Clinical and genetic features of hereditary periodic fever syndromes in Hispanic patients: The Chilean experience

Hereditary periodic fever syndromes (HPFS) are rare genetic diseases characterized by recurrent episodes of inflammation. Little information is available concerning HPFS in Latin American Hispanic population. The purpose of this study was to determine the clinical and genetic features of HPFS in Chilean population. A multicenter retrospective study of Hispanic Chilean patients with genetically confirmed HPFS was performed. We included 13 patients, 8 with familial Mediterranean fever (FMF) and 5 with TNF receptor-associated periodic syndrome (TRAPS), evaluated at rheumatology or pediatric rheumatology clinics between January 2007 and December 2010. Median age of symptoms onset was 8 years (range 1–35) and 8 years (range 0.3–21) for FMF and TRAPS, respectively. Median duration of fever was 3 days (range 2.5–15) for FMF and 21 days (range 9.5–30) for TRAPS. Genotyping of the MEFV gene in FMF patients revealed a homozygous M694V missense mutation in one patient, and heterozygous missense mutations in seven patients: M694V (n = 3), E148Q, R717H, A744S, and A511V. Sequencing of the TNFRSF1A gene in TRAPS patients revealed heterozygous missense mutations in four patients: T50M, C30R, R92Q, and IVS3+30:G→A, and a two-base pair deletion (IVS2-17_18del2bpCT) in one patient. Mutation in MEFV R717H and mutations in TNFRSF1A IVS2-17_18del2bpCT and IVS3+30:G→A are novel and have not been described previously. This study reports the largest series of genetically confirmed HPFS in Latin America, and adds evidence regarding the clinical and genetic characteristics of patients with FMF and TRAPS in Hispanic population. Mutations identified in MEFV and TNFRSF1A genes include defects reported in other ethnicities and novel mutations

Design of an algorithm for the diagnostic approach of patients with joint pain

Background Rheumatic diseases are a reason for frequent consultation with primary care doctors. Unfortunately, there is a high percentage of misdiagnosis. Objective To design an algorithm to be used by primary care physicians to improve the diagnostic approach of the patient with joint pain, and thus improve the diagnostic capacity in four rheumatic diseases. Methods Based on the information obtained from a literature review, we identified the main symptoms, signs, and paraclinical tests related to the diagnosis of rheumatoid arthritis, spondyloarthritis with peripheral involvement, systemic lupus erythematosus with joint involvement, and osteoarthritis. We conducted 3 consultations with a group of expert rheumatologists, using the Delphi technique, to design a diagnostic algorithm that has as a starting point “joint pain” as a common symptom for the four diseases. Results Thirty-nine rheumatologists from 18 countries of Ibero-America participated in the Delphi exercise. In the first consultation, we presented 94 items to the experts (35 symptoms, 31 signs, and 28 paraclinical tests) candidates to be part of the algorithm; 74 items (25 symptoms, 27 signs, and 22 paraclinical tests) were chosen. In the second consultation, the decision nodes of the algorithm were chosen, and in the third, its final structure was defined. The Delphi exercise lasted 8 months; 100% of the experts participated in the three consultations. Conclusion We present an algorithm designed through an international consensus of experts, in which Delphi methodology was used, to support primary care physicians in the clinical approach to patients with joint pain

Clinical and Serological Features in Latin American IgG4-Related Disease Patients Differ According to Sex, Ethnicity, and Clinical Phenotype

