The HyperPed-COVID international registry: Impact of age of onset, disease presentation and geographical distribution on the final outcome of MIS-C.

OBJECTIVES: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome. STUDY DESIGN: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (<1, 1-4, 5-11, 12-16, >16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified. RESULTS: Time to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (<1 year), in older patients (>16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes. CONCLUSIONS: The stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities.

Risk Factors Associated with Intensive Care Admission in Children with Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome (MIS-C) in Latin America: A Multicenter Observational Study of the REKAMLATINA Network.

Background: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 varies widely in its presentation and severity, with low mortality in high-income countries. In this study in 16 Latin American countries, we sought to characterize patients with MIS-C in the pediatric intensive care unit (PICU) compared with those hospitalized on the general wards and analyze the factors associated with severity, outcomes, and treatment received. Study Design: An observational ambispective cohort study was conducted including children 1 month to 18 years old in 84 hospitals from the REKAMLATINA network from January 2020 to June 2022. Results: A total of 1239 children with MIS-C were included. The median age was 6.5 years (IQR 2.5-10.1). Eighty-four percent (1043/1239) were previously healthy. Forty-eight percent (590/1239) were admitted to the PICU. These patients had more myocardial dysfunction (20% vs 4%; P < 0.01) with no difference in the frequency of coronary abnormalities (P = 0.77) when compared to general ward subjects. Of the children in the PICU, 83.4% (494/589) required vasoactive drugs, and 43.4% (256/589) invasive mechanical ventilation, due to respiratory failure and pneumonia (57% vs 32%; P = 0.01). On multivariate analysis, the factors associated with the need for PICU transfer were age over 6 years (aOR 1.76 95% CI 1.25-2.49), shock (aOR 7.06 95% CI 5.14-9.80), seizures (aOR 2.44 95% CI 1.14-5.36), thrombocytopenia (aOR 2.43 95% CI 1.77-3.34), elevated C-reactive protein (aOR 1.89 95% CI 1.29-2.79), and chest x-ray abnormalities (aOR 2.29 95% CI 1.67-3.13). The overall mortality was 4.8%. Conclusions: Children with MIS-C who have the highest risk of being admitted to a PICU in Latin American countries are those over age six, with shock, seizures, a more robust inflammatory response, and chest x-ray abnormalities. The mortality rate is five times greater when compared with high-income countries, despite a high proportion of patients receiving adequate treatment.

Clinical Presentation and Outcomes of Kawasaki Disease in Children from Latin America: A Multicenter Observational Study from the REKAMLATINA Network.

OBJECTIVES: To describe the clinical presentation, management, and outcomes of Kawasaki disease (KD) in Latin America and to evaluate early prognostic indicators of coronary artery aneurysm (CAA). STUDY DESIGN: An observational KD registry-based study was conducted in 64 participating pediatric centers across 19 Latin American countries retrospectively between January 1, 2009, and December 31, 2013, and prospectively from June 1, 2014, to May 31, 2017. Demographic and initial clinical and laboratory data were collected. Logistic regression incorporating clinical factors and maximum coronary artery z-score at initial presentation (between 10 days before and 5 days after intravenous immunoglobulin [IVIG]) was used to develop a prognostic model for CAA during follow-up (>5 days after IVIG). RESULTS: Of 1853 patients with KD, delayed admission (>10 days after fever onset) occurred in 16%, 25% had incomplete KD, and 11% were resistant to IVIG. Among 671 subjects with reported coronary artery z-score during follow-up (median: 79 days; IQR: 36, 186), 21% had CAA, including 4% with giant aneurysms. A simple prognostic model utilizing only a maximum coronary artery z-score ≥2.5 at initial presentation was optimal to predict CAA during follow-up (area under the curve: 0.84; 95% CI: 0.80, 0.88). CONCLUSION: From our Latin American population, coronary artery z-score ≥2.5 at initial presentation was the most important prognostic factor preceding CAA during follow-up. These results highlight the importance of early echocardiography during the initial presentation of KD.

