Rituximab therapy has a rapid and durable response for refractory cytopenia in childhood-onset systemic lupus erythematosus.

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 in pediatric systemic lupus erythematosus: prevalence and clinical manifestations.

UNLABELLED: 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 < 0.01 as compared to total SLE cohort), persistent fevers on prednisone in seven and nephrotic syndrome in four. Laboratory findings included: anemia in seven, lymphopenia in five, elevated liver enzymes in four, with anti-dsDNA and anti-RNP antibodies present in six and five, respectively. Six patients received ganciclovir and CMV hyperimmune globulin (Cytogam®) with the continuation of prednisone during CMV treatment. Six of seven fully recovered without sequelae (one without treatment) but one patient died with active CMV infection. 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.

Weight change associated with corticosteroid therapy in adolescents with systemic lupus erythematosus.

UNLABELLED: Physical appearance is very important to adolescents and weight gain secondary to corticosteroid (CS) treatment may have a direct impact on adolescent development. Understanding weight gain in adolescents with SLE who are being treated with CS will help clinicians develop strategies for prevention of nonadherence, obesity and eating disorders in this population. METHODS: Patients aged 11-18 years old with newly diagnosed SLE between January,1995 and December, 2006 were identified through the Rheumatology database at the Sickkids hospital, Canada. All charts were reviewed. Patients were categorized based on final BMI status as normal, overweight and obese. Risk factors for being obese were examined by logistic regression model analysis. RESULTS: Of 236 patients, 78% fulfilled the criteria. 85% were female with mean age at onset of diagnosis was 14 ± 1.7 years. Mean duration of CS treatment was 50 ± 31 months and mean cumulative CS dosage was 34.11 ± 32.7 g of prednisone. At baseline, 10% had BMI >25 kg/m(2) while at the end of the study, 20% were overweight and 10.4% were obese. In addition, 61% gained <10 kg while 15% gained ≥20 kg. Initial BMI was a significant predictors for final BMI (OR = 27.59, 95%CI = 6.04-126.09, p < .001) while male (OR = 8.50, 95%CI = 2.95-24.5, p < 0.000) and cumulative CS dosage (OR = 1.53, 95%CI = 1.05-2.23, p < .05) were the significant predictors for weight gain >10 kg. Duration of CS treatment did not correlate with obesity. CONCLUSION: Although a significant number of patients became overweight or obese after being treated with CS, most gained <10 kg. Obesity secondary to CS treatment in SLE patients was significantly correlated with baseline BMI, gender and cumulative CS dosage.

Early determinants of atherosclerosis in paediatric systemic lupus erythematosus.

OBJECTIVES: To assess traditional and non-traditional cardiovascular risk factors and to determine the prevalence and correlates of early vascular markers of atherosclerosis in paediatric systemic lupus erythematosus (pSLE). METHODS: Fifty-four adolescents with pSLE had cardiovascular risk factor assessment, disease activity and vascular testing including carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD), arterial stiffness measures, and myocardial perfusion studies. RESULTS: The traditional risk factors of hypertension, elevated triglycerides, apolipoprotein B, haemoglobin A1c and insulin levels and non-traditional risk factors of elevated homocysteine and fibrinogen were present (all p<0.001). Some arterial stiffness measures, central pulse wave velocity and characteristic impedance were elevated (p<0.001), but CIMT, FMD and myocardial perfusion were normal. Cumulative prednisone dose correlated with total cholesterol (r=0.5790, p<0.001) and elevated LDL-C (r=0.4488, p=0.0012). Hydroxychloroquine treatment correlated negatively with total cholesterol (r=-0.4867, p=0.0002), LDL-C (r=-0.4805, p=0.0002) and apolipoprotein B (r=-0.4443, p=0.0011). In multivariate analysis LDL-C correlated with cumulative prednisone dose and negatively with hydroxychloroquine treatment (R2=0.40, p<0.001). CONCLUSIONS: An increased burden of traditional and non-traditional risk factors and early evidence of insulin resistance and increased central arterial stiffness were present in paediatric SLE. Disease-specific and therapy-related factors are likely modifying these cardiovascular risk profiles warranting prospective longitudinal studies.

