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Ciclofosfamida , Granulomatosis con Poliangitis , Rituximab , Humanos , Rituximab/uso terapéutico , Ciclofosfamida/uso terapéutico , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/diagnóstico , Resultado del Tratamiento , Femenino , Masculino , Persona de Mediana Edad , Inmunosupresores/uso terapéutico , Inducción de Remisión , Adulto , Factores de Tiempo , Quimioterapia de Inducción , Anciano , Estudios RetrospectivosRESUMEN
BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of autoimmune vasculitis. The involvement of IgG4 and HBsAg in EGPA is less common but can occur and may present unique challenges in management. CASE PRESENTATION: We present a case study of a 70-year-old female diagnosed with EGPA confirmed via renal biopsy. She initially presented with recurrent purpura, diarrhea and progressive numbness in the hands and feet, accompanied by general weakness. Complete remission was achieved with a one-year course of prednisone acetate and cyclophosphamide treatment. However, upon discontinuation of self-medication, the disease relapsed, manifesting as a generalized rash and weakness in the extremities.Skin biopsy revealed eosinophil infiltration, with inflammatory cells predominantly surrounding blood vessels. Notably, during treatment, the patient's hepatitis B markers transitioned from negative to positive for HBsAg. Subsequent administration of entecavir, along with monitoring for a decrease in HBV DNA levels, preceded the initiation of steroids and rituximab to attain remission once more. Among the remaining 15 patients analyzed, all exhibited elevated serum IgG4 levels, with none testing positive for hepatitis B. Notably, only one patient was diagnosed with immunoglobulin G4-related disease (IgG4-RD), suggesting that elevated IgG4 levels alone may not necessarily indicate IgG4-RD. CONCLUSIONS: Our case report highlights the first instance of recurrent EGPA accompanied by elevated IgG4 and positivity for hepatitis B, which was successfully treated with rituximab. In cases of concurrent hepatitis B, rituximab treatment may be considered once viral replication is under control. However, emphasis on maintenance therapy is crucial following the induction of disease remission.
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Antígenos de Superficie de la Hepatitis B , Inmunoglobulina G , Rituximab , Humanos , Femenino , Rituximab/uso terapéutico , Anciano , Inmunoglobulina G/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Recurrencia , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/diagnóstico , Factores Inmunológicos/uso terapéutico , Hepatitis B/tratamiento farmacológico , Hepatitis B/complicacionesRESUMEN
Granulomatosis with polyangiitis (GPA) is a pauci-immune vasculitis typically involving upper and lower respiratory tract involvement and crescentic glomerulonephritis. Salivary gland involvement in GPA is rare. When it occurs in GPA, it is commonly seen with sinonasal and lung involvement and rarely with renal involvement. Easy accessibility of salivary glands allows early biopsy and timely treatment. In our case with GPA, salivary gland involvement was unresponsive to cyclophosphamide but remitted with rituximab.
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Granulomatosis con Poliangitis , Rituximab , Sialadenitis , Humanos , Sialadenitis/diagnóstico , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/complicaciones , Rituximab/uso terapéutico , Ciclofosfamida/uso terapéutico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Masculino , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Inmunosupresores/uso terapéutico , Persona de Mediana Edad , FemeninoRESUMEN
Conventional immunosuppressants are ineffective for the management of EGPA-related asthma. Tezepelumab is a human monoclonal antibody that inhibits thymic stromal lymphopoietin (TLSP) that has proven efficacy in several phase 3 studies for the treatment of asthma. We treated with off-label tezepelumab the first two patients with severe refractory EPGA-related asthma. These preliminary findings suggest that targeting upstream signaling of the T2 inflammatory pathway can improve symptoms, reduce BVAS and increase Asthma Control Test scores, even in patients with refractory asthma who have failed several previous lines of treatment. Nevertheless, by analogy with dupilumab-induced IL-4/13 blockade, the persistence of sputum eosinophilia (reported in both patients) raises questions as to whether TSLP inhibition could lead to a rebound of eosinophilia and potentially to eosinophil-related symptoms in patients with EGPA.
