RESUMO
OBJECTIVE: To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. RESULTS: The development set for EGPA consisted of 107 cases of EGPA and 450 comparators. The validation set consisted of an additional 119 cases of EGPA and 437 comparators. From 91 candidate items, regression analysis identified 11 items for EPGA, 7 of which were retained. The final criteria and their weights were as follows: maximum eosinophil count ≥1 × 109 /liter (+5), obstructive airway disease (+3), nasal polyps (+3), cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti-proteinase 3 ANCA positivity (-3), extravascular eosinophilic predominant inflammation (+2), mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1), and hematuria (-1). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having EGPA if the cumulative score was ≥6 points. When these criteria were tested in the validation data set, the sensitivity was 85% (95% confidence interval [95% CI] 77-91%) and the specificity was 99% (95% CI 98-100%). CONCLUSION: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for EGPA demonstrate strong performance characteristics and are validated for use in research.
Assuntos
Síndrome de Churg-Strauss/diagnóstico , Adulto , Idoso , Síndrome de Churg-Strauss/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
The different sets of criteria for diagnosis or classification of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) lead to numerous overlapping and reclassified diagnoses in clinical practice. We designed this study to assess the difficulties in classifying patients with AAV. As a secondary objective, different variables were tested to predict prognosis. We conducted a retrospective chart review in a Western Spain multicentre survey. A total of 115 adult patients diagnosed with AAV from 2002 to 2013 and followed for at least 3 years were included. They were classified according to (1) Chapel Hill Consensus Conference (CHCC), (2) European Medicines Agency algorithm and (3) French Vasculitis Study Group/European Vasculitis Society phenotypes. Fifty-three patients (46%) had neither distinctive histopathological data of a single AAV definition nor any surrogate markers for granulomatous inflammation and thus did not fulfill any diagnostic criteria. Ocular, ear, nose, throat, skin, and lung involvement were more frequent with proteinase 3 (PR3) antibodies, whereas peripheral neuropathy was more frequent with myeloperoxidase (MPO) antibodies. When the disease was severe at diagnosis, the HR for mortality was 10.44. When induction treatment was not given in accordance with the guidelines, the HR for mortality was 4.00. For maintenance treatment, the HR was 5.49 for mortality and 2.48 for relapse. AAV classification is difficult because many patients had neither specific clinical data nor distinctive histological features of a single CHCC definition. A structured clinical assessment of patient severity is the best tool to guide the management of AAV.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/fisiopatologia , Mortalidade , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Síndrome de Churg-Strauss/classificação , Síndrome de Churg-Strauss/imunologia , Síndrome de Churg-Strauss/patologia , Síndrome de Churg-Strauss/fisiopatologia , Epistaxe/imunologia , Epistaxe/patologia , Epistaxe/fisiopatologia , Oftalmopatias/imunologia , Oftalmopatias/patologia , Oftalmopatias/fisiopatologia , Feminino , Gastroenteropatias/imunologia , Gastroenteropatias/patologia , Gastroenteropatias/fisiopatologia , Granulomatose com Poliangiite/classificação , Granulomatose com Poliangiite/imunologia , Granulomatose com Poliangiite/patologia , Granulomatose com Poliangiite/fisiopatologia , Humanos , Hipertensão/imunologia , Hipertensão/patologia , Hipertensão/fisiopatologia , Nefropatias/imunologia , Nefropatias/patologia , Nefropatias/fisiopatologia , Falência Renal Crônica/fisiopatologia , Pneumopatias/imunologia , Pneumopatias/patologia , Pneumopatias/fisiopatologia , Masculino , Poliangiite Microscópica/classificação , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/patologia , Poliangiite Microscópica/fisiopatologia , Pessoa de Meia-Idade , Mieloblastina/imunologia , Doenças do Sistema Nervoso Periférico/imunologia , Doenças do Sistema Nervoso Periférico/patologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Peroxidase/imunologia , Prevenção Primária , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Índice de Gravidade de Doença , Sinusite/imunologiaRESUMO
To investigate the relevance of RF in patients with EGPA, we reviewed consecutive patients who were newly diagnosed with EGPA from August 1998 to February 2019 in Keio University Hospital with RF titer at diagnosis available. We divided the patients according to the median level of RF titer of 75 IU/mL and compared clinical features between the two groups. Among 16 patients identified, 8 patients were in the RF high group and the other 8 patients were in the RF low group. All patients in the high RF group were negative for MPO-ANCA, whereas all in the low RF group was positive for MPO-ANCA with a mean titer of 103 IU/mL. The eosinophil count at diagnosis was significantly higher in the RF high group than the RF low group (20001/µL vs 5144/µL, p < 0.01). Gastrointestinal lesion was significantly more frequent in the RF high group, and parenchymal organ lesions, such as heart and renal organ involvement, were frequent in the RF low group. With principal component analysis, RF high and low groups were clearly divided by the combination of eosinophil count, MPO-ANCA titer, gastrointestinal lesions, musculoskeletal symptoms, and disease activity score. Those results suggest EGPA can be divided into two groups in association with RF.Key Points⢠Our study showed that patients with EGPA can be separated into two groups according to RF titer.⢠The two subtypes reflect different underlying pathogenesis in EGPA, and the optimal treatment for them may be different.