Risk factors for development of uveitis differ between girls and boys with juvenile idiopathic arthritis.

OBJECTIVE: Uveitis is the most common extraarticular manifestation of juvenile idiopathic arthritis (JIA) and is associated with considerable morbidity. The aim of this study was to examine the risk factors associated with uveitis in JIA. METHODS: We conducted a chart review of 1,047 patients with JIA from a single tertiary care pediatric rheumatology center for factors associated with the development of uveitis. Special emphasis was put on the following known risk factors: oligoarthritis, antinuclear antibody (ANA) status, sex, and age at the time of onset of JIA. RESULTS: The risk of uveitis developing was age dependent in girls but not in boys. Among girls, the risk was maximal (47%) in those who were ANA positive and were ages 1-2 years at the time of the onset of JIA; this risk decreased to <10% in those in whom the age at onset was >7 years. Only girls had an age-dependent and ANA-associated increased risk of uveitis. The time interval from the diagnosis of JIA to the diagnosis of uveitis was statistically significantly longer in patients in whom the onset of JIA occurred at a younger age (P = 0.04). This effect was even more pronounced in ANA-positive patients (P = 0.004). The JIA subtype did not influence a patient's risk of the development of uveitis. CONCLUSION: An age-associated risk of uveitis was observed only in girls who were younger than 7 years of age at the time of the onset of JIA. The duration of time between the diagnosis of JIA and the onset of uveitis was longer in patients in whom JIA was diagnosed at a younger age, especially in those who were ANA positive. We suggest that our findings have implications for uveitis screening in patients with JIA.

The benefits of transplacental treatment of isolated congenital complete heart block associated with maternal anti-Ro/SSA antibodies: a review.

Isolated congenital complete atrio-ventricular block (CAVB) is associated with the transplacental passage of maternal autoantibodies directed to foetal Ro/SSA ribonucleoproteins. Their interactions most likely trigger the inflammation of the atrio-ventricular node and the myocardium in susceptible foetuses. The inflamed tissues may then heal with fibrosis that may cause heart block, endocardial fibroelastosis, and dilated cardiomyopathy. CAVB, the most common cardiac complication, typically develops between 18 and 24 gestational weeks. Untreated, the condition carries a significant mortality risk as the foetus needs to overcome the sudden drop in ventricular rate, the loss of normal atrial systolic contribution to ventricular filling, and perhaps concomitant myocardial inflammation and fibrosis. The rationale to treat a foetus at the stage of CAVB is primarily to mitigate myocardial inflammation and to augment foetal cardiac output. Maternal dexamethasone administration has been shown to improve incomplete foetal AV block, myocardial dysfunction, and cavity effusions. Beta-sympathomimetics may be useful to increase the foetal heart rate and myocardial contractility. Published data from our institution suggest an improved survival >90% if maternal high-dose dexamethasone was initiated at the time of CAVB detection and maintained during the pregnancy and if a beta-adrenergic drug was added at foetal heart rates below 55 beats/min. Despite the improvement in outcome, there is an ongoing debate about treatment-related risks. In this review, we will appraise the natural history of untreated CAVB, discuss currently available management options, and examine the results and risks of in-utero treatment of antibody-mediated CAVB.

Novel diagnostic and clinical aspects of anti-PCNA antibodies detected by novel detection methods.

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.

Acute renal failure in paediatric systemic lupus erythematosus: treatment and outcome.

