Severe infections in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study with a clinical phenotype approach.

Severe infections are common in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We aimed to describe the characteristics of patients with AAV and severe infections according to clinical phenotype. Retrospective cohort study including patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Baseline characteristics were compared between patients with and without at least one severe infection. Demographics, comorbidities, clinical characteristics, laboratory and treatment were retrieved at diagnosis and at every infectious event. One hundred and eight patients were included (57 with and 51 without infections). Patients with an infection had received more frequently methylprednisolone boluses at AAV diagnosis than patients without infections (OR 2.6, 95% CI 1.1-5.9, p = 0.01). There were a total of 108 severe infections in 57 patients (median follow-up 18 months). Thirty-two patients (56%) had an infectious complication within the first year of AAV diagnosis, 43 (75%) had pulmonary involvement during the first infection. The most frequent type of infection was pneumonia. Phenotypes were: Non-severe AAV (n = 11), severe PR3-AAV (n = 30), severe MPO-AAV (n = 9); the number of infectious events in each group was 11, 69, 18, respectively. Patients with severe MPO phenotype were older and required more frequently ICU stay compared to other phenotypes. Positive correlation was found between total of infections and pulmonary infiltrates due to vasculitis (ρ = 0.40, p = 0.003), endobronchial involvement (ρ = 0.40, p = 0.003), and alveolar hemorrhage (ρ = 0.34, p = 0.015). Severe infections, most commonly pneumonia, were frequent in this cohort, especially during the first year after diagnosis, in patients with pulmonary involvement and severe PR3 phenotype who received methylprednisolone boluses.

Increased renal damage in hypocomplementemic patients with ANCA-associated vasculitis: retrospective cohort study.

INTRODUCTION: The complement system has an important role in the pathogenesis of vasculitis associated with antineutrophilic cytoplasmic antibody (AAV) mainly at the level of the kidneys because patients with complement deposits on the glomerular basal membrane present more aggressive disease compared with those with pauci-immune vasculitis. AIM: To analyze the association of hypocomplementemia with the clinical manifestations, laboratory data, renal histology, progress to renal insufficiency, and mortality of patients with AAV. METHODS: Retrospective cohort study (2000-2007) included 93 patients with AAV. Hypocomplementemia is defined as having C3 values lower than 80 mg/dL or C4 values below 15 mg/dL. Demographic, statistical, clinical, hematological, serological, and histopathological characteristics of all the patients with and without diagnosis of hypocomplementemia were compared. In order to evaluate variable independence, a logistic regression analysis was used. RESULTS: Ninety-three patients were studied of whom 63 (67.7%) had complement dosage at the moment of AAV diagnosis. Seven patients (11.1%) presented hypocomplementemia and a greater kidney involvement compared with normocomplementemic patients. Thirty renal biopsies were analyzed and 4 (13.3%) showed immunocomplex (IC) or complement deposits by an immunofluorescence test (IFT). Patients with "non-pauci-immune" AAV also presented terminal chronic renal disease (TCRD). CONCLUSION: There is an association between low complement and the degree of renal damage in patients with AAV. Patients with renal biopsies confirming IC and/or complement deposits showed more aggressive renal disease. Key Points • The complement system has an important role in the pathogenesis of vasculitis associated to antineutrophilic cytoplasmic antibody. • The studies in murine models confirming the complement activation by alternative pathway and particularly the receptor C5a (C5aR) is necessary for the development of glomerulonefritis. • Complement deposit observed in the renal biopsies of patients diagnosed with AAV was correlated to greater kidney damage, greater proteinuria and major disease activity compared to patients diagnosed with typical pauci-immune vasculitis. • The presence of hypocomplementemia at the onset of the disease was also associated with a greater organ involvement, poor prognosis and greater mortality.

Incidence of Cytomegalovirus Antigenemia in patients with autoimmune rheumatic diseases: a 3-year retrospective study.

