Munchausen by proxy syndrome mimicking childhood-onset systemic lupus erythematosus.

Childhood-onset systemic lupus erythematosus (cSLE) is a chronic inflammatory multisystem autoimmune disease that requires multiple differential diagnoses. Munchausen by proxy syndrome (MBPS) is a form of child abuse, where a caregiver intentionally creates a medical history and induces or fabricates signs or disease in a patient. To our knowledge, there is no case report of MBPS mimicking cSLE diagnosis. We reported herein a 9-year-old male patient, with a history of multiple hospitalizations due to seizures with altered levels of consciousness. The mother reported malar rash, photosensitivity, alopecia, arthralgia, arterial hypertension, macroscopic hematuria, seizure and positive antinuclear antibodies. In the other service, he was treated with intravenous methylprednisolone, prednisone and mycophenolate mofetil. At 8 years and 8 months, he was admitted to our tertiary center with history of fever and macroscopic hematuria. Laboratory examinations were normal, including negative for antinuclear antibodies, anti-double stranded DNA, anticardiolipin, anti-Ro/SSA, anti-La/SSB, anti-RNP and anti-Sm antibodies. Multiple urine cultures revealed the presence of Enterococcus faecium, Acinetobacter sp., Stenotrophomonas maltophilia and Serratia marcescens, without any association with pyuria. At 8 years and 9 months, he was readmitted at emergency room with history of severe fever, headache, vomiting, photophobia, phonophobia and dizziness. The physical examination showed agitation, confusion, ataxic gait, slurred speech, horizontal nystagmus, painful facial expressions, tachycardia and weight loss. Brain magnetic resonance angiography and cerebrospinal fluid analysis were normal. During hospitalization, he had an acute episode of epistaxis and otalgia with excoriation in the auditory canal. At that moment, the suspicion of MBPS mimicking cSLE was raised and phenytoin intoxication was confirmed (peak phenytoin concentration was 45.4 mcg/mL, therapeutic range 10-20 mcg/mL). The mother and the patient were immediately separated, and she was replaced by another legal guardian. One week later, the neurological and other signs and symptoms were completely resolved. The child was placed under paternal custody with a court order and moved to another state. After that, the mother reported phenytoin use for her child and was referred to psychiatric follow-up. In conclusion, the first case of MBPS mimicking cSLE, resulting in multiple unnecessary examinations and treatments with delayed diagnosis was reported.

Characteristics of 1555 childhood-onset lupus in three groups based on distinct time intervals to disease diagnosis: a Brazilian multicenter study.

Objective The objective of this study was to compare demographic data, clinical/laboratorial features and disease activity at diagnosis in three different groups with distinct time intervals between onset of signs/symptoms and disease diagnosis. Methods A multicenter study was performed in 1555 childhood-onset systemic lupus erythematosus (American College of Rheumatology criteria) patients from 27 pediatric rheumatology services. Patients were divided into three childhood-onset systemic lupus erythematosus groups: A: short time interval to diagnosis (<1 month); B: intermediate time interval (≥1 and <3 months); and C: long time interval (≥3 months). An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2 K were evaluated. Results The number of patients in each group was: A = 60 (4%); B = 522 (33.5%); and C = 973 (62.5%). The median age at diagnosis (11.1 (4.2-17) vs. 12 (1.9-17.7) vs. 12.5 (3-18) years, P = 0.025) was significantly lower in group A compared with groups B and C. The median number of diagnostic criteria according to SLICC (7 (4-12) vs. 6 (4-13) vs. 6 (4-12), P < 0.0001) and SLEDAI-2 K (18 (6-57) vs. 16 (2-63) vs. 13 (1-49), P < 0.0001) were significantly higher in group A than the other two groups. The frequency of oral ulcers in the palate (25% vs. 15% vs. 11%, P = 0.003), pleuritis (25% vs. 24% vs. 14%, P < 0.0001), nephritis (52% vs. 47% vs. 40%, P = 0.009), neuropsychiatric manifestations (22% vs. 13% vs. 10%, P = 0.008), thrombocytopenia (32% vs. 18% vs. 19%, P = 0.037), leucopenia/lymphopenia (65% vs. 46% vs. 40%, P < 0.0001) and anti-dsDNA antibodies (79% vs. 66% vs. 61%, P = 0.01) were significantly higher in group A compared with the other groups. In contrast, group C had a less severe disease characterized by higher frequencies of synovitis (61% vs. 66% vs. 71%, P = 0.032) and lower frequencies of serositis (37% vs. 33% vs. 25%, P = 0.002), proteinuria >500 mg/day (48% vs. 45% vs. 36%, P = 0.002) and low complement levels (81% vs. 81% vs. 71%, P < 0.0001) compared with groups A or B. Conclusions Our large Brazilian multicenter study demonstrated that for most childhood-onset systemic lupus erythematosus patients, diagnosis is delayed probably due to mild disease onset. Conversely, the minority has a very short time interval to diagnosis and a presentation with a more severe and active multisystemic condition.

Outcomes of 847 childhood-onset systemic lupus erythematosus patients in three age groups.

Objective The objective of this study was to assess outcomes of childhood systemic lupus erythematosus (cSLE) in three different age groups evaluated at last visit: group A early-onset disease (<6 years), group B school age (≥6 and <12 years) and group C adolescent (≥12 and <18 years). Methods An observational cohort study was performed in ten pediatric rheumatology centers, including 847 cSLE patients. Results Group A had 39 (4%), B 395 (47%) and C 413 (49%). Median disease duration was significantly higher in group A compared to groups B and C (8.3 (0.1-23.4) vs 6.2 (0-17) vs 3.3 (0-14.6) years, p < 0.0001). The median Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) (0 (0-9) vs 0 (0-6) vs 0 (0-7), p = 0.065) was comparable in the three groups. Further analysis of organ/system damage revealed that frequencies of neuropsychiatric (21% vs 10% vs 7%, p = 0.007), skin (10% vs 1% vs 3%, p = 0.002) and peripheral vascular involvements (5% vs 3% vs 0.3%, p = 0.008) were more often observed in group A compared to groups B and C. Frequencies of severe cumulative lupus manifestations such as nephritis, thrombocytopenia, and autoimmune hemolytic anemia were similar in all groups ( p > 0.05). Mortality rate was significantly higher in group A compared to groups B and C (15% vs 10% vs 6%, p = 0.028). Out of 69 deaths, 33/69 (48%) occurred within the first two years after diagnosis. Infections accounted for 54/69 (78%) of the deaths and 38/54 (70%) had concomitant disease activity. Conclusions This large multicenter study provided evidence that early-onset cSLE group had distinct outcomes. This group was characterized by higher mortality rate and neuropsychiatric/vascular/skin organ damage in spite of comparable frequencies of severe cumulative lupus manifestations. We also identified that overall death in cSLE patients was an early event mainly attributed to infection associated with disease activity.

Subclinical pulmonary abnormalities in childhood-onset systemic lupus erythematosus patients.

OBJECTIVE: The aims of this study were to analyze the pulmonary function of childhood-onset systemic lupus erythematosus (cSLE) patients and to identify possible correlations between the high-resolution computed chest tomography (HRCT) score, disease activity, disease cumulative damage, and the participants' quality of life. METHODS: Forty cSLE patients, median age: 14.1 years (range: 7.4-17.9), underwent spirometry and plethysmography. Carbon monoxide diffusing capacity (DLCO), HRCT, disease activity, disease cumulative damage, and quality of life were assessed. RESULTS: Pulmonary abnormalities were evident in 19/40 (47.5%) cSLE patients according to spirometry/DLCO. Forced expired volume in one second (FEV1%) was the parameter most affected (30%). The HRCT showed some abnormality in 22/30 patients (73%), which were minimal in 43%. Signs of airway affects were found in 50%. Twelve patients were hospitalized due to cSLE-related pulmonary complications before the study began (median discharge: 2.1 years earlier). Total lung capacity (TLC%), vital capacity (VC%), forced vital capacity (FVC%), and FEV1% were significantly lower in the group with hospitalization compared to the group without hospitalization (p = 0.0025, p = 0.0022, p = 0.0032, and p = 0.0004, respectively). Of note, DLCO was positively correlated with disease duration (r = +0.4; p = 0.01). The HRCT-score was negatively correlated with FEV1/VC (r = -0.63; p = 0.0002), FEV1 (r = -0.54; p = 0.018), FEF25%-75% (r = -0.67; p < 0.0001), and HRCT-score was positively correlated with resistance (r = +0.49; p = 0.0056). CONCLUSIONS: Almost half of patients with cSLE had subclinical pulmonary abnormalities, especially airway abnormalities. The cSLE-related pulmonary complications seem to determine long-term functional damage.

Herpes zoster infection in childhood-onset systemic lupus erythematosus patients: a large multicenter study.

