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Background There are no validated screening measures for depressive or anxiety disorders in childhood Systemic Lupus Erythematosus (cSLE). We investigated cross-sectionally (1) the prevalence of depressive and anxiety disorder in cSLE. (2) the validity of the Centre for Epidemiologic Studies Depression Scale for Children (CES-DC) and the Screen for Childhood Anxiety and Related Disorders (SCARED) measures in identifyingthese disorders. Methods Participants 8-18 years with cSLE/incipient cSLE completed CES-DC, SCARED, and Quality OfMy Life (QOML) measures. Parents completed the SCARED-Parent measure. Diagnosis was by gold-standard psychiatric interview and determined prevalence of psychiatric disorder. Receiver Operating Characteristics Area under the Curve (ROCAUC) evaluated screening measure diagnostic performance. Results Ofseventy-two parent-child dyads, 56 interviews were completed. Mean screen scores were: CES-DC = 15 (range 1-49, SD 12), SCARED-C = 22 (range 2-61, SD 14), SCARED-P = 13 (range 0-36, SD 8). Depressive disorder screen positivity (CES-DC ≥ 15) was 35% (vs. prevalence 5%). Anxiety disorder screen positivity (SCARED ≥ 25) was 39% (vs. prevalence 16%). CES-DC ROCAUC = 0.98 and SCARED-C ROCAUC = 0.7 (cut-points 38 and 32 respectively). Conclusions Diagnostic thresholds for depressive and anxiety disorderscreening measures are high for both CES-DC and SCARED-C in cSLE. Brief focused interview should follow to determine whether psychiatric evaluation is warranted.

Neuropsychiatric (NP) manifestations are found in approximately 25% of children and adolescents with pediatric SLE (pSLE). In 70% of those, NP involvement will occur within the first year from the time of diagnosis. Headaches (66%), psychosis (36%), cognitive dysfunction (27%) and cerebrovascular disease (24%) are the most common presentations. The support of a psychiatrist is often required. Anti-phospholipid antibodies are associated with distinct NP disease entities and may be implicated in the pathogenesis of several manifestations of NP-pSLE including chorea, cerebrovascular disease and seizures. The role of novel auto-antibodies and imaging modalities is currently explored. The treatment of NP-pSLE is not based on prospective studies; however, an immunosuppressive combination therapy consisting of high doses of prednisone and a second line agent such as cyclophosphamide or azathioprine is commonly suggested for children with NP-pSLE. The role of novel therapies is currently studied. The outcome of children with NP-pSLE is relatively good. The overall survival is 95—97%, 20% of children experience a disease flare during childhood and 25% have evidence of permanent neuropsychiatric damage. Lupus (2007) 16, 564—571.

The antiphospholipid syndrome (APS) is recognized increasingly as the most common acquired hypercoagulation state of autoimmune etiology and may occur as an isolated clinical entity (primary APS) or in association with an underlying systemic disease, particularly systemic lupus erythematosus (SLE). The major differences between pediatric and adult APS include absence of common acquired risk factors for thrombosis, absence of pregnancy-related morbidity, increased incidence of infection-induced antibodies, differences in cut-off values for determination of aPL and specific factors regarding long-term therapy in children. APS in children has been largely reported in patients with arterial or venous thromboses and less frequently in association with neurological or hematological manifestations. The presence of aPL in pediatric SLE can modify the disease expression and may be an important predictor of the development of irreversible organ damage. Two recently established international registries of neonates and children with APS provide a good opportunity to conduct large, prospective studies on the clinical significance of aPL and long-term outcome of pediatric APS. Lupus (2007) 16, 627—633.

Objectives Autoimmune thrombocytopenia (AITP) and hemolytic anemia (AIHA) are common in childhood-onset systemic lupus erythematosus (cSLE) and may be refractory to conventional therapies. Our objectives were to: (a) examine our experience; (b) determine the rate and durability of response to rituximab; and (c) evaluate its safety in our cSLE population with refractory cytopenias. Methods We performed a single-center retrospective cohort study of cSLE patients with refractory AITP or AIHA treated with rituximab between 2003 and 2012. Outcomes included the time to complete clinical response, time to B-cell depletion, duration of response and time to flare. Adverse events were also analyzed. Results Twenty-four (6%) of 394 cSLE patients received rituximab for refractory cytopenia. The indication was AITP in 16 (67%), AIHA in five (21%) and both in three (13%) patients. The median (interquartile range (IQR)) time from cytopenia onset to rituximab therapy was 16 (7–27) months for AITP and 10 (2–29) months for AIHA. Complete response following the first course of rituximab occurred at a median (IQR) of 48 (14–103) days, only one patient failed to respond. Five (21%) patients had one or more flare episodes at 22 (15–27) months. Infusion reactions were rare and one infection with herpes zoster required hospitalization in the first 12 months. Three of four patients with low IgG levels prior to the first rituximab course developed persistent hypogammaglobulinemia, and three patients have required intravenous immunoglobulin replacement. Conclusion Rituximab appears to be a well-tolerated, safe and long-lasting therapy for cSLE patients with refractory AITP and/or AIHA. Caution should be exercised when considering rituximab for patients with preexisting hypogammaglobulinemia.

Cytomegalovirus (CMV) is a beta-herpesvirus and antibodies to this virus are common in patients with systemic lupus erythematosus (SLE). However, few studies have examined the relationship between CMV infection and SLE. Objectives Our objectives were: 1) to determine the prevalence of CMV infection at the time of SLE diagnosis, and 2) to determine the risk factors for CMV infection. Methods A database review of 670 patients with pediatric SLE (pSLE) seen over a 20-year period identified seven patients with a CMV infection detected at the time of diagnosis of SLE. CMV was diagnosed by serology, urine and bronchoalveolar lavage. Clinical manifestations, laboratory findings, virology studies and treatments were reviewed. Results CMV infection was detected in seven patients at the time of SLE diagnosis (1.04% of total cohort): six were female: mean age was 13 years. Predominant features included non-Caucasian ethnicity ( p Conclusions There were 1.04% of patients with pSLE who developed CMV infection. All were of non-Caucasian ethnicity. Persistent fever despite prednisone, with concomitant anemia, may be additional clues to CMV infection in pSLE. We suggest all patients have routine testing for CMV immunity at initial presentation of pSLE.

Autoantibodies targeting the proliferating cell nuclear antigen have been considered as a specific biomarker for systemic lupus erythematosus, and were historically identified by indirect immunofluorescence and then confirmed by other more specific immunoassays. Our objective was to investigate the anti-PCNA immune response in various disease conditions. Unselected sera referred to a clinical diagnostic laboratory and other sera from various diseases cohorts and controls were tested for anti-PCNA antibodies by enzyme-linked immunosorbent assay (ELISA), line immunoassay (LIA) and an addressable laser bead assay (ALBIA) using full-length human proliferating cell nuclear antigen. Two out of 2500 sequential, unselected sera (0.07%) referred to a diagnostic laboratory for autoantibody analysis showed a proliferating cell nuclear antigen-like staining pattern. Good agreement was found between ELISA, ALBIA and LIA. At cut-off values resulting in 100% specificity, 52.5% (ELISA), 42.5% (ALBIA) and 35% (LIA) of samples with a proliferating cell nuclear antigen-like indirect immunofluorescence staining pattern were positive. In the indirect immunofluorescence proliferating cell nuclear antigen immunoblot (IB)-positive group, anti-PCNA antibodies were frequently accompanied by anti-Ro52, and in the indirect immunofluorescence PCNA-negative but LIA PCNA-positive group by various other autoantibodies. The prevalence of anti-PCNA antibodies was highest in Sjögren’s syndrome (5.0%). In conclusion, the proliferating cell nuclear antigen-like staining pattern was rarely found (0.07%) in sequential, unselected sera. Further, indirect immunofluorescence is not an accurate screening method to identify anti-PCNA antibodies as their presence may be masked by other autoantibodies. The specific association of anti-PCNA antibodies with systemic lupus erythematosus was not confirmed in our study. Lupus (2010) 19, 1527—1533.

Paediatric patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPL), specifically lupus anticoagulants(LAC) are at high risk of developingthromboembolicevents (TE). Our objectiveswere to determine the prevalenceof TE in paediatricSLE patientswith LAC and to determine if anticoagulation was effective to decrease morbidity, and prevent recurrent TE. We reviewed data on 149 paediatric SLE patients treated over 10 years. In all, 24 patients (16%) were LAC positive, and 21 TE occurred in 13 of these LAC positive patients (54% incidence of TE in LAC positive patients). The events were cerebral venous thrombosis (9), arterial stroke (3), deep venous thrombosis (4), pulmonary embolism (2), other venous event (1) and other arterial events (2). The median duration between SLE diagnosis and first TE was 15.2 months (range 0-62), and the median age at first TE was 15.1 years (range11.4-18.4). Long-termanticoagulationwas prescribed, and eight patients (62%) were transferred to adult care on lifelong oral warfarin; four (31%) remain under our care on lifelong warfarin, and one patient died of causes unrelated to her TE. No patient has been identified with deficiencies of protein C, protein S or antithrombinIII. One patient is heterozygousfor Factor V Leiden, and one is heterozygous for both the Prothrombin 20210A mutation and the MTHFR (methylene tetrahydrofolate reductase) mutation. Four patients had recurrent TE (31%), and three were not anticoagulated at the time of their second event. One patient had two recurrences on therapeuticanticoagulation.Thromboembolic events are prevalent in the LAC positive paediatric SLE population, and consideration for lifelong anticoagulation must occur after an initial TE.