Faculty Bibliography

PURPOSE OF REVIEW: To provide new insights into pathogenesis, prevention and management of cardiac manifestations of neonatal lupus (cardiac neonatal lupus) and issues pertinent to all anti-SSA/Ro positive individuals of childbearing age. RECENT FINDINGS: Antibody specificity with high risk for cardiac neonatal lupus remains elusive, but high titers of Ro60, Ro52 or Ro52p200 antibodies appear to be required. Varying antibody specificities to the p200 region of Ro52 can induce first-degree block in a rodent model. In consideration of the contribution of macrophages to inflammation and fibrosis in cardiac neonatal lupus, hydroxychloroquine (HCQ) is being considered as preventive therapy. Cord blood biomarkers support the association of fetal reactive inflammatory and fibrotic components with the development and morbidity of cardiac neonatal lupus. Data from U.S. and French registries do not provide evidence that the prompt use of fluorinated steroids in cases of isolated block significantly alters fetal/neonatal morbidity or mortality. SUMMARY: The search for a high-risk cardiac neonatal lupus antibody profile remains, but high-titer antibodies to Ro60 and R052 are a consistent finding, and this may guide the need for fetal echocardiographic surveillance. The uniform use of fluorinated steroids to prevent progression of cardiac neonatal lupus or reduce mortality does not appear justified. HCQ, based on diminishing an inflammatory component of cardiac neonatal lupus, is under consideration as a potential preventive approach.

While the relationship between maternal connective tissue diseases and neonatal rashes was described in the 1960s and congenital heart block in the 1970s, the "culprit" antibody reactivity to the SSA/Ro-SSB/La ribonucleoprotein complex was not identified until the 1980s. However, studies have shown that approximately 10-15% of cases of congenital heart block are not exposed to anti-SSA/Ro-SSB/La. Whether those cases represent a different disease entity or whether another antibody is associated has yet to be determined. Moreover, the cutaneous manifestations of neonatal lupus have also been identified in infants exposed only to anti-U1RNP antibodies. In this review, we describe what we believe to be the first case of congenital heart block exposed to maternal anti-U1RNP antibodies absent anti-SSA/Ro-SSB/La. The clinical and pathologic characteristics of this fetus are compared to those typically seen associated with SSA/Ro and SSB/La. Current guidelines for fetal surveillance are reviewed and the potential impact conferred by this case is evaluated.

Background Several studies have evaluated mortality and shortterm morbidity in neonatal lupus (NL), however there is minimaldata on long term outcomes in children exposed to maternalanti-Ro antibodies in utero. A previous pilot study utilising theResearch Registry for Neonatal Lupus (RRNL) raised concernregarding the development of autoimmune disease in childhood, however the numbers evaluated were small and the patientsstudied were young. This study was initiated to ascertain the current prevalence of autoimmune disease in NL children and theirunaffected siblings, and to evaluate whether fetal or maternal factors associated with the development of future autoimmunity.Materials and methods A retrospective cohort of family membersfrom the RRNL were contacted to evaluate for autoimmune disease. Follow-up questionnaires were completed which included35 items describing symptoms and diagnoses associated withautoimmunity in 138 cardiac NL children, 74 cutaneous NL children, and 134 unaffected siblings. Medical records were obtainedand evaluated from the patient's physicians to confirm diagnoses.Maternal diagnosis of systemic lupus and/or Sjogren's syndromeand fetal cardiac disease severity based on a previously describedseverity score were associated with postnatal autoimmune diseases using chi square and Mann-Whitney analyses.Results Seventeen (8.0%) of NL affected children developed anautoimmune disease at the time of follow up (mean age 11.6+/-9.0 years). These included 3 patients with SLE, 1 with JIA, 3with thyroid disease, 5 with psoriasis, 1 with IBD, 1 with uveitis,1 with UAS and 2 with type 1 DM. Six (4.5%) unaffected siblingsdeveloped an autoimmune disease (mean age 10.6+/-7.1 years),which included 1 with JIA, 1 with Sarcoidosis/ITP, 1 with Myasthenia Gravis/Celiac disease, 1 with psoriasis, 1 with UAS and1 with type 1 DM,. There was a significant association ofbetween having an autoimmune disease and having advancedheart block (11.0% vs. 4.2%, p = 0.03) and a trend towards anassociation with cardiac NL disease severity score (4.43+/-4.89 vs.2.58+/-4.24, p = 0.06). Mother's diagnosis of SLE or Sjogren'sdid not associate with the children's development of autoimmunedisease (p = 0.828).Conclusions Fetuses that develop advanced congenital heartblock as a manifestation of NL may be at greater risk for developing autoimmune diseases later in life. This could potentially relateto a genetic component that makes a Ro exposed fetus both moreprone to inflammatory effects of passive immunity and predisposes to future autoimmunity, independent of the mother's rheumatic disease status

