RESUMO
BACKGROUND: Systemic lupus erythematosus (SLE) and Primary Antiphospholipid Syndrome (PAPS) overlap clinical and immunological features. Therefore, misclassification of PAPS patients as SLE is a concern. The ACR/EULAR 2019 SLE classification has never been studied in PAPS. OBJECTIVE: To verify if the ACR/EULAR 2019 SLE classification can correctly classify a PAPS patient as not having SLE and compare its performance with the SLICC 2012 SLE classification. Methods: One-hundred thrombotic PAPS patients who fulfilled the Sidney criteria were consecutively screened and those who attended the inclusion criteria were submitted to ACR/EULAR 2019 and SLICC 2012 classifications. RESULTS: Sixty-seven PAPS patients were included in this study. The majority was female (89.6%) with median age at study inclusion of 45 years (35-53) and median PAPS disease duration of 13 years (8-19). PAPS correct classification was observed more often with ACR/EULAR 2019 than SLICC 2021 criteria (94.0% vs. 64.2%; p < 0.001). The 4 misclassified patients in ACR/EULAR 2019 were also misclassified in SLICC 2012. The comparison of misclassified patients to those correctly not classified as SLE resulted, for both criteria, in higher frequencies of hematological domain [ACR/EULAR 2019 (100% vs. 28.6%, p = 0.010) and SLICC 2012 (95.8% vs. 11.6%, p < 0.001)]. Further analysis of hematological manifestations revealed that for the ACR/EULAR 2019 leukopenia (100% vs. 22.2%, p = 0.004) and for the SLICC 2012 leukopenia/lymphopenia (91.7% vs. 7%, p < 0.001) were more frequent in misclassified group. Proteinuria (20.8% vs. 0%, p = 0.004) and low complement (45.8% vs. 20.9%, p = 0.033) were also more often observed in the incorrectly SLICC 2012 classified patients. CONCLUSION: ACR/EULAR 2019 had high accuracy for distinguishing PAPS from SLE, whereas the SLICC 2012 incorrectly classified more than one third of the PAPS patients as having SLE.
Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Trombose , Adulto , Síndrome Antifosfolipídica/classificação , Síndrome Antifosfolipídica/diagnóstico , Erros de Diagnóstico , Feminino , Indicadores Básicos de Saúde , Humanos , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Trombose/diagnósticoRESUMO
Neurofibromatosis type I (NF1) has been only rarely reported in association with anti-phospholipid syndrome (APS). We report a 38 year-old female with NF1, who developed a cervix carcinoma at the age of 30 years and was successfully treated with conization, without requiring chemotherapy or radiation. She experienced two miscarriages prior to the diagnosis of the carcinoma. When she was 38 years old, an APS was diagnosed based on repeatedly positive lupus anticoagulant tests. The patient continued to smoke and using oral contraceptives. At 38 years of age she had a myocardial infarction, despite the use of oral anticoagulation. She required coronary stenting. Aspirin and clopidrogel were indicated thereafter.
Es inusual la asociación entre neurofibromatosis tipo I (NF1) y síndrome antifosfolípidos (APS). Presentamos una paciente mujer de 38 años con un NF1 que desarrolló un cáncer cervicouterino a los 30 años y que fue tratada exitosamente con una conización, sin requerir quimioterapia o radiación. La paciente tuvo dos abortos espontáneos antes del diagnóstico del carcinoma. A los 38 años, se le diagnosticó un APS, basado en pruebas de anticoagulante lúpico que resultaron positivas en repetidas oportunidades. La paciente continuó fumando y usando contraceptivos orales y, a pesar de estar con anticoagulantes orales, tuvo un infarto agudo de miocardio a los 38 años. Se colocó un stent coronario y se indicó aspirina y clopidogrel.
Assuntos
Adulto , Feminino , Humanos , Síndrome Antifosfolipídica/complicações , Neurofibromatose 1/complicações , Síndrome Antifosfolipídica/classificação , Síndrome Antifosfolipídica/diagnóstico , Infarto do Miocárdio/complicações , Neurofibromatose 1/diagnóstico , Fatores de RiscoRESUMO
Neurofibromatosis type I (NF1) has been only rarely reported in association with anti-phospholipid syndrome (APS). We report a 38 year-old female with NF1, who developed a cervix carcinoma at the age of 30 years and was successfully treated with conization, without requiring chemotherapy or radiation. She experienced two miscarriages prior to the diagnosis of the carcinoma. When she was 38 years old, an APS was diagnosed based on repeatedly positive lupus anticoagulant tests. The patient continued to smoke and using oral contraceptives. At 38 years of age she had a myocardial infarction, despite the use of oral anticoagulation. She required coronary stenting. Aspirin and clopidogrel were indicated thereafter.