Background/Objective Data on IgG4-related disease (IgG4-RD) come almost exclusively from cohorts from Asia, Europe, and North America. We conducted this study to describe the clinical presentation, phenotype distribution, and association with sex, ethnicity, and serological markers in a large cohort of Latin American patients with IgG4-RD. Methods We performed a multicenter medical records review study including 184 Latin American IgG4-RD patients. We assigned patients to clinical phenotypes: group 1 (pancreato-hepato-biliary), group 2 (retroperitoneal/aortic), group 3 (head and neck-limited), group 4 (Mikulicz/systemic), and group 5 (undefined). We focused the analysis on how sex, ethnicity, and clinical phenotype may influence the clinical and serological presentation. Results The mean age was 50.8 ± 15 years. Men and women were equally affected (52.2% vs 48.8%). Fifty-four patients (29.3%) were assigned to group 1, 21 (11.4%) to group 2, 57 (30.9%) to group 3, 32 (17.4%) to group 4, and 20 (10.8%) to group 5. Male sex was associated with biliary tract (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.36-8.26), kidney (OR, 3.4; 95% CI, 1.28-9.25), and retroperitoneal involvement (OR, 5.3; 95% CI, 1.45-20). Amerindian patients presented more frequently with atopy history and gallbladder involvement. Group 3 had a female predominance. Conclusions Latin American patients with IgG4-RD were younger, and men and women were equally affected compared with White and Asian cohorts. They belonged more commonly to group 1 and group 3. Retroperitoneal and aortic involvement was infrequent. Clinical and serological features differed according to sex, ethnicity, and clinical phenotype.Fil: Martín-Nares, Eduardo. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Department of Immunology and Rheumatology; MéxicoFil: Baenas, Diego Federico. Hospital Privado Universitario de Córdoba. Servicio de Reumatología; ArgentinaFil: Cuellar Gutiérrez, María Carolina. Hospital Del Salvador. Departamento de Medicina Interna. Servicio de Reumatología; ChileFil: Hernández-Molina, Gabriela. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Department of Immunology and Rheumatology; MéxicoFil: Ortiz, Alberto Christian. Hospital José María Cullen. Sección de Reumatología; ArgentinaFil: Neira, Oscar. Universidad de Chile. Hospital Del Salvador. Sección Reumatología; ChileFil: Neira, Oscar. Clínica Alemana de Santiago-Universidad Del Desarrollo. Unidad Reumatología; ChileFil: Gutiérrez, Miguel A. Universidad de Valparaíso. Hospital Naval Almirante Nef. Departamento de Reumatologia; ChileFil: Calvo, Romina. Hospital José María Cullen. Sección de Reumatología; ArgentinaFil: Saad, Emanuel José. Hospital Privado Universitario de Córdoba. Departamento de Clínica Médica; ArgentinaFil: Elgueta Pinochet, Sergio. Hospital Clínico de la Universidad de Chile. Sección Reumatología. Departamento de Medicina; ChileFil: Gallo, Jesica. Hospital Central de Reconquista. Sección de Reumatología; ArgentinaFil: Herrera Moya, Alejandra. Pontificia Universidad Católica de Chile. Departamento de Inmunología Clínica y Reumatología; ChileFil: Mansilla Aravena, Bellanides Agustina. Hospital Clínico Magallanes; ArgentinaFil: Crespo Espíndola, María Elena. Hospital Señor Del Milagro; ArgentinaFil: Cairoli, Ernesto. Hospital Evangélico. Unidad de Enfermedades Autoinmunes; BrasilFil: Cairoli, Ernesto. Centro Asistencial Del Sindicato Médico Del Uruguay. Unidad de Enfermedades Autoinmunes; UruguayFil: Cairoli, Ernesto. Institut Pasteur. Laboratorio de Inmunorregulación e Inflamación; UruguayFil: Bertoli, Ana María. Universidad Católica de Córdoba. Clínica Universitaria Reina Fabiola. Servicio de Reumatología; ArgentinaFil: Córdoba, Mercedes. Universidad Católica de Córdoba. Clínica Universitaria Reina Fabiola. Servicio de Reumatología; ArgentinaFil: Wurmann Kiblisky, Pamela. Hospital Clínico Universidad de Chile.Fil: Basualdo Arancibia, Washington Javier. Departamento de Medicina. Sección Reumatología; ChileFil: Badilla Piñeiro, María Natalia. Hospital Del Salvador, Universidad de Chile. Sección Reumatología; ChileFil: Gobbi, Carla Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Hospital Córdoba; ArgentinaFil: Berbotto, Guillermo Ariel. Sanatorio Británico. Servicio de Reumatología; ArgentinaFil: Pisoni, Cecilia N. Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno. Sección Reumatología e Inmunología; ArgentinaFil: Juárez, Vicente. Hospital Señor Del Milagro; ArgentinaFil: Cosatti, Micaela Ana. Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno. Sección Reumatología e Inmunología; ArgentinaFil: Aste, Nora María. Reumatología; ArgentinaFil: Airoldi, Carla. Hospital Provincial. Reumatología; ArgentinaFil: Llanos, Carolina. Pontificia Universidad Católica de Chile. Departamento de Inmunología Clínica y Reumatología; ArgentinaFil: Vergara Melian, Cristian Fabián. Hospital San Martin de Quillota; ChileFil: Vergara Melian, Cristian Fabián. Clinica Ciudad Del Mar; ChileFil: Erlij Opazo, Daniel. Universidad de Chile. Hospital Del Salvador. Departamento de Medicina Oriente; ChileFil: Goecke, Annelise. Hospital Clínico Universidad de Chile. Departamento de Medicina. Servicio de Reumatología; ChileFil: Pastenes Montaño, Paula Andrea. Hospital Carlos Van Buren. Servicio de Medicina. Departamento de Reumatología; ChileFil: Tate, Patricio. Organización Médica de Investigación; ArgentinaFil: Pirola, Juan Pablo. Sanatorio Argentino; ArgentinaFil: Stange Núñez, Lilith. Clínica Ciudad Del Mar. Centro de Artritis Reumatoide; ChileFil: Burgos, Paula I. Pontificia Universidad Católica de Chile. Departamento de Inmunología Clínica y Reumatología; ChileFil: Mezzano Robinson, María Verónica. Hospital Del Salvador. Clínica Las Condes; ChileFil: Michalland H, Susana. Universidad de Chile. Hospital Del Salvador. Sección Reumatología; ChileFil: Silva Labra, Francisco. Hospital Padre Hurtado. Facultad de Medicina Clínica Alemana-Universidad Del Desarrollo; ChileFil: Labarca Solar, Cristián Humberto. Hospital Padre Hurtado. Facultad de Medicina Clínica Alemana-Universidad Del Desarrollo; ChileFil: Lencina, María Verónica. Hospital Señor Del Milagro; ArgentinaFil: Izquierdo Loaiza, Jorge Hernán. Clínica de Occidente S.A. Grupo de Reumatología; ColombiaFil: Del Castillo Gil, David Julián. Clínica de Occidente S.A. Grupo de Reumatología; ColombiaFil: Caeiro, Francisco. Hospital Privado Universitario de Córdoba. Servicio de Reumatología; ArgentinaFil: Paira, Sergio. Hospital José María Cullen. Sección de Reumatología; Argentin