Assuntos
Síndrome de Churg-Strauss/classificação , Fator Reumatoide/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Síndrome de Churg-Strauss/sangue , Síndrome de Churg-Strauss/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Estudos RetrospectivosRESUMO
OBJECTIVES: We applied the ACR/EULAR 2017 provisional classification criteria for granulomatosis with polyangiitis (GPA) to 150 Korean patients with previously diagnosed antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and investigated how many patients with AAV were reclassified as GPA. METHODS: We included patients with 30 GPA, 30 eosinophilic GPA (EGPA) and 90 microscopic polyangiitis (MPA) patients. Patients can be classified as GPA, when the sum of scores is more than 5. RESULTS: At diagnosis the mean age of 150 patients with AAV was 60.1 years old, and 101 patients (67.3%) were women. Overall, 33 of 150 patients with AAV (22.0%) were classified as GPA according to the 2017 provisional criteria for GPA. The 2017 provisional criteria for GPA dropped to 10.0% of previously diagnosed GPA patients and the major factor to drop 3 GPA patients was the deletion of 2 items of the 1990 criteria, urinary sediment and infiltrates on chest radiograph. Meanwhile, one of 30 patients with EGPA (3.3%) and 5 of 90 patients with MPA (5.6%) were newly classified as GPA based on the 2017 provisional criteria for GPA. We could also find that items of the 2017 provisional criteria to contribute to reclassifying EGPA and MPA patients as GPA were PR3-ANCA, mass-like lung lesion and nasal congestion in Korean patients with AAV. CONCLUSIONS: The use of the 2017 provisional criteria for GPA excluded 10.0% of previously classified GPA patients and newly classified 3.3% of EGPA patients and 5.6% of MPA patients as GPA in Korean patients with AAV.
Assuntos
Síndrome de Churg-Strauss/diagnóstico , Granulomatose com Poliangiite/diagnóstico , Poliangiite Microscópica/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Síndrome de Churg-Strauss/classificação , Síndrome de Churg-Strauss/imunologia , Europa (Continente) , Feminino , Granulomatose com Poliangiite/classificação , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/imunologia , Humanos , Pneumopatias/etiologia , Masculino , Poliangiite Microscópica/classificação , Poliangiite Microscópica/imunologia , Pessoa de Meia-Idade , Mieloblastina/imunologia , República da Coreia , Reumatologia , Sociedades Médicas , Estados UnidosRESUMO
This article provides an update on the diagnosis and management of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides, granulomatosis with polyangiitis (formerly Wegener), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss). Focus is on new schemes of classification and the importance of ANCAs in the diagnosis and prognosis of these systemic vasculitides. Current therapeutic strategies consisting of glucocorticoids in conjunction with conventional or biologic agents for both induction of remission and remission maintenance are outlined. Future research directions include investigation of the optimal duration and frequency of maintenance therapy and development of targeted therapeutic agents.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Autoanticorpos/imunologia , Síndrome de Churg-Strauss/classificação , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Granulomatose com Poliangiite/classificação , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Quimioterapia de Manutenção/métodos , Poliangiite Microscópica/classificação , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/tratamento farmacológico , Mieloblastina/imunologia , Peroxidase/imunologia , Indução de Remissão/métodosRESUMO
Recently, a group of experts in the field suggested to rename Churg-Strauss syndrome as eosinophilic granulomatosis with polyangiitis (EGPA). This condition, first described in 1951, is a rare small- and medium-sized-vessel vasculitis characterized by an almost constant association with asthma and eosinophilia, and, by the presence of anti-myeloperoxidase (MPO) antineutrophil cytoplasm antibodies (ANCA) in 30-38% of the patients. Vasculitis typically develops in a previously asthmatic and eosinophilic middle-aged patient. Asthma is severe, associated with eosinophilia and extrapulmonary symptoms. Most frequently EGPA involves the peripheral nerves and skin. Other organs, however, may be affected and must be screened for vasculitis, especially those associated with a poorer prognosis, such as the heart, kidney and gastrointestinal tract, as assessed by the recently revised Five-Factor Score (FFS). Recent insights, particularly concerning clinical differences associated with ANCA status, showed that EGPA patients might constitute a heterogeneous group. Thus, EGPA patients with anti-MPO ANCA suffered more, albeit not exclusively, from vasculitis symptoms, such as glomerulonephritis, mononeuritis multiplex and alveolar hemorrhage, whereas ANCA-negative patients more frequently develop heart involvement. This observation led to the hypothesis that EGPA might be divided into different clinical and pathophysiological subtypes, which could be managed better with more specifically adapted therapies. For now, EGPA treatment still relies mainly on corticosteroids and, when necessary for patients with poorer prognoses, combined immunosuppressant drugs, especially cyclophosphamide. Overall survival of EGPA patients is good, despite not uncommon relapses.