OBJECTIVE: The aim of this multicenter study in a large childhood-onset systemic lupus erythematosus (cSLE) population was to assess the herpes zoster infection (HZI) prevalence, demographic data, clinical manifestations, laboratory findings, treatment, and outcome. METHODS: A retrospective multicenter cohort study (Brazilian cSLE group) was performed in ten Pediatric Rheumatology services in São Paulo State, Brazil, and included 852 cSLE patients. HZI was defined according to the presence of acute vesicular-bullous lesions on erythematous/edematous base, in a dermatomal distribution. Post-herpetic neuralgia was defined as persistent pain after one month of resolution of lesions in the same dermatome. Patients were divided in two groups for the assessment of current lupus manifestations, laboratory findings, and treatment: patients with HZI (evaluated at the first HZI) and patients without HZI (evaluated at the last visit). RESULTS: The frequency of HZI in cSLE patients was 120/852 (14%). Hospitalization occurred in 73 (61%) and overlap bacterial infection in 16 (13%). Intravenous or oral aciclovir was administered in 113/120 (94%) cSLE patients at HZI diagnosis. None of them had ophthalmic complication or death. Post-herpetic neuralgia occurred in 6/120 (5%). After Holm-Bonferroni correction for multiple comparisons, disease duration (1.58 vs 4.41 years, p < 0.0001) was significantly lower in HZI cSLE patients compared to those without HZI. Nephritis (37% vs 18%, p < 0.0001), lymphopenia (32% vs 17%, p < 0.0001) prednisone (97% vs 77%, p < 0.0001), cyclophosphamide (20% vs 5%, p < 0.0001) and SLE Disease Activity Index 2000 (6.0 (0-35) vs 2 (0-45), p < 0.0001) were significantly higher in the former group. The logistic regression model showed that four independent variables were associated with HZI: disease duration < 1 year (OR 2.893 (CI 1.821-4.597), p < 0.0001), lymphopenia <1500/mm(3) (OR 1.931 (CI 1.183-3.153), p = 0.009), prednisone (OR 6.723 (CI 2.072-21.815), p = 0.002), and cyclophosphamide use (OR 4.060 (CI 2.174-7.583), p < 0.0001). CONCLUSION: HZI is an early viral infection in cSLE with a typical dermatomal distribution. Lymphopenia and immunosuppressive treatment seem to be major factors underlying this complication in spite of a benign course.

Subclinical right ventricle systolic dysfunction in childhood-onset systemic lupus erythematosus: insights from two-dimensional speckle-tracking echocardiography.

OBJECTIVE: The objective of this article is to evaluate right ventricle strain imaging by two-dimensional speckle-tracking (2DST) in childhood-onset systemic lupus erythematosus (c-SLE). METHODS: Thirty-five c-SLE patients with no signs or symptoms of heart failure and 33 healthy volunteers were evaluated by standard echocardiogram and 2DST. Conventional parameters included tricuspid annular plane systolic excursion (TAPSE), RV tissue-Doppler-derived Tei index and systolic pulmonary artery pressure. Global peak longitudinal systolic strain (PLSS) and strain rate (PLSSR) of RV were obtained by 2DST. Demographic/clinical features, SLEDAI-2K/SLICC/ACR-DI and treatment were also assessed. RESULTS: The median current age was similar in patients and controls (14.75 vs. 14.88 years, p = 0.62). RV PLSS was significantly reduced in c-SLE (-24.5 ± 5.09 vs. -27.62 ± 3.02%, p = 0.003). Similar findings were observed after excluding patients with pulmonary hypertension (-24.62 ± 4.87% vs. -27.62 ± 3.02%, p = 0.0041). RV PLSS was positively correlated with TAPSE (r = +0.49, p = 0.0027) and negatively correlated with Tei index (r = -0.34, p = 0.04) in c-SLE. RV PLSSR was not different comparing patients and controls (-0.65 s(-1 )± 0.47 vs. -1.87 ± 0.49 s(-1), p = 0.07). Further analysis of c-SLE patients revealed higher frequencies of neuropsychiatric manifestations (39% vs. 0%, p = 0.007) and antiphospholipid antibodies (55% vs. 18%, p = 0.035) in those with RV PLSS ≤ -23.7% vs >-23.7%. No differences were evidenced in demographic data, disease activity/damage or treatments (p > 0.05). CONCLUSIONS: The present study, using a new and more sensitive technique, revealed subclinical RV systolic dysfunction in c-SLE patients that may have future prognostic implications. The novel association of asymptomatic RV dysfunction with neuropsychiatric manifestations and antiphospholipid antibodies may suggest common physiopathological pathways.