Assuntos
Síndrome Antifosfolipídica/complicações , Neurofibromatose 1/complicações , Adulto , Síndrome Antifosfolipídica/classificação , Síndrome Antifosfolipídica/diagnóstico , Feminino , Humanos , Infarto do Miocárdio/complicações , Neurofibromatose 1/diagnóstico , Fatores de RiscoRESUMO
El Síndrome Antifosfolípido (SAFL) es una afección autoinmune que se diagnostica ante la concomitancia de un evento clínico (trombosis vascular o morbilidad obstétrica) y la presencia de autoanticuerpos que reconocen epítopes de proteínas plasmáticas que se unen a fosfolípidos aniónicos. La heterogeneidad de estos pacientes ha llevado a la definición por parte de grupos de expertos de diferentes Criterios de Clasificación o consensos sobre los hallazgos serológicos y clínicos requeridos para su correcta clasificación. No obstante, cuando se contrastan las series clínicas de SAFL publicadas en la literatura con los diversos Criterios de Clasificación, se observa que ciertas manifestaciones clínicas que no cumplen dichos criterios, o no criterio, presentan importancia diagnóstica y pronóstica. En la presente revisión analizamos algunas de estas manifestaciones clínicas no criterio y presentamos información que sugiere que la trombocitopenia y el livedo reticularis presentan sensibilidad y especificidad suficientes para su inclusión en los Criterios de Clasificación del SAFL.
The antiphospholipid syndrome (APS) is an autoimmune condition characterized by vascular thrombosis and/or pregnancy morbidity in the presence of autoantibodies that recognize epitopes of plasma proteins that bind to anionic phospholipids. The heterogeneity of APS patients has led to the definition by groups of experts, of different Classification Criteria or consensus regarding the clinical and serological findings required for their correct classification. However, when the published series of APS patients are contrasted with such Classification Criteria, it appears that some of the clinical findings not fulfilling criteria or non criteria manifestations, exhibit diagnostic and prognostic importance. In this review we analyze some of these non criteria manifestations and present data suggesting that the sensitivity and specificity of thrombocytopenia and livedo reticularis warrant their inclusion among the Classification Criteria for APS.
Assuntos
Humanos , Consenso , Síndrome Antifosfolipídica/classificaçãoRESUMO
The updated Sapporo classification criteria for antiphospholipid syndrome (APS) only include thrombosis or pregnancy morbidity as clinical criteria. To test this notion, we studied 55 patients (80% women) with hematologic manifestations. All fulfilled the laboratory criteria for primary APS. Thirty-five patients (64%) had thrombocytopenia, 14 (25%) had autoimmune hemolytic anemia, and 6 (11%) had both. Twenty-five patients (22 women, 88%) also fulfilled one clinical criterion for APS after a median follow-up of 13.2 years (range, 1.45-37 years), whereas the remaining 30 patients (22 women, 73%) have not had any thrombotic event nor pregnancy morbidity after a median follow-up of 5.4 years (range, 0.12-24 years). No patient developed systemic lupus erythematosus during follow-up. The hematologic manifestation was asynchronous with the APS onset in 84% of patients. The response to treatment was similar regardless of the APS status. Patients with definite APS were more frequently positive for the lupus anticoagulant (63%) than lupus anticoagulant-positive patients without APS (30%; odds ratio, 3.5; 95% confidence interval, 1.07-11.4; P < .02). Anticardiolipin or anti-ß(2)-glycoprotein-I antibodies were highly prevalent among the study groups. Our study suggests that, depending upon their antiphospholipid profile, patients with hemocytopenias appear to comprise a peculiar subset of patients with APS; some develop thrombotic and/or obstetric APS whereas others continue with hematologic APS.
Assuntos
Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/imunologia , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Trombocitopenia/complicações , Trombocitopenia/imunologia , Adulto , Síndrome Antifosfolipídica/classificação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , GravidezRESUMO
Catastrophic antiphospholipid syndrome (CAPS) is characterized by life-threatening diffuse thrombotic manifestations involving particularly small vessels of kidney, lungs, brain and skin. We report a 20-year-old female with systemic lupus erythematosus and secondary antiphospholipid syndrome who presented typical organ and histological involvement as seen in CAPS but with protracted course suggesting a "smoldering" form of the disease.