OBJECTIVES: Extension of disease beyond the atrioventricular (AV) node is associated with increased mortality in cardiac neonatal lupus (NL). Treatment of isolated heart block with fluorinated steroids to prevent disease progression has been considered but published data are limited and discordant regarding efficacy. This study evaluated whether fluorinated steroids given to manage isolated advanced block prevented development of disease beyond the AV node and conferred a survival benefit. METHODS: In this retrospective study of cases enrolled in the Research Registry for NL, inclusion was restricted to anti-SSA/Ro-exposed cases presenting with isolated advanced heart block in utero who either received fluorinated steroids within 1 week of detection (N=71) or no treatment (N=85). Outcomes evaluated were: development of endocardial fibroelastosis, dilated cardiomyopathy and/or hydrops fetalis; mortality and pacemaker implantation. RESULTS: In Cox proportional hazards regression analyses, fluorinated steroids did not significantly prevent development of disease beyond the AV node (adjusted HR=0.90; 95% CI 0.43 to 1.85; p=0.77), reduce mortality (HR=1.63; 95% CI 0.43 to 6.14; p=0.47) or forestall/prevent pacemaker implantation (HR=0.87; 95% CI 0.57 to 1.33; p=0.53). No risk factors for development of disease beyond the AV node were identified. CONCLUSIONS: These data do not provide evidence to support the use of fluorinated steroids to prevent disease progression or death in cases presenting with isolated heart block.

INTRODUCTION: Participants who sustain a fragility fracture are at increased risk for subsequent fractures. Despite the consequences of recurrent fractures, bone mineral density (BMD) testing and treatment rates for osteoporosis after a fracture remain low. The New York University (NYU) Langone Osteoporosis Model of Care was developed to identify women at increased risk for recurrent fractures and to reduce the rates of subsequent fracture through patient and physician education. METHODS: Women aged 50 years and older who had a fracture and received their care at NYU affiliated hospitals were contacted via mail after discharge. Participants were provided educational materials explaining decreased bone strength and its possible relationship to their fracture and were asked to complete a questionnaire. One year postfracture, participants were sent follow-up questionnaires requesting their most recent fracture treatment and BMD information. Educational material was also provided to the treating orthopedic surgeons. RESULTS: Overall, 524 patients were contacted and 210 (40%) enrolled. By the end of 24 months, 92 participants completed their 1-year questionnaire (44% of the enrollees). Forty-two (46%) participants had undergone new BMD testing and 37 (40%) were receiving antiresorptive medications, including 6 (6%) who had not been prescribed these medications before enrolling in the program. CONCLUSIONS: The Osteoporosis Model of Care is a simple and cost-effective educational program, which improved comprehensive fracture care in an actual clinical setting. Patient enrollment remains a challenge in implementing the program. Our program highlights difficulties in providing community-dwelling participants with appropriate postfracture care. With increasing concern among the public regarding the use of bone strengthening medications and continued low postfracture treatment rates, educating patients with high fracture risk is critical to reducing the rate of subsequent fracture. Our Model of Care Program demonstrates both the success and limitations of a postfracture educational approach using discharge diagnosis data to identify patients with fracture.

BACKGROUND: Glucocorticoid-induced osteoporosis (GIO) is the most common secondary form of osteoporosis, and glucocorticoid users are at increased risk for fracture compared with nonusers. There is no established relationship between bone mineral density (BMD) and fracture risk in GIO. We used 3 Tesla (T) MRI to investigate how proximal femur microarchitecture is altered in subjects with GIO. METHODS: This study had institutional review board approval. We recruited 6 subjects with long-term (> 1 year) glucocorticoid use (median age = 52.5 (39.2-58.7) years) and 6 controls (median age = 65.5 [62-75.5] years). For the nondominant hip, all subjects underwent dual-energy x-ray absorptiometry (DXA) to assess BMD and 3T magnetic resonance imaging (MRI, 3D FLASH) to assess metrics of bone microarchitecture and strength. RESULTS: Compared with controls, glucocorticoid users demonstrated lower femoral neck trabecular number (-50.3%, 1.12 [0.84-1.54] mm(-1) versus 2.27 [1.88-2.73] mm(-1) , P = 0.02), plate-to-rod ratio (-20.1%, 1.48 [1.39-1.71] versus 1.86 [1.76-2.20], P = 0.03), and elastic modulus (-64.8% to -74.8%, 1.54 [1.22-3.19] GPa to 2.31 [1.87-4.44] GPa versus 6.15 [5.00-7.09] GPa to 6.59 [5.58-7.31] GPa, P < 0.05), and higher femoral neck trabecular separation (+192%, 0.705 [0.462-1.00] mm versus 0.241 [0.194-0.327] mm, P = 0.02). There were no differences in femoral neck trabecular thickness (-2.7%, 0.193 [0.184-0.217] mm versus 0.199 [0.179-0.210] mm, P = 0.94) or femoral neck BMD T-scores (+20.7%, -2.1 [-2.8 to -1.4] versus -2.6 [-3.3 to -2.5], P = 0.24) between groups. CONCLUSION: The 3T MRI can potentially detect detrimental changes in proximal femur microarchitecture and strength in long-term glucocorticoid users. J. MAGN. RESON. IMAGING 2015;42:1489-1496.