Pan American League of Associations for Rheumatology guidelines for the treatment of giant cell arteritis.

Considerable variability exists in the way that health-care providers treat patients with giant cell arteritis in Latin America, with patients commonly exposed to excessive amounts of glucocorticoids. In addition, large health disparities prevail in this region due to socioeconomic factors, which influence access to care, including biological treatments. For these reasons, the Pan American League of Associations for Rheumatology developed the first evidence-based giant cell arteritis treatment guidelines tailored for Latin America. A panel of vasculitis experts from Mexico, Colombia, Peru, Brazil, and Argentina generated clinically meaningful questions related to the treatment of giant cell arteritis in the population, intervention, comparator, and outcome (PICO) format. Following the grading of recommendations, assessment, development, and evaluation methodology, a team of methodologists did a systematic literature search, extracted and summarised the effects of the interventions, and graded the quality of the evidence. The panel of vasculitis experts voted on each PICO question and made recommendations, which required at least 70% agreement among the voting members to be included in the guidelines. Nine recommendations and one expert opinion statement for the treatment of giant cell arteritis were developed considering the most up-to-date evidence and the socioeconomic characteristics of Latin America. These recommendations include guidance for the use of glucocorticoids, tocilizumab, methotrexate, and aspirin for patients with giant cell arteritis.

A proposed role of neutrophil extracellular traps and their interplay with fibroblasts in ANCA-associated vasculitis lung fibrosis.

ANCA-associated vasculitides (AAV) comprise three diseases: granulomatosis with polyangiitis, microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis. They are characterised by small vessel inflammation and have a broad range of clinical manifestations and multiorgan involvement which endanger the patient's life. An increasingly recognised complication of AAV, especially in MPA is lung fibrosis, for which no clearcut therapy in this context is available. The release of neutrophil extracellular traps (NETs) in these diseases has been related to the development of fibrosis, but the precise mechanisms are not fully unravelled. This review provides an overview of some of the important proteins known to compose NETs, and proposes some mechanisms by which these remarkable components may exert an impact on the different fibroblastic phenotypes leading to lung fibrosis.

Limited pulmonary MPA, a new MPA entity? A rheumatologist's perspective.

Microscopic polyangiitis (MPA) frequently involves the lungs. However, as opposed to granulomatosis with polyangiitis (Wegener's), limited forms are not recognised. In recent years, cases have been reported in which the lungs were affected without other organ manifestations. For years, many have been labelled as idiopathic pulmonary fibrosis (IPF). In this review, support for the existence of a limited form of MPA affecting the lungs as well as questions and discussions concerning the similarities and differences to IPF are offered.

[The complement system in the pathogenesis of antineutrophil cytoplasm antibodies-associated vasculitis]. / El sistema del complemento en la patogenia de las vasculitis asociadas a anticuerpos anticitoplasma de neutrófilo.

One of the main characteristics of the vasculitis associated with antineutrophil cytoplasm autoantibodies (AASV) is the absence of immune complex deposition in biopsies of affected tissues as well as a lack of complement depletion. However, in early stages of disease induced in animal models, it has been observed that the complement system may be involved in the generation of these diseases. There are various animal models which have been developed with the aim of knowing which are the pathogenic mechanisms in granulomatosis with polyangiitis (Wegener) (GPA) and microscopic polyangiitis (MPA), the latter being explained using these approaches in a more satisfactory manner, as there is lack of a model which reproduces the changes leading to a granulomatous vasculitis associated with antibodies against proteinase-3, as in GPA. This short review presents recent evidence of the presence of complement in biopsies of patients with AASV and the most recent animal models, which show the participation of complement in their etiology.

