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.

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Familial Hemophagocytic Lymphohistiocytosis type 2 (FHL2) results from mutations in PRF1. We described two unrelated individuals who presented with FHL, in whom severely impaired NK cytotoxicity and decrease perforin expression was observed. DNA sequencing of PRF1 demonstrated that both were not only heterozygous for the p.54R > C/91A > V haplotype but also presented with the novel variant p.47G > V at the perforin protein. Perforin mRNA was found to be increased in a individual with that genotype. A carrier of the novel variant also demonstrated altered perforin mRNA and protein expression. Phylogenetic analysis and multiple alignments with perforin orthologous demonstrated a high level of conservation at Gly47. PolyPhen-2 and PROVEAN predicted p.47G > V to be "probably damaging" and "deleterious", respectively. A thermodynamic analysis showed that this variant was highly stabilizing, decreasing the protein internal energy. The ab initio perforin molecular modeling indicated that Gly47 is buried inside the hydrophobic core of the MACPF domain, which is crucial for the lytic pore formation and protein oligomerization. After the in silico induction of the p.47G > V mutation, Val47 increased the interactions with the surrounding amino acids due to its size and physical properties, avoiding a proper conformational change of the domain. To our knowledge, this is the first description supporting that p.47G > V is a pathogenic variant that in conjunction with p.54R > C/91A > V might result in the clinical phenotype of FHL2.

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Background:Polyarteritis nodosa (PAN) is the third most frequent vasculitis in pediatrics, Cutaneous PAN (CPAN) being more common that Systemic PAN (SPAN). CPAN is frequently described as a benign disease. In children, PAN onset is frequent between 9 and 11 years of age, with no sex differences, and its clinical features may be nonspecific.Objectives:To characterize pediatric patients who were diagnosed with CPAN and SPAN and to compare their clinical features, treatments, and outcome.Methods:A descriptive study was conducted in two centers from Medellin- Colombia, using retrospective data from January 2010 to December 2019. Patients under 18 years of age classified as PAN according to EULAR/PRINTO/PRES(1) criteria were included. CPAN patients were defined according to EULAR/PRES definition (2). Data from medical records were registered, and were expressed in median and ranges and mean and standard deviation (SD) according to their distribution. A univariate analysis was carried out by comparing signs, symptoms, and treatment between CPAN and SPAN, and ap-value < 0,05was considered as significant.Results:Twenty patients were included. The median age at diagnosis was ten years. 60% were boys. The median follow-up period was 27 months. CPAN was diagnosed in 11 (55%) and SPAN in 9 patients (45%). The most frequent symptoms were cutaneous manifestations (95%), fever (60%) and Calf Pain (55%). Mucosal ulcers were described in four patients; 3 of them were defined as CPAN. Lingual necrosis was present in two CPAN, and peripheral nervous system involvement was found in one SPAN and two CPAN patients in skin affected with lesions; even though, no significant statistical differences between CPAN and SPAN were found in constitutional, cutaneous, muscle-skeletal symptoms, and acute phase reactants. Arteriographic anomalies as hepatic and renal microaneurysms, carotidal aneurysms without aortic involvement, and renal infarction were found in one patient each. Skin Biopsy was performed in 18 patients, being compatible with PAN in 16. All PAN patients (CPAN and SPAN) required treatment with glucocorticoids. None of the patients died during the follow-up period.Conclusion:In this Colombian pediatric cohort of PAN patients, the disease was more common in boys than girls, and CPAN was more frequent than SPAN, as already been described. As is evident in this cohort, although CPAN has been considered a benign disease, these patients may be severely ill, requiring glucocorticoid treatment. Pediatric CPAN patients should be strictly followed with particular attention to identify systemic involvement, considering that constitutional, cutaneous, and muscle-skeletal features may be very similar between CPAN and SPAN.References:[1]Ozen S, Pistorio A, Iusan S, et al. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010 May;69(5):798–806.[2]Ozen S, Ruperto N, Dillon M, et al. EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann Rheum Dis. 2006;65(7):936–41.Disclosure of Interests:None declared

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Objective To identify determinants and outcomes associated with infection in paediatric systemic lupus erythematosus (SLE) patients at admission and during hospitalization in intensive care units (ICUs). Patients and methods A retrospective cohort study of paediatric SLE patients admitted to two ICUs was conducted. Frequency and risk factors of infection as well as mortality were studied. Results Seventy-three infection episodes amongst 55 patients were analysed. The median age was 14.4 years (IQR 12.5–16). The median SLEDAI was 16 (IQR 12–20). Twenty-nine episodes were documented at admission; the CRP was higher in these patients (6.58 versus 1.04 mg/dl, p<0.001) than in non-infected patients, even after multivariate adjustment (OR 8.6, 95% CI = 2.1–34.8, p = 0.003). Twenty-five (34.7%) episodes occurred during hospitalization. Lupus activity (OR 1.14, 95% CI = 1.01–1.27, p = 0.029), cyclophosphamide (OR 17.9, 95% CI = 2–156, p = 0.009) and mechanical ventilation (OR 16, 95% CI = 2.1–122, p = 0.008) were associated with infection. Ten episodes (14%) led to death. Admission to the ICU due to infection was strongly associated with mortality (90% versus 31.8%, OR 19.4, 95% CI = 2.3–163, p = 0.006). Conclusion In paediatric lupus patients admitted to the ICU, elevated CRP should alert clinicians to possible infection. During hospitalization, SLE activity and cyclophosphamide were associated with infection. Infection at admission to the ICU was strongly associated with mortality.

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