Long-term safety of COVID vaccination in individuals with idiopathic inflammatory myopathies: results from the COVAD study

Limited evidence on long-term COVID-19 vaccine safety in patients with idiopathic inflammatory myopathies (IIMs) continues to contribute to vaccine hesitancy. We studied delayed-onset vaccine adverse events (AEs) in patients with IIMs, other systemic autoimmune and inflammatory disorders (SAIDs), and healthy controls (HCs), using data from the second COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. A validated self-reporting e-survey was circulated by the COVAD study group (157 collaborators, 106 countries) from Feb-June 2022. We collected data on demographics, comorbidities, IIM/SAID details, COVID-19 history, and vaccination details. Delayed-onset (> 7 day) AEs were analyzed using regression models. A total of 15165 respondents undertook the survey, of whom 8759 responses from vaccinated individuals [median age 46 (35-58) years, 74.4% females, 45.4% Caucasians] were analyzed. Of these, 1390 (15.9%) had IIMs, 50.6% other SAIDs, and 33.5% HCs. Among IIMs, 16.3% and 10.2% patients reported minor and major AEs, respectively, and 0.72% (n = 10) required hospitalization. Notably patients with IIMs experienced fewer minor AEs than other SAIDs, though rashes were expectedly more than HCs [OR 4.0; 95% CI 2.2-7.0, p < 0.001]. IIM patients with active disease, overlap myositis, autoimmune comorbidities, and ChadOx1 nCOV-19 (Oxford/AstraZeneca) recipients reported AEs more often, while those with inclusion body myositis, and BNT162b2 (Pfizer) recipients reported fewer AEs. Vaccination is reassuringly safe in individuals with IIMs, with AEs, hospitalizations comparable to SAIDs, and largely limited to those with autoimmune multimorbidity and active disease. These observations may inform guidelines to identify high-risk patients warranting close monitoring in the post-vaccination period

COVID-19 vaccine safety during pregnancy and breastfeeding in women with autoimmune diseases: results from the COVAD study

Objectives: We investigated COVID-19 vaccine safety in pregnant and breastfeeding women with autoimmune diseases (AID) in the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. Methods: Delayed-onset (>7 days) vaccine-related adverse events (AE), disease flares (DF), and AID-related treatment modifications were analyzed upon diagnosis of AID versus healthy controls (HC) and the pregnancy/breastfeeding status at the time of at least one dose of vaccine. Results: Among the 9201 participants to the self-administered online survey, 6787 (73.8%) were women. Forty pregnant and 52 breastfeeding patients with AID were identified, of whom the majority had received at least one dose of COVID-19 vaccine (100% and 96.2%, respectively). AE were reported significantly more frequently in pregnant than in non-pregnant patients (overall AE 45% vs 26%, p= 0.01; minor AE 40% vs 25.9%, p= 0.03; major AE 17.5% vs 4.6%, p< 0.01), but no difference was found in comparison with pregnant HC. No difference was observed between breastfeeding patients and HC with respect to AE. Post-vaccination DF were reported by 17.5% of pregnant and 20% of breastfeeding patients, and by 18.3% of age- and disease-matched non-pregnant and non-breastfeeding patients (n = 262). All pregnant/breastfeeding patients who experienced a DF were managed with glucocorticoids; 28.6% and 20% of them required initiation or change in immunosuppressants, respectively. Conclusion: This study provides reassuring insights into the safety of COVID-19 vaccines administered to women with AID during the gestational and post-partum periods, helping overcome hesitant attitudes, as the benefits for the mother and the fetus by passive immunization appear to outweigh potential risks

COVAD survey 2 long-term outcomes: unmet need and protocol

Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups