 months) 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. RESULTS: A total of 274 patients (nsNSAID, n = 219; celecoxib, n = 55) 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. CONCLUSIONS: The 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 REGISTRATION: ClinicalTrials.gov identifier NCT00688545.

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.

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.

Successful treatment of severe or methotrexate-resistant juvenile localized scleroderma with mycophenolate mofetil.

OBJECTIVE: To evaluate the efficacy of mycophenolate mofetil (MMF) in the treatment of severe refractory juvenile localized scleroderma (JLS). METHODS: A retrospective chart review was performed in patients with JLS who had been treated with MMF after the failure of a combination of MTX and corticosteroids for at least 4 months, or whose JLS had concomitant severe extracutaneous manifestations. Outcome was assessed through clinical examination and thermography. Adverse events were recorded. RESULTS: Ten patients (six females and four males) were enrolled in the study. JLS clinical subtypes were deep morphoea (two patients with disabling pansclerotic morphoea), generalized morphoea (three patients), linear scleroderma (five patients) affecting the limbs in two and face in three patients (en coup de sabre). The age at onset of disease was 8 (range 2-16) years, and the disease duration at the time of treatment with MMF was 18 (range 8-62) months. All MMF-treated patients experienced clinical improvement that allowed withdrawal or reduction of doses of corticosteroids and MTX. Over a follow-up of 27 (range 6-36) months, mild abdominal discomfort was reported in only one patient. CONCLUSIONS: MMF appears to be effective in arresting disease progression in severe or MTX-refractory JLS and is generally well tolerated. Further controlled studies are needed to confirm these data.