Childhood-onset systemic lupus erythematosus (cSLE) and malignancy: a nationwide multicentre series review.

BACKGROUND: Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. METHOD: A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. RESULTS: Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min-max) SLEDAI-2 K scores were 9 (0-38), median (min-max) SLICC/ACR-DI (SDI) score were 1 (1-5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. CONCLUSION: Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.

Childhood-onset systemic lupus erythematosus (cSLE) and malignancy: a nationwide multicentre series review

Abstract Background Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. Method A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. Results Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min-max) SLEDAI-2 K scores were 9 (0-38), median (min-max) SLICC/ACR-DI (SDI) score were 1 (1-5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. Conclusion Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.

A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2).

INTRODUCTION: The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. PATIENTS AND METHODS: This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. RESULTS: Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. CONCLUSION: The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2)

Abstract Introduction The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. Patients and methods This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. Results Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. Conclusion The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

Expression of the miR-9-5p, miR-125b-5p and its target gene NFKB1 and TRAF6 in childhood-onset systemic lupus erythematosus (cSLE).

Childhood- onset systemic lupus erythematosus (cSLE) is a multisystem inflammatory disease that can lead to severe clinical conditions resulting in early comorbidities. Several genetic, environmental, and immunological factors are known to influence the onset of the disease. MiRNAs have been already considered as potential actors involved in the development and activity of the SLE. Thus, understanding the behavior of these regulators can contribute to clarify the inflammatory process affecting SLE patients. Among miRNAs, miR-125b-5p and miR-9-5p targeting NFKB1 and TRAF6 genes can be involved in the etio-pathogenesis of the disease by modulating inflammation. In this study we evaluated miR-9-5p and miR-125b-5p expression and its target genes NFKB1 and TRAF6 in peripheral blood samples (PBMC) from the 35 cSLE patients and 35 healthy controls. MiRNAs and gene target expression have been evaluated by using RT-PCR with specific TaqMan® probes. Both miR-9-5p [Fold Change (FC) = -2.21; p = 0.002] and miR-125b-5p (FC= -3.30; p < 0.0001) and NFKB1 (FC = -1.84; p < 0.001) were downregulated in cSLE patients, while TRAF6 was upregulated (FC = 1.80; p = 0.006) in cSLE patients when compared to controls. A significant correlation was found between miR-125b-5p and its target gene NFKB1 [Spearman (r) = 0.47; p = 0.023]. Our results showed miR-125b-5p and miR-9-5p differential expression in cSLE patients, possibly contributing to better understanding the role of these regulators in cSLE development and disease pathogenesis.

Streptococcus mutans detection in saliva and colostrum samples.

OBJECTIVE: To detect Streptococcus mutans in colostrum and saliva of neonates and compare with its detection in saliva of mothers. METHODS: Forty-three healthy women, full-term gestations with no complications, submitted to elective Cesarean section, and their newborns were included in the study. Samples were investigated by polymerase chain reaction to detect S. mutans in genetic material from the samples. RESULTS: Approximately 16% of colostrum samples showed S. mutans , but not correlated with the presence of the bacteria in both samples of saliva. S. mutans was detected in 49 and 30% of saliva samples of mothers and neonates, respectively. There was a positive correlation in S. mutans detection between types of saliva. The number of maternal samples of saliva with detectable S. mutans was smaller in women receiving dental treatment during pregnancy. Tooth brushing, three times a day, influenced the detection of S. mutans in both the saliva and the colostrum. CONCLUSION: Although maternal saliva may present S. mutans , few samples of colostrum present the bacteria. The presence of bacteria in neonate saliva may be related to contact before birth. Dental treatment and hygiene habits seem to influence the detection of S. mutans in samples of maternal saliva and colostrum.

Panniculitis in childhood-onset systemic lupus erythematosus: a multicentric cohort study.

