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Background: Cutaneous eruptions in neonatal lupus erythematosus (NLE) are thought to be self-resolving. Limited literature suggests cutaneous changes may persist.Objective: To characterize cutaneous residua in NLE and identify predictors for their development.Methods: A retrospective cohort study of patients with cutaneous NLE born between January 1980 and May 2017 was performed. Primary outcome was the proportion of patients with cutaneous residua. Secondary outcomes included associations/predictors of sequelae.Results: At the last follow-up, at a mean age of 4 years (range, 0.5-18.7 years), 34% of 106 patients had cutaneous sequelae, 13% had telangiectasia, 17% had dyspigmentation, and 9% had atrophic scarring. Scarring at the last follow-up was significantly associated with the presence of skin lesions at birth (P < .001).Limitations: This study was limited by the retrospective design, short follow-up duration in a subset of patients, and small sample size.Conclusion: Cutaneous NLE can exhibit long-term cutaneous residua. These findings underlie the importance of accurate diagnosis, long-term monitoring, and appropriate counseling. [ABSTRACT FROM AUTHOR]

Objectives: The (ever) prevalence of neuropsychiatric systemic lupus erythematosus (NPSLE) can vary widely depending on the definition used. We determined the prevalence of NPSLE in 1000 Faces of Lupus, a large multicenter Canadian cohort. Methods: Adults enrolled at 10 sites who satisfied the American College of Rheumatology (ACR) classification for systemic lupus erythematosus (SLE) were included. NPSLE was defined as (i) NPSLE by ACR classification criteria (seizures or psychosis), (ii) ACR, SLEDAI (seizure, psychosis, organic brain syndrome, cranial nerve disorder, headache, and cerebrovascular accident (CVA)), SLAM (CVA, seizure, cortical dysfunction, and headache), and SLICC (cognitive impairment, psychosis, seizures, CVA, cranial or peripheral neuropathy, and transverse myelitis) with and (iii) without minor nonspecific NPSLE manifestations (including mild depression, mild cognitive impairment, and electromyogram-negative neuropathies), and (iv) by ACR and SLEDAI neuropsychiatric (NP) indexes alone. Factors associated with NPSLE were explored using regression models. Results: Cohort size was 1253, with mean disease 12 ± 10 years, mean age 41 ± 16 years, and 86% female. Subgroup size was dependent on the specific definition of NPSLE. Prevalence of NPSLE was 6.4% in group (i), n = 1253 (n = 80); 38.6% in group (ii), n = 681(n = 263); 28.7% in group (iii), n = 586 (n = 168); and 10.2% in group (iv), n = 1125 (n = 115). In univariate analysis, Aboriginals had a nearly 2-fold increase in frequency of NPSLE in all groups. Education level and income were not associated with NPSLE (P = 0.32 and 0.03, respectively). As well, number of ACR criteria, SLAM, age at diagnosis, disease duration, and gender were not associated with NPSLE. Anti-Ro was significantly associated in groups (i) and (iv) and antiphospholipid antibodies (aPL) were increased in groups (i), (ii), and (iii); however, this lost significance when thromboembolic events were excluded from SLICC, SLEDAI, and SLAM indexes. In group (iv), absence of anti-Sm was significant. In multivariate analysis, anti-Ro and aPL (i) and anti-Ro+ and lack of anti-Sm (iv) were significant. NPSLE was not increased in those with +anti-DNA, La, or ribonucleoprotein (RNP), lupus anticoagulant (LAC), or anticardiolipin (aCL) antibody. Conclusions: The prevalence and factors associated with NPSLE varied depending on the definition used, was highest in Aboriginals, and may be higher if +anti-Ro or aPL are present. SLAM and SLICC include mild subjective disease manifestations, which contributed to a 10% higher prevalence of NPSLE compared to a more strict definition. NPSLE may be less in this database than other publications as its overall prevalence may be decreasing, or because of selection bias inherent to those who enter an observational cohort. NPSLE was associated with aPL and often anti-Ro and varied by ethnicity. [Copyright &y& Elsevier]

