André de Souza Cavalcanti

Brazilian multicenter study of 71 patients with juvenile-onset Takayasu's arteritis: clinical and angiographic features

OBJECTIVE To describe the clinical and angiographic characteristics of Takayasus arteritis in Brazilian children and adolescents. METHODS A retrospective data collection was performed in 71 children and adolescents followed in 10 Brazilian reference centers in Pediatric Rheumatology. The evaluation was carried out in three different time points: from onset of symptoms to diagnosis, from the 6th to 12th month of diagnosis, and in the last visit. RESULTS Of 71 selected patients, 51 (71.8%) were girls. The mean age of onset of symptoms and of time to diagnosis was 9.2 (±4.2) years and 1.2 (±1.4) years, respectively. At the end of the study, 20 patients were in a state of disease activity, 39 in remission and 5 had evolved to death. The most common symptoms in baseline assessment, second evaluation, and final evaluation were, respectively: constitutional, musculoskeletal, and neurological symptoms. A decrease in peripheral pulses was the most frequent cardiovascular signal, and an increase in erythrocyte sedimentation rate was the most frequent laboratory finding in all three evaluation periods. The tuberculin test was positive in 41% of those tested. Stenosis was the most frequent angiographic lesion, abdominal artery was the most affected segment, and angiographic type IV the most frequent. Most (90%) participants were treated with glucocorticoids, 85.9% required another immunosuppressive drug, and 29.6% underwent angioplasty. CONCLUSION This is the largest study on juvenile-onset Takayasu arteritis, and a high number of patients under the age of 10 years, with predominance of constitutional symptoms early in the disease, was observed.

First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)–Pan-American League of Associations of Rheumatology (PANLAR)

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an ‘overarching’ treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.

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.

Takayasu arteritis in childhood: misdiagnoses at disease onset and associated diseases

Juvenile-Takayasu arteritis (j-TA) is a difficult diagnosis and some patients develop uncommon manifestations and associated diseases that may contribute to the delayed diagnosis. Our aim was to identify the misdiagnoses, the associated diseases and the atypical manifestations observed in a j-TA Brazilian multicentre study. 71 children and adolescents who met the classification criteria for j-TA were included. The misdiagnoses, the associated diseases and the atypical manifestations were evaluated. 19 (26.8%) patients had misdiagnoses. The most common of them was aortic coarctation in six (8.4%) patients, followed by rheumatic fever in five (7.0%) and one patient presented with both former diagnoses. Limb pain (two patients), spondyloarthropathy, juvenile idiopathic arthritis (JIA), spinal arteriovenous malformation, polyarteritis nodosa (PAN) and fever of unknown origin (FUO) were other misdiagnoses. Patients who had misdiagnoses previously to j-TA diagnosis presented a trend to have a longer diagnosis delay. 11 (15.5%) patients had 14 TA-associated diseases, such as pulmonary tuberculosis (5 patients), rheumatic fever (2 patients), spondyloarthropathy, polyarticular JIA, Crohn’s disease, Prader–Willi disease, diabetes mellitus, Moyamoya and primary immunodeficiency. 7 (9.9%) patients presented 10 atypical manifestations, such as pyoderma gangrenosum, erythema nodosum, myositis, chorea, enthesitis, episcleritis, uveitis, hepatomegaly, splenomegaly and necrosis of extremities. Our study emphasizes the main misdiagnoses, associated diseases and atypical manifestations that occur in patients with j-TA and warns of the features that may alert paediatricians to this diagnosis, such as constitutional symptoms and elevated inflammatory markers.

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.

FRI0363 Children have a longer delay in diagnosis of takayasu arteritis than adolescents: lack of awareness about the disease?

Background Takayasu’s arteritis (TA) is a chronic granulomatous vasculitis affecting the large and medium arteries and can result in end organ damage. The disease is rare and there are few reports about the clinical features in the pediatric population. Objectives To evaluate and to compare the clinical features of TA in Brazilian children and adolescents. Methods In this Brazilian multicenter retrospective study including 10 pediatric rheumatology centers we identified 71 children and adolescents with TA diagnosed before the age of 18 years according to the validated classification criteria for pediatric age1. Patients’ demographic, clinical, laboratory and angiographic data were collected. The angiographic type was classified according to the 1994 International Conference of Takayasu arteritis in Tokyo2. Patients were divided in 2 groups: children, younger than 10 years – group 1, and adolescents, older than or equal to 10 years – group 2 and their disease characteristics at initial presentation were compared. Results Thirty-six (50.7%) patients were in group 1 and 35 (49.3%) were in group 2. Twenty-one (58.3%) patients in group 1 and 30 (85.7%) patients in group 2 were girls (p=0.010). The mean onset age was 5.7 and 12.7 in groups 1 and 2 (p<0.001); the mean time to diagnosis was 1.8 and 0.7 in groups 1 and 2 (p= 0.001) and the mean follow-up time was 7.2 and 3.6 in groups 1 and 2 (p <0.001). The predominant clinical symptoms at onset were decreased pulses (85.9%), followed by arterial hypertension (84.5%), constitutional (77.5%) and neurological symptoms (70.4%), however without statistical differences between the two groups. The main laboratory finding was an increased erythrocyte sedimentation rate followed by leukocytosis. Anemia and thrombocytosis were significantly more frequent in group 1 (p = 0.031; p= 0.001). Angiographic data were similar in both groups. Conclusions Children under the age of 10 had more laboratory abnormalities, but similar clinical and angiographic features when compared to adolescents with TA. A delay in diagnosis is more common in younger patients and clinicians must be aware about this disease in this age group. References Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R et al. EULAR/PRINTO/PRES criteria for Henoch-Schoenlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu’s arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010;69:798-806. Hata A, Noda M, Moriwaki R, Numano F. Angiographic findings of Takayasu arteritis: New classification. Int J Cardiol.1996;54(suppl):S155-S163. Disclosure of Interest: None Declared

Brazilian multicentre study of Takayasu’s arteritis in children and adolescents – preliminary results of a clinical, imaging and therapeutic study

We retrospectively evaluated 55 patients with Takayasu’s arteritis from 8 Pediatric Rheumatology centers in Brazil. All patients fulfilled the specific classification criteria for TA that have most recently been developed for the pediatric age group. Clinical, data were collected at two time points (at disease onset and at the last available visit). Results The majority of patients were girls (84%), with mean age at disease onset of 9.3 years, mean age at diagnosis of 10.6 years and a mean follow-up period of 5.6 years. The most common initial clinica lm anifestations included headache (56.3%), malaise (56.3%), weight loss (45.4%), dyspnea (41.8%) and limb pain (41.8%). The most common cardiovascular finding was hypertension (85.4%). The most frequent laboratory abnormality was an increased erythrocyte sedimentation rate (70.9%). The Mantoux test was positive in 38% of patients. The most common alteration was narrowing or stenosis. The most involved vessels were abdominal aorta (71.8%) followed by left (56.2%) and right renal artery (53.1%). At the last visit the most common clinical manifestations were: headache (22%), inferior limb claudication (14%) and arthralgias (12%); Cardiovascular finding included the absence or decrease of the inferior limb pulses (52%). The treatment included imunossupressors other than corticosteroids in 83.6% and anti-TNF antagonists in 7.2% of patients. Seventeen (30.9%) patients underwent surgical intervention and 5 (9%) died of complication from treatment or from disease related complications. Conclusion In this large survey of children and adolescents with Takayasu’s arteritis from Brazil a delay in the diagnosis and a high rate of Mantoux test positivity were observed. A death rate similar to the described in literature was found.