OBJECTIVE: To determine the incidence of positive CMV antigenemia (CMV-Ag) in patients with autoimmune rheumatic diseases (AIRD) and to describe the outcomes of these patients. METHODS: From January 2011 to December 2014, a total of 443 patients with AIRD were enrolled in this retrospective analysis. Demographic, clinical and laboratory data, current clinical manifestations, organs affected by CMV infection, therapeutic management and outcomes were evaluated. The CMV-Ag was considered positive when one cell was detected at least. RESULTS: CMV-Ag was requested in 70 (15.8%) patients with suspicious CMV infection and was positive in 24 (34.3%). The incidence rate of positive CMV-Ag was 4.97% (95% CI 3.1-7.4%). Systemic lupus erythematosus (SLE) (59%), followed by ANCA-related vasculitis (18.2%) and rheumatoid arthritis (9%) were the diseases more associated with positive CMV-Ag. At the time of CMV infection, SLE patients had moderate to severe disease activity, with high frequency of positive anti-dsDNA antibody (69.2%) and complement consumption (61.5%), as well as high doses of corticosteroids and use of immunosuppressants. The main CMV sites involved were lung (45.5%), bone marrow (40.9%) and gut (27.3%). Mortality rate was 45.5%, especially in those with higher doses of daily oral corticosteroids (107 ± 55.4 mg vs. 71.7 ± 46.3 mg; p = 0.07) and lower number of lymphocytes (309 ± 368.2/mm3 vs. 821 ± 692.9/mm3; p = 0.06). CONCLUSIONS: Our data showed high incidence of CMV-Ag in AIRD patients, particularly those with SLE and greater disease severity. In addition, it was observed high mortality in these patients, highlighting the CMV infection should be included in differential diagnosis.

Granulomatosis de Wegener. A propósito de un caso / Wegener's granulomatosis: a case report andr review of the literature

Las enfermedades vasculares se encuentran divididas para su mejor comprensión en patologías de vasos grandes medianos o pequeños calibres; en este apartado nos dedicamos a revisar un caso específico de enfermedad granulomatosa de Wegener que corresponde directamente a una enfermedad de pequeños vasos, que comprometió los ojos, los oídos, los pulmones, los riñones y la piel; logrando reunir la parte clínica, patología, las imágenes diagnósticas, laboratorios y el manejo farmacológico. Se debe tener en cuenta que los sistemas de mayor compromiso son el respiratorio y el renal no dejando a un lado el otorrino la piel, el gastrointestinal y sistema nervioso entre otros. Siendo de importancia la pesquisa de los ANCA (anticuerpos anticitoplasma de neutrófilos) siendo el más específico el pr3 (proteinasa3) y la biopsia anatomopatológica, la cual confirma el diagnostico

Vascular diseases are divided for better understanding in pathologies of medium large vessels or small calibers; in this section, we review a specific case of Wegener's granulomatous disease that corresponds directly to a disease of small vessels, which affected the eyes, ears, lungs, kidneys and skin; managing to gather the clinical part, pathology, diagnostic images, laboratories, pharmacological management. It must be taken into account that the systems of greatest commitment are the respiratory and the renal, not leaving aside the otorrino skin, gastrointestinal and nervous system among others. The ANCA (antineutrophil cytoplasmic antibodies) is of importance, with the most specific being pr3 (proteinase3) and the anatomopathological biopsy, which confirms the diagnosis

ANCA-associated pauci-immune glomerulonephritis: always pauci-immune?