Childhood-onset bullous systemic lupus erythematosus.

Bullous systemic lupus erythematosus has rarely been described in pediatric lupus population and the real prevalence of childhood-onset bullous systemic lupus erythematosus has not been reported. From January 1983 to November 2013, 303 childhood-onset SLE (c-SLE) patients were followed at the Pediatric Rheumatology Unit of the Childrens Institute of Hospital das Clínicas da Faculdade de Medicina Universidade da Universidade de São Paulo, three of them (1%) diagnosed as childhood-onset bullous systemic lupus erythematosus. All three cases presented tense vesiculobullous lesions unassociated with lupus erythematosus lesions, with the median duration of 60 days (30-60). All patients fulfilled bullous systemic lupus erythematosus criteria. Two had nephritis and serositis and presented specific autoantibodies. The histological pattern demonstrated subepidermal blisters with neutrophils-predominant infiltrates within the upper dermis. Direct immunofluorescence (DIF) showed deposits of IgG and complement along the epidermal basement membrane, in the presence or absence of IgA and/or IgM. A positive indirect immunofluorescence on salt-split skin demonstrating dermal binding was observed in two cases. All of them had moderate/severe disease activity at diagnosis with median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 18 (14-24). Two patients received dapsone and one with severe nephritis received immunosuppressive drugs. In conclusion, in the last 30 years the prevalence of bullous lupus in childhood-onset lupus population was low (1%) in our tertiary University Hospital. A diagnosis of SLE should always be considered in children with recurrent tense vesiculobullous lesions with or without systemic manifestations.

Immunogenicity and safety of two doses of a non-adjuvanted influenza A H1N1/2009 vaccine in young autoimmune rheumatic diseases patients.

OBJECTIVES: The aim of this study was to evaluate the immunogenicity and safety of the influenza A H1N1/2009 vaccine in children under 9 years old with autoimmune rheumatic diseases (ARD). METHODS: Thirty-eight ARD patients and 11 healthy children received two doses of non-adjuvanted influenza A/California/7/2009 (H1N1) virus-like vaccine. Subjects were evaluated before and 21 days after vaccination. Seroprotection (SP) and seroconversion (SC) rates, geometric mean titers (GMT) and factor increases (FI) in GMT were calculated. RESULTS: Mean ages were comparable between patients and controls. Pre-vaccination SP and GMT were similar in patients and controls (p > 0.05). Three weeks after immunization, SP (81.6% vs. 81.8%, p = 1.0), SC (81.6% vs. 90.9%, p = 0.66), GMT (151.5 vs. 282.1, p = 0.26) and the FI in GMT (16.7 vs. 36.3, p = 0.23) were similar in patients and controls, with both groups achieving an adequate response, according to the European Medicines Agency and Food and Drug Administration standards. Analysis of the possible factors influencing SC showed no difference in demographic data, leukocyte/lymphocyte counts or immunosuppressant use between seroconverted and non-seroconverted patients (p > 0.05). The vaccine demonstrated a satisfactory safety profile in this population. CONCLUSIONS: Two doses of influenza A H1N1/2009 vaccination induced an effective antibody response and caused adverse events in rare instances, suggesting this vaccine is appropriate and can be recommended for this age group.

Validation of the Portuguese Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY) in Brazil.

BACKGROUND AND OBJECTIVE: Simple Measure of the Impact of Lupus Erythematosus in Youngsters (SMILEY) is a health-related quality of life (HRQOL) assessment tool for pediatric systemic lupus erythematosus (SLE), which has been translated into Portuguese for Brazil. We are reporting preliminary data on cross-cultural validation and reliability of SMILEY in Portuguese (Brazil). METHODS: In this multi-center cross-sectional study, Brazilian children and adolescents 5-18 years of age with SLE and parents participated. Children and parents completed child and parent reports of Portuguese SMILEY and Portuguese Pediatric Quality of Life Inventory (PedsQL™) Generic and Rheumatology modules. Parents also completed the Childhood Health Assessment Questionnaire (CHAQ). Physicians completed the SLE disease activity index (SLEDAI), Physician's Global Assessment of disease activity (PGA) and Systemic Lupus Erythematosus International Collaborating Clinics ACR Damage Index (SDI). RESULTS: 99 subjects (84 girls) were enrolled; 93 children and 97 parents filled out the SMILEY scale. Subjects found SMILEY relevant and easy to understand and completed SMILEY in 5-15 minutes. Brazilian SMILEY was found to have good psychometric properties (validity and reliability), and the child-parent agreement was moderate. CONCLUSION: SMILEY may eventually be used routinely as a research/clinical tool in Brazil. It may be also adapted for other Portuguese-speaking nations offering critical information regarding the effect of SLE on HRQOL for children with SLE.