Objectives: We prospectively examined the prevalence and outcome of untreated fetal atrioventricular (AV) prolongation in the presence of maternal anti-Ro antibodies. Background: It has been suggested that antibody-mediated congenital complete atrioventricular block (CAVB) may be preventable if detected and treated early when low-grade block is present. With this rationale in mind, dexamethasone has been advocated by others to treat prolonged fetal AV conduction >2 z-scores, consistent with first-degree heart block. Methods: Between July 2003 and June 2009, 165 fetuses of 142 anti-Ro/La antibody–positive women were referred to our center for serial echocardiography. Our protocol included weekly evaluation of the fetal AV conduction between 19 (range 17 to 23) and 24 (range 23 to 35) gestational weeks. AV times were compared with institutional reference data and with post-natal electrocardiograms. Results: Of 150 fetuses with persistently normal AV conduction throughout the observation period, a diagnosis of CAVB was subsequently made in 1 at 28 weeks, after the serial evaluation had ended. Of 15 untreated fetuses either with AV prolongation between 2 and 6 z-scores or with type 1 second-degree block, progressive heart block developed in none of them. Three of these 15 fetuses (20%) had a neonatal diagnosis of first-degree block that spontaneously resolved (n = 2) or has not progressed (n = 1) on follow-up examinations. No other cardiac complications were detected. Conclusions: Fetal AV prolongation did not predict progressive heart block to birth. Our findings question the rationale of a management strategy that relies on the early identification and treatment of fetal AV prolongation to prevent CAVB. [ABSTRACT FROM AUTHOR]

Purpose: To describe the clinical features of uveitis in patients with juvenile idiopathic arthritis (JIA). Methods: Retrospective chart review of a subset of 1,081 consecutive JIA patients who were younger than 18 years of age and had uveitis, with a minimum of 1-year follow-up at a single center. Results: One hundred forty-two patients (13.1%) developed uveitis after a mean follow-up of 6.3 years (range, 0.10-23.2). Uveitis types were chronic anterior (97/142, 68.3%), acute anterior (23/142, 16.2%), recurrent anterior (17/142, 12%), and panuveitis (5/142, 3.5%). Uveitic complications were observed in 37.3% of cases (53/142) and 32.5% of eyes (74/228). When we compared uveitic eyes with complications to uveitic eyes without complications, we found the following significant differences: time interval from diagnosis of JIA to diagnosis of uveitis was shorter (mean, 1.3 years vs. 2.2 years; p = 0.003) and use of oral prednisone was greater (59.1% vs 15.6%; p < 0.0001) in the eyes with complications. Twenty-one children (21/142, 14.8%) with uveitis underwent a total of 62 ocular surgeries. Good visual acuity (20/40 or better) was found in 90.8% of eyes (159/175) and in both eyes of 87% of cases (94/108), impaired visual acuity in 6 eyes of 4 cases (6/175, 3.4%), and blindness in 10 eyes of 10 cases (10/175, 5.7%). Only 2 patients had reduced visual acuity in both eyes. Surgery was the single most important risk factor for reduced visual acuity at the last follow-up (p = 0.0086). Conclusions: Most uveitic eyes with JIA achieved good visual outcome despite uveitic complications. [Copyright &y& Elsevier]

Objectives: To determine the frequency and characteristics of clinical signs, symptoms, laboratory findings, and medication use in children with pediatric systemic lupus erythematosus (pSLE) at presentation and during the course of the disease, and to examine correlations among disease manifestations, disease activity, and damage over time. Study design: The study involved an analysis of medical records and the SLE database of an inception cohort of 256 patients with pSLE (female:male ratio, 4.7:1). Results: The most common clinical manifestations were arthritis (67%), malar rash (66%), nephritis (55%), and central nervous system (CNS) disease (27%). At diagnosis, patients with both renal and CNS disease had the highest SLE Disease Activity Index (SLEDAI) scores (P < .0001), but these scores were similar to those of the total group at 1 year (P = .11). Patients who developed renal and CNS disease more than 1 year after diagnosis had higher SLEDAI scores at disease onset. Some 34% of patients had Systemic Lupus International Collaborative Clinics Damage Index (SLICC-DI) scores >1 at a mean follow-up of 3.5 years. A greater proportion of patients with renal and CNS disease had SLICC-DI scores of >1, and these patients had higher mean scores compared with patients without major organ involvement (70% vs 11% [P < .0001] and 1.4 vs 0.1 [P < .0001], respectively). Conclusions: Most of the patients in our cohort exhibited major organ involvement. These patients had the highest SLEDAI scores at diagnosis, which normalized at 1 year but preceded development of renal and CNS disease. The average SLICC-DI score was lower than that previously reported in patients with pSLE. [Copyright &y& Elsevier]

