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1.
Ann Rheum Dis ; 83(1): 30-47, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36927642

RESUMO

BACKGROUND: Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. METHODS: Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. RESULTS: Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. CONCLUSIONS: In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos , Azatioprina/uso terapêutico , Ciclofosfamida/uso terapêutico , Granulomatose com Poliangiite/diagnóstico , Poliangiite Microscópica/diagnóstico , Indução de Remissão , Rituximab/uso terapêutico , Guias de Prática Clínica como Assunto
3.
RMD Open ; 7(3)2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34880128

RESUMO

BACKGROUND: The persistence of the SARS-CoV2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Questions remain as to which cohorts require SARS-CoV2 boosters. However, there is a critical lack of data on the dynamics of vaccine responses in patients with chronic inflammatory diseases (CID) undergoing immunosuppressive/disease modifying anti-rheumatic (DMARD) treatment. Here, we present the first data regarding the decline of the vaccine-induced humoral immune responses in patients with CID. METHODS: 23 patients with CID were monitored clinically and for anti-spike IgG and IgA levels, neutralization efficacy and antigen-specific CD4+ T cell responses over the first 6 months after SARS-CoV2 vaccination. 24 healthy individuals were included as controls. RESULTS: While anti-spike IgG-levels declined in CID patients and healthy controls, patients receiving anti-TNF treatment showed significantly greater declines at 6 months post second vaccination in IgG and especially neutralizing antibodies. IgA levels were generally lower in CID patients, particularly during anti-TNF therapy. No differences in SARS-CoV2 spike-specific CD4+ T-cell frequencies were detected. CONCLUSION: Although the long-term efficacy of SARS-CoV2 vaccination in CID patients undergoing disease-modifying therapy is still not known, the pronounced declines in humoral responses towards SARS-CoV2 6 months after mRNA vaccination in the context of TNF blockade should be considered when formulating booster regimens. These patients should be considered for early booster vaccinations.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19 , Imunidade Humoral , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Anticorpos Antivirais/sangue , Antirreumáticos/efeitos adversos , COVID-19/imunologia , COVID-19/prevenção & controle , Humanos , Imunossupressores/efeitos adversos
4.
Ann Rheum Dis ; 80(10): 1306-1311, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33762264

RESUMO

INTRODUCTION: In light of the SARS-CoV-2 pandemic, protecting vulnerable groups has become a high priority. Persons at risk of severe disease, for example, those receiving immunosuppressive therapies for chronic inflammatory cdiseases (CIDs), are prioritised for vaccination. However, data concerning generation of protective antibody titres in immunosuppressed patients are scarce. Additionally, mRNA vaccines represent a new vaccine technology leading to increased insecurity especially in patients with CID. OBJECTIVE: Here we present for the first time, data on the efficacy and safety of anti-SARS-CoV-2 mRNA vaccines in a cohort of immunosuppressed patients as compared with healthy controls. METHODS: 42 healthy controls and 26 patients with CID were included in this study (mean age 37.5 vs 50.5 years). Immunisations were performed according to national guidelines with mRNA vaccines. Antibody titres were assessed by ELISA before initial vaccination and 7 days after secondary vaccination. Disease activity and side effects were assessed prior to and 7 days after both vaccinations. RESULTS: Anti-SARS-CoV-2 antibodies as well as neutralising activity could be detected in all study participants. IgG titres were significantly lower in patients as compared with controls (2053 binding antibody units (BAU)/mL ±1218 vs 2685±1102). Side effects were comparable in both groups. No severe adverse effects were observed, and no patients experienced a disease flare. CONCLUSION: We show that SARS-CoV-2 mRNA vaccines lead to development of antibodies in immunosuppressed patients without considerable side effects or induction of disease flares. Despite the small size of this cohort, we were able to demonstrate the efficiency and safety of mRNA vaccines in our cohort.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Hospedeiro Imunocomprometido/imunologia , Imunogenicidade da Vacina/imunologia , Inflamação/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Estudos de Coortes , Feminino , Humanos , Imunossupressores/uso terapêutico , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/imunologia , SARS-CoV-2 , Vacinas Sintéticas/imunologia , Vacinas de mRNA
5.
Dtsch Med Wochenschr ; 144(24): 1726-1730, 2019 12.
Artigo em Alemão | MEDLINE | ID: mdl-31791079