OBJECTIVE: To evaluate prevalence, clinical manifestations, laboratory abnormalities, treatment and outcome in a multicenter cohort of childhood-onset systemic lupus erythematosus (cSLE) patients with and without panniculitis. METHODS: Panniculitis was diagnosed due to painful subcutaneous nodules and/or plaques in deep dermis/subcutaneous tissues and lobular/mixed panniculitis with lymphocytic lobular inflammatory infiltrate in skin biopsy. Statistical analysis was performed using Bonferroni correction(p < 0.004). RESULTS: Panniculitis was observed in 6/847(0.7%) cSLE. Painful subcutaneous erythematosus and indurated nodules were observed in 6/6 panniculitis patients and painful subcutaneous plaques in 4/6. Generalized distribution was evidenced in 3/6 and localized in upper limbs in 2/6 and face in 1/6. Cutaneous hyperpigmentation and/or cutaneous atrophy occurred in 5/6. Histopathology features showed lobular panniculitis without vasculitis in 5/6(one of them had concomitant obliterative vasculopathy due to antiphospholipid syndrome) and panniculitis with vasculitis in 1/6. Comparison between cSLE with panniculitis and 60 cSLE without panniculitis with same disease duration [2.75(0-11.4) vs. 2.83(0-11.8) years,p = 0.297], showed higher frequencies of constitutional involvement (67% vs. 10%,p = 0.003) and leukopenia (67% vs. 7%,p = 0.002). Cutaneous atrophy and hyperpigmentation occurred in 83% of patients. CONCLUSIONS: Panniculitis is a rare skin manifestation of cSLE occurring in the first three years of disease with considerable sequelae. The majority of patients have concomitant mild lupus manifestations.

Streptococcus mutans detection in saliva and colostrum samples / Detecção de Streptococcus mutans em amostras de saliva e colostro

ABSTRACT Objective To detect Streptococcus mutans in colostrum and saliva of neonates and compare with its detection in saliva of mothers. Methods Forty-three healthy women, full-term gestations with no complications, submitted to elective Cesarean section, and their newborns were included in the study. Samples were investigated by polymerase chain reaction to detect S. mutans in genetic material from the samples. Results Approximately 16% of colostrum samples showed S. mutans , but not correlated with the presence of the bacteria in both samples of saliva. S. mutans was detected in 49 and 30% of saliva samples of mothers and neonates, respectively. There was a positive correlation in S. mutans detection between types of saliva. The number of maternal samples of saliva with detectable S. mutans was smaller in women receiving dental treatment during pregnancy. Tooth brushing, three times a day, influenced the detection of S. mutans in both the saliva and the colostrum. Conclusion Although maternal saliva may present S. mutans , few samples of colostrum present the bacteria. The presence of bacteria in neonate saliva may be related to contact before birth. Dental treatment and hygiene habits seem to influence the detection of S. mutans in samples of maternal saliva and colostrum.

RESUMO Objetivo Detectar Streptococcus mutans no colostro e na saliva de recém-nascido, e comparar com a detecção na saliva da mãe. Métodos Foram incluídos no estudo 43 mulheres saudáveis, com gestações a termo e sem complicações, que tiveram cesariana eletiva, e seus recém-nascidos. As amostras foram investigadas por reação de polimerase em cadeia para a detecção de S. mutans em material genético extraído das amostras. Resultados Cerca de 16% das amostras de colostro apresentaram S. mutans , não sem correlação com a presença das bactérias em ambas amostras de saliva. S. mutans foi detectado em 49 e 30% das amostras de saliva das mães e recém-nascidos, respectivamente. Houve correlação positiva na detecção de S. mutans entre os tipos de saliva. O número de amostras de saliva materna com S. mutans detectável foi menor nas mulheres que receberam tratamento odontológico durante a gravidez. A escovação três vezes ao dia influenciou na detecção do S. mutans tanto no saliva quanto no colostro. Conclusão Embora a saliva materna possa apresentar S. mutans , poucas amostras de colostro apresentam a bactéria. A presença de bactéria na saliva de neonatos pode estar relacionada ao contato antes do nascimento. O tratamento odontológico e os hábitos de higiene parecem influenciar na detecção de S. mutans em amostras de saliva e colostro maternos.