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Anticuerpos Monoclonales Humanizados , Asma , Humanos , Asma/tratamiento farmacológico , Asma/diagnóstico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Persona de Mediana Edad , Femenino , Masculino , Resultado del Tratamiento , Antiasmáticos/uso terapéutico , Síndrome de Churg-Strauss/tratamiento farmacológico , Síndrome de Churg-Strauss/diagnóstico , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/diagnósticoRESUMEN
Objective: This paper aimed to describe another form of aggressive limited Granulomatosis with polyangiitis (GPA) revealed by dacryoadenitis. Methods and results: We report an unusually limited GPA in a 48-year-old man presenting with bilateral proptosis. She had never presented kidney or pulmonary manifestations, but her disease was persistently active including oto-rhino-laryngological manifestations, dacryoadenitis, and neurological manifestations unresponsive to corticosteroids and immunosuppressors. Discussion: Granulomatosis with polyangiitis (GPA) is an auto-immune inflammatory vasculitis. Involvement of lacrimal glands as the first presentation is uncommon. It is characterized by the development of granulomas. Patients with orbital mass without lacrimal gland involvement have a higher rate of systemic disease, a severe clinical course, and a higher rate of recurrences. A patient with dacryoadenitis seems to be with a good prognosis. Eye manifestations were significantly more common in patients with pachymeningitis. MPO-ANCA-positive pachymeningitis was more frequent in older female patients. PR3-ANCA-positive pachymeningitis had more severe neurological damage. Induction treatment consists of intravenous methylprednisolone (IV) associated with cyclophosphamide. Conclusion: Faced with dacryoadenitis, it is important to screen for ANCA-associated vasculitis. Abbreviations: GPA = Granulomatosis with polyangiitis, ANCA = Antineutrophil Cytoplasmic Antibodies.
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Dacriocistitis , Granulomatosis con Poliangitis , Humanos , Persona de Mediana Edad , Dacriocistitis/diagnóstico , Dacriocistitis/etiología , Dacriocistitis/tratamiento farmacológico , Masculino , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Femenino , Diagnóstico DiferencialRESUMEN
Objective: To explore the clinical characteristics and treatment outcomes of children with central nervous system (CNS) involvement in eosinophilic granulomatosis with polyangiitis (EGPA). Methods: A child who presented with EGPA complicated by CNS involvement was admitted to our hospital in June 2023. The clinical features were analyzed retrospectively, and relevant literatures were reviewed to provide a comprehensive overview of this condition. Results: A ten-year-old girl, who had a history of recurrent cough and asthma accompanied by peripheral blood eosinophilia for eight months, was admitted to our hospital. On admission, spotted papules were visible on her hands and feet, bilateral pulmonary rales were audible. The laboratory examination revealed that the proportion of eosinophils (EOS) exceeded 10% of white blood cells, the anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, the immunoglobulin G level was 15.80g/L, and the immunoglobulin E level was greater than 2500.00IU/mL. The imaging examination showed multiple patchy and nodular high-density shadows in both lungs as well as sinusitis. Pulmonary function tests indicated moderate ventilation and diffusion dysfunction. Bone marrow cytology demonstrated a significant increase in the proportion of eosinophils. Skin pathology confirmed leukocytoclastic vasculitis. During the hospitalization, the child had a convulsion. The magnetic resonance imaging (MRI) scan of the brain showed multiple abnormal signal shadows in the bilateral cerebral cortex and the electroencephalogram (EEG) showed epileptic waves. Following the administration of methylprednisolone pulse therapy in combination with cyclophosphamide treatment, her cough and asthma resolved, the skin rash disappeared without any further convulsions. We found that only a young EGPA patient with CNS involvement had been previously reported. The previously reported case began with long-term fever, weight loss, and purpuric rash. Both patients responded well to treatment with glucocorticoids and cyclophosphamide, experiencing significant improvement in their clinical symptoms and normalization of their peripheral blood eosinophils. Conclusion: The diagnosis of EGPA in children can be challenging. When a child is affected by EGPA, it is essential to remain vigilant for signs of CNS involvement. The treatment with glucocorticoids and cyclophosphamide is effective in managing EGPA in children.