OBJECTIVE: To determine the outcome of paediatric SLE (pSLE) patients with nephritis who developed acute renal failure (ARF). Efficacy and safety of treatment regimens were compared. METHODS: A total of 249 pSLE patients were diagnosed and prospectively followed at a single centre between July 1973 and July 2003; 127 children (51%) had lupus nephritis. ARF was defined as serum creatinine of > 250 micromol/l or > 75% above baseline. Standardized assessments included clinical data and medications, laboratory testing, disease activity and damage scores were obtained. Subsequent renal flares were documented. PRIMARY OUTCOME: renal function at last follow-up. SECONDARY OUTCOMES: treatment efficacy and safety. AZA- and cyclophosphamide (CYCLO)-treated patients were compared. Propensity score methods were applied to balance covariates. An intention to treat approach was chosen. RESULTS: The ARF study cohort included 50 patients; 13 boys and 37 girls with a median age of 13.2 yrs at diagnosis and a mean follow-up of 45 months. Renal histology: Class III nephritis in 16; Class IV in 34. Dialysis requirement and disease activity were similar in both groups. TREATMENT: AZA in 33 patients, CYCLO in 9 and corticosteroids only in 8. OUTCOME: no statistically significant or clinically relevant differences were found for any of the outcome measures including last serum creatinine, time to renal flare, overall renal survival, disease activity over time, disease damage, mean annual corticosteroid dose and rate of infection. CONCLUSION: The treatment of renal failure in this pSLE cohort was associated with an excellent outcome. AZA and CYCLO were equally efficacious.

Corticosteroid use in childhood-onset systemic lupus erythematosus-practice patterns at four pediatric rheumatology centers.

OBJECTIVE: To evaluate corticosteroid prescribing patterns in childhood-onset systemic lupus erythematosus (SLE), comparing four academic pediatric rheumatology practices. METHODS: Patients with childhood-onset SLE (n=72) treated at four large pediatric rheumatology centers were studied at 3-month intervals for 18 months. Information on medication use, disease activity as measured by the SLEDAI and the SLAM; and disease damage by the SLICC/ACR Damage Index was collected. RESULTS: At the time of enrollment, patients at each center were similar for disease duration, age, frequency of renal involvement and disease damage. Prednisone (mean 9 mg/day) was continued during 72% of periods of inactive disease for at least 3 months (SLEDAI=0). Centers differed in the use of intravenous pulse methylprednisolone (p<0.0001). Even when adjusted for between-center differences in patient weight, race and disease activity, centers also significantly differed in the dose of prednisone (p<0.05). The center with the largest between-patient variability in the dose of prednisone prescribed to its patients showed the smallest between-patient variance in patient disease activity. CONCLUSIONS: Corticosteroids are commonly used for the treatment of childhood-onset SLE, even when the disease is inactive. There appears to be important between-center differences in the use of intravenous and oral corticosteroids for childhood-onset SLE therapy that cannot be explained by patient disease activity corticosteroid prescribing patterns influence disease control. Further studies are needed to determine whether differences in practice patterns lead to significant differences in longer-term disease outcomes with childhood-onset SLE.

Immunoregulatory T cells in man. Histamine-induced suppressor T cells are derived from a Leu 2+ (T8+) subpopulation distinct from that which gives rise to cytotoxic T cells.

One mechanism of histamine-mediated inhibition of the immune response in man is to activate T suppressor cells that bear the Leu 2 (OKT8) marker. The current study was undertaken to characterize the histamine-induced suppressor cell using a monoclonal antibody (9.3) shown previously to distinguish cytotoxic T cells from antigen-specific suppressor T cells. Leu 2+ cells isolated from peripheral blood were further separated with antibody 9.3 into Leu 2+, 9.3+, and Leu 2+, 9.3- subsets and each subset was incubated with different concentrations of histamine before determining their ability to suppress immune responses in vitro. The results indicate that the Leu 2+, 9.3- subpopulation includes all histamine-induced suppressor cells, that 10(-4) M histamine is the optimal concentration for suppressor cell induction, and that exposure of Leu 2+, 9.3- cells to histamine for 30 s is sufficient to initiate the induction process. After treatment with histamine these cells inhibit both phytohemagglutinin-induced T cell proliferation and pokeweed mitogen-induced B cell differentiation. The suppression of phytohemagglutinin-induced proliferation was resistant to x-irradiation with 1,200 rad, either before or after histamine exposure, suggesting that Leu 2+, 9.3- cells need not proliferate to become suppressor cells or exert suppression. Moreover, suppression by these cells was not due to altered kinetics of the response. Finally, a histamine type 2 receptor antagonist (cimetidine) but not a type 1 receptor antagonist (mepyramine) blocked the induction of suppressor cells. On the basis of these results and our previous studies of antigen specific suppressor cells, we conclude that Leu 2+ suppressor cells in man are derived from a precursor pool that is phenotypically distinct from cells that can differentiate into cytotoxic T cells.

