Daniela Gerent Petry Piotto

Frequência elevada de calcinose em dermatomiosite juvenil: estudo de fatores de risco

OBJECTIVE: To assess the frequency of calcinosis in patients with juvenile dermatomyositis, and the possible risk factors for that manifestation. METHODS: Medical record review of 34 patients, with an emphasis on the following characteristics: demographic, clinical and laboratory data; type of treatment; adherence to treatment; disease course (monocyclic, chronic and polycyclic); and disease severity. Patients were divided into two groups as follows: those who developed calcinosis (up to the sixth month of follow-up and after six months of follow-up) and those who did not develop calcinosis. Twentyseven patients underwent two nailfold capillaroscopies (NFC), which were considered altered when the scleroderma pattern was found. RESULTS: The mean age of symptom onset of the 34 patients was 6.5 years, the time until diagnosis was 1.2 years, and 70% were females. Half of the patients had a monocyclic disease course, and only 14.7% had severe vasculitis. Almost 90% of the patients undergoing NFC showed a change on the first assessment, 74% showed a change on the second assessment, and the mean interval between both assessments was 1.6 year. Calcinosis was evidenced in 16 (47.1%) patients. No association was observed between the variables analyzed and the development of calcinosis. CONCLUSION: No risk factors for calcinosis were identified in this study, although that complication was found in half of the patients with juvenile dermatomyositis studied.

Laser Doppler imaging for assessment of microcirculation in juvenile systemic sclerosis

OBJECTIVES The objectives of this study were to evaluate the dynamic behaviour of digital skin microvascular blood flow before and after cold stimulation using laser Doppler imaging (LDI) in children and adolescents with RP secondary to juvenile systemic sclerosis (JSS), primary RP (PRP) and healthy controls and to compare functional abnormalities measured by LDI with structural microvascular abnormalities evaluated by nailfold capillaroscopy (NFC). METHODS Five JSS patients, five children and adolescents with PRP and five healthy controls matched for gender and age were included. All subjects had NFC performed. Finger blood flow (FBF) was measured using the LDI system (Moor Instruments) at baseline and after cold stimulus (CS). RESULTS There were a decreased number of capillaries, a greater number of enlarged capillaries and a higher deletion score in JSS patients compared with controls and patients with PRP. The mean baseline FBF was significantly lower in JSS patients compared with controls. There was no difference between the mean baseline FBF in JSS patients compared with patients with PRP. There was a significant decrease in FBF 1 min after CS in all groups followed by blood flow recovery at 20 min after CS in comparison with basal FBF values in controls, but not in JSS and PRP patients. CONCLUSION In JSS patients, LDI showed a lower FBF before and after CS compared with healthy controls and may be an objective and sensitive method for the measurement of digital skin blood flow in RP children.

Evans Syndrome at Childhood-Onset Systemic Lupus Erythematosus Diagnosis: A Large Multicenter Study.

Evans syndrome (ES) in childhood‐onset systemic lupus erythematosus (cSLE) patients has been rarely reported and limited to small populations.

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.

Symptomatic polyautoimmunity at diagnosis of 1463 childhood-onset lupus: A Brazilian multicenter study