Assuntos
Síndrome de Churg-Strauss/classificação , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/epidemiologia , Diagnóstico Diferencial , Humanos , Incidência , Poliangiite Microscópica/classificação , Poliangiite Microscópica/diagnóstico , Prevalência , Terminologia como AssuntoRESUMO
INTRODUCTION: Systemic vasculitides are great masqueraders and at times their presenting manifestations can be very different from the usual recognized patterns. Such uncommon presentations of granulomatosis with polyangiitis (Wegener's granulomatosis), classical polyarteritis nodosa and unclassifiable vasculitides are described here with the relevant review of literature. METHODS: All patients diagnosed as having systemic vasculitides and classified as having granulomatosis with polyangiitis (Wegener's granulomatosis), classic polyarteritis nodosa, microscopic polyangiitis and unclassifiable vasculitis according to EMEA consensus methodology and followed up prospectively from June 2007 to December, 2011 were included. Details of uncommon presentations of these disorders were identified. RESULTS: Seventy-nine patients with systemic vasculitides were seen under our rheumatology services during this period. These included 45 patients with granulomatosis with polyangiitis (Wegener's granulomatosis), 18 with classic polyarteritis nodosa, five with microscopic polyangiitis, four with Churg-Strauss syndrome and seven with unclassifiable vasculitis. The uncommon presentations of granulomatosis with polyangiitis were a tumefactive subcutaneous mass in the thigh; prostatomegaly with obstructive uropathy and advanced renal failure; and predominant gastrointestinal (GI) vasculitis with thrombocytopenia and coagulopathy at presentation. The uncommon manifestations of classic polyarteritis nodosa were secondary antiphospholipid antibody syndrome and Budd-Chiari syndrome. One patient with massive lower GI bleeding required surgical resection of the large bowel which showed isolated necrotizing granulomatous GI vasculitis. Single organ vasculitis of the GI tract was diagnosed. CONCLUSIONS: Systemic necrotizing vasculitides may present with uncommon manifestations and a high index of suspicion is required for early diagnosis and prompt treatment to prevent adverse outcomes.
Assuntos
Síndrome de Churg-Strauss/diagnóstico , Granulomatose com Poliangiite/diagnóstico , Poliangiite Microscópica/diagnóstico , Poliarterite Nodosa/diagnóstico , Adulto , Biópsia , Síndrome de Churg-Strauss/classificação , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/terapia , Progressão da Doença , Diagnóstico Precoce , Feminino , Granulomatose com Poliangiite/classificação , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/terapia , Humanos , Masculino , Poliangiite Microscópica/classificação , Poliangiite Microscópica/complicações , Poliangiite Microscópica/terapia , Pessoa de Meia-Idade , Poliarterite Nodosa/classificação , Poliarterite Nodosa/complicações , Poliarterite Nodosa/terapia , Valor Preditivo dos Testes , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
AIM: Many patients with systemic necrotizing vasculitis (SNV) satisfy classification criteria of different disease entities when different classification systems are used. A new classification algorithm has been proposed recently by using the American College of Rheumatology criteria, Chapel Hill Consensus Criteria (CHCC) and Sorensen surrogate markers for a more uniform classification of patients suffering from these rare disorders. METHODS: We applied this algorithm to patients diagnosed as having systemic vasculitis between 2007 and 2011. We also analyzed the data using this algorithm by incorporating the recently proposed revised CHCC nomenclature of vasculitis in place of the older criteria. RESULTS: Seventy-nine patients with SNV were studied. One patient diagnosed as microscopic polyangiitis (MPA) had to be excluded from analysis as she had previously been diagnosed as having Behcet's disease. All patients of eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA) and MPA were reclassified to the same diagnostic subcategory after application of the algorithm. Three (16.7%) of 18 polyarteritis nodosa patients were unclassifiable after application of the consensus algorithm while two (11.1%) were reclassified as MPA. All previously unclassifiable patients could be classified either as MPA or GPA after application of the new algorithm. There was no difference in the results when the CHCC 2012 nomenclature was used instead of the older CHCC in the consensus algorithm. CONCLUSION: The new classification algorithm is a reliable method for classification of SNV for epidemiological purposes in our population.
