RESUMEN
OBJECTIVE: To describe the clinical characteristics, treatment, and outcomes of a multinational cohort of patients with macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). STUDY DESIGN: International pediatric rheumatologists were asked to collect retrospectively the data of patients with the co-occurrence of MAS and TMA. Clinical and laboratory features of patients with systemic juvenile idiopathic arthritis (sJIA)-associated MAS and TMA were compared with those of an historical cohort of patients with sJIA and MAS. RESULTS: Twenty-three patients with MAS and TMA were enrolled: 17 had sJIA, 2 systemic lupus erythematosus, 1 juvenile dermatomyositis, 1 mixed connective tissue disease, and 2 undifferentiated connective tissue disease. Compared with the historical cohort of MAS, patients with sJIA with coexistent MAS and TMA had higher frequencies of renal failure and neurologic involvement, hemorrhage, jaundice, and respiratory symptoms, as well as more severe anemia and thrombocytopenia, higher levels of alanine aminotransferase, lactate dehydrogenase, bilirubin and D-dimer, and lower levels of albumin and fibrinogen. They also required admission to the intensive care unit more frequently. Among patients tested, complement abnormalities and reduced ADAMTS13 activity were observed in 64.3% and 44.4% of cases, respectively. All patients received glucocorticoids. Treatment for TMA included plasma-exchange, eculizumab, and rituximab. CONCLUSIONS: The possible coexistence of MAS and TMA in rheumatic diseases may be underrecognized. This association should be considered in patients with MAS who develop disproportionate anemia, thrombocytopenia, and lactate dehydrogenase increase, or have multiorgan failure.
Asunto(s)
Artritis Juvenil/fisiopatología , Síndrome de Activación Macrofágica/fisiopatología , Microangiopatías Trombóticas/fisiopatología , Adolescente , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Juvenil/complicaciones , Artritis Juvenil/tratamiento farmacológico , Biomarcadores/sangre , Niño , Preescolar , Glucocorticoides/uso terapéutico , Humanos , Síndrome de Activación Macrofágica/complicaciones , Síndrome de Activación Macrofágica/tratamiento farmacológico , Intercambio Plasmático , Estudios Retrospectivos , Microangiopatías Trombóticas/complicaciones , Microangiopatías Trombóticas/tratamiento farmacológicoRESUMEN
OBJECTIVE: To identify clinical and laboratory predictors for early macrophage activation syndrome (MAS) associated with systemic juvenile idiopathic arthritis (sJIA). STUDY DESIGN: This is a retrospective cohort study of 149 patients with sJIA, of whom 27 had 31 episodes of MAS. We evaluated the clinical and laboratory features of patients with sJIA and MAS and compared them with those without MAS. We focused our analysis on the overall process of MAS development, especially MAS onset. RESULTS: As shown in previous studies, we found a high percentage of fever, absence of arthritis, and central nervous system dysfunction at MAS onset in our study cohort. We also found that 35% of patients with MAS had hypotension although not shock, and 22.6% of patients with MAS had gastrointestinal involvement at MAS onset. Compared with patients with MAS without hypotension, patients with MAS and hypotension had greater rates of admission to the intensive care unit; presented with more arthritis, serositis, pneumonia, and gastrointestinal involvement; and had greater white blood cell and absolute neutrophil counts and serum bilirubin levels and lower serum total protein. We confirmed laboratory markers such as platelet counts, lactate dehydrogenase, and aspartate aminotransferase can help to identify early MAS and that ferritin/erythrocyte sedimentation rate ratio of approximately 20.0 had a high diagnostic sensitivity and specificity for MAS. In addition, we discovered that the combination of interferon-γ >17.1 pg/mL and interleukin-10 >7.8 pg/mL appeared to be a good cytokine pattern for the recognition of MAS onset. CONCLUSIONS: Sudden hypotension, elevated ferritin/erythrocyte sedimentation rate ratio, and the cytokine pattern of significantly increased interferon-γ and interleukin-10 levels are important markers for early identification of MAS in addition to the traditional characteristics of sJIA-associated MAS.
Asunto(s)
Artritis Juvenil/complicaciones , Hipotensión/complicaciones , Síndrome de Activación Macrofágica/diagnóstico , Biomarcadores/sangre , Sedimentación Sanguínea , Niño , Preescolar , Femenino , Ferritinas/sangre , Humanos , Interferón gamma/sangre , Interleucina-10/sangre , Síndrome de Activación Macrofágica/sangre , Síndrome de Activación Macrofágica/etiología , Síndrome de Activación Macrofágica/fisiopatología , Masculino , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Primary and secondary haemophagocytic lymphohistiocytosis (HLH) are hyperferritinaemic hyperinflammatory syndromes with a common terminal pathway triggered by different etiopathogenetic factors. HLH is characterised by a decreased capacity of interferon gamma production with an activated NK phenotype profile similar to other hyperinflammatory syndromes. Viruses are closely linked to the development of HLH as infectious triggers, and the break of tolerance to self-antigens is considered a critical mechanism involved in the development of immune-mediated conditions triggered by viral infections. Emerging studies in patients with COVID-19 are suggesting a key role of monocytes/macrophages in the pathogenesis of this viral infection, and there is a significant overlap between several features reported in severe COVID-19 and the features included in the HLH-2004 diagnostic criteria. Therefore, SARS-Cov-2, as other respiratory viruses, may also be considered a potential etiological trigger of HLH. The frequency of HLH in adult patients with severe COVID-19 is lower than 5%, although this figure could be underestimated considering that most reported cases lacked information about some specific criteria (mainly the histopathological criteria and the measurement of NK cell function and sCD25 levels). Because HLH is a multi-organ syndrome, the diagnostic approach in a patient with severe COVID-19 in whom HLH is suspected must be carried out in a syndromic and holistic way, and not in the light of isolated clinical or laboratory features. In COVID-19 patients presenting with persistent high fever, progressive pancytopenia, and hepatosplenic involvement, together with the characteristic triad of laboratory abnormalities (hyperferritinaemia, hypertriglyceridaemia, and hypofibrinogenaemia), the suspicion of HLH is high, and the diagnostic workup must be completed with specific immunological and histopathological studies.
Asunto(s)
Síndrome de Liberación de Citoquinas/diagnóstico , Linfohistiocitosis Hemofagocítica/diagnóstico , Síndrome de Activación Macrofágica/diagnóstico , Adulto , COVID-19/clasificación , COVID-19/diagnóstico , Niño , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/fisiopatología , Diagnóstico Diferencial , Humanos , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/fisiopatología , Síndrome de Activación Macrofágica/fisiopatología , Pandemias , Reumatología/métodos , SARS-CoV-2RESUMEN
Kawasaki disease is a febrile, acute and multisystemic vasculitis that mainly affects children under 5 years of age. We describe the clinical characteristics, evolution and therapeutic considerations in a patient with a diagnosis of complete Kawasaki disease with severe multisystem manifestations, among which stands out the macrophage activation syndrome, which represents an unusual and potentially life-threatening complication of the illness.
La enfermedad de Kawasaki es una vasculitis febril, aguda y multisistémica, que afecta, principalmente, a niños menores de 5 años. Se describen las características clínicas, la evolución y las consideraciones terapéuticas en un paciente con diagnóstico de enfermedad de Kawasaki completo con manifestaciones multisistémicas graves, dentro de las cuales se resalta el síndrome de activación de macrófagos, que representa una complicación inusual y potencialmente mortal de la enfermedad.
Asunto(s)
Fiebre/etiología , Síndrome de Activación Macrofágica/diagnóstico , Síndrome Mucocutáneo Linfonodular/diagnóstico , Preescolar , Humanos , Síndrome de Activación Macrofágica/fisiopatología , Masculino , Síndrome Mucocutáneo Linfonodular/fisiopatología , Índice de Severidad de la EnfermedadRESUMEN
ABSTRACT Objective: To highlight the importance of the new classification criteria for the macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis in order to reduce morbidity and mortality outcome related to this disease. Case description: A 12-year-old female patient with diagnosis of systemic juvenile idiopathic arthritis under immunosuppression therapy for two years developed cough, acute precordial chest pain, tachypnea, tachycardia and hypoxemia for two days. Chest tomography showed bilateral laminar pleural effusion with bibasilar consolidation. The electrocardiogram was consistent with acute pericarditis and the echocardiogram showed no abnormalities. Laboratory exams revealed anemia, leukocytosis and increased erythrocyte sedimentation rate, as well as C-reactive protein rate and serum biomarkers indicative of myocardial injury. Systemic infection and/or active systemic juvenile idiopathic arthritis were considered. She was treated with antibiotics and glucocorticoids. However, 10 days later she developed active systemic disease (fever, evanescent rash and myopericarditis with signs of heart failure) associated with macrophage activation syndrome, according to the 2016 Classification Criteria for Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis. She was treated for five days with pulse therapy, using glucocorticoids, immunoglobulin and cyclosporine A, with improvement of all clinical signs and laboratory tests. Comments: Myopericarditis with signs of heart failure associated with MAS is a rare clinical presentation of systemic juvenile idiopathic arthritis. Macrophage activation syndrome occurs mainly during periods of active systemic juvenile idiopathic arthritis and may be triggered by infection. Knowledge about this syndrome is crucial to reduce morbidity and mortality.
RESUMO Objetivo: Destacar a importância do conhecimento sobre os novos critérios de classificação para síndrome de ativação macrofágica (SAM) na artrite idiopática juvenil sistêmica para reduzir a morbidade e mortalidade desse desfecho. Descrição do caso: Adolescente do sexo feminino de 12 anos de idade, em terapia imunossupressora por diagnóstico de artrite idiopática juvenil sistêmica há 2 anos, com quadro de tosse, dor precordial aguda, taquipneia, taquicardia e hipoxemia há 2 dias. A tomografia de tórax evidenciou efusão pleural laminar bilateral com consolidação bibasal. O eletrocardiograma foi compatível com pericardite aguda, e o ecocardiograma foi normal. Os exames laboratoriais revelaram anemia, leucocitose e aumento da velocidade de hemossedimentação, proteína C-reativa e marcadores séricos de lesão miocárdica. Infecção sistêmica e/ou doença sistêmica em atividade foram consideradas. A paciente foi tratada com antibióticos e glicocorticoide. Entretanto, dez dias depois, evoluiu com doença sistêmica em atividade (febre, exantema e miopericardite com insuficiência cardíaca) associada à SAM, de acordo com o 2016 Classification Criteria for Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis, e necessitou de cinco dias de pulsoterapia com glicocorticoide, imunoglobulina e ciclosporina A, com melhora de todos os parâmetros clínicos e laboratoriais. Comentários: A miopericardite com sinais de insuficiência cardíaca associada à SAM é uma apresentação clínica rara da artrite idiopática juvenil sistêmica, que ocorre principalmente em períodos de atividade sistêmica da doença e pode ser deflagrada por infecções. O conhecimento sobre essa síndrome é fundamental para reduzir morbidade e mortalidade desse grave desfecho.
Asunto(s)
Humanos , Femenino , Niño , Ciclosporina/administración & dosificación , Glucocorticoides/administración & dosificación , Artritis Juvenil/complicaciones , Artritis Juvenil/diagnóstico , Artritis Juvenil/fisiopatología , Artritis Juvenil/inmunología , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Inmunoglobulinas Intravenosas/administración & dosificación , Quimioterapia por Pulso/métodos , Electrocardiografía/métodos , Síndrome de Activación Macrofágica/etiología , Síndrome de Activación Macrofágica/fisiopatología , Síndrome de Activación Macrofágica/sangre , Síndrome de Activación Macrofágica/terapia , Inmunosupresores/administración & dosificación , Leucocitosis/diagnóstico , Leucocitosis/etiologíaRESUMEN
OBJECTIVE: To highlight the importance of the new classification criteria for the macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis in order to reduce morbidity and mortality outcome related to this disease. CASE DESCRIPTION: A 12-year-old female patient with diagnosis of systemic juvenile idiopathic arthritis under immunosuppression therapy for two years developed cough, acute precordial chest pain, tachypnea, tachycardia and hypoxemia for two days. Chest tomography showed bilateral laminar pleural effusion with bibasilar consolidation. The electrocardiogram was consistent with acute pericarditis and the echocardiogram showed no abnormalities. Laboratory exams revealed anemia, leukocytosis and increased erythrocyte sedimentation rate, as well as C-reactive protein rate and serum biomarkers indicative of myocardial injury. Systemic infection and/or active systemic juvenile idiopathic arthritis were considered. She was treated with antibiotics and glucocorticoids. However, 10 days later she developed active systemic disease (fever, evanescent rash and myopericarditis with signs of heart failure) associated with macrophage activation syndrome, according to the 2016 Classification Criteria for Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis. She was treated for five days with pulse therapy, using glucocorticoids, immunoglobulin and cyclosporine A, with improvement of all clinical signs and laboratory tests. COMMENTS: Myopericarditis with signs of heart failure associated with MAS is a rare clinical presentation of systemic juvenile idiopathic arthritis. Macrophage activation syndrome occurs mainly during periods of active systemic juvenile idiopathic arthritis and may be triggered by infection. Knowledge about this syndrome is crucial to reduce morbidity and mortality.