OBJECTIVE To evaluate symptomatic polyautoimmunity (PA) at childhood-onset systemic lupus erythematosus(cSLE) diagnosis, and its association with demographic data, disease activity, clinical manifestations and laboratorial abnormalities in a large Brazilian cSLE population. METHODS A multicenter retrospective study was performed in 1463 cSLE(ACR criteria) patients from 27 Pediatric Rheumatology services. Symptomatic PA was defined according to the presence of more than one concomitant autoimmune disease(AD) and symptomatic multiple autoimmune syndrome(MAS) was defined as three or more AD. An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2K were evaluated. RESULTS At cSLE diagnosis symptomatic PA was observed in 144/1463(9.8%) and symptomatic MAS occurred in solely 10/1463(0.7%). In the former group the more frequently observed associated AD were Hashimoto thyroiditis n = 42/144(29%), antiphospholipid syndrome n = 42/144(29%), autoimmune hepatitis n = 26/144(18%) and type 1 diabetes mellitus n = 23/144(15.9%). Further comparisons between cSLE patients with and without PA showed a higher median age(p = 0.016) and lower mean SLICC criteria (p = 0.039) in those with PA. Additionally, these cSLE patients had less renal involvement(35% vs. 44%, p = 0.038) and red blood cell cast(6% vs. 12%, p = 0.042) and more antiphospholipid antibodies(29% vs. 15%, p < 0.0001). CONCLUSIONS Approximately 10% of cSLE had symptomatic PA at diagnosis, particularly endocrine autoimmune disorders and antiphospholipid syndrome. Lupus was characterized by a mild disease onset and MAS was infrequently evidenced. Further studies are necessary to determine if this subgroup of cSLE patients have a distinct genetic background with a less severe disease and a better long-term outcome.

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-1β inhibitors, such studies are limited to a few case reports.

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-1β inhibitors prevents progression of bone lesions.

SAT0253 Evans Syndrome at Childhood-Onset Systemic Lupus Erythematosus Diagnosis: A Large Multicenter Study

Background Evans syndrome (ES) is an uncommon manifestation characterized by autoimmune destruction of red cells and platelets and concomitant or sequential appearance of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). This involvement has been associated to severe disease activity in adult patients with systemic lupus erythematosus (SLE), particularly at disease onset. However, ES studies in childhood-onset SLE (cSLE) patients have been rarely reported and limited to small populations. Objectives The objective of the present multicenter study was to assess ES in a large cSLE cohort at diagnosis evaluating prevalence, clinical features, laboratory findings and outcomes. Methods A retrospective multicenter cohort study (Brazilian cSLE group) was performed in 10 Pediatric Rheumatology services including 850 patients with cSLE (ACR criteria). None of them had secondary etiologies of autoimmune cytopenias, such as infections, primary immunodeficiencies and malignancies. Patients were divided in two groups for the assessment of lupus manifestations, laboratory exams and treatment at cSLE diagnosis: patients with ES and patients without ES. Results ES was observed in 11/850 (1.3%) cSLE patients at diagnosis. The majority of them had hemorrhagic manifestations (58%) and active disease (82%). All patients with ES were hospitalized and none of them died. Comparisons of cSLE patients with and without ES at diagnosis revealed similar frequencies of female gender, multi-organ involvement, autoantibody profile and low complement levels (p>0.05). Patients with ES had a lower frequency of malar rash (9% vs. 53%, p=0.003) and musculoskeletal involvement (18% vs. 69%, p=0.001) than those without this complication. The median of hemoglobin [7.4 (5.4–9.4) vs. 10.3 (3.5–16.4)g/dL, p<0.001] and platelets [27 (15–54) vs. 231 (2–761)x103/mm3, p=0.005] were significantly lower in ES compared to non-ES patients, whereas lymphocytes were significantly higher in ES patients [1.8 (1–2.38) vs. 1.16 (0.07–7)x103/mm3, p<0.001]. The frequencies of intravenous methylprednisolone (82% vs. 43%, p=0.013) and intravenous immunoglobulin use (64% vs. 3%, p<0.0001) were significantly higher in the former group. Current prednisone dose between the two groups was similar [1.1 (0.76–1.5) vs. 1.0 mg/kg/day (0–30), 0.195]. Conclusions Our large multicenter study identified that ES was a rare and severe cSLE manifestation with a difficult diagnosis due to the absence of typical lupus manifestations, often requiring hospitalization and intravenous treatment. Disclosure of Interest G. Lube: None declared, M. Ferriani: None declared, L. Campos: None declared, M. Terreri: None declared, E. Bonfá: None declared, C. Magalhães: None declared, N. Aikawa: None declared, D. Piotto: None declared, O. Peracchi: None declared, M. C. Santos: None declared, S. Appenzeller: None declared, V. Ferriani: None declared, R. Pereira: None declared, C. Silva Grant/research support from: Conselho Nacional de Desenvolvimento Científico e Tecnolόgico (CNPq 302724/2011–7 to CAS), Federico Foundation (to CAS) and by Núcleo de Apoio à Pesquisa “Saúde da Criança e do Adolescente” da USP (NAP-CriAd) to CAS