Multisystem inflammatory syndrome in children related to COVID-19: Data from a Mexican national referral children's hospital.

Objectives: To describe characteristics of patients with the pediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV-2 (PIMS-TS)/multisystem inflammatory syndrome in children (MIS-C) and to identify factors associated with admission to the pediatric intensive care unit (PICU) in the Mexican children without coronavirus disease 2019 (COVID-19) vaccination. Methods: This was a cross-sectional study performed at Hospital Infantil de Mexico Federico Gomez, a referral children's hospital in Mexico. The study included all cases that met the criteria for PIMS-TS/MIS-C, unvaccinated, between March 2020 and January 2022. The primary outcome was the admission to PICU. Associations of PICU admission with demographic and clinical variables were estimated using logistic regression analyses. Results: We identified a total of 90 cases, with a median age of 7.5 years old, 47 (52.2%) girls. A previously healthy status was recorded in 76 (85%) children. All patients had positive PCR, serology test, or COVID-19 exposure. PICU admission was reported in 41 (45.6%) children. No deaths were reported. Patients received as treatment only corticosteroids in 53.3% of the cases. In univariable analyses, baseline factors associated with PICU admission were older age, hypotension or shock, positive PCR test, hypoalbuminemia, elevated procalcitonin, ferritin, and lymphopenia. Age, shock at admission, and hypoalbuminemia remained independently associated in the multivariable analysis adjusted by gender and previously healthy status. Conclusion: We found a high proportion of previously healthy children in patients with PIMS-TS/MIS-C in our center. Critical care attention was received by nearly half of the children. The main treatment used was steroids. Age, shock at admission, and hypoalbuminemia were factors associated with PICU admission.

Psychosocial and economic impact of rheumatic diseases on caregivers of Mexican children.

BACKGROUND: Pediatric rheumatic disease (PRD) patients and their caregivers face a number of challenges, including the consequences of the PRD in patients and the impact on multiple dimensions of the caregivers' daily lives. The objective of this study is to measure the economic, psychological and social impact that PRD has on the caregivers of Mexican children. METHODS: This is a multicenter, cross-sectional study including primary caregivers of children and adolescents with PRD (JIA, JDM and JSLE) during April and November, 2019. A trained interviewer conducted the CAREGIVERS questionnaire, a specific, 28-item multidimensional tool validated to measure the impact on different dimensions of the lives of caregivers. Sociodemographic, clinical, and healthcare system data were collected for further analysis. RESULTS: Two hundred participants were recruited (women 169, 84.5%, aged 38 [IQR 33-44] years); 109 (54.5%) cared for patients with JIA, 28 (14%) JDM and 63 (31.5%) JSLE. The healthcare system was found to be determinant on the impact of the disease. The emotional impact was higher in all the participants, regardless of the specific diagnoses. The social dimension showed significant differences regarding PRD, healthcare system, time to reach the center, presence of disability, active disease, cutaneous and systemic manifestations, treatment and partner. Financial and work impacts were more frequent in those caring for JSLE and less so in those with a partner. Family relationships changed in 81 caregivers (25 [12.5%] worsened and 56 [28%] improved). No variables affecting spirituality were found. For caregivers without a partner, the social networks impact increased. CONCLUSION: The influence of sociodemographic factors can be devastating on families with children with a PRD. These data will help physicians to identify the areas with the greatest need for intervention to achieve comprehensive care for caregivers and their patients.

Childhood-onset of primary Sjögren's syndrome: phenotypic characterization at diagnosis of 158 children.