Assuntos
Algoritmos , Vasculite Sistêmica/classificação , Terminologia como Assunto , Síndrome de Churg-Strauss/classificação , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/epidemiologia , Consenso , Erros de Diagnóstico/prevenção & controle , Granulomatose com Poliangiite/classificação , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/epidemiologia , Humanos , Índia/epidemiologia , Poliangiite Microscópica/classificação , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/epidemiologia , Poliarterite Nodosa/classificação , Poliarterite Nodosa/diagnóstico , Poliarterite Nodosa/epidemiologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Vasculite Sistêmica/diagnóstico , Vasculite Sistêmica/epidemiologiaRESUMO
Classification of the ANCA-associated vasculitides remains controversial. Existing systems, developed by the American College of Rheumatology (ACR) in 1990, the Chapel Hill Consensus Conference (CHCC) in 1994 and updated in 2012, and the European Medicines Agency algorithm, all have deficiencies, especially when applied to unselected patients. The ACR system did not include ANCA or microscopic polyangiitis, and the CHCC (1994) included MPA but not ANCA (this was rectified in the 2012 revision). These systems were developed as classification criteria and not as diagnostic criteria. There are currently no validated diagnostic criteria for AAV. The Diagnostic and Classification Criteria for Vasculitis (DCVAS) study is a global study with the objective of developing and validating diagnostic criteria.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Síndrome de Churg-Strauss/classificação , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/patologia , Previsões , Granulomatose com Poliangiite/classificação , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/patologia , Humanos , Poliangiite Microscópica/classificação , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/patologiaAssuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Poliarterite Nodosa/classificação , Algoritmos , Síndrome de Churg-Strauss/classificação , Estudos de Coortes , Europa (Continente) , Granulomatose com Poliangiite/classificação , Humanos , Poliangiite Microscópica/classificaçãoRESUMO
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are a heterogeneous group of diseases corresponding to necrotising inflammation of small vessels with a wide range of clinical presentations. At least two of the diseases are believed to exhibit a common ground of pathophysiological mechanisms. These are granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis) and microscopic polyangiitis (MPA). ANCA directed against proteinase 3 (PR3) are preferentially associated with GPA, and anti-myeloperoxidase (MPO) ANCA are associated mainly with MPA and eosinophilic GPA (formerly known as Churg-Strauss syndrome). Anti-MPO and anti-PR3 antibodies can activate neutrophils in vitro. In vivo data are available for humans and mice on the pathogenicity of anti-MPO but it is more controversial for PR3-ANCA. A recent genome-wide association study of patients with ANCA-associated vasculitides confirmed the genetic contribution to the pathogenesis of these conditions, with significant association of PR3-ANCA and human leukocyte antigen-DP and the genes encoding α1-antitrypsin and PR3. MPO-ANCA were significantly associated with human leukocyte antigen-DQ. Thus, recent results from epidemiological studies, genome-wide association study and therapeutic trials have suggested that these entities are, in fact, distinct. We have summarised these results and discuss the idea that these two entities should be studied separately as the nature of the two auto-antigens suggests at a molecular level despite shared ANCA involvement.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Terminologia como Assunto , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/fisiopatologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Autoantígenos/genética , Autoantígenos/imunologia , Síndrome de Churg-Strauss/classificação , Síndrome de Churg-Strauss/imunologia , Síndrome de Churg-Strauss/fisiopatologia , Estudo de Associação Genômica Ampla , Granulomatose com Poliangiite/classificação , Granulomatose com Poliangiite/imunologia , Granulomatose com Poliangiite/fisiopatologia , Humanos , Camundongos , Poliangiite Microscópica/classificação , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/fisiopatologia , Mieloblastina/genética , Mieloblastina/imunologia , Peroxidase/imunologia , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/imunologiaAssuntos