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Síndrome de Churg-Strauss , Humanos , Femenino , Niño , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/tratamiento farmacológico , Síndrome de Churg-Strauss/complicaciones , Síndrome de Churg-Strauss/inmunología , Resultado del Tratamiento , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/inmunología , Ciclofosfamida/uso terapéutico , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Anticuerpos Anticitoplasma de Neutrófilos/sangreRESUMEN
The association between the use of certain medications (including sulfonamides, hydralazine, and procainamide) and the occurrence of drug-induced lupus or hepatitis is well established. More recently, cases of immune-related adverse events ranging from inflammatory polyarthritis to necrotizing myositis in patients taking checkpoint inhibitors have been reported. However, data linking drugs to systemic vasculitis are scarce and at times debatable. Propylthiouracil, hydralazine, and minocycline have been associated with rare cases of ANCA-associated syndromes, including life-threatening pulmonary-renal syndromes and systemic polyarteritis nodosa-like diseases. Eosinophilic granulomatosis with polyangiitis (EGPA) has been reported in patients taking leukotriene inhibitors. Since the link between the use of leukotriene inhibitors and occurrence of EGPA remains highly controversial, we performed a literature review for cases of EGPA in patients taking montelukast without prior history of oral corticosteroid use. We found 24 cases, along with our own two cases described, making 26 cases in total. The mean age was 43 and a majority (18/26) were female. In majority of cases EGPA-like disease never relapsed after they were taken off leukotriene inhibitors suggesting a clear causal relationship between the use of these drugs and occurrence of eosinophil-rich systemic EGPA.
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Acetatos , Ciclopropanos , Antagonistas de Leucotrieno , Quinolinas , Sulfuros , Humanos , Quinolinas/efectos adversos , Quinolinas/uso terapéutico , Acetatos/efectos adversos , Acetatos/uso terapéutico , Antagonistas de Leucotrieno/efectos adversos , Antagonistas de Leucotrieno/uso terapéutico , Femenino , Síndrome de Churg-Strauss/inducido químicamente , Masculino , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/inducido químicamente , Persona de Mediana Edad , AdultoAsunto(s)
Anticuerpos Monoclonales Humanizados , Granulomatosis con Poliangitis , Humanos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome de Churg-Strauss/tratamiento farmacológico , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/inmunología , Interleucina-5/antagonistas & inhibidores , Estudios de Equivalencia como Asunto , Ensayos Clínicos como AsuntoRESUMEN
OBJECTIVES: Prospective long-term observational data on the disease course of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were missing in Germany to date. Therefore, the Joint Vasculitis Registry in German-speaking countries (GeVas) has been established to follow the course of patients with AAV. The aim of this study is to present baseline data of patients with newly diagnosed and relapsing AAV enrolled in the GeVas registry. METHODS: GeVas is a prospective, web-based, multicentre, clinician-driven registry for the documentation of organ manifestations, damage, long-term outcomes, and therapy regimens in various types of vasculitis. Recruitment started in June 2019. RESULTS: Between June 2019 and October 2022, 266 patients with AAV were included in the GeVas registry: 173 (65%) with new-onset and 93 (35%) with relapsing AAV. One hundred and sixty-two (61%) patients were classified as granulomatosis with polyangiitis (GPA), 66 (25%) as microscopic polyangiitis (MPA), 36 (13%) as eosinophilic granulomatosis with polyangiitis (EGPA), and 2 (1%) as renal limited AAV. The median age was 59 years (51-70 years, IQR), 130 (51%) patients were female. Most patients were ANCA positive (177; 67%) and affected by general symptoms, pulmonary, ear nose throat (ENT), renal and neurological involvement. For induction of remission, the majority of patients received glucocorticoids (247, 93%) in combination with either rituximab (118, 45%) or cyclophosphamide (112, 42%). CONCLUSIONS: Demographic characteristics are comparable to those in other European countries. Differences were found regarding ANCA status, frequencies of organ manifestations, and therapeutic regimens. The GeVas registry will allow longitudinal observations and prospective outcome measures in AAV.