Panniculitis in childhood-onset systemic lupus erythematosus: a multicentric cohort study

Abstract Objective: To evaluate prevalence, clinical manifestations, laboratory abnormalities, treatment and outcome in a multicenter cohort of childhood-onset systemic lupus erythematosus (cSLE) patients with and without panniculitis. Methods: Panniculitis was diagnosed due to painful subcutaneous nodules and/or plaques in deep dermis/subcutaneous tissues and lobular/mixed panniculitis with lymphocytic lobular inflammatory infiltrate in skin biopsy. Statistical analysis was performed using Bonferroni correction(p < 0.004). Results: Panniculitis was observed in 6/847(0.7%) cSLE. Painful subcutaneous erythematosus and indurated nodules were observed in 6/6 panniculitis patients and painful subcutaneous plaques in 4/6. Generalized distribution was evidenced in 3/6 and localized in upper limbs in 2/6 and face in 1/6. Cutaneous hyperpigmentation and/or cutaneous atrophy occurred in 5/6. Histopathology features showed lobular panniculitis without vasculitis in 5/6(one of them had concomitant obliterative vasculopathy due to antiphospholipid syndrome) and panniculitis with vasculitis in 1/6. Comparison between cSLE with panniculitis and 60 cSLE without panniculitis with same disease duration [2.75(0-11.4) vs. 2.83(0-11.8) years,p = 0.297], showed higher frequencies of constitutional involvement (67% vs. 10%,p = 0.003) and leukopenia (67% vs. 7%,p = 0.002). Cutaneous atrophy and hyperpigmentation occurred in 83% of patients. Conclusions: Panniculitis is a rare skin manifestation of cSLE occurring in the first three years of disease with considerable sequelae. The majority of patients have concomitant mild lupus manifestations.

Streptococcus mutans in Umbilical Cord Blood, Peripheral Blood, and Saliva from Healthy Mothers.

The aims of this study were to analyze the presence of Streptococcus mutans (SM)-DNA in cord blood (CB), maternal peripheral blood (PB), and maternal saliva (SA) and compare with data collected in health surveys. Sixty-four healthy women with pregnancies to term and without complications attending for elective cesarean section in the Clinical Hospital of Ribeirao Preto, Sao Paulo were included. Samples of PB and unstimulated SA were obtained on the day of hospitalization and samples of CB were collected after the delivery section. Samples were investigated using polymerase chain reaction for the presence of SM-DNA using specific primers. The results show over 50% of the sample of PB and CB showed SM-DNA detectable. There was a positive correlation between the SM detection in PB/CB and SA (P < 0.05). Pregnant women, who reported tooth brushing more than three times a day, often showed detectable SM-DNA in PB and CB (P < 0.05). In conclusion, the majority of children can have contact with SM-DNA during the intrauterine life by the CB. SM probably transferred from salivary habitat to PB and CB. The tooth brushing can be associated to S. mutans detection in blood samples.

Homocysteine, folate, hs-C-reactive protein, tumor necrosis factor alpha and inflammatory proteins: are these biomarkers related to nutritional status and cardiovascular risk in childhood-onset systemic lupus erythematosus?

BACKGROUND: Childhood-onset systemic lupus erythematosus (c-SLE) is a chronic autoimmune disease which increases cardiovascular risk factors (CRF) such as elevated homocysteine, TNF-α, and hs-C reactive protein. METHODS: We evaluated BMI, waist circumference (WC), 24-h recalls, SLEDAI-2 K, SLICC/ACR-DI, serum levels of homocysteine, folate, TNF-α, hs-C reactive protein, lipid profile, proteomic data, and duration of corticosteroid therapy in 19 c-SLE and 38 healthy volunteers. Physiological and anthropometric variables of c-SLE and healthy controls were compared by ANCOVA. k-cluster was used to separate c-SLE into two different groups with the best and the worst metabolic profile according to previous analysis showing some metabolites that were statistically different from controls, such as homocysteine, TNF-α, hs-CRP and folate levels. These two clusters were again compared with the control group regarding nutritional parameters, lipid profile and also proteomic data. RESULTS: Individuals with c-SLE presented higher BMI, WC, homocysteine, triglycerides, TNF-α, hs-CRP and lower folate levels when compared to controls. We found 10 proteins whose relative abundances were statistically different between control group and lupus clusters with the best (LCBMP) and the worst metabolic profile (LCWMP). A significant positive correlation was found between TNF-α and triglycerides and between hs-CRP and duration of corticosteroid therapy. CONCLUSION: Cardiovascular disease (CVD) risk parameters were worse in c-SLE. A less protective CVD proteomic profile was found in LCWMP.