Effective seroconversion and safety following the pandemic influenza vaccination (anti-H1N1) in patients with juvenile idiopathic arthritis.

OBJECTIVES: To assess the vaccine response in juvenile idiopathic arthritis (JIA) as an extension of previous observation of immunogenicity and safety of a non-adjuvanted influenza A H1N1/2009 vaccine in a large population of juvenile rheumatic diseases. Moreover, to assess the possible influence of demographic data, disease subtypes, disease activity, and treatment on immunogenicity and the potential deleterious effect of the vaccine in the disease itself, particularly in the number of arthritis and inflammatory markers. METHODS: A total of 95 patients with JIA and 91 healthy controls were evaluated before and 21 days after vaccination, and serology for anti-H1N1 was performed by haemagglutination inhibition assay (HIA). Patient and physician visual analogue scales (VAS), Childhood Health Assessment Questionnaire (CHAQ), number of active joints, acute phase reactants, and treatments were evaluated before and after vaccination. Adverse events were also reported. RESULTS: JIA patients and controls were comparable regarding mean current age (14.9 ± 3.2 vs. 14.6 ± 3.7 years, p = 0.182). After vaccination, the seroconversion rate was significantly lower in JIA patients compared to controls (83.2% vs. 95.6%, p = 0.008), particularly in the polyarticular subtype (80% vs. 95.6%, p = 0.0098). Of note, JIA subtypes, number of active joints, acute phase reactants, CHAQ, patient and physician VAS, and use of disease-modifying anti-rheumatic drugs (DMARDs)/immunosuppressive drugs were similar between seroconverted and non-seroconverted patients (p > 0.05). Regarding vaccine safety, no deterioration was observed in the number of active joints and acute phase reactants during the study period. CONCLUSION: Influenza A H1N1/2009 vaccination in JIA induces a lower but effective protective antibody response probably independent of disease parameters and treatment with an adequate disease safety profile.

Effects of dietary starch and ruminally undegraded protein on glucogenic precursors in lactating dairy cows.

Gluconeogenesis is a large contributor to the blood supply of glucose carbons. The impact of varying dietary starch and ruminally degraded protein (RDP) on glucose entry, and the contributions of propionate and lactate to total plasma glucose entry were evaluated. Six cannulated, lactating, Holstein cows were fed one of four treatment diets arranged as a 2 × 2 factorial within a 4 × 4 partially replicated Latin Square design: (1) 8% RDP (LRDP) and 16% starch (LSt), (2) LRDP and 30% starch (HSt), (3) 11% RDP (HRDP) and LSt, or (4) HRDP and HSt. On d 12 of each period, 2-[13C]-sodium propionate (0.15 g/h) was ruminally infused for 4 h; on d 13, 1,2-[13C2]-glucose (0.2 g/h) was infused into the jugular vein for 1 h followed by 1-[13C]-lactate (0.1 g/h) for 1 h. Blood samples were serially collected starting prior to the infusions, and analyzed for plasma glucose, propionate, and lactate isotopic ratios. A one-compartment, glucose carbon model with inputs from lactate, propionate, and other glucogenic precursors (Oth, primarily absorbed glucose plus amino acids) was fitted to the isotope ratio data to derive glucose entry rates and conversion of the precursors to glucose. Milk protein production additively increased when HSt and HRDP were fed (P = 0.05 and P = 0.02, respectively). Plasma glucose and propionate concentrations increased with HSt (P = 0.04 and P = 0.01, respectively) and LRDP (P = 0.02 and P < 0.01, respectively). Total glucose and Oth entry increased (P = 0.03 and P = 0.03, respectively) with HSt, indicating greater glucose absorption from the small intestine or conversion of amino acids to glucose in the liver. However, neither entry rate was affected by RDP. The lack of an RDP effect suggests the increase in microbial outflow in response to RDP did not significantly alter glucose precursor supplies. Entry rates of propionate and lactate carbon to glucose carbon were not affected by treatment suggesting that neither starch nor RDP significantly affected fermentation or lactate production. Derivation of absolute entry rates and contributions to glucose using isotopic tracers is complicated by single carbon removals in the pentose phosphate (PPP), tri-carboxylic acid (TCA), and gluconeogenic pathways, and label randomization with the PPP and TCA pathways. Multiple tracers must be used to avoid assumptions regarding the proportional entries. These results provide insights on glucose supply and contributors, and draw attention to significant label cycling when utilizing isotope techniques.