Síndrome de Churg-Strauss/tratamento farmacológico , Anticorpos Anticitoplasma de Neutrófilos/sangue , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Síndrome de Churg-Strauss/classificação , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/imunologia , Ciclofosfamida/uso terapêutico , Previsões , Glucocorticoides/uso terapêutico , Humanos , Síndrome Hipereosinofílica/classificação , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/imunologia , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Interleucina-5/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , RituximabAssuntos
Síndrome de Churg-Strauss/imunologia , Corticosteroides/uso terapêutico , Síndrome de Churg-Strauss/classificação , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/tratamento farmacológico , Diagnóstico Diferencial , Eosinófilos/imunologia , Humanos , Síndrome Hipereosinofílica/classificação , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/imunologia , Imunossupressores/uso terapêutico , Prognóstico , Terminologia como AssuntoAssuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Síndrome de Churg-Strauss/genética , Síndrome de Churg-Strauss/imunologia , Epitopos/genética , Epitopos/imunologia , Granulomatose com Poliangiite/genética , Granulomatose com Poliangiite/imunologia , Poliangiite Microscópica/genética , Poliangiite Microscópica/imunologia , Mieloblastina/genética , Mieloblastina/imunologia , Peroxidase/genética , Peroxidase/imunologia , Fenótipo , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Autoanticorpos/sangue , Síndrome de Churg-Strauss/classificação , Síndrome de Churg-Strauss/diagnóstico , Diagnóstico Diferencial , Progressão da Doença , Genótipo , Glomerulonefrite/classificação , Glomerulonefrite/diagnóstico , Glomerulonefrite/genética , Glomerulonefrite/imunologia , Granulomatose com Poliangiite/classificação , Granulomatose com Poliangiite/diagnóstico , Humanos , Pneumopatias/classificação , Pneumopatias/diagnóstico , Pneumopatias/genética , Pneumopatias/imunologia , Poliangiite Microscópica/diagnóstico , Prognóstico , Fatores de RiscoAssuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Síndrome de Churg-Strauss/genética , Estudo de Associação Genômica Ampla/métodos , Granulomatose com Poliangiite/genética , Poliangiite Microscópica/genética , Alelos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/sangue , Anticorpos Anticitoplasma de Neutrófilos/genética , Síndrome de Churg-Strauss/classificação , Síndrome de Churg-Strauss/diagnóstico , Loci Gênicos/genética , Genótipo , Granulomatose com Poliangiite/classificação , Granulomatose com Poliangiite/diagnóstico , Cadeias beta de HLA-DP/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/imunologia , Humanos , Poliangiite Microscópica/classificação , Poliangiite Microscópica/diagnóstico , Mieloblastina/sangue , Mieloblastina/genética , Peroxidase/genética , Peroxidase/imunologia , Polimorfismo de Nucleotídeo Único/genética , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/imunologiaAssuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Glomerulonefrite/patologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Biópsia , Síndrome de Churg-Strauss/classificação , Síndrome de Churg-Strauss/patologia , Seguimentos , Glomerulonefrite/classificação , Glomerulonefrite/mortalidade , Humanos , Falência Renal Crônica/patologia , Glomérulos Renais/patologia , Peroxidase/imunologia , Prognóstico , Taxa de SobrevidaAssuntos
Anticorpos Anticitoplasma de Neutrófilos/fisiologia , Síndrome de Churg-Strauss/classificação , Granulomatose com Poliangiite/classificação , Poliangiite Microscópica/classificação , Síndrome de Churg-Strauss/epidemiologia , Síndrome de Churg-Strauss/genética , Saúde Global , Granulomatose com Poliangiite/epidemiologia , Granulomatose com Poliangiite/genética , Humanos , Poliangiite Microscópica/epidemiologia , Poliangiite Microscópica/genéticaRESUMO
OBJECTIVE: Granulomatosis with polyangiitis (Wegener's; GPA) and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare in childhood and are sometimes difficult to discriminate. We compared use of adult-derived classification schemes for GPA against validated pediatric criteria in the ARChiVe (A Registry for Childhood Vasculitis e-entry) cohort, a Childhood Arthritis and Rheumatology Research Alliance initiative. METHODS: Time-of-diagnosis data for children with physician (MD) diagnosis of AAV and unclassified vasculitis (UCV) from 33 US/Canadian centers were analyzed. The European Medicines Agency (EMA) classification algorithm and European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) and