Angiography of primary central nervous system angiitis of childhood: conventional angiography versus magnetic resonance angiography at presentation.

BACKGROUND AND PURPOSE: To systematically analyze conventional angiographic (CA) features of children with primary central nervous system angiitis (cPACNS), to compare and correlate CA and MR angiography (MRA) lesion characteristics, and to define the sensitivity and specificity of MRA with CA as a reference standard. METHODS: A retrospective, single-center cohort study of consecutive patients with cPACNS was performed. Patients with CA and MRA studies at diagnosis were included. Imaging studies were blindly reviewed by 2 neuroradiologists using a standard analysis protocol. CA and MRA studies were compared using nonparametric analysis. RESULTS: Of 45 patients with MRA at diagnosis, there were 25 for whom CA and MRA studies were performed within 1 month of each other. These comprised the study group. The CA distribution of lesions was multifocal (76%) and proximal (86%) (P < .05) with a trend toward unilaterality (P = .06) with anterior circulation involvement (P = .08). The sensitivity and specificity of MRA for CA abnormality was 70% and 98%, respectively. There was no significant difference between MRA and CA for lesion detection or characterization (P = .87), and the modalities showed a fair correlation (kappa = 0.4). CONCLUSION: Angiographic lesions are multifocal and occur proximally and unilaterally within the anterior circulation. There is no significant difference in the ability of MRA to detect and characterize lesions when compared with CA.

MR imaging and angiography of primary CNS vasculitis of childhood.

BACKGROUND AND PURPOSE: Primary angiitis of the central nervous system of childhood (cPACNS) is a rare and ill-defined disease. In the absence of a brain biopsy, the diagnosis is based on typical clinical and imaging abnormalities. The aim of this study was to analyze systematically the MR imaging and MR angiographic (MRA) abnormalities in a large cohort of children with cPACNS. METHODS: We analyzed the MR imaging features of a single pediatric center cohort of 45 cPACNS patients. MR imaging studies were performed for all patients, and both MR imaging and MRA were performed for 42 patients, who formed the cohort for review of the presence and correlation of lesions. Proportions were calculated by using the Fisher exact test, and agreement between MR imaging and MRA was calculated by using the McNemar test. The sensitivity of each diagnostic technique was established. RESULTS: The most-common pattern of parenchymal abnormality was multifocal, unilateral involvement, each in 42/45 patients (93%). The lateral lenticulostriate artery terrritory was affected in 56% of cases, with involvement of a supratentorial deep gray matter structure in 91%. No infratentorial lesion occurred in the absence of supratentorial abnormality. MRA was normal in 12/42 patients (28.6%). Among the abnormal studies, stenosis was detected on MRA in 83% and was "benign" in appearance in 73% of patients and "aggressive" in 16.7%. Involvement was proximal in 83% and distal in 27% of patients. Multiple ipsilateral lesions were seen in 63%. MR imaging was abnormal in every patient where MRA was abnormal. With the assumption of MR imaging as the gold standard, the sensitivity of MRA was 72%. The agreement between MR imaging and MRA for abnormality was significant (P = .04). CONCLUSION: We have illustrated the MR imaging and MRA appearances of cPACNS in the largest cohort to date. Both parenchymal and vascular lesions were predominantly proximal, unilateral, and multifocal within the anterior circulation. There was good agreement between MR imaging and MRA for lesion location. MR imaging findings were abnormal in all cases at diagnosis, and this remains the most sensitive technique to the detection of vasculitis.

Changes in serum triiodothyronine (T3) kinetics after prolonged Antarctic residence: the polar T3 syndrome.