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Sistema de Registros , Humanos , Femenino , Persona de Mediana Edad , Masculino , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Anciano , Estudios Prospectivos , Alemania/epidemiología , Inmunosupresores/uso terapéutico , Resultado del Tratamiento , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/epidemiología , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/inmunología , Granulomatosis con Poliangitis/terapia , Recurrencia , Poliangitis Microscópica/epidemiología , Poliangitis Microscópica/tratamiento farmacológico , Poliangitis Microscópica/diagnóstico , Poliangitis Microscópica/terapia , Poliangitis Microscópica/inmunología , Síndrome de Churg-Strauss/epidemiología , Síndrome de Churg-Strauss/tratamiento farmacológico , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/inmunología , Progresión de la Enfermedad , Factores de Tiempo , Rituximab/uso terapéuticoRESUMEN
Granulomatosis with polyangiitis (GPA) is an uncommon disorder that mainly involves the upper and lower respiratory tract and kidney, presenting as sinusitis, saddle nose, otitis media, pulmonary nodule and cavity, rapidly progressive glomerulonephritis. It also affects skin, eye, heart, joint and nervous system. Renal involvement in GPA is commonly manifested as necrotising glomerulonephritis, while renal mass is very rare. We herein present two hospitalised cases with fever, pulmonary cavity and renal mass. Clinical course and examinations of the cases, from symptoms to diagnosis, will be discussed in detail, along with a relevant literature review of this unusual renal manifestation.
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Granulomatosis con Poliangitis , Humanos , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/diagnóstico , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Femenino , Hallazgos Incidentales , Adulto , Biopsia , Riñón/patología , Resultado del TratamientoRESUMEN
Granulomatosis with polyangiitis is a systemic vasculitis. While the classic triad typically comprises otorhinolaryngologic, pulmonary, and renal manifestations, it is essential to recognize that granulomatosis with polyangiitis can affect any organ. Furthermore, reports have documented less common sites of involvement, such as the gastrointestinal tract. In this case-based review, we focus on a case of granulomatosis with polyangiitis presenting with intestinal perforation and the added challenge of concurrent pancytopenia.A 25-year-old female was diagnosed with granulomatosis with polyangiitis, with her clinical course progressing from joint pain to severe multi-organ involvement, including gastrointestinal complications. Treatment challenges emerged with the development of pancytopenia. While this may not directly result from granulomatosis with polyangiitis, it introduced an additional layer of complexity and delayed the induction of remission with immunosuppressants. Despite initial stabilization, an unexpected jejunal perforation occurred, requiring surgical intervention and subsequent postoperative care. The case underscores the complex nature of granulomatosis with polyangiitis and its potential complications. A literature search yielded discrete relevant cases in the context of our patient's intricate presentation, which has been summarized.We highlight the complexities in diagnosing and managing granulomatosis with polyangiitis-related complications, especially in uncommon presentations, and emphasize the importance of a personalized approach to patient care in these circumstances.
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Granulomatosis con Poliangitis , Perforación Intestinal , Pancitopenia , Humanos , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/diagnóstico , Femenino , Perforación Intestinal/etiología , Perforación Intestinal/cirugía , Adulto , Pancitopenia/etiología , Pancitopenia/terapia , Inmunosupresores/uso terapéutico , Resultado del Tratamiento , Enfermedades del Yeyuno/etiologíaRESUMEN
Proteinase 3 (PR3)-specific antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is one of two major ANCA-associated vasculitis variants and is pathogenically linked to granulomatosis with polyangiitis (GPA). GPA is characterised by necrotising granulomatous inflammation that preferentially affects the respiratory tract. The small vessel vasculitis features of GPA are shared with microscopic polyangiitis. Necrotising granulomatous inflammation of GPA can lead to PR3-ANCA and small vessel vasculitis via activation of neutrophils and monocytes. B cells are central to the pathogenesis of PR3-ANCA-associated vasculitis. They are targeted successfully by remission induction and maintenance therapy with rituximab. Relapses of PR3-ANCA-associated vasculitis and toxicities associated with current standard therapy contribute substantially to remaining mortality and damage-associated morbidity. More effective and less toxic treatments are sought to address this unmet need. Advances with cellular and novel antigen-specific immunotherapies hold promise for application in autoimmune disease, including PR3-ANCA-associated vasculitis. This Series paper describes the inter-related histopathological and clinical features, pathophysiology, as well as current and future targeted treatments for PR3-ANCA-associated vasculitis.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Humanos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/patología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Granulomatosis con Poliangitis/inmunología , Granulomatosis con Poliangitis/patología , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/terapia , Mieloblastina/inmunología , Rituximab/uso terapéuticoAsunto(s)
Granulomatosis con Poliangitis , Meningitis , Humanos , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/tratamiento farmacológico , Meningitis/diagnóstico por imagen , Meningitis/tratamiento farmacológico , Hipertrofia/complicaciones , Anticuerpos Anticitoplasma de NeutrófilosRESUMEN
BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Granulomatosis con Poliangitis , Poliangitis Microscópica , Humanos , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/tratamiento farmacológico , Poliangitis Microscópica/diagnóstico , Poliangitis Microscópica/complicaciones , Anticuerpos Anticitoplasma de Neutrófilos/uso terapéutico , Estudios Retrospectivos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Mieloblastina , RecurrenciaRESUMEN
OBJECTIVE: To report on a series of patients with cANCA/PR3-positive, granulomatosis with polyangiitis (GPA)-associated subglottic stenosis (SGS) and evaluate response to medical maintenance therapy with rituximab versus other immunosuppressants following initial endoscopic laser excision. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic center. METHODS: A retrospective chart review of patients with SGS and cANCA/PR3-positive GPA who received immunosuppressive maintenance therapy following endoscopic laser excision at our institution from June 1989 to March 2020 was performed. Data pertaining to patient demographics, clinical features, medications, and endoscopic laser procedures were collected. RESULTS: A total of 27 patients (15 women) with mean age (range) of 40 (19-59) years and mean (range) follow-up of 12.6 years (1.5-28.6) were identified. Sixteen patients (60%) had limited GPA. Six patients (24%) had previously received local intervention with open surgery (n = 1, 4%) or endoscopic techniques (n = 5, 20%). All patients experienced symptom improvement following initial CO2 laser excision at our institution without any procedural complications or adverse events. Following initial laser excision, 15 patients (60%) were treated with rituximab and 10 patients (40%) were treated with nonrituximab immunosuppressive agents. Patients treated with rituximab were less likely to recur (P = 0.040). Limited GPA was associated with an increased incidence of recurrence (P = 0.031). Median time (years) to recurrence (range) was 3.2 (0.3-19.3) and was not significantly associated with treatment or GPA subtype. CONCLUSION: Endoscopic CO2 laser excision is a safe and effective local intervention for GPA-associated SGS. Medical maintenance therapy with rituximab reduces risk of recurrence following initial laser excision relative to treatment with non-rituximab agents.