OBJECTIVES: To characterize the phenotypic presentation at diagnosis of childhood-onset primary SS. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry using worldwide data-sharing cooperative merging of pre-existing clinical SS databases from the five continents. For this study, we selected those patients in whom the disease was diagnosed below the age of 19 years according to the fulfilment of the 2002/2016 classification criteria. RESULTS: Among the 12 083 patients included in the Sjögren Big Data Registry, 158 (1.3%) patients had a childhood-onset diagnosis (136 girls, mean age of 14.2 years): 126 (80%) reported dry mouth, 111 (70%) dry eyes, 52 (33%) parotid enlargement, 118/122 (97%) positive minor salivary gland biopsy and 60/64 (94%) abnormal salivary US study, 140/155 (90%) positive ANA, 138/156 (89%) anti-Ro/La antibodies and 86/142 (68%) positive RF. The systemic EULAR Sjögren's syndrome disease activity index (ESSDAI) domains containing the highest frequencies of active patients included the glandular (47%), articular (26%) and lymphadenopathy (25%) domains. Patients with childhood-onset primary SS showed the highest mean ESSDAI score and the highest frequencies of systemic disease in 5 (constitutional, lymphadenopathy, glandular, cutaneous and haematological) of the 12 ESSDAI domains, and the lowest frequencies in 4 (articular, pulmonary, peripheral nerve and CNS) in comparison with patients with adult-onset disease. CONCLUSIONS: Childhood-onset primary SS involves around 1% of patients with primary SS, with a clinical phenotype dominated by sicca features, parotid enlargement and systemic disease. Age at diagnosis plays a key role in modulating the phenotypic expression of the disease.

Kawasaki disease presenting with hoarseness: A multinational study of the REKAMLATINA network.

BACKGROUND: Recently, hoarseness affecting the supraglottic structure has been reported in Kawasaki disease (KD). The objective of this study was to characterize the frequency of hoarseness in acute KD patients in Latin America. METHODS: We used prospective data from the multinational Red de Enfermedad de Kawasaki en America Latina (REKAMLATINA) network. A total of 865 patients from 20 countries were enrolled during the 3 year study period. Data on hoarseness were available in 858 (99.2%) patients. The clinical and laboratory characteristics between hoarse and non-hoarse KD were compared. RESULTS: Hoarseness was documented in 100 (11.6%) patients. Hoarse patients were younger than those with KD without hoarseness (median age 18 vs 26 months; P = 0.002) and presented with lower hemoglobin (10.7 g/dL vs 11.3 g/dL; P = 0.040) and hematocrit levels (32% vs 33%, P = 0.048). CONCLUSIONS: Hoarseness was found to be prevalent as a presenting sign of acute KD in younger children. Anemia may indicate the presence of active inflammation.

Use of Adjunctive Therapy in Acute Kawasaki Disease in Latin America.

Objective: To characterize the use of adjunctive therapy in Kawasaki disease (KD) in Latin America. Methods: The study included 1,418 patients from the Latin American KD Network (REKAMLATINA) treated for KD between January 1, 2009, and May 31, 2017. Results: Of these patients, 1,152 received only a single dose of IVIG, and 266 received additional treatment. Age at onset was similar in both groups (median 2 vs. 2.2 years, respectively). The majority of patients were male (58 vs. 63.9%) and were hospitalized with the first 10 days of fever (85.1 vs. 84.2%). The most common adjunctive therapy administered was steroids for IVIG-resistance, followed by additional doses of IVIG. The use of biologics such as infliximab was limited. KD patients who received adjunctive therapy were more likely to have a lower platelet count and albumin level as well as a higher Z score of the coronary arteries. Conclusion: This is the first report of adjunctive therapies for KD across Latin America. IVIG continues to be the initial and resistance treatment, however, steroids are also used and to a lesser extent, biological therapy such as infliximab. Future studies should address the barriers to therapy in children with acute KD throughout Latin America.

Presentation and Outcomes of Kawasaki Disease in Latin American Infants Younger Than 6 Months of Age: A Multinational Multicenter Study of the REKAMLATINA Network.