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is considered "pauci-immune" with absent or mild glomerular tuft staining for immunoglobulin (Ig) and/or complement. However, it is not unusual to see some immune deposits (ID) within glomeruli on immunofluorescence (IF). We determined to evaluate the prevalence and clinical significance of immune deposits in ANCA-associated GN. METHODS: We included all patients with ANCA associated vasculitis with renal biopsies between January 2002 and May 2014: granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis and renal limited vasculitis. Patients were divided into Group A: biopsy without ID (≤2+ intensity of immunostaining) and Group B: biopsy with ID (>2+ intensity of immunostaining). Serum creatinine, estimated glomerular filtration rate (eGFR) at time of the biopsy, amount of proteinuria and hematuria, requirement of dialysis and extra renal involvement were recorded. RESULTS: Fifty-three patients (75.4% females) were included. Mean age at biopsy was 66.3 years. Typical pauci-immune GN was found in 39 patients (73.5%, group A). In 14 patients (26.4%, group B) examination revealed substantial deposition of Ig or complement in the mesangium and/or along the glomerular capillary wall. The only difference comparing both groups was significantly higher proteinuria in group B (mean 1.6/24 h (SD: 10.7) vs. 0.8/24 h (SD: 7.6), p=0.0036). CONCLUSIONS: In ANCA GN at least a quarter of patients were not "pauci-immune" (26.4%). In this subgroup, immune deposits were only associated with a significantly higher proteinuria. Further basic and clinical research is needed to elucidate the significance of immune deposition in ANCA GN.

[Pulmonar pseudotumor in granulomatosis with polyangiitis (GPA). Pulmonary cancer and/or GPA? Diagnostic implications of pulmonary nodules]. / Pseudotumor pulmonar en granulomatosis con poliangeítis (GPA). ¿Cáncer pulmonar y/o GPA?, implicaciones diagnósticas de los nódulos pulmonares.

Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a systemic necrotizing vasculitis, which affects small and medium sized blood vessels and is often associated with cytoplasmic anti-neutrophil cytoplasmic antibodies (ANCA). Inflammatory pseudotumor is a rare condition characterized by the appearance of a mass lesion that mimics a malignant tumor both clinically and on imaging studies, but that is thought to have an inflammatory/reactive pathogenesis. We report a patient with a GPA which was originally diagnosed as malignancy.

Rituximab for induction and maintenance therapy in granulomatosis with polyangiitis (Wegener's). Results of a single-center cohort study on 66 patients.

The aim of this study was to evaluate the efficacy and safety of rituximab (RTX) associated with glucocorticoid treatment based on disease severity, as a remission induction treatment for granulomatosis with polyangiitis (GPA) (Wegener's) and to analyze the results of long-term maintenance therapy with low doses of RTX in a routine time-based protocol. This single-center retrospective study used standardized data collection from all GPA patients receiving RTX between 2002 and 2013. The remission induction regimen consisted of RTX and glucocorticoids, adapted according to disease severity. Once remission was achieved, patients received RTX maintenance treatment (500 mg every 6 months) for 18 months. Sixty-six GPA patients received RTX for remission induction. After six months, a response had been achieved in 78.8% of these patients, with a moderate oral prednisone regimen (mean dose at baseline, 32.8 ± 23.4 mg/day). Subglottic stenosis increased the risk of treatment failure (OR = 31.2, P = 0.0104). RTX maintenance treatment was continued for 18 months in 92% of the GPA patients, who were followed for 34.2 ± 26.2 months (mean total cumulative RTX dose of 4.6 ± 1.7 g). The relapse rate was 11.2/100 patient-years. The relapses occur a mean of 13.5 ± 14.7 months after the last RTX infusion. Twenty-one severe adverse events were recorded; 13.6% patients had severe infections. We conclude that in this single-center cohort, RTX associated with glucocorticoid treatment adapted for disease severity appeared to induce remission effectively in GPA patients. Maintenance treatment with low doses of RTX in a routine time-based protocol was safe and associated with low rates of relapse on treatment.

Granulomatosis with polyangiitis: recurrence presenting as ependimoplexitis.

A 55-year-old man with granulomatosis with polyangiitis (GPA) developed continuous parietal headache, malaise, nasal crusting and dry cough. Neurological exam revealed only left hand hypoesthesia in 4th and 5th finger. Brain MRI showed enlarged right choroid plexus, hyperintense periventricular white matter, thalami and right side of corpus callosum. The suspected diagnosis was ependimoplexitis due to GPA, the patient received three 500 mg methylprednisolone pulses followed by 1 mg/kg of meprednisone with gradual tapering and was switched to oral cyclophosphamide. He had complete resolution of headache. An MRI following this treatment for relapse revealed only minimal ependimal changes.

[Anti-neutrophil cytoplasmic antibody-associated vasculitis. Clinical aspects and treatment]. / Vasculitis asociadas a anticuerpos anti-citoplasma de neutrófilos. Clínica y tratamiento.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis, comprise a group of diseases characterized by inflammation of the wall of small vessels. We analyzed epidemiological and clinical characteristics in a series of 47 patients, 23 (49%) with Wegener granulomatosis (WG), 15 (32%) with microscopic polyangiitis (MPA) and nine (19%) with renal limited vasculitis (RLV). The mean age at onset of symptoms was 50.7 ± 14.9 years. The most frequent clinical manifestation was renal involvement in 41 (87%), followed by pulmonary manifestations in 26 (55%) and ENT involvement in 17 (36%). In 26 (55%) it presented with simultaneous pulmonary and renal involvement. The most frequent clinical category was the generalized form in 23 (49%), followed by the severe form in 18 (38%). Eighty nine percent of patients had positive ANCA test. Four (8%) received no immunosuppressive treatment. Of the 43 patients who were treated, 29 (67%) achieved complete remission with an average length of remission of 35.3 months. Eleven (26%) had a relapse, ten (91%) had a major relapse and one had a minor relapse. Twelve (28%) patients died, seven died early and five late during the course of the disease. Fifteen (31%) progressed to chronic renal failure. All 26 patients in follow-up had response to treatment and 20 (77%) were in remission at the end of the study. Despite the improvements achieved with immunosuppressive treatments, morbidity and mortality rates in ANCA-associated vasculitis remain high.

Vasculitis asociadas a anticuerpos anti-citoplasma de neutrófilos: Clínica y tratamiento / Anti-neutrophil cytoplasmic antibody-associated vasculitis: Clinical aspects and treatment

Las vasculitis asociadas a anticuerpos anti-citoplasma de neutrófilos (ANCA) comprenden a un grupo de enfermedades caracterizadas por la inflamación de la pared de pequeños vasos. Analizamos las características epidemiológicas y clínicas en una serie de 47 pacientes: 23 (49%) granulomatosis de Wegener (GW), 15 (32%) poliangeítis microscópica (PAM) y nueve (19%) vasculitis limitada al riñón (VLR). La edad media al inicio de los síntomas fue de 50.7 ± 14.9 años. La manifestación clínica más frecuente fue el compromiso renal en 41 (87%) pacientes, seguido por el pulmonar en 26 (55%) y el otorrinolaringológico en 17 (36%). En 26 (55%) se asoció compromiso renal y pulmonar. La forma clínica más frecuente fue la generalizada en 23 (49%), seguida por la grave en 18 (38%). El 89% presentaron determinaciones de ANCA positivas. Cuatro (8%) no recibieron tratamiento inmunosupresor de inicio. De los 43 que recibieron tratamiento de inicio, 29 (67%) tuvieron remisión completa, con un tiempo de remisión promedio de 35.3 meses. Once (26%) presentaron recaídas, diez (91%) recaídas mayores y uno (9%) menor. Doce (28%) fallecieron, siete en forma temprana y cinco durante la evolución de la enfermedad. Quince (31%) evolucionaron a insuficiencia renal crónica. Los 26 pacientes en seguimiento tuvieron respuesta al tratamiento y 20 (77%) de ellos estaban en remisión al finalizar el estudio. Las vasculitis asociadas a ANCA continúan siendo enfermedades de alta morbilidad y mortalidad, a pesar de las mejorías logradas con los tratamientos inmunosupresores.(AU)

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis, comprise a group of diseases characterized by inflammation of the wall of small vessels. We analyzed epidemiological and clinical characteristics in a series of 47 patients, 23 (49%) with Wegener granulomatosis (WG), 15 (32%) with microscopic polyangiitis (MPA) and nine (19%) with renal limited vasculitis (RLV). The mean age at onset of symptoms was 50.7 ± 14.9 years. The most frequent clinical manifestation was renal involvement in 41 (87%), followed by pulmonary manifestations in 26 (55%) and ENT involvement in 17 (36%). In 26 (55%) it presented with simultaneous pulmonary and renal involvement. The most frequent clinical category was the generalized form in 23 (49%), followed by the severe form in 18 (38%). Eighty nine percent of patients had positive ANCA test. Four (8%) received no immunosuppressive treatment. Of the 43 patients who were treated, 29 (67%) achieved complete remission with an average length of remission of 35.3 months. Eleven (26%) had a relapse, ten (91%) had a major relapse and one had a minor relapse. Twelve (28%) patients died, seven died early and five late during the course of the disease. Fifteen (31%) progressed to chronic renal failure. All 26 patients in follow-up had response to treatment and 20 (77%) were in remission at the end of the study. Despite the improvements achieved with immunosuppressive treatments, morbidity and mortality rates in ANCA-associated vasculitis remain high.(AU)

Vasculitis asociadas a anticuerpos anti-citoplasma de neutrófilos: Clínica y tratamiento / Anti-neutrophil cytoplasmic antibody-associated vasculitis: Clinical aspects and treatment

Las vasculitis asociadas a anticuerpos anti-citoplasma de neutrófilos (ANCA) comprenden a un grupo de enfermedades caracterizadas por la inflamación de la pared de pequeños vasos. Analizamos las características epidemiológicas y clínicas en una serie de 47 pacientes: 23 (49%) granulomatosis de Wegener (GW), 15 (32%) poliangeítis microscópica (PAM) y nueve (19%) vasculitis limitada al riñón (VLR). La edad media al inicio de los síntomas fue de 50.7 ± 14.9 años. La manifestación clínica más frecuente fue el compromiso renal en 41 (87%) pacientes, seguido por el pulmonar en 26 (55%) y el otorrinolaringológico en 17 (36%). En 26 (55%) se asoció compromiso renal y pulmonar. La forma clínica más frecuente fue la generalizada en 23 (49%), seguida por la grave en 18 (38%). El 89% presentaron determinaciones de ANCA positivas. Cuatro (8%) no recibieron tratamiento inmunosupresor de inicio. De los 43 que recibieron tratamiento de inicio, 29 (67%) tuvieron remisión completa, con un tiempo de remisión promedio de 35.3 meses. Once (26%) presentaron recaídas, diez (91%) recaídas mayores y uno (9%) menor. Doce (28%) fallecieron, siete en forma temprana y cinco durante la evolución de la enfermedad. Quince (31%) evolucionaron a insuficiencia renal crónica. Los 26 pacientes en seguimiento tuvieron respuesta al tratamiento y 20 (77%) de ellos estaban en remisión al finalizar el estudio. Las vasculitis asociadas a ANCA continúan siendo enfermedades de alta morbilidad y mortalidad, a pesar de las mejorías logradas con los tratamientos inmunosupresores.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis, comprise a group of diseases characterized by inflammation of the wall of small vessels. We analyzed epidemiological and clinical characteristics in a series of 47 patients, 23 (49%) with Wegener granulomatosis (WG), 15 (32%) with microscopic polyangiitis (MPA) and nine (19%) with renal limited vasculitis (RLV). The mean age at onset of symptoms was 50.7 ± 14.9 years. The most frequent clinical manifestation was renal involvement in 41 (87%), followed by pulmonary manifestations in 26 (55%) and ENT involvement in 17 (36%). In 26 (55%) it presented with simultaneous pulmonary and renal involvement. The most frequent clinical category was the generalized form in 23 (49%), followed by the severe form in 18 (38%). Eighty nine percent of patients had positive ANCA test. Four (8%) received no immunosuppressive treatment. Of the 43 patients who were treated, 29 (67%) achieved complete remission with an average length of remission of 35.3 months. Eleven (26%) had a relapse, ten (91%) had a major relapse and one had a minor relapse. Twelve (28%) patients died, seven died early and five late during the course of the disease. Fifteen (31%) progressed to chronic renal failure. All 26 patients in follow-up had response to treatment and 20 (77%) were in remission at the end of the study. Despite the improvements achieved with immunosuppressive treatments, morbidity and mortality rates in ANCA-associated vasculitis remain high.

Autoimmune liver disorders and small-vessel vasculitis: four case reports and review of the literature.

Autoimmune liver diseases (AILD) are a group of immunologically induced hepatic disorders that can lead to liver cirrhosis and end-stage liver disease. Extra-hepatic involvement and association with rheumatic diseases (such as Sjögren's syndrome, systemic sclerosis and rheumatoid arthritis) are well known, whereas the coexistence of AILD with small-vessel vasculitis in the same patients have been only occasionally reported. In the present paper we report four such cases and an extensive review of the literature. Clinical features of autoimmune-liver diseases associated with small-vessel vasculitis are discussed, as well as possible common pathogenic pathways including HLA genomics, costimulatory molecules and autoantibodies. In conclusion, knowledge about this association can help physicians in recognising and treating an aggressive disease which could otherwise result in severe and multiple organ damage, compromising the overall prognosis and the indication to liver transplantation.

Vasculitis asociadas a anticuerpos anti-citoplasma de neutrófilos. Clínica y tratamiento. / [Anti-neutrophil cytoplasmic antibody-associated vasculitis. Clinical aspects and treatment].

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis, comprise a group of diseases characterized by inflammation of the wall of small vessels. We analyzed epidemiological and clinical characteristics in a series of 47 patients, 23 (49

) with Wegener granulomatosis (WG), 15 (32

) with microscopic polyangiitis (MPA) and nine (19

) with renal limited vasculitis (RLV). The mean age at onset of symptoms was 50.7 ± 14.9 years. The most frequent clinical manifestation was renal involvement in 41 (87

), followed by pulmonary manifestations in 26 (55

) and ENT involvement in 17 (36

). In 26 (55

) it presented with simultaneous pulmonary and renal involvement. The most frequent clinical category was the generalized form in 23 (49

), followed by the severe form in 18 (38

). Eighty nine percent of patients had positive ANCA test. Four (8

) received no immunosuppressive treatment. Of the 43 patients who were treated, 29 (67

) achieved complete remission with an average length of remission of 35.3 months. Eleven (26

) had a relapse, ten (91

) had a major relapse and one had a minor relapse. Twelve (28

) patients died, seven died early and five late during the course of the disease. Fifteen (31

) progressed to chronic renal failure. All 26 patients in follow-up had response to treatment and 20 (77

) were in remission at the end of the study. Despite the improvements achieved with immunosuppressive treatments, morbidity and mortality rates in ANCA-associated vasculitis remain high.

Wegener's granulomatosis: experience from a Brazilian tertiary center.

Most epidemiological studies with Wegener's granulomatosis (WG) patients are based on populations from the Northern hemisphere, whereas very few studies have been conducted in Southern hemisphere populations, particularly from South America. The authors performed a large retrospective, demographic study including clinical and laboratory profiles of 134 consecutive WG patients seen at one Brazilian center from 1999 to 2009. Mean age at initial WG diagnosis was 43.4 +/- 15.5 years, and mean disease duration was 8.6 +/- 6.6 years. Sixty-four (47.8%) patients were male and a total of 113 (84.3%) subjects were white. Ear/nose/throat involvement occurred in 85.8%. The classic lung and renal involvement were observed in 77.6% and 75.4%, respectively, followed by ocular (35.8%), musculoskeletal (33.4%), cutaneous (29.1%), neurological (20.1%), cardiac (11.2%), and genitourinary involvement in 2.2% of cases. Cytoplasmic pattern-antineutrophil cytoplasmic antibody was detected in 83 (61.9%) cases. Ten (7.5%) individuals presented limited forms of WG. Classic therapy with corticosteroids and cyclophosphamide was used in 97 cases (72.4%). There were no cases of tuberculosis or Pneumocystis jiroveci pneumonia, but cutaneous herpes zoster occurred in eight (6.0%) individuals. There were 29 deaths (21.6%). Eighteen patients died of septic shock (mainly bacterial pneumonia), whereas four died of alveolar hemorrhage, four of myocardial infarction, and three of other causes. In summary, our data from a very large retrospective and descriptive study mirrored the main clinical features of WG described in other countries, demonstrating that they may serve as a reference for South American populations.

[Clinical features of Wegener granulomatosis and microscopic polyangiitis in Chilean patients]. / Manifestaciones clínicas de la granulomatosis de Wegener y la poliangeítis microscópica en Santiago-Chile, 1990-2001.

BACKGROUND: Systemic vasculitis are a group of heterogeneous diseases characterized by inflammation and necrosis of blood vessel walls. The etiology is not known, but geographic and environmental factors are implicated. AIM: To describe the clinical features of microscopic polyangiitis (MPA) and Wegener's granulomatosis (WG) in a Chilean cohort of patients. PATIENTS AND METHODS: Retrospective review of the medical records of 123 patients with the diagnosis of systemic vasculitis (65 MPA and 58 WG), seen from 1990 to 2001. The diagnosis were made based on the American College of Rheumatology and Chapel Hill criteria. RESULTS: The mean follow-up for MPA was 15 months (1-120) and for WG, 20 months (1-120). The median age (years) at diagnosis for MPA was 61 (19-82) and WG 50 (20-82). Gender distribution was similar in both groups (male: 68% and 57% respectively). The main clinical features in the MPA group were renal involvement (68%), peripheral nervous system involvement (57%), pulmonary hemorrhage (28%), and skin disease (32%). In the WG group were alveolar hemorrhage (62%), renal involvement (78%), paranasal sinus involvement (57%), and ocular disease (26%). In both, creatinine levels above 2.0 mg/dl were associated with a higher mortality (p< 0.01). ANCA by immunofluorescence was performed in 56 MPA patients (75% had pANCA, 4% had cANCA and 21% were ANCA negative) and in 55 WG patients (17% had pANCA, 79% had cANCA and 4% were ANCA negative). Global mortality was 18% and 17% respectively, and the most common causes of death were infections. CONCLUSIONS: The clinical features of our patients are similar to other published data. In our WG and MPA patients the main predictor for death was a serum creatinine above 2 mg/dl.

Manifestaciones clínicas de la granulomatosis de Wegener y la poliangeítis microscópica en Santiago-Chile, 1990-2001 / Clinical features of Wegener granulomatosis and microscopic polyangiitis in Chilean patients