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Granulomatosis con Poliangitis , Inmunosupresores , Laringoestenosis , Terapia por Láser , Rituximab , Humanos , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/tratamiento farmacológico , Femenino , Masculino , Laringoestenosis/cirugía , Laringoestenosis/etiología , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Rituximab/uso terapéutico , Terapia por Láser/métodos , Inmunosupresores/uso terapéutico , Resultado del Tratamiento , Adulto Joven , Laringoscopía , Quimioterapia de MantenciónRESUMEN
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis consists of two main diseases, granulomatosis with polyangiitis and microscopic polyangiitis, and remains among the most devastating and potentially lethal forms of autoimmune inflammatory disease. Granulomatosis with polyangiitis and microscopic polyangiitis are characterised by a necrotising vasculitis that can involve almost any organ, and have generally been studied together. The diseases commonly affect the kidneys, lungs, upper respiratory tract, skin, eyes, and peripheral nerves. Granulomatous inflammation and multinucleated giant cells are key pathological hallmarks of granulomatosis with polyangiitis, but are absent in microscopic polyangiitis. Many immune system events are essential to disease aetiopathogenesis, such as activation of the alternative complement pathway, neutrophil activation via complement receptors, and the influx of inflammatory cells, including monocytes and macrophages. These cells perpetuate inflammation and lead to organ damage. During the 21st century, the management of ANCA-associated vasculitis has moved away from reliance on cytotoxic medications and towards targeted biological medications for both the induction and maintenance of disease remission. Earlier diagnosis, partly the result of more reliable ANCA testing, has led to improved patient outcomes and better survival. Reductions in acute disease-related mortality have now shifted focus to long-term morbidities related to ANCA-associated vasculitis and their treatments, such as chronic kidney disease and cardiovascular disease. Therapeutic approaches in both clinical trials and clinical practice still remain too reliant on glucocorticoids, and continued efforts to reduce toxicity from glucocorticoids remain a priority in the development of new treatment strategies.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Enfermedades Autoinmunes , Granulomatosis con Poliangitis , Poliangitis Microscópica , Humanos , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/tratamiento farmacológico , Poliangitis Microscópica/diagnóstico , Poliangitis Microscópica/tratamiento farmacológico , Anticuerpos Anticitoplasma de Neutrófilos/uso terapéutico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , InflamaciónRESUMEN
BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis characterized by eosinophilic inflammation. Benralizumab, a monoclonal antibody against the interleukin-5α receptor expressed on eosinophils, may be an option for treating EGPA. METHODS: We conducted a multicenter, double-blind, phase 3, randomized, active-controlled noninferiority trial to evaluate the efficacy and safety of benralizumab as compared with mepolizumab. Adults with relapsing or refractory EGPA who were receiving standard care were randomly assigned in a 1:1 ratio to receive benralizumab (30 mg) or mepolizumab (300 mg) subcutaneously every 4 weeks for 52 weeks. The primary end point was remission at weeks 36 and 48 (prespecified noninferiority margin, -25 percentage points). Secondary end points included the accrued duration of remission, time to first relapse, oral glucocorticoid use, eosinophil count, and safety. RESULTS: A total of 140 patients underwent randomization (70 assigned to each group). The adjusted percentage of patients with remission at weeks 36 and 48 was 59% in the benralizumab group and 56% in the mepolizumab group (difference, 3 percentage points; 95% confidence interval [CI], -13 to 18; P = 0.73 for superiority), showing noninferiority but not superiority of benralizumab to mepolizumab. The accrued duration of remission and the time to first relapse were similar in the two groups. Complete withdrawal of oral glucocorticoids during weeks 48 through 52 was achieved in 41% of the patients who received benralizumab and 26% of those who received mepolizumab. The mean (±SD) blood eosinophil count at baseline was 306.0±225.0 per microliter in the benralizumab group and 384.9±563.6 per microliter in the mepolizumab group, decreasing to 32.4±40.8 and 71.8±54.4 per microliter, respectively, at week 52. Adverse events were reported in 90% of the patients in the benralizumab group and 96% of those in the mepolizumab group; serious adverse events were reported in 6% and 13%, respectively. CONCLUSIONS: Benralizumab was noninferior to mepolizumab for the induction of remission in patients with relapsing or refractory EGPA. (Funded by AstraZeneca; MANDARA ClinicalTrials.gov number, NCT04157348.).