El sistema del complemento en la patogenia de las vasculitis asociadas a anticuerpos anticitoplasma de neutrófilo / The complement system in the pathogenesis of antineutrophil cytoplasm antibodies-associated vasculitis

Una de las características principales de las vasculitis asociadas a ANCA (VAA) es la ausencia de depósito de complejos inmunes en las biopsias de los tejidos afectados y de consumo de complemento. Sin embargo, en etapas tempranas de enfermedades similares producidas en modelos animales, se ha observado que el sistema del complemento puede participar en la génesis de estas patologías. Varios modelos se han desarrollado en el intento de disecar los mecanismos patogénicos de enfermedades como granulomatosis con poliangitis (Wegener) (GPA) o poliangitis microscópica siendo más exitosos en esta última, sin que hasta el momento se disponga de un modelo satisfactorio para explicar los cambios que llevan a enfermedad granulomatosa vasculítica, máxime si se asocia a anticuerpos contra proteinasa-3 (PR-3), como es el caso en la GPA. Este manuscrito revisa en forma sucinta las evidencias recientes de la presencia de complemento en biopsias de pacientes con VAA, así como modelos animales que ponen de manifiesto la participación del sistema de complemento en su patogenia (AU)

One of the main characteristics of the vasculitis associated with antineutrophil cytoplasm autoantibodies (AASV) is the absence of immune complex deposition in biopsies of affected tissues as well as a lack of complement depletion. However, in early stages of disease induced in animal models, it has been observed that the complement system may be involved in the generation of these diseases. There are various animal models which have been developed with the aim of knowing which are the pathogenic mechanisms in granulomatosis with polyangiitis (Wegener) (GPA) and microscopic polyangiitis (MPA), the latter being explained using these approaches in a more satisfactory manner, as there is lack of a model which reproduces the changes leading to a granulomatous vasculitis associated with antibodies against proteinase-3, as in GPA. This short review presents recent evidence of the presence of complement in biopsies of patients with AASV and the most recent animal models, which show the participation of complement in their etiology (AU)

Rituximab en el tratamiento de las vasculitis asociadas a ANCA: ¿el futuro hoy? / Rituximab for the treatment of ANCA associated vasculitis. The future today?

Gracias al tratamiento con ciclofosfamida la letalidad de las vasculitis asociadas a ANCA ha disminuido considerablemente. Sin embargo, dicho tratamiento se relaciona con efectos adversos agudos y crónicos que contribuyen a la morbimortalidad de estas enfermedades. Por ello, uno de los retos actuales en el manejo de estas patologías consiste en encontrar terapias que sean tan efectivas como la ciclofosfamida pero con un margen de seguridad más favorable. Bajo estas condiciones, el rituximab (RTX), un anticuerpo monoclonal anti-CD20, encabeza la lista de nuevas opciones en el tratamiento de las vasculitis asociadas a ANCA y es el más firme candidato para establecerse como opción terapéutica de primera elección. En este artículo de revisión examinamos la evidencia actual sobre la eficacia y seguridad de RTX como tratamiento para las vasculitis de vasos de pequeño calibre asociadas a ANCA (AU)

Since cyclophosphamide was introduced for the treatment of ANCA-associated vasculitis, the mortality of these diseases has decreased considerably. However, such treatment is related to acute and chronic serious adverse effects, which contribute to the morbidity and mortality of such diseases. Therefore, one of the main challenges in the treatment of such conditions is to find newer and effective therapies with a safer profile. Rituximab (RTX), an anti-CD20 monoclonal antibody stands at the top of new options for the treatment of ANCA-associated vasculitis, and is the strongest candidate to establish itself as a first choice therapeutic agent. Here, we review the rationale of RTX treatment in ANCA-associated small vessel vasculitis, and the current evidence of both its efficacy and toxicity (AU)

[Rituximab for the treatment of ANCA associated vasculitis: the future today?]. / Rituximab en el tratamiento de las vasculitis asociadas a ANCA: ¿el futuro hoy?

Since cyclophosphamide was introduced for the treatment of ANCA-associated vasculitis, the mortality of these diseases has decreased considerably. However, such treatment is related to acute and chronic serious adverse effects, which contribute to the morbidity and mortality of such diseases. Therefore, one of the main challenges in the treatment of such conditions is to find newer and effective therapies with a safer profile. Rituximab (RTX), an anti-CD20 monoclonal antibody stands at the top of new options for the treatment of ANCA-associated vasculitis, and is the strongest candidate to establish itself as a first choice therapeutic agent. Here, we review the rationale of RTX treatment in ANCA-associated small vessel vasculitis, and the current evidence of both its efficacy and toxicity.