Background: Systemic vasculitis are a group of heterogeneous diseases characterized by inflammation and necrosis of blood vessel walls. The etiology is not known, but geographic and environmental factors are implicated. Aim: To describe the clinical features of microscopic polyangiitis (MPA) and Wegener's granulomatosis (WG) in a Chilean cohort of patients. Patients and methods: Retrospective review of the medical records of 123 patients with the diagnosis of systemic vasculitis (65 MPA and 58 WG), seen from 1990 to 2001. The diagnosis were made based on the American College of Rheumatology and Chapel Hill criteria. Results: The mean follow-up for MPA was 15 months (1-120) and for WG, 20 months (1-120). The median age (years) at diagnosis for MPA was 61 (19-82) and WG 50 (20-82). Gender distribution was similar in both groups (male: 68percent and 57percent respectively).The main clinical features in the MPA group were renal involvement (68percent), peripheral nervous system involvement (57percent), pulmonary hemorrhage (28percent), and skin disease (32percent). In the WG group were alveolar hemorrhage (62percent), renal involvement (78percent), paranasal sinus involvement (57percent), and ocular disease (26percent). In both, creatinine levels above 2.0 mg/dl were associated with a higher mortality (p< 0.01). ANCA by immunofluorescence was performed in 56 MPA patients (75percent had pANCA, 4percent had cANCA and 21percent were ANCA negative) and in 55 WG patients (17percent had pANCA, 79percent had cANCA and 4percent were ANCA negative). Global mortality was 18percent and 17percent respectively, and the most common causes of death were infections. Conclusions: The clinical features of our patients are similar to other published data. In our WG and MPA patients the main predictor for death was a serum creatinine above 2 mg/dl.

[Wegener's granulomatosis. Report of a pediatric case and review of the literature]. / Granulomatosis de Wegener. Reporte de un caso pediátrico y revisión de la literatura.

Wegener's granulomatosis is a form of systemic vasculitis of unknown etiology that affects the small blood vessels. The disease is characterized by the formation of granulomas on small and medium blood vessels, and often affects the respiratory tract and renal system. In 86% of diagnosed cases, renal compromise is in the form of glomerulonephritis. Wegener's granulomatosis can occur at any age, principally during the 4th and 5th decades of life, and 85% of cases occur over the age of 19 years. In the United States about 3 per 100,000 cases are reported, with a major occurrence in males. The present report is about a case of a 12 year old female with Wegener's granulomatosis of 18 months of evolution, with symptoms such as epistaxis, generalized edema, cough, dyspnea, hemoptysis, high blood pressure and macroscopic hematuria. Out of the five criteria for the diagnosis of Wegener's granulomatosis, she had perinuclear anti-neutrophil cytoplasmic antibody positive to serum p-ANCA mark, which is the least frequent, which makes more difficult the diagnosis. Over a period of five years, in our hospital, we have diagnosed 11 patients with Wegener's granulomatosis, and the present case is the only pediatric case.

C-ANCA-positive IgG fraction from patients with Wegener's granulomatosis induces lung vasculitis in rats.

The aim of the present study was to analyse in rats the ability of C-ANCA-positive IgG fraction in triggering inflammatory response on pulmonary tissue. Wistar rats (n = 18) were injected via the the internal jugular vein with 20 mg of total C-ANCA-positive IgG fraction isolated from serum of three different Wegener's granulomatosis patients obtained before therapy. Similarly, control rats were treated with IgG fraction from two rheumatoid arthritis patients (n = 7), IgG from six normal human sera (n = 15) or saline (n = 18), respectively. Animals were sacrificed after 24h of injection for histological analysis of the lungs. Vasculitis and inflammatory infiltrate were consistently absent in rats injected with rheumatoid arthritis IgG or saline and in 14/15 of normal IgG treated animals. In contrast, marked vasculitis was observed in all 18 animals injected with C-ANCA-positive IgG fraction. The histological features were characterized by the presence of a perivascular pleomorphic cellular sheath, particularly around small vessels, endothelial adherence and diapedesis of polymorphonuclear leucocytes and presence of granuloma-like lesions. A dose-response relationship was observed between protein concentration of C-ANCA IgG sample and the intensity of the inflammatory response in the animals. In addition, IgG fraction with undetectable C-ANCA, obtained from one patient in remission after treatment, was not able to reproduce the pulmonary tissue alterations induced by its paired IgG that was positive for C-ANCA taken before therapy. The experimental model described herein may be useful to characterize more effectively the pathogenic mechanism of C-ANCA in Wegener's disease.