RESUMO

IgG4-related disease (IgG4-RD) is an entity first described less than 20 years ago, characterized by tumorous swelling of affected organs. Differentiation from malignant disease, systemic infections and other systemic autoimmune diseases can be challenging. Typical histopathologic findings facilitate a diagnosis in a compatible clinical context. Because nearly every organ system can be affected, management of IgG4-RD is a challenging task requiring multidisciplinary work-up and treatment. Medical treatment usually consists of glucocorticoids, which may be combined with other immunosuppressives. Surgical or interventional treatment may be necessary if complications arise. Since high-quality evidence is lacking for most aspects of the management of IgG4-RD, international collaborative studies are urgently needed.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Glucocorticoides/uso terapêutico , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/patologia , Doença Relacionada a Imunoglobulina G4/terapia , Imunossupressores/uso terapêutico
6.
Z Rheumatol ; 77(5): 397-408, 2018 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-29808333

RESUMO

Polyarteritis nodosa (PAN) is a necrotizing arteritis of medium-sized vessels, which is often fatal if untreated. It frequently affects the skin (nodules and ulcers), the peripheral nervous system (mononeuritis multiplex) and the visceral vessels (stenoses and microaneurysms). The complex diagnostic work-up requires discriminating PAN from infectious, malignant, drug-induced and other inflammatory conditions. It can be subclassified into further variants (idiopathic, associated with hepatitis B, associated with hereditary inflammatory diseases or isolated cutaneous disease). While idiopathic and hereditary inflammatory variants require immunosuppressive treatment, the hepatitis B-associated variant is treated with virustatic agents and plasmapheresis. The isolated cutaneous variant has a good prognosis and rarely requires highly potent immunosuppressives.


Assuntos
Hepatite B , Poliarterite Nodosa , Hepatite B/complicações , Humanos , Imunossupressores , Plasmaferese , Poliarterite Nodosa/complicações , Poliarterite Nodosa/diagnóstico , Poliarterite Nodosa/terapia
7.
Arthritis Rheumatol ; 68(12): 2953-2963, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27333332

RESUMO

OBJECTIVE: To compare the phenotype, clinical course, and outcome of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-positive granulomatosis with polyangiitis (Wegener's) (GPA) to proteinase 3 (PR3)-ANCA-positive GPA and to MPO-ANCA-positive microscopic polyangiitis (MPA). METHODS: We characterized all MPO-ANCA-positive patients classified as having GPA by the European Medicines Agency algorithm who attended our center, in a retrospective chart review. A second cohort of patients with PR3-ANCA-positive GPA matched for age and sex was characterized. Patients with MPO-ANCA-positive MPA from a recently published cohort were also included in the analysis. All patients were diagnosed and treated according to a standardized interdisciplinary approach at a vasculitis referral center. RESULTS: Comprehensive data were available for 59 patients with MPO-ANCA-positive GPA, and they were compared to 118 patients with PR3-ANCA-positive GPA and 138 patients with MPO-ANCA-positive MPA. We observed a distinct phenotype in MPO-ANCA-positive GPA as compared to the other 2 cohorts. Patients with MPO-ANCA-positive GPA frequently had limited disease without severe organ involvement, had a high prevalence of subglottic stenosis, and had less need for aggressive immunosuppressive therapy (cyclophosphamide/rituximab). The patients with MPO-ANCA-positive GPA were also younger than the MPA patients and were predominantly female (significantly different than the MPA cohort). While GPA patients had higher survival rates compared to MPA patients (due to a high prevalence of pulmonary fibrosis in MPA), patients with MPO-ANCA had significantly lower relapse rates than those with PR3-ANCA. CONCLUSION: Patients with MPO-ANCA-positive GPA show significantly different clinical courses compared to those with PR3-ANCA-positive GPA or MPO-ANCA-positive MPA, which should be considered in their clinical management. Classification according to ANCA specificity may improve the evaluation of relapse risk.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Granulomatose com Poliangiite/imunologia , Peroxidase/imunologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Estudos de Casos e Controles , Ciclofosfamida/uso terapêutico , Oftalmopatias/epidemiologia , Oftalmopatias/etiologia , Feminino , Alemanha , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/epidemiologia , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Nefropatias/epidemiologia , Nefropatias/etiologia , Laringoestenose/epidemiologia , Laringoestenose/etiologia , Masculino , Pessoa de Meia-Idade , Mieloblastina/imunologia , Otorrinolaringopatias/epidemiologia , Otorrinolaringopatias/etiologia , Doenças do Sistema Nervoso Periférico/epidemiologia , Doenças do Sistema Nervoso Periférico/etiologia , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Rituximab/uso terapêutico , Taxa de Sobrevida , Adulto Jovem
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