Assuntos
Síndrome Antifosfolipídica/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Síndrome Antifosfolipídica/classificação , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Doença Catastrófica , Doença Crônica , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: The 2006 revised criteria for antiphospholipid syndrome (APS) provide a new classification challenge, and studies validating the updated criteria against the older ones are still scanty. We compared the 1999 preliminary with the 2006 revised classification criteria for APS, and evaluated if the revised criteria provide an added value over the original ones. METHODS: A laboratory-based registry population was obtained on the basis of the positivity of antiphospholipid (aPL) antibodies. Patients were analysed for fulfillment of the 1999 and 2006 classification criteria for APS, non-criteria features of APS, and autoantibody profile. RESULTS: Of 144 aPL-positive identified patients, 119 had at least 2 aPL tests on separated occasions, and were included in this study. According to the 1999 criteria, 23 patients had APS (15 had thrombosis alone, 4 pregnancy morbidity, and 4 both); while 26 fulfilled the 2006 revised criteria (15 had thrombosis alone, 5 pregnancy morbidity, and 6 both). One patient with isolated thrombosis who met 1999 criteria did not meet those of 2006 (aCL positivity but not >12 weeks apart). One patient with thrombosis, other with pregnancy morbidity, and 2 with both only fulfilled the 2006 criteria because they had isolated anti-Beta(2)GPI antibody-positivity. High concordance between criteria was found, with kappa index of 0.87 (95%; CI, 0.76-0.98). CONCLUSIONS: The 2006 revised criteria represent a step-forward since it allows the inclusion of patients with anti-Beta(2)GPI antibodies as an isolated serological feature. However, a wider time interval between serologic tests seems unlikely to make differences.
Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/classificação , Adulto , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Distribuição de Qui-Quadrado , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hipertensão/complicações , Hipertensão/imunologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Gravidez , Complicações na Gravidez/imunologia , Estudos Retrospectivos , Fatores de Risco , Trombocitopenia/complicações , Trombocitopenia/imunologia , Trombose/complicações , Trombose/imunologiaRESUMO
The association of the lupus anticoagulant with thrombosis and recurrent pregnancy loss was first recognized over a 20-year period between the early 1960s and early 1980s. The introduction of the anticardiolipin test in 1983 and the recognition of its association with clinical features similar to the lupus anticoagulant led to an exponential growth of interest in this disorder. The belief that anticardiolipin antibodies and lupus anticoagulant belonged to the family of antiphospholipid antibodies led to the disorder being named the antiphospholipid syndrome (APS). Efforts by individual investigators to introduce criteria for classification of APS and to standardize anticardiolipin antibody and lupus anticoagulant tests were started in the mid-1980s to ensure more reliable recognition and treatment of affected patients. Another layer of complexity was introduced with recognition that many anticardiolipin antibody-positive sera also bound the antigen beta (2) glycoprotein I. With increasingly sophisticated epidemiologic and prospective studies in the 1990s, more structured and better-documented criteria for APS were introduced in 1999 and modified in 2006. These criteria have been widely adopted. Whereas data supporting subclassification of APS into primary and secondary subgroups remain tenuous, a small percentage of patients do appear subject to clinical features termed the catastrophic antiphospholipid syndrome. Introduction of classification criteria for APS has enabled more reliable prospective studies, the promise of better management, and more valid tests for recognition of the disorder.
Assuntos
Síndrome Antifosfolipídica/classificação , Aborto Habitual/etiologia , Anticorpos Anticardiolipina/sangue , Anticorpos Anticardiolipina/imunologia , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/etiologia , Síndrome Antifosfolipídica/imunologia , Autoantígenos/imunologia , Feminino , Humanos , Inibidor de Coagulação do Lúpus/sangue , Inibidor de Coagulação do Lúpus/imunologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Gravidez , Complicações Hematológicas na Gravidez/imunologia , Terminologia como Assunto , Trombofilia/etiologia , beta 2-Glicoproteína I/imunologiaRESUMO
Doença de natureza auto-imune, a Síndrome Antifosfolípide(SAF) é uma trombofilia adquirida caracterizada por eventos trombóticos e complicações obstétricas. Estas são definidas como abortos ou mortes fetais, resultantes de trombose dos vasos placentários. Os critérios diagnósticos incluem fatores clínicos (trombose/abortamentos) aliados à detecção laboratorial de anticorpos antifosfolípides. Relatamos o caso de uma paciente com 33 anos, na quarta gestação (2 fetos mortos e 1 aborto), com complicações obstétricas consecutivas e eventos trombóticos de longa data, além de alta dosagem de IgM para cardiolipina. Depois de firmado o diagnóstico de SAF, estabelecemos um plano terapêutico com heparina e AAS. Na trigésima-quarta semana de gestação, optou-se por antecipação do parto devido a alterações no perfil biofísico fetal e na dopplervelocimetria. Após 17 dias na UTI por insuficiência respiratória aguda, o recém-nascido evoluiu em boas condições. O diagnóstico de SAF deve sempre ser suspeitado em história de complicações obstétricas recorrentes (mesmo sem eventos trombóticos associados), na ausência de alterações cromossomiais ou falta de história familiar de malformações, natimortos ou abortos de repetição. Este relato reafirma a importância do diagnóstico da SAF, já que a melhora do prognóstico gestacional depende, via de regra, da instituição de medidas terapêuticas adequadas e específicas.