Signs and symptoms of rheumatic diseases as first manifestation of pediatric cancer: diagnosis and prognosis implications / Sinais e sintomas sugestivos de doenças reumáticas como primeira manifestação de doenças neoplásicas na infância: implicações no diagnóstico e prognóstico

ABSTRACT Objective: To assess the prevalence and describe the clinical, laboratory and radiological findings, treatment and outcome of children with cancer initially referred to a tertiary outpatient pediatric rheumatology clinic. Methods: Retrospective analysis of medical records from patients identified in a list of 250 new patients attending the tertiary Pediatric Rheumatology Clinic, Ribeirão Preto Medical School hospital, University of São Paulo, from July 2013 to July 2015, whose final diagnosis was cancer. Results: Of 250 patients seen during the study period, 5 (2%) had a cancer diagnosis. Among them, 80% had constitutional symptoms, especially weight loss and asthenia, and 60% had arthritis. Initially, all patients had at least one alteration in their blood count, lactate dehydrogenase was increased in 80% and a bone marrow smear was conclusive in 60% of patients. Bone and intestine biopsies were necessary for the diagnosis in 2 patients. JIA was the most common initial diagnosis. The definitive diagnosis was acute lymphoblastic leukemia (2 patients), M3 acute myeloid leukemia, lymphoma, and neuroblastoma (one case each). Of 5 patients studied, 3 (60%) are in remission and 2 (40%) died, one of them with prior use of steroids. Conclusion: The constitutional and musculoskeletal symptoms common to rheumatic and neoplastic diseases can delay the diagnosis and consequently worsen the prognosis of neoplasms. Initial blood count and bone marrow smear may be normal in the initial framework of neoplasms. Thus, the clinical follow-up of these cases becomes imperative and the treatment, mainly with corticosteroids, should be delayed until diagnostic definition.

RESUMO Objetivo: Avaliar a prevalência e descrever as principais manifestações clínicas, os exames complementares, o tratamento e a evolução de crianças com doenças neoplásicas atendidas inicialmente em um serviço terciário de reumatologia pediátrica. Métodos: Analisamos retrospectivamente o prontuário médico de pacientes com diagnóstico definitivo de neoplasia, identificados entre 250 casos novos atendidos no ambulatório de reumatologia pediátrica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto-USP, de julho de 2013 a julho de 2015. Resultados: Dos 250 pacientes, cinco (2%) tiveram diagnóstico de neoplasia. Desses, 80% apresentavam sintomas constitucionais, principalmente perda de peso e astenia e 60% artrite. Inicialmente, todos apresentavam pelo menos uma série alterada no hemograma, 80% aumento da desidrogenase lática (LDH) e 60% mielograma confirmatório. Dois pacientes necessitaram de biópsia, óssea e de intestino, para o diagnóstico final. Artrite idiopática juvenil foi o diagnóstico inicial mais frequente. Os diagnósticos definitivos foram leucemia linfoide aguda (dois casos), leucemia mieloide aguda-M3, neuroblastoma e linfoma (um caso cada). Dos pacientes estudados, três (60%) estão em remissão. Dois pacientes foram a óbito (40%), um deles com uso prévio de corticoide. Conclusão: Os sintomas constitucionais e musculoesqueléticos comuns às doenças reumáticas e neoplásicas podem retardar o diagnóstico e consequentemente agravar o prognóstico das neoplasias. O hemograma inicial, assim como o mielograma, podem estar normais no quadro inicial das neoplasias. Dessa forma, o seguimento clínico evolutivo desses casos torna-se imperativo e o tratamento, principalmente com corticoides, deve ser retardado até definição diagnóstica.

Signs and symptoms of rheumatic diseases as first manifestation of pediatric cancer: diagnosis and prognosis implications.

OBJECTIVE: To assess the prevalence and describe the clinical, laboratory and radiological findings, treatment and outcome of children with cancer initially referred to a tertiary outpatient pediatric rheumatology clinic. METHODS: Retrospective analysis of medical records from patients identified in a list of 250 new patients attending the tertiary Pediatric Rheumatology Clinic, Ribeirão Preto Medical School hospital, University of São Paulo, from July 2013 to July 2015, whose final diagnosis was cancer. RESULTS: Of 250 patients seen during the study period, 5 (2%) had a cancer diagnosis. Among them, 80% had constitutional symptoms, especially weight loss and asthenia, and 60% had arthritis. Initially, all patients had at least one alteration in their blood count, lactate dehydrogenase was increased in 80% and a bone marrow smear was conclusive in 60% of patients. Bone and intestine biopsies were necessary for the diagnosis in 2 patients. JIA was the most common initial diagnosis. The definitive diagnosis was acute lymphoblastic leukemia (2 patients), M3 acute myeloid leukemia, lymphoma, and neuroblastoma (one case each). Of 5 patients studied, 3 (60%) are in remission and 2 (40%) died, one of them with prior use of steroids. CONCLUSION: The constitutional and musculoskeletal symptoms common to rheumatic and neoplastic diseases can delay the diagnosis and consequently worsen the prognosis of neoplasms. Initial blood count and bone marrow smear may be normal in the initial framework of neoplasms. Thus, the clinical follow-up of these cases becomes imperative and the treatment, mainly with corticosteroids, should be delayed until diagnostic definition.

Comparisons of IgA response in saliva and colostrum against oral streptococci species.

The present study compared IgA specificity against oral streptococci in colostrum and saliva samples. Sixty-two mother-and-child pairs were included; samples of colostrum (C) and saliva (MS) were collected from the mothers and saliva samples were collected from babies (BS). The specificity of IgA against Streptococcus mutans and S. mitis were analyzed by western blot. Only 30% of babies' samples presented IgA reactivity to S. mutans, while 74 and 80% of MS and C, respectively, presented this response. IgA reactivity to S. mutans virulence antigens (Ag I/II, Gtf and GbpB) in positive samples showed differences between samples for Gtf and especially for GbpB (p < 0.05), but responses to Ag I/II were similar (p > 0.05). The positive response of Gtf-reactive IgA was different between C (90%) and MS (58%) samples (p < 0.05), but did not differ from BS (p > 0.05). GbpB was the least detected, with 48 and 26% of C and MS, and only 5% of BS samples presenting reactivity (p > 0.05). Eight percent of MS and C samples presented identical bands to SM in the same time-point. In conclusion, the differences of IgA response found between C and MS can be due to the different ways of stimulation, proliferation and transportation of IgA in those secretions. The colostrum has high levels of IgA against S. mutans virulence antigens, which could affect the installation and accumulation process of S. mutans, mainly by supplying anti-GbpB IgA to the neonate.

Uveitis in childhood-onset systemic lupus erythematosus patients: a multicenter survey.

The aim of this study is to assess uveitis prevalence in a large cohort of childhood-onset systemic lupus erythematosus (cSLE) patients. A retrospective multicenter cohort study including 852 cSLE patients was performed in ten pediatric rheumatology centers (Brazilian cSLE group). An investigator meeting was held and all participants received database training. Uveitis was diagnosed through clinical assessment by the uveitis expert ophthalmologist of each center. Patients with and without uveitis were assessed for lupus clinical/laboratory features and treatments. Uveitis was observed in 7/852 cSLE patients (0.8%). Two of them had ocular complications: cataract and irreversible blindness in one patient and retinal ischemia with subsequent neovascularization and unilateral blindness in another. Uveitis was identified within the first 6 months of cSLE diagnosis in 6/7 patients (86%). Comparison of a subgroup of cSLE patients with (n = 7) and without uveitis (n = 73) and similar length of disease duration showed that patients with uveitis had increased SLEDAI-2K score (19 vs. 6; p < 0.01). In addition, fever (71 vs. 12%; p < 0.01), lymphadenopathy (29 vs. 1.4%; p = 0.02), arthritis (43 vs. 7%; p = 0.02), and use of intravenous methylprednisolone (71 vs. 22%; p = 0.01) were higher in cSLE patients with uveitis, as compared to those without this manifestation, respectively. Presence of fever was significantly associated with uveitis, independently of SLEDAI scores or use of intravenous methylprednisolone pulses, as shown by adjusted regression analysis (adjusted prevalence ratio 35.7, 95% CI 2.4-519.6; p < 0.01). Uveitis was a rare and initial manifestation of active cSLE patients. Early recognition is essential due to the possibility of irreversible blindness.