Objective: To characterize the clinical presentation and outcomes of Kawasaki disease (KD) in infants <6 months of age as compared to those ≥6 months in Latin America. Methods: We evaluated 36 infants <6 months old and 940 infants ≥6 months old diagnosed with KD in Latin America. We compared differences in laboratory data, clinical presentation, treatment response, and coronary artery outcomes between the two cohorts. Results: The majority (78.1%) of infants and children ≥6 months of age were initially diagnosed with KD, as compared to only 38.2% of infants <6 months. Clinical features of KD were more commonly observed in the older cohort: oral changes (92 vs. 75%, P = 0.0023), extremity changes (74.6 vs. 57.1%, P = 0.029), and cervical lymphadenopathy (67.6 vs. 37.1%, P = 0.0004). Whether treated in the first 10 days of illness or after the 10th day, infants <6 months were at greater risk of developing a coronary artery aneurysm compared to KD patients ≥6 months treated at the same point in the course of illness [ ≤ 10 days (53.8 vs. 9.4%, P = 0.00012); >10 days (50 vs. 7.4%, P = 0.043)]. Conclusion: Our data show that despite treatment in the first 10 days of illness, infants <6 months of age in Latin America have a higher risk of developing a coronary artery aneurysm. Delay in the diagnosis leads to larger coronary artery aneurysms disproportionately in these infants. Thus, suspicion for KD should be high in this vulnerable population.

Enfermedad de Kawasaki en un hospital pediátrico en México / Kawasaki disease at a pediatric hospital in Mexico

Resumen: Introducción: La enfermedad de Kawasaki (EK) es una de las vasculitis sistémicas más comunes en niños menores de 5 años de edad. La epidemiología de la enfermedad no está bien establecida en México. El objetivo de este trabajo fue describir la epidemiología, características clínicas y tratamiento de los pacientes con EK atendidos en el Hospital Infantil de México Federico Gómez (HIMFG). Métodos: Se realizó un estudio retrospectivo, descriptivo y analítico de pacientes diagnosticados con EK en el HIMFG en el periodo comprendido entre enero de 2004 y diciembre de 2014. Resultados: Se analizaron 204 casos, la mayoría de sexo masculino (55%), con mediana de edad de 32.5 meses (6-120) y una tasa de hospitalización del 96%. El 20% de los pacientes presentó EK incompleto. No se reportaron diferencias en la somatometría ni signos vitales. La sintomatología más frecuente fue fiebre, conjuntivitis (89%), cambios orales (84%), faringitis (88%) y lengua en fresa (83%). Se encontraron reactantes de fase aguda más elevados en las presentaciones clásicas. Se reportaron alteraciones ecocardiográficas en 60 pacientes (29%), de las cuales el 12% fueron ectasia y el 11% aneurismas coronarios. Por otro lado, 169 pacientes (83%) recibieron inmunoglobulina intravenosa (IGIV), 18 (9%) resistencia a IGIV, 6 (3%) requirieron corticosteroides y 2 (1%) infliximab; todos recibieron ácido acetilsalicílico. Conclusiones: No se encontraron diferencias importantes entre las presentaciones clásicas e incompletas. La incidencia de alteraciones cardiacas es menor a la reportada previamente en México, pero similar a la de otros países.

Abstract: Background: Kawasaki disease (KD) is one of the most common systemic vasculitis in children under 5 years of age. The epidemiology of the disease is not well established in Mexico. The objective of this study was to describe the epidemiology, clinical features and treatment of patients with KD at the Hospital Infantil de Mexico Federico Gomez (HIMFG). Methods: We conducted a retrospective, descriptive and analytical study of patients diagnosed from January 2004 to December 2014 with KD in the HIMFG. Results: We analyzed 204 cases from which 55% were male, with a median age of 32.5 months (6-120) and a rate of hospitalization of 96%. Twenty percent of patients presented incomplete KD. No differences in the somatometric measurements or vitals were reported. The most frequent symptoms were fever, conjunctivitis (89%), oral changes (84%), pharyngitis (88%) and strawberry tongue (83%). We found higher acute phase reactants in the classic presentation. Echocardiographic alterations in 60 patients (29%), of which 12% were ectasia and 11% reported coronary aneurysms. On the other hand, 169 (83%) patients received intravenous immunoglobulin (IVIG), 18 (9%) presented resistance to IVIG, 6 (3%) required corticosteroids, and 2 (1%) infliximab; all received acetylsalicylic acid. Conclusions: There were no important differences between classic and incomplete presentations. The incidence of cardiac alterations is less than previously reported in Mexico, but similar to that of other countries.