We describe 3 patients who presented with features of macrophage activation syndrome (MAS) at the time of presentation of systemic lupus erythematosus (SLE), systemic juvenile idiopathic arthritis, and Kawasaki disease. Immunohistochemical studies in the patient with SLE demonstrated extensive expression of CD163 on hemophagocytic macrophages, suggesting a possible role as a marker of MAS. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to document the association of endocardial fibroelastosis (EFE) and maternal autoantibodies.: BackgroundNeonatal lupus erythematosus is associated with the transplacental passage of maternal anti-Ro and anti-La antibodies, leading to complete atrioventricular block (CAVB). In some cases, CAVB is associated with EFE. Isolated EFE may be independently related to maternal anti-Ro and anti-La antibodies.: MethodsWe identified three cases (one fetus and two infants, all female) of isolated EFE in infants born to autoantibody-positive mothers in the absence of CAVB. Demographics, echocardiograms, and pathology were reviewed. Immunohistochemical analyses for immunoglobulin (Ig)G, IgM, IgA, T-cell, B-cell, and terminal deoxynucleoleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) (test for cell apoptosis) staining were performed on multiple sections of the heart in each case and compared with negative controls.: ResultsTwo cases died and one received a cardiac transplant. All three cases had histologically confirmed EFE. All cases demonstrated significant diffuse IgG infiltration. To a lesser extent, myocardial tissue was also positive for IgM, CD43, and Granzyme B. None of the specimens were TUNEL positive.: ConclusionsThese are the first reported cases of isolated EFE associated with maternal anti-Ro and anti-La antibodies in the absence of CAVB. The diffuse deposition of IgG and the presence of a T-cell infiltrate throughout the myocardium suggest that the transplacental passage of maternal autoantibodies induces an immune reaction within the myocardium, leading to isolated EFE. Autoantibody-mediated EFE may be an etiologic factor in cases of fetal and neonatal “idiopathic” dilated cardiomyopathy. [Copyright &y& Elsevier]

Electrocardiograms taken at rest of 2 children with transplacental exposure to anti-Ro antibody but 1:1 atrioventricular conduction demonstrated sinus node disease. Treadmill exercise testing of 28 patients with congenital complete heart block found 3 patients with chronotropic incompetence of the sinus node. [ABSTRACT FROM AUTHOR]

: ObjectivesWe reviewed our institution’s experience with isolated (congenital) third-degree atrioventricular block (CAVB) to identify pre- and post-natal predictors of mortality and the requirement for pacemakers in infancy and childhood.: BackgroundBecause of the relative rarity of the disease, there is a paucity of data concerning the outcome of fetuses and children with isolated CAVB.: MethodsThe medical records of all cases of CAVB encountered at our institution from January 1965 to December 1998 were analyzed.: ResultsOf 102 cases identified, 29 were diagnosed in utero (F) at 26.1 ± 5.6 weeks gestation, 33 as neonates (N; ≤28 days), and 40 as children (C) at 5.7 ± 4.8 years of age. Anti-Ro and/or anti-La were present in 95% of F and 90% of N, but only in 5% of C mothers tested (p < 0.0001). Patients with CAVB having F, N and C diagnosis had a mortality of 43%, 6% and 0%, respectively, in the first two decades of life. Increased mortality risk was associated with a fetal diagnosis of CAVB (13/15 deaths; p < 0.05), fetal hydrops (6/6 cases; p < 0.0001), endocardial fibroelastosis (5/5 cases; p < 0.0001) and delivery at ≤32 weeks (4/6 cases; p < 0.05). Timing of pacemaker implantation differed significantly among F versus N (p < 0.05) and N versus C (p < 0.001) cases. At 20 years of age only 11% and 12% of CAVB patients with N and C diagnosis, respectively, were not paced.: ConclusionsPre-natal diagnosis of CAVB is associated with high fetal and neonatal mortality. Among survivors, whether the diagnosis is made before or after birth, most undergo pacemaker implantation by adulthood, with earlier intervention and a significantly greater need for reintervention among those diagnosed in utero. [Copyright &y& Elsevier]

Objectives: Physicians often assess the effectiveness of treatments on a small number of patients. Multiple-baseline designs (MBDs), based on the Wampold--Worsham (WW) method of randomization and applied to four subjects, have relatively low power. Our objective was to propose another approach with greater power that does not suffer from the time requirements of the WW method applied to a greater number of subjects. Study Design and Setting: The power of a design that involves the combination of two four-subject MBDs was estimated using computer simulation and compared with the four- and eight-subject designs. The effect of a delayed linear response to treatment on the power of the test was also investigated. Results: Power was found to be adequate (>80%) for a standardized mean difference (SMD) greater than 0.8. The effect size associated with 80% power from combined tests was smaller than that of the single four-subject MBD (SMD = 1.3) and comparable with the eight-subject MBD (SMD = 0.6). A delayed linear response to the treatment resulted in important reductions in power (20--35%). Conclusions: By combining two four-subject MBD tests, an investigator can detect better effect sizes (SMD = 0.8) and be able to complete a comparatively timelier and feasible study. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to evaluate the outcome of maternal autoantibody-mediated fetal cardiomyopathy/endocardial fibroelastosis following intravenous gamma globulin (IVIG) and corticosteroid therapy. Background: We have previously shown that 85% of fetuses and infants with maternal autoantibody-mediated fetal cardiomyopathy/endocardial fibroelastosis suffer demise or need for transplant. In an attempt to improve this outcome, in 1998, we began to empirically treat affected patients with IVIG and corticosteroids. Methods: We reviewed the clinical records and echocardiograms of 20 affected patients encountered in our institutions and treated with IVIG and corticosteroids from 1998 to 2009. Results: All 20 were initially referred at a median gestational age of 23 weeks (range 18 to 38 weeks). Nineteen mothers were anti-Ro antibody positive, 8 anti-La antibody positive, and 7 had clinical autoimmune disease. Endocardial fibroelastosis was seen in 16 and was not obvious in 4 others with reduced ventricular function, and 16 (80%) had reduced or borderline ventricular shortening fraction (≤30%) before or after birth. Eighteen had atrioventricular block at referral (16 in 3°). During pregnancy, maternal IVIG was given in 9 and dexamethasone in 17. After birth, 17 infants received IVIG (n = 14) and/or corticosteroids (n = 15). Twelve underwent pacemaker implantation. Four with hydrops at presentation died perinatally, despite initial improvement in function in 3. At a median follow-up of 2.9 years (1.1 to 9.8 years), 16 (80%) patients are currently alive with normal systolic ventricular function and 6 are not paced. Conclusions: Treatment of maternal autoantibody-mediated fetal cardiomyopathy/endocardial fibroelastosis with IVIG and corticosteroids potentially improves the outcome of affected fetuses. Further studies are needed to determine the optimal dose and timing of IVIG administration. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to determine whether cardiac complications of neonatal lupus erythematosus (NLE) are related to maternal anti-Ro and anti-La autoantibody-levels. Background: Autoantibody-positive mothers are frequently referred for serial echocardiography because of the elevated fetal risk of developing immune-mediated heart block. Little is known why only some and not all offspring are affected. Methods: All cases referred since 2000 for serial fetal echocardiography or cardiac complications related to maternal antibodies were included. Patients without cardiac NLE (group 1) and with cardiac NLE (group 2) were compared. Antibody levels were measured by enzyme-linked immunosorbent assay with a cutoff value of 8 U/ml for a positive test result. Results: Group 1 included 146 serially screened fetuses with normal pregnancy outcomes. Group 2 consisted of 40 fetuses/neonates with a diagnosis of heart block or endocardial fibroelastosis or both, and included 4 fetuses diagnosed during serial screening. All cardiac complications were associated with moderate (≥50 U/ml; 15%) or high (≥100 U/ml; 85%) maternal anti-Ro levels, independently of anti-La antibody titres. The event rate of complete heart block was 5% for prospectively screened fetuses with Ro-values ≥50 U/ml (odds ratio: 7.8) and 0% for fetuses with lower titres (p < 0.0001). Infants with pre-natal exposure to high-titre anti-La levels ≥100 U/ml were the most likely to have noncardiac features of NLE (event rate: 57%; odds ratio: 4.7). Conclusions: Our findings support that the amount of maternal antibodies, rather than their presence, is associated with fetal tissue injury. As anti-Ro levels correlate with the risk of cardiac complications, serial echocardiography should be limited to women with high anti-Ro-titres. [Copyright &y& Elsevier]