Anti-RO/SSA and anti-La/SSB antibodies: Association with mild lupus manifestations in 645 childhood-onset systemic lupus erythematosus.

BACKGROUND: To our knowledge there are no studies assessing anti-Ro/SSA and anti-La/SSB autoantibodies in a large population of childhood-systemic lupus erythematosus (cSLE) patients. METHODS: This was a retrospective multicenter cohort study performed in 10 Pediatric Rheumatology services, São Paulo state, Brazil. Anti-Ro/SSA and anti-La/SSB antibodies were measured by enzyme linked immunosorbent assay (ELISA) in 645 cSLE patients. RESULTS: Anti-Ro/SSA and anti-La/SSB antibodies were evidenced in 209/645 (32%) and 102/645 (16%) of cSLE patients, respectively. Analysis of cSLE patients with and without anti-Ro/SSA antibodies revealed higher frequencies of malar rash (79% vs. 71%, p=0.032), photosensitivity (73% vs. 65%, p=0.035), cutaneous vasculitis (43% vs. 35%, p=0.046) and musculoskeletal involvement (82% vs. 75%, p=0.046) in spite of long and comparable disease duration in both groups (4.25 vs. 4.58years, p=0.973). Secondary Sjögren syndrome was observed in only five patients with this antibody (2.5% vs. 0%, p=0.0035), two of them with concomitant anti-La/SSB. The presence of associated autoantibodies: anti-Sm (50% vs. 30%, p<0.0001), anti-RNP (39% vs. 21%, p<0.0001) and anti-ribossomal P protein (46% vs. 21%, p=0.002) was also significantly higher in patients with anti-Ro/SAA antibodies. Further evaluation of cSLE patients with the presence of anti-La/SSB antibodies compared to those without these autoantibodies showed that the frequency of alopecia (70% vs. 51%, p=0.0005), anti-Sm (59% vs. 31%, p<0.0001) and anti-RNP (42% vs. 23%, p<0.0001) were significantly higher in the former group. CONCLUSIONS: Our large multicenter cohort study provided novel evidence in cSLE that anti-Ro/SSA and/or anti-La/SSB antibodies were associated with mild manifestations, particularly cutaneous and musculoskeletal. Secondary Sjögren syndrome was rarely observed in these patients, in spite of comparable frequencies of anti-Ro/SSA and/or anti-La/SSB reported for adult SLE.

Comparisons of IgA response in saliva and colostrum against oral streptococci species

Abstract The present study compared IgA specificity against oral streptococci in colostrum and saliva samples. Sixty-two mother-and-child pairs were included; samples of colostrum (C) and saliva (MS) were collected from the mothers and saliva samples were collected from babies (BS). The specificity of IgA against Streptococcus mutans and S. mitis were analyzed by western blot. Only 30% of babies’ samples presented IgA reactivity to S. mutans, while 74 and 80% of MS and C, respectively, presented this response. IgA reactivity to S. mutans virulence antigens (Ag I/II, Gtf and GbpB) in positive samples showed differences between samples for Gtf and especially for GbpB (p < 0.05), but responses to Ag I/II were similar (p > 0.05). The positive response of Gtf-reactive IgA was different between C (90%) and MS (58%) samples (p < 0.05), but did not differ from BS (p > 0.05). GbpB was the least detected, with 48 and 26% of C and MS, and only 5% of BS samples presenting reactivity (p > 0.05). Eight percent of MS and C samples presented identical bands to SM in the same time-point. In conclusion, the differences of IgA response found between C and MS can be due to the different ways of stimulation, proliferation and transportation of IgA in those secretions. The colostrum has high levels of IgA against S. mutans virulence antigens, which could affect the installation and accumulation process of S. mutans, mainly by supplying anti-GbpB IgA to the neonate.