Alveolar hemorrhage: distinct features of juvenile and adult onset systemic lupus erythematosus.

We compared outcomes of alveolar hemorrhage (AH) in juvenile (JSLE) and adult onset SLE (ASLE). From 263 JSLE and 1522 ASLE, the AH occurred in 13 (4.9%) and 15 (1.0%) patients, respectively (p < .001). Both groups had comparable disease duration (2.6 ± 3.0 vs. 5.6 ± 7.0 years, p = .151) and median SLEDAI scores [17.5 (2 to 32) vs. 17.5 (3 to 28), p = 1.000]. At AH onset, a higher frequency of JSLE were already on a high prednisone dose ( > 0.5 mg/kg/day) compared to ASLE (54% vs. 15%, p = .042). The mean drop of hemoglobin was significantly lower in JSLE (2.9 ± 0.9 vs. 5.5 ± 2.9 g/dL, p = .006). Although treatments with methylprednisolone, plasmapheresis, intravenous immunoglobulin and cyclophosphamide were similar in both groups (p > .050), regarding outcomes, there was a trend in high frequency of mechanical ventilation use (85% vs. 47%, p = .055) and also significant mortality (69% vs. 13%, p = .006) in JSLE compared to ASLE. The sepsis frequency was comparable in both groups (50% vs. 27%, p = .433). We have identified that AH in JSLE has a worse outcome most likely related to respiratory failure. The AH onset in JSLE already treated with high-dose steroids raises the concern of inadequate response to this treatment and reinforces the recommendation of early aggressive alternative therapies in this group of patients.

Invasive aspergillosis: a severe infection in juvenile systemic lupus erythematosus patients.

Infections are an important cause of morbidity and mortality in juvenile systemic lupus erythematosus (JSLE). Among them, invasive aspergillosis (IA), which is usually related to immunosuppressed patients, has been rarely reported in JSLE. From 1983 to 2011, 5604 patients were followed at our institution and 283 (5%) met the American College of Rheumatology (ACR) classification criteria for SLE. Six (2.1%) of our JSLE patients had IA. One of them was previously reported and five will be described herein. Four of them were female. The median age at JSLE diagnosis was 12 years (8-16) and the median interval between diagnosis of JSLE and IA was 6 months (1-38). All had pulmonary involvement and three of them had systemic involvement. The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was 19 (7-22). Diagnosis of IA was performed by isolation of Aspergillus spp., two in bronchoalveolar lavage culture and by way of autopsy in the others. All of them were treated with corticosteroids and/or immunosuppressive drugs at IA diagnosis (azathioprine and/or intravenous cyclophosphamide). They all required treatment in the pediatric intensive care unit with mechanical ventilation and antifungal therapy (fluconazole, amphotericin B, itraconazole and/or voriconazole); nonetheless, none of them survived. In conclusion, this was the first report that evaluated the prevalence of IA in a large population of JSLE patients from a tertiary pediatric hospital, and clearly showed the severity of the outcome, especially in patients with active disease and treated with immunosuppressive agents. This study reinforces the importance of early diagnosis and treatment with certain antifungals, especially in critically ill patients.

Atmospheric pollution: influence on hospital admissions in paediatric rheumatic diseases.

OBJECTIVE: To investigate the lag structure effects from exposure to atmospheric pollution in acute outbursts in hospital admissions of paediatric rheumatic diseases (PRDs). METHODS: Morbidity data were obtained from the Brazilian Hospital Information System in seven consecutive years, including admissions due to seven PRDs (juvenile idiopathic arthritis, systemic lupus erythematosus, dermatomyositis, Henoch-Schönlein purpura, polyarteritis nodosa, systemic sclerosis and ankylosing spondylitis). Cases with secondary diagnosis of respiratory diseases were excluded. Daily concentrations of inhaled particulate matter (PM(10)), sulphur dioxide (SO(2)) nitrogen dioxide (NO(2)), ozone (O(3)) and carbon monoxide (CO) were evaluated. Generalized linear Poisson regression models controlling for short-term trend, seasonality, holidays, temperature and humidity were used. Lag structures and magnitude of air pollutants' effects were adopted to estimate restricted polynomial distributed lag models. RESULTS: The total number of admissions due to acute outbursts PRD was 1,821. The SO(2) interquartile range (7.79 µg/m(3)) was associated with an increase of 1.98% (confidence interval 0.25-3.69) in the number of hospital admissions due to outcome studied after 14 days of exposure. This effect was maintained until day 17. Of note, the other pollutants, with the exception of O(3), showed an increase in the number of hospital admissions from the second week. CONCLUSION: This study is the first to demonstrate a delayed association between SO(2) and PRD outburst, suggesting that oxidative stress reaction could trigger the inflammation of these diseases.