Asunto(s)
Antiinflamatorios , Anticuerpos Monoclonales Humanizados , Síndrome de Churg-Strauss , Subunidad alfa del Receptor de Interleucina-5 , Adulto , Humanos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedad Crónica , Síndrome de Churg-Strauss/tratamiento farmacológico , Síndrome de Churg-Strauss/inmunología , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéutico , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/inmunología , Recurrencia , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Método Doble Ciego , Inducción de Remisión , Inyecciones Subcutáneas , Subunidad alfa del Receptor de Interleucina-5/antagonistas & inhibidores , Eosinófilos/efectos de los fármacos , Eosinófilos/inmunologíaRESUMEN
PURPOSE: Intravitreal Ganciclovir has been one of the treatments of choice for cytomegalovirus (CMV) retinitis and has been used extensively for its treatment since 1987. It has not been shown to have any major adverse effects. There are no reports on any retinal toxicity even after multiple, repeated injections. Herein, we report a rare case of retinal toxicity after multiple intravitreal injections in a patient of CMV retinitis. CASE REPORT: A 69-year-old one eyed male, who was on oral corticosteroids and systemic immunosuppression for Granulomatosis with Polyangiitis, presented with CMV retinitis in both eyes. His visual acuity was 20/60 in his right eye and no perception of light in his left eye. He was treated with multiple injections of intravitreal Ganciclovir in his right eye. The left eye was not treated since it had no vision potential. The right eye of the patient which had received multiple injections went on to developed a progressive diffuse atrophy of Retinal Pigment Epithelium (RPE). No such changes were noted in the left eye of the patient. CONCLUSION AND IMPORTANCE: We present a case of progressive diffuse RPE atrophy as a result of toxicity of intravitreal ganciclovir injections. It is important to be aware of this rare potential toxicity of intravitreal Ganciclovir.
Asunto(s)
Antivirales , Retinitis por Citomegalovirus , Ganciclovir , Inyecciones Intravítreas , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Retinitis por Citomegalovirus/diagnóstico , Retinitis por Citomegalovirus/tratamiento farmacológico , Anciano , Masculino , Antivirales/efectos adversos , Epitelio Pigmentado de la Retina/patología , Epitelio Pigmentado de la Retina/efectos de los fármacos , Angiografía con Fluoresceína , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/tratamiento farmacológico , CitomegalovirusRESUMEN
BACKGROUND: Hypertrophic cranial pachymeningitis (HCP) is uncommon but a poorly understood complication of granulomatosis with polyangiitis (GPA). OBJECTIVES: We conducted this retrospective study to elucidate the clinical characteristics and factors independently associated with granulomatosis with polyangiitis (GPA) complicated by hypertrophic cranial pachymeningitis (HCP) in China. METHODS: We collected the medical records of 78 patients diagnosed with GPA who were admitted to the inpatient department of Peking Union Medical College Hospital between January 2003 and September 2021. Clinical features, laboratory and radiological findings, and Birmingham Vasculitis Activity Scores (excluding meningitis score) were recorded. A binary logistic regression analysis was performed to analyze factors independently associated with GPA-related HCP. RESULTS: Headache (100%) and cranial nerve palsy (61.5%) were common manifestations of HCP. Compared to 52 GPA patients without HCP, 26 patients with HCP required more time from initial symptoms to diagnosis, with a lower ratio of pulmonary and renal involvement, a higher ratio of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positivity, conductive or sensorineural hearing loss, mastoiditis, and decreased vision or sudden visual loss. Binary logistic regression analysis indicated that proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) negativity (OR 10.698, p = 0.001), conductive or sensorineural hearing loss (OR 10.855, p = 0.005), and decreased vision or sudden visual loss (OR 8.647, p = 0.015) were significantly associated with GPA-related HCP. Of the 26 patients, 18 received methylprednisolone pulse treatment, and 18 received intrathecal injections of dexamethasone and methotrexate. CONCLUSIONS: HCP was a severe manifestation of GPA in our study. Independent factors associated with the occurrence of HCP in patients with GPA included PR3-ANCA negativity, conductive or sensorineural hearing loss, and decreased vision or sudden visual loss. Furthermore, GPA-related HCP was associated with higher disease activity, requiring more intensive treatments.