Guidelines for the management and treatment of periodic fever syndromes familial Mediterranean fever.

OBJECTIVE: To establish guidelines based on scientific evidence for the management of familial Mediterranean fever. DESCRIPTION OF THE EVIDENCE COLLECTION METHOD: The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. RESULTS: 10,341 articles were retrieved and evaluated by title and abstract; from these, 46 articles were selected to support the recommendations. RECOMMENDATIONS: 1. The diagnosis of FMF is based on clinical manifestations, characterized by recurrent febrile episodes associated with abdominal pain, chest or arthritis of large joints. 2. FMF is a genetic disease presenting an autosomal recessive trait, caused by mutation in the MEFV gene. 3. Laboratory tests are not specific, demonstrating high serum levels of inflammatory proteins in the acute phase of the disease, but also often showing high levels even between attacks. SAA serum levels may be especially useful in monitoring the effectiveness of treatment. 4. The therapy of choice is colchicine; this drug has proven its effectiveness in preventing acute inflammatory episodes and progression toward amyloidosis in adults. 5. Based on the available information, the use of biological drugs appears to be an alternative for patients with FMF who do not respond or are intolerant to therapy with colchicine.

Guidelines for the management and treatment of periodic fever syndromes: Cryopyrin-associated periodic syndromes (cryopyrinopathies - CAPS).

OBJECTIVE: To establish guidelines based on cientific evidences for the management of cryopyrin associated periodic syndromes. DESCRIPTION OF THE EVIDENCE COLLECTION METHOD: The Guideline was prepared from 4 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. RESULTS: 1215 articles were retrieved and evaluated by title and abstract; from these, 42 articles were selected to support the recommendations. RECOMMENDATIONS: 1. The diagnosis of CAPS is based on clinical history and clinical manifestations, and later confirmed by genetic study. CAPS may manifest itself in three phenotypes: FCAS (mild form), MWS (intermediate form) and CINCA (severe form). Neurological, ophthalmic, otorhinolaryngological and radiological assessments may be highly valuable in distinguishing between syndromes; 2. The genetic diagnosis with NLRP3 gene analysis must be conducted in suspected cases of CAPS, i.e., individuals presenting before 20 years of age, recurrent episodes of inflammation expressed by a mild fever and urticaria; 3. Laboratory abnormalities include leukocytosis and elevated serum levels of inflammatory proteins; and 4. Targeted therapies directed against interleukin-1 lead to rapid remission of symptoms in most patients. However, there are important limitations on the long-term safety. None of the three anti-IL-1ß inhibitors prevents progression of bone lesions.

Guidelines for the management and treatment of periodic fever syndromes: periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome.

OBJECTIVE: To establish guidelines based on scientific evidence for the management of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. DESCRIPTION OF THE EVIDENCE COLLECTION METHOD: The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. RESULTS: 806 articles were retrieved and evaluated by title and abstract; from these, 32 articles were selected to support the recommendations. RECOMMENDATIONS: 1. PFAPA is a diagnosis of exclusion established on clinical grounds, and one must suspect of this problem in children with recurrent and periodic febrile episodes of unknown origin, or with recurrent tonsillitis interspersed with asymptomatic periods, especially in children in good general condition and with preservation of weight and height development. 2. Laboratory findings are nonspecific. Additional tests do not reveal pathognomonic changes. 3. The evidence supporting an indication for surgical treatment (tonsillectomy with or without adenoidectomy), is based on two non-blinded randomized clinical trials with small numbers of patients. 4. The use of prednisone at the onset of fever in patients with PFAPA proved to be an effective strategy. There is still need for more qualified evidence to support its use in patients with PFAPA. 5. Despite promising results obtained in studies with IL-1ß inhibitors, such studies are limited to a few case reports.