Asunto(s)
Artritis Juvenil , Dolor en el Pecho , Ciclosporina/administración & dosificación , Glucocorticoides/administración & dosificación , Leucocitosis , Síndrome de Activación Macrofágica , Artritis Juvenil/complicaciones , Artritis Juvenil/diagnóstico , Artritis Juvenil/inmunología , Artritis Juvenil/fisiopatología , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Niño , Electrocardiografía/métodos , Femenino , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunosupresores/administración & dosificación , Leucocitosis/diagnóstico , Leucocitosis/etiología , Síndrome de Activación Macrofágica/sangre , Síndrome de Activación Macrofágica/etiología , Síndrome de Activación Macrofágica/fisiopatología , Síndrome de Activación Macrofágica/terapia , Quimioterapia por Pulso/métodos , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: We previously reported a case series of acute pancreatitis (AP) and macrophage activation syndrome (MAS) in childhood (cSLE) patients; however, there are no data regarding the comparison of AP and MAS in large populations of cSLE and adult SLE (aSLE). METHODS: A study included 362 cSLE and 1830 aSLE patients. MAS was diagnosed according to preliminary diagnostic guidelines and AP according to the presence of abdominal pain or vomiting associated to an increase of pancreatic enzymes and/or pancreatic radiological abnormalities. Demographic data, clinical features, SLEDAI-2K, SLICC/ACR-DI, and treatment were assessed. RESULTS: Age in MAS patients was significantly lower compared with those without this complication [15 (8.8-55) vs. 33.5 (10.2-45.7) years, p = 0.007]. The frequencies of fever (94% vs. 37%, p = 0.001), leucopenia (82% vs. 19%, p = 0.0001), thrombocytopenia (65% vs. 19%, p = 0.013), hypertriglyceridemia (87% vs. 42%, p = 0.037), and hyperferritinemia (93% vs. 37%, p = 0.011) were also more frequently observed in AP patients with MAS compared in AP patients without MAS. Fever and hyperferritinemia concomitantly were more frequent in the former group (86% vs. 12%, p = 0.0015). Higher and significant frequency of AP in cSLE compared to aSLE patients [12/362 (3.3%) vs. 20/1830 (1.1%), p = 0.003], with similar AP duration [22 (6-60) vs. 15 (4-90) days, p = 0.534]. MAS (85% vs. 30%, p = 0.003) and death by MAS complication (31% vs. 0%, p = 0.017) were significantly higher in children compared with aSLE. CONCLUSIONS: This study provides novel data demonstrating that MAS occur in the majority of cSLE with AP with a higher mortality compared to aSLE. In addition, we identified in AP patients, a cluster of MAS clinical and laboratorial parameters more associated with this complication.
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Lupus Eritematoso Sistémico/fisiopatología , Síndrome de Activación Macrofágica/fisiopatología , Pancreatitis/fisiopatología , Adolescente , Adulto , Factores de Edad , Edad de Inicio , Niño , Femenino , Ferritinas/sangre , Fiebre/etiología , Humanos , Hipertrigliceridemia/etiología , Leucopenia/etiología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Síndrome de Activación Macrofágica/sangre , Síndrome de Activación Macrofágica/etiología , Masculino , Persona de Mediana Edad , Pancreatitis/sangre , Pancreatitis/complicaciones , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Trombocitopenia/etiología , Adulto JovenRESUMEN
Acute pancreatitis (AP) is a rare and life-threatening manifestation of juvenile systemic lupus erythematosus (JSLE). The objective of this study was to evaluate the prevalence and clinical features of AP in our JSLE population. AP was defined according to the presence of abdominal pain or vomiting associated to an increase of pancreatic enzymes and/or pancreatic radiological abnormalities. Of note, in the last 26 years, 5367 patients were followed up at our Pediatric Rheumatology Unit and 263 (4.9%) of them had JSLE diagnosis (ACR criteria). AP was observed in 4.2% (11/263) of JSLE patients. The median of age of the JSLE patients at AP diagnosis was 12.4 years (8.8-17.9). All of them had lupus disease activity at AP onset. Three patients were receiving corticosteroids before AP diagnosis. Interestingly, 10/11 JSLE patients fulfilled preliminary guidelines for macrophage activation syndrome, three of them with macrophage hemophagocytosis in bone marrow aspirate and hyperferritinemia. The hallmark of this syndrome is excessive activation and proliferation of T lymphocytes and macrophages with massive hypersecretion of proinflammatory cytokines and clinically it is characterized by the occurrence of unexplained fever, cytopenia and hyperferritinemia. AP treatment was mainly based on intravenous methylprednisolone. Four JSLE patients with AP died and two developed diabetes mellitus. In conclusion, AP was a rare and severe manifestation in active pediatric lupus. The association between AP and macrophage activation syndrome suggests that the pancreas could be a target organ of this syndrome and that pancreatic enzyme evaluation should also be carried out in all patients.