American College of Rheumatology (ACR) criteria for GPA were applied to all patients. Sensitivity and specificity were calculated (MD-diagnosis as reference). RESULTS: MD-diagnoses for 155 children were 100 GPA, 25 microscopic polyangiitis (MPA), 6 ANCA-positive pauciimmune glomerulonephritis, 3 Churg-Strauss syndrome, and 21 UCV. Of these, 114 had GPA as defined by EMA, 98 by EULAR/PRINTO/PRES, and 87 by ACR. Fourteen patients were identified as GPA by EULAR/PRINTO/PRES but not by ACR; 3 were identified as GPA by ACR but not EULAR/PRINTO/PRES. Using the EMA algorithm, 135 (87%) children were classifiable. The sensitivity of the EMA algorithm, the EULAR/PRINTO/PRES, and ACR criteria for classifying GPA was 90%, 77%, and 69%, respectively, with specificities of 56%, 62%, and 67%. The relatively poor sensitivity of the 2 criteria related to their inability to discriminate patients with MPA. CONCLUSION: EULAR/PRINTO/PRES was more sensitive than ACR criteria in classifying pediatric GPA. Neither classification system has criteria for MPA; therefore usefulness in discriminating patients in ARChiVe was limited. Even when using the most sensitive EMA algorithm, many children remained unclassified.
Assuntos
Síndrome de Churg-Strauss/diagnóstico , Granulomatose com Poliangiite/classificação , Granulomatose com Poliangiite/diagnóstico , Poliangiite Microscópica/diagnóstico , Algoritmos , Criança , Síndrome de Churg-Strauss/classificação , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Poliangiite Microscópica/classificação , Sistema de Registros , Sensibilidade e EspecificidadeRESUMO
The aim of this study was to clarify the differences in the pathogenesis of neuropathy between myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-positive and -negative patients with Churg-Strauss syndrome (CSS). Eight MPO-ANCA-positive and 14 MPO-ANCA-negative patients were included. In addition to the standard histology, nerve biopsies were examined, employing immunohistochemistry for eosinophil major basic protein and electron microscopy. The groups did not differ significantly in clinical profiles, including the peak disability score and number of blood eosinophils. In nerve biopsies, necrotizing vasculitis was found in 63% (5/8) of the ANCA-positive and 21% (3/14) of the ANCA-negative patients. Fibrinoid necrosis of vessel walls was noted in 4 ANCA-positive patients (50%), and in one ANCA-negative patient (p = 0039). In contrast, a large number of eosinophilic infiltrations in the epineurium was shown in 36% (5/14) of the ANCA-negative patients, with no eosinophilic infiltrations shown in ANCA-positive patients. In 3 ANCA-negative patients, endoneurial eosinophils were seen where focal axonal loss and capillary dilatation were occasionally noted. There may be 2 pathogenetic mechanisms of neuropathy with CSS: ANCA-related vascular fibrinoid necrosis, and a toxic eosinophilic effect on nerve fibers which is independent of ANCA. Therapy targeting activated eosinophils may be a possible treatment for intractable neuropathy of CSS.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Síndrome de Churg-Strauss , Eosinófilos/patologia , Doenças do Sistema Nervoso/imunologia , Doenças do Sistema Nervoso/patologia , Adulto , Idoso , Biópsia , Síndrome de Churg-Strauss/classificação , Síndrome de Churg-Strauss/imunologia , Síndrome de Churg-Strauss/patologia , Eosinófilos/ultraestrutura , Feminino , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Necrose , Fibras Nervosas Mielinizadas/imunologia , Fibras Nervosas Mielinizadas/patologia , Fibras Nervosas Mielinizadas/ultraestrutura , Peroxidase/imunologia , Estudos RetrospectivosRESUMO
Vasculitis is still being classified according the criteria of the American College of Rheumatology and the Chapel Hill Consensus Conference Definitions. Diagnostic criteria are currently being established. The classification criteria are based on the size of the inflamed blood vessel (e.g. large vessel vasculitis with inflammation of the aorta and its branches), clinical symptoms and findings (such as cephalalgia in giant cell arteritis) and histological findings. In recent years a definition of disease stages and activity has been established and a number of controlled trials have been carried out in order to provide evidence-based stage and activity adapted therapy regimens. Recommendations for the management of vasculitis have been published in 2009 by EULAR (European League Against Rheumatism). This article gives a review of the classification of vasculitis and summarizes the current European guidelines on management.