[Kawasaki disease at a pediatric hospital in Mexico]. / Enfermedad de Kawasaki en un hospital pediátrico en México.

BACKGROUND: Kawasaki disease (KD) is one of the most common systemic vasculitis in children under 5 years of age. The epidemiology of the disease is not well established in Mexico. The objective of this study was to describe the epidemiology, clinical features and treatment of patients with KD at the Hospital Infantil de Mexico Federico Gomez (HIMFG). METHODS: We conducted a retrospective, descriptive and analytical study of patients diagnosed from January 2004 to December 2014 with KD in the HIMFG. RESULTS: We analyzed 204 cases from which 55% were male, with a median age of 32.5 months (6-120) and a rate of hospitalization of 96%. Twenty percent of patients presented incomplete KD. No differences in the somatometric measurements or vitals were reported. The most frequent symptoms were fever, conjunctivitis (89%), oral changes (84%), pharyngitis (88%) and strawberry tongue (83%). We found higher acute phase reactants in the classic presentation. Echocardiographic alterations in 60 patients (29%), of which 12% were ectasia and 11% reported coronary aneurysms. On the other hand, 169 (83%) patients received intravenous immunoglobulin (IVIG), 18 (9%) presented resistance to IVIG, 6 (3%) required corticosteroids, and 2 (1%) infliximab; all received acetylsalicylic acid. CONCLUSIONS: There were no important differences between classic and incomplete presentations. The incidence of cardiac alterations is less than previously reported in Mexico, but similar to that of other countries.

Factors associated with mortality and infections in patients with systemic lupus erythematosus with diffuse alveolar hemorrhage.

OBJECTIVE: To evaluate factors associated with mortality and infections in patients with systemic lupus erythematosus (SLE) and diffuse alveolar hemorrhage (DAH). METHODS: A retrospective chart review was carried out for medical admissions of patients with a diagnosis of SLE and DAH in 9 hospitals. Clinical and laboratory data were recorded for each patient at DAH diagnosis. RESULTS: We included 57 episodes of DAH of 50 patients (7 recurrences), 49 women (86%), 14 juvenile SLE (24.6%); 24 had died (42.1%). In the chart review we detected infection in 22 episodes (38.6%): 8 invasive fungal infections, 16 bacterial infections, and 2 patients had both types. In the bivariate analysis, factors associated with mortality were high Acute Physiology and Chronic Health Evaluation II scores, requirement of mechanical ventilation (OR 15.0, 95% CI 1.9 to 662.2), infections (fungal or bacterial; OR 3.2, CI 0.9 to 11.1), renal failure (OR 4.9, CI 1.4 to 18.0), and thrombocytopenia (OR 4.3, CI 1.2 to 15.6). We found similar mortality between children and adults. Infections were associated with treatment for SLE, requirement of mechanical ventilation, hypocomplementemia, and high levels of C-reactive protein. CONCLUSION: Infection is a frequent finding in patients with DAH and SLE; we found similar mortality between adult SLE and juvenile SLE. Factors that we describe associated with infections may influence the therapeutic selection for these patients.

Type III Takayasu's arteritis in a pediatric patient. Case report and review of the literature.