Stevens-Johnson syndrome in a juvenile systemic lupus erythematosus patient.

Stevens-Johnson syndrome (SJS) is a severe and rare immune-mediated cutaneous reaction usually induced by drugs or infections. Few case reports have demonstrated SJS associated with adult systemic lupus erythematosus (SLE), and rarely in juvenile SLE (JSLE) patients. However, to the best of our knowledge the prevalence of this life-threatening cutaneous disease in the pediatric lupus population has not been studied. Therefore, from January 1983 to December 2010, 5508 patients were followed-up at the Pediatric Rheumatology Unit of our University Hospital and 279 (5%) of them met the American College of Rheumatology (ACR) classification criteria for SLE. Only one (0.4%) of our JSLE patients had SJS and was described. This female patient was diagnosed with JSLE at 14 years old. After four years of follow-up, she was hospitalized due to congestive heart failure and renal insufficiency. During hospitalization, the patient developed sepsis with positive blood culture for Stenotrophomonas maltophilia and was treated with vancomycin and meropenem. One week later, she developed septic shock and chest x-ray showed acute widespread pulmonary infiltrate. Antimicrobials were changed to linezolid and trimethoprim-sulfamethoxazole. After four days, the blood culture isolated Staphylococcus aureus resistant to vancomycin, and she presented with erythematous cutaneous lesions involving her face, trunk, and limbs, with evolution in a few hours to diffuse hemorrhagic vesicles and blisters. Epidermal detachment was observed on 5% of the body surface area. Concomitantly, she had conjunctivitis, cheilitis, oral erosions, and hemorrhagic crust on the nasal mucosa. Vulva, vagina, and perianal erosions were also evidenced. The diagnosis of SJS was established and intravenous immunoglobulin was promptly administered. Three days later, she died of pulmonary hemorrhage. The autopsy findings demonstrated generalized infection and widespread subepidermal detachment with necrotic keratinocytes. In conclusion, SJS is a rare and severe vesiculobullous disease in a pediatric lupus population and is probably associated with infections and drug therapy.

Acute pancreatitis in juvenile systemic lupus erythematosus: a manifestation of macrophage activation syndrome?

Acute pancreatitis (AP) is a rare and life-threatening manifestation of juvenile systemic lupus erythematosus (JSLE). The objective of this study was to evaluate the prevalence and clinical features of AP in our JSLE population. AP was defined according to the presence of abdominal pain or vomiting associated to an increase of pancreatic enzymes and/or pancreatic radiological abnormalities. Of note, in the last 26 years, 5367 patients were followed up at our Pediatric Rheumatology Unit and 263 (4.9%) of them had JSLE diagnosis (ACR criteria). AP was observed in 4.2% (11/263) of JSLE patients. The median of age of the JSLE patients at AP diagnosis was 12.4 years (8.8-17.9). All of them had lupus disease activity at AP onset. Three patients were receiving corticosteroids before AP diagnosis. Interestingly, 10/11 JSLE patients fulfilled preliminary guidelines for macrophage activation syndrome, three of them with macrophage hemophagocytosis in bone marrow aspirate and hyperferritinemia. The hallmark of this syndrome is excessive activation and proliferation of T lymphocytes and macrophages with massive hypersecretion of proinflammatory cytokines and clinically it is characterized by the occurrence of unexplained fever, cytopenia and hyperferritinemia. AP treatment was mainly based on intravenous methylprednisolone. Four JSLE patients with AP died and two developed diabetes mellitus. In conclusion, AP was a rare and severe manifestation in active pediatric lupus. The association between AP and macrophage activation syndrome suggests that the pancreas could be a target organ of this syndrome and that pancreatic enzyme evaluation should also be carried out in all patients.

Risk factors associated with the death of patients hospitalized for juvenile systemic lupus erythematosus.