Humans who live in Antarctica for greater than 5 continuous months demonstrate alterations in the hypothalamic-pituitary-thyroid axis. These changes are characterized by 1) increased pituitary release of TSH in response to iv TRH, 2) increased serum clearance of orally administered T3, and 3) normal serum total, free T4, and unstimulated TSH levels. To clarify the mechanism responsible for these findings, serum kinetic studies of 125I-labeled T4 and T3 were carried out in a group of normal men, first in California, then after 20 and 42 weeks of continuous Antarctic residence. The kinetic parameters were calculated by noncompartmental analysis. The mean T4 residence time (MRT) was not different before and after 42 weeks (5.54 +/- 0.50 and 5.08 +/- 0.43 days). The total T4 volume of distribution (TVd) tended to fall over the same period (4.30 +/- 0.12, 3.56 +/- 0.27 L/m2), but was not significantly different (P = 0.075). In contrast to T4, there was an increase from control values for the T3 MRT from 0.83 +/- 0.03 to 1.10 +/- 0.03 days (P less than 0.002) and a more than doubling of the T3 TVd from 15.55 +/- 0.52 to 47.24 +/- 5.09 L/m2 (P less than 0.002) after 42 wk of Antarctic residence. Energy intake increased approximately 40% throughout the study without a change in body weight. The changes in T3 kinetic parameters may be accounted for by increased extravascular tissue binding. The marked increase in T3 TVd and the small increase in MRT are associated with increased T3 production and clearance and only minor changes in T4 kinetics. This is the first description of a mechanism for the change in thyroid hormone economy occurring with extended residence in Antarctica.

Treatment of dermatomyositis with intravenous gammaglobulin.

PURPOSE: The mainstay of pharmacologic therapy in patients with dermatomyositis is corticosteroids. However, because patients sometimes become refractory to these drugs and because these drugs have potential short- and long-term toxicities, alternate therapy is highly desirable. Therefore, a pilot study was initiated using high-dose intravenous gammaglobulin (IVGG) in the treatment of dermatomyositis. PATIENTS AND METHODS: IVGG was administered to five patients with juvenile dermatomyositis. Prior to IVGG treatment, all patients had persistent muscle weakness despite daily corticosteroids and three patients had developed unacceptable steroid toxicity. Two of the patients had previously developed toxicity while receiving immunosuppressive therapy. RESULTS: IVGG therapy resulted in improved muscle strength and ameliorated skin rash in all patients. The percentage increase in muscle strength as measured by sphygmomanometry following the 9-month course of IVGG ranged from 56% to 606% in the proximal lower extremities and from 30% to 186% in the proximal upper extremities. Following IVGG therapy, prednisone could be discontinued or the dose reduced in all patients. CONCLUSION: This study suggests that IVGG may allow steroid sparing in dermatomyositis and may provide a safe alternative to cytotoxic therapy.

Long-term outcome of mothers of children with complete congenital heart block.

OBJECTIVES: To determine the health of mothers of offspring with complete congenital heart block (CHB) both at the time of delivery of the affected child and in the long-term, and the percentage of mothers and children with CHB who had anti-SSA/Ro and/or SSB/La antibodies. PATIENTS AND METHODS: Sixty-four mothers of 64 children with CHB (seen between 1964 and 1993) were identified through the Cardiology database of The Hospital for Sick Children, Toronto, Canada. Medical information from these of children with CHB was evaluated. Data were obtained from the mothers by mailed questionnaire, telephone interview, and/or from the attending physicians. The presence of anti-Ro antibodies and anti-La antibodies were evaluated by ELISA assay. RESULTS: The mean age at the time of delivery of the first child with CHB was 28 +/- 6 years. At the time of delivery 42 (66%) mothers were healthy, 2 (3%) had systemic lupus erythematosus (SLE), 2 (3%) had linear scleroderma, 2 (3%) had rheumatoid arthritis; 3 (5%) had a history of rheumatic fever (but were otherwise well), 1 (2%) had Sjogren's syndrome (SS), and 12 (19%) had an undifferentiated autoimmune syndrome (UAS) (arthralgia, myalgia, photosensitivity, skin vasculitis, Raynaud's phenomenon). The mean time to follow-up from deliver to study was 121 +/- 88 months. The mean maternal age at study was 38 +/- 9 years. Three of 12 mothers who initially had a UAS progressed to SLE (average follow-up time of 80 months, median 96), and 2 developed SS (with average follow-up time 140 months, median 132) and 1 went into remission. The mean follow-up time for the other mothers who did not develop an autoimmune disease was 150 +/- 102 months. Thirty-six of the 42 initially healthy mothers remained well. One mother developed SLE; 1 developed hyperthyroidism; 1 developed anky-losing spondylitis; and 3 developed an UAS. The mean follow-up time of the 36 mothers who remained healthy was similar (123 +/- 97 months) to the 6 initial healthy mothers who developed an autoimmune disease (121 +/- 36 months). Anti-Ro and/or anti-La antibodies were positive in 32 of 53 (60%) mothers tested. Fourteen of the 53 mothers were symptomatic at the time of delivery and 39 were asymptomatic. Anti-Ro and/or anti-La antibodies were positive in 12 of 13 mothers tested at the time of delivery. CONCLUSIONS: The long-term maternal outcome in our cohort was very good as most of the initially healthy mothers remained well at follow-up. Twenty-five percent of the mothers with a UAS and only 2% of the initially healthy mothers developed SLE. The development of an autoimmune disease in an asymptomatic mother identified by the birth of a child with CHB was less common in our study than in previous studies. However, close follow-up of mothers with UAS is warranted.

Naproxen-associated renal failure in a child with arthritis and inflammatory bowel disease.

Renal failure occurred in a 14-year-old girl with peripheral arthritis associated with inflammatory bowel disease while she was being treated with naproxen. She had previously received aspirin and tolmetin sodium and had no complications. A renal biopsy showed a severe tubulointerstitial nephritis. Although her renal function improved somewhat with corticosteroid treatment, it worsened when the steroids were discontinued. This case emphasizes that renal failure can develop insidiously in children on nonsteroidal anti-inflammatory drug therapy and that such children must be monitored closely for signs of nephrotoxicity.

Autopsy of a cadaver containing strontium-89-chloride.

An autopsy was performed on a patient who died after receiving 89Sr-chloride for treatment of bone pain from metastatic prostate carcinoma. Coordination between nuclear medicine physicians, radiation safety division personnel and pathologists resulted in minimal radiation exposure and the acquisition of dosimetry data.

Scintigraphic detection of hemobilia complicating angiodysplasia.

A 78-yr-old man underwent 99mTc-labeled red cell examination for a gastrointestinal bleeding episode. Gallbladder visualization was noted during the examination. Hemobilia has been reported in a variety of pathologic conditions; scintigraphic gallbladder visualization has also been reported as a result of the unusual radiolabeling characteristics of 99mTc during red cell scintigraphy. Postmortem examination revealed angiodysplasia of the gallbladder and other sites in the gastrointestinal tract. Angiodysplasia must be considered in the pathologic spectrum of causes of hemobilia.

Scintigraphic detection of metoclopramide esophageal stimulation in progressive systemic sclerosis.

Supine radionuclide esophageal scintigraphy (RES) and manometry were used to prospectively evaluate metoclopramide effect on esophageal function and pressure amplitudes in 14 patients (12 females and two males; median time since diagnosis: 2 yr) with progressive systemic sclerosis (PSS). Quantitation of RES included calculation of percent emptying at 30 sec, and standard manometric measurements were obtained. RES and manometry were performed before and 10 min following the i.v. administration of metoclopramide. RES showed a significant increase in mean percent emptying from 36% to 46% after drug administration (p less than 0.01), while mean lower esophageal pressure (end-expiratory) increased from 2 to 11 mm of Hg (p less than 0.001). Manometry failed to reveal a significant increase in either distal or proximal mean esophageal contractile amplitude, and no correlation was found between the increase in percent emptying at RES and the change in lower esophageal pressure in the individual patient. RES is the only quantitative method presently available to evaluate bolus propagation in the esophagus, and it documented improved esophageal function after metoclopramide administration in a PSS population. When drug therapy is directed at augmentation of esophageal emptying, RES is an ideal method to evaluate drug response.