Takayasu's arteritis (TA), also known as "pulseless disease", is the third most common vasculitis in childhood. It is a chronic, idiopathic, granulomatous vasculitis that involves large vessels. It occurs most commonly in females with a 4:1 ratio over males; the average age of appearance is 26 years. Its cause is unknown. Here we report the case of a 7-year-old girl, with type III TA according to the Numano classification, in the ischemic phase, treated with corticosteroids and immunosuppressive agents and early angioplasty due to the severity of the disease. The outcome was satisfactory. The diagnosis of TA in children under 10 years of age is made only in 2% of them. The delay in diagnosis reaches a mean of 19 months. The course of the disease is variable despite surgical and immunosuppressive treatment.

[Kawasaki's disease in remission with cardiac involvement: intrasacular thrombus in a giant aneurism of both coronary arteries. Case report]. / Enfermedad de Kawasaki en fase de convalecencia con afección cardiaca: trombo intra-sacular en aneurisma gigante de ambas coronarias. A propósito de un caso.

Kawasaki disease is of relevance in pediatric practice because it is a systemic vasculitis of unknown origin and the most common cause of acquired heart disease in young patients. Its main complication is the formation of a coronary aneurysm in 25% of patients, unless they receive timely medical treatment. We report the case of a 4 month old male child with Kawasaki's disease, received treatment with gammaglobulin and acetyl-salicylic acid, in which the initial echocardiogram showed aneurysms. Admitted to our hospital with cardiogenic shock, we documented by echocardiography the presence of coronary aneurysms with intra-saccular thrombus and acute myocardial infarction. He received fibrinolytic therapy, with an adequate response: the size of aneurysms decreased, as did the intra-saccular thrombus. Currently the patient is asymptomatic and receiving treatment with warfarin and acetylsalicylic acid. The diagnosis and treatment, as well as identification of risk factors can prevent fatal complications at the cardiovascular level. The treatment in the first 10 days of illness with gammaglobulin and acetyl-salicylic acid reduced cardiac complications from 4.7 to 25%.

[Juvenile dermatomyositis and extensive calcinosis. Treatment with methylprednisolone and methotrexate]. / Dermatomiositis juvenil y calcinosis extensa. Tratamiento con metilprednisolona y metotrexato.

Juvenile dermatomyositis (JDM) is considered a multisystemic disease of uncertain etiology. The clinical manifestation is a non-suppurative inflammation of the striated muscle, gastrointestinal tract and skin. Dystrophic calcifications are present in 30%-70% of children with JDM. The clinical case we are presenting is a 4 years old female with diagnosis of JDM in accordance to the Bohan and Peters criteria (very early presentation age) with extensive calcinosis, classified as functional class III, without being able to sit down or flex her knees. She was treated with IV methylprednisolone (MPS) bolus every 14 days and oral methotrexate, with improvement of her clinical condition. Even though calcinosis is a frequent finding in connective tissue disease and can cause severe disability, there are no treatment protocols at this time. The simultaneous use of IV MPS and oral methotrexate allows for a faster control of the disease, improvement in muscular force, reduction of erythema and regression of the calcinosis without important collateral effects.

[Systemic lupus erythematosus in a 6 year old female child]. / Lupus eritematoso sistémico en una lactante de 6 meses.

Systemic lupus erythematosus (SLE) is an uncommon disease, particularly in the first decade of life. Finding it before the first year of life is very rare and it entails a difficult diagnosis to document because the clinical manifestations can be very variable and can simulate a great variety of diseases. In the pediatric age, incidence of SLE is 0.36-0.9/100 000 children, with greater prevalence in females 3:1 under 12 years of age and 10:1 in patients over 12 years. There is a very low incidence of SLE before 4 years of age. We present the clinical case of a 9 month-old female in whom four criteria of SLE were clearly documented at 6 months of age. In a review of literature, this is the youngest patient reported with SLE. Physicians must be very alert of the higher risk of systemic complications in children that are diagnosed with SLE at an early age.