We assessed the risk factors associated with death in patients hospitalized for juvenile systemic lupus erythematosus (JSLE) and evaluated the autopsy reports. A total of 57,159 hospitalizations occurred in our institution from 1994 to 2003, 169 of them involving 71 patients with JSLE. The most recent hospitalization of these patients was evaluated. Patients were divided into two groups based on mortality during hospitalization: those who survived (N = 53) and those who died (N = 18). The main causes of hospitalization were JSLE activity associated with infection in 52% and isolated JSLE activity in 44%. Univariate analysis showed that a greater risk of death was due to severe sepsis (OR = 17.8, CI = 4.5-70.9), systemic lupus erythematosus disease activity index (SLEDAI) >or=8 (OR = 7.6, CI = 1.1-53.8), general infections (OR = 6.1, CI = 1.5-25), fungal infections (OR = 5.4, CI = 3.2-9), acute renal failure (OR = 5.1, CI = 2.5-10.4), acute thrombocytopenia (OR = 3.9, CI = 1.9-8.4), and bacterial infections (OR = 2.3, CI = 1.2-7.5). Stratified analysis showed that severe sepsis and SLEDAI >or=8 were not confounder variables. In the multivariate analysis, logistic regression showed that the only independent variable in death prediction was severe sepsis (OR = 98, CI = 16.3-586.2). Discordance between clinical diagnosis and autopsy was observed in 6/10 cases. Mortality of hospitalized JSLE patients was associated with severe sepsis. Autopsy was important to determine events not detected or doubtful in dead patients and should always be requested.

The primate seahorse rhythm.

The main Zeitgeber, the day-night cycle, synchronizes the central oscillator which determines behaviors rhythms as sleep-wake behavior, body temperature, the regulation of hormone secretion, and the acquisition and processing of memory. Thus, actions such as acquisition, consolidation, and retrieval performed in the hippocampus are modulated by the circadian system and show a varied dependence on light and dark. To investigate changes in the hippocampus' cellular mechanism invoked by the day and night in a diurnal primate, this study analyzed the expression of PER2 and the calcium binding proteins (CaBPs) calbindin, calretinin and parvalbumin in the hippocampus of Sapajus apella, a diurnal primate, at two different time points, one during the day and one during the dark phase. The PER2 protein expression peaked at night in the antiphase described for the suprachiasmatic nucleus (SCN) of the same primate, indicating that hippocampal cells can present independent rhythmicity. This hippocampal rhythm was similar to that presented by diurnal but not nocturnal rodents. The CaBPs immunoreactivity also showed day/night variations in the cell number and in the cell morphology. Our findings provide evidence for the claim that the circadian regulation in the hippocampus may involve rhythms of PER2 and CaBPs expression that may contribute to the adaptation of this species in events and activities relevant to the respective periods.

(111)In-octreotide SPECT-CT in head and neck paragangliomas.

Head and neck paragangliomas are rare neuroendocrine tumors expressing somatostatin receptors on their cell surface, particularly subtype 2. Due to this distinctive feature, images can be obtained in Nuclear Medicine using synthetic analogues of somatostatin, mainly octreotide, which allow selective display by planar scintigraphy, SPECT-CT or PET-CT imaging after radiolabeling with (111)In or (68)Ga. Three cases have been selected and presented from a series of patients that illustrate the utility of SPECT-CT studies with (111)In-octreotide in the diagnosis and monitoring of this type of tumor. These are characterization at initial diagnosis, staging, and detection of local recurrence or metastasis, with added value with respect to anatomical images (nuclear magnetic resonance, computed axial tomography, angiography), for example in the differentiation between functional tissue or scar in patients who had previously undergone surgery.

Influence of insulin on the metabolism of glucose in uteri isolated from ovariectomized and non ovariectomized underfed rats.

The effects of insulin on the metabolism of U14C-glucose in uteri isolated from ovariectomized and non-ovariectomized rats receiving a restricted diet (50% of the normal food intake) for 25 days, were studied. As a result of food restriction, the production of 14CO2 diminishes in intact rats, while results are reversed in ovariectomized ones. Various concentrations of insulin were added to the medium, but only 0.50 IU. ml(-1)was effective in increasing glucose metabolism in intact rats receiving a restricted diet; neither underfed castrated animals nor control ones receiving a normal diet, reacted to this concentration. The increase of 14CO2 produced by insulin is not affected by acetyl salicylic acid. Insulin does not alter the effect of underfeeding over arachidonic acid metabolism. On the contrary, the increase in glucose metabolism was blocked by N(G)methyl-L-arginine or by hemoglobin, increased with the addition of L arginine and is not affected by acetyl salicylic acid. Hemoglobin and L-arginine show no effects without insulin. We can conclude that the stimulating effect of insulin on glucose metabolism in uteri isolated from intact rats subjected to dietary restriction, is nitric oxide dependent.