FRI0460 Normal Patterns of Nailfold Videocapillaroscopy in Healthy Children and Adolescents Based on Different Age Ranges

Background Videocapillaroscopy (NVC) is a safe, non-invasive, and cost-effective tool useful in the detection of individuals who are at risk for developing autoimmune rheumatic diseases (ARDs). However, few studies have assessed the use of NVC in the pediatric population. Objectives 1. to describe the normal patterns of NVC in healthy children and adolescents in different age groups; 2. to quantify the linear relationship between the age and the capillary dimensions, intercapillary distance and number of capillaries/mm; 3. to evaluate the inter and intraobserver concordance in capillary measurements. Methods This was a cross-sectional study including 100 healthy participants aged 5 to 18 years. NVC was performed using the stereomicroscope under 100x magnification. The capillary dimensions (capillary loop length, capillary width and intercapillary distance) and the number of capillaries/mm were evaluated. Three consecutive images were acquired in nine capillaries per individual, totalizing 900 capillaries examined and photographed. Four age groups were studied: 5-7 years (17); 8-10 years (24); 11-14 years (30) and 15-18 years (29). The intra and inter observer agreement were tested in 25% of subjects. Results The capillary dimensions (mean ± SD) were: capillary loop length 278.6±60.3 μm, intercapillary distance 124.1±28.1 μm, capillary width 15.0±2.6 μm. The intercapillary distance was higher in girls (p=0.011). The intercapillary distance remained constant over time (p=0.088). Teenagers between 15 and 18 years had longer (318.7±64.4 μm) and more enlarged (16.2±3.3 μm) capillaries when compared to other age groups (p<0.001 and p=0.012 respectively). There was a significant increase in the number of capillaries/mm with age: 6.1 capillaries/mm (5-7 years); 7.0 (8 to 10 years); 8.0 (11-14 years) and 9.3 (15-18 years) (p<0.001). Additionally, there was a positive correlation between age and the number of capillaries/mm, capillary length, and capillary width (p<0.001, R=0.796; p<0.001, R=0.368; p=0.004, R=0.285, respectively). There was a good intra and interobserver concordance in all capillary measurements. Morphological abnormalities including enlarged capillary (capillary width percentile>97.5) and avascular areas (intercapillary distance percentile>97.5) were present in 11% and 10% of the capillaries respectively. A weak negative correlation was found between the intercapillary distance and the number of capillaries/mm (p=0.05; R=-0.20). Conclusions There is a wide variability in the capillary morphology among healthy individuals. There was a positive correlation between age and the number of capillaries/mm, capillary length, and capillary width. There was a significant difference in the capillary length and width between the older and younger participants. In addition, NVC has been showed to be a reproducible method. References Cutolo M, Suli A, Smith V. How to perform and interpret capillaroscopy. Best Pract Res Clin Rheumatol. 2013; 27:237-48. Ingegnoli F, Herrick AL. Nailfold capillaroscopy in pediatrics. Arthritis Care Res. 2013;65:1393-00. Herrick AL, Moore T, Hollis S, Jayson MI. The influence of age on nailfold capillary dimensions in childhood. J Rheumatol. 2000;27:797-00. Disclosure of Interest None declared

Laboratorial significance of autoantibodies of dense fine speckled pattern

Purpose Indirect immunofluorescence (IIF) in Hep-2 cells is the standard screening test for antinuclear antibodies (ANA). Advances in this methodology have brought up a considerable increase in sensitivity and consequently a decrease in its specificity. This has resulted in an increasing number of positive tests in apparently healthy subjects. In particular, autoantibodies associated with the dense fine speckled (DSF) ANA-Hep-2 pattern, has been largely detected in apparently healthy individuals.