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2.
AIDS ; 15(12): 1584-6, 2001 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-11504995

RESUMO

A retrospective person-time analysis of the randomized and non-randomized extension phases of four phase III trials was performed to assess the incidence of adverse cardiovascular events in 2680 HIV-infected patients receiving indinavir or nucleoside reverse transcriptase inhibitor therapy, or both. The observed rate of cardiovascular events was not increased in patients receiving indinavir-based regimens compared with therapy without a protease inhibitor. Extrapolation of these findings is limited by the brief length of therapy and the small number of cases.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Doenças Cardiovasculares/etiologia , Infecções por HIV/tratamento farmacológico , Indinavir/efeitos adversos , Inibidores da Transcriptase Reversa/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Quimioterapia Combinada , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fatores de Risco
3.
Am J Med ; 81(1): 79-85, 1986 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2873744

RESUMO

Ten patients were prospectively studied who had features of systemic vasculitis that could not be classified into one of the well-defined vasculitic syndromes. Since many of these syndromes had overlapping features of several distinct vasculitides, they were classified as the polyangiitis overlap syndrome. Cutaneous disease was common (nine of 10 patients) and, some patients, had been mistakenly diagnosed as "hypersensitivity" or isolated cutaneous vasculitis. The polyangiitis overlap syndrome is a systemic vasculitis, and all of the patients required therapy with cyclophosphamide (2 mg/kg per day). Nine of 10 patients were also treated with corticosteroids, which were administered initially on a daily basis followed by an alternate-day regimen. A complete remission was induced in all of the patients, with a mean follow-up duration of 58.4 months. In eight of 10 patients, remission was maintained following discontinuation of cyclophosphamide. The mean duration of remission was 45.9 months, with a mean interval after discontinuation of all therapy of 22.3 months. Two patients had relapses after the immunosuppressive therapy was discontinued; however, complete remissions were reinduced following reinstitution of therapy.


Assuntos
Vasculite/classificação , Adolescente , Corticosteroides/uso terapêutico , Adulto , Criança , Ciclofosfamida/uso terapêutico , Feminino , Arterite de Células Gigantes/classificação , Arterite de Células Gigantes/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Necrose , Poliarterite Nodosa/classificação , Poliarterite Nodosa/patologia , Síndrome , Vasculite/tratamento farmacológico , Vasculite/patologia
4.
Am J Med ; 80(5): 1003-5, 1986 May.
Artigo em Inglês | MEDLINE | ID: mdl-3706362

RESUMO

Buerger's disease or thromboangiitis obliterans is characterized by peripheral arterial occlusions in young male cigarette smokers. It is rarely considered in the differential diagnosis of vascular disease in women, although there have been several well-documented cases in the literature. This report presents a young woman with both angiographic and histopathologic evidence for Buerger's disease who was initially treated with daily corticosteroids for presumed vasculitis. This case emphasizes the fact that Buerger's disease can present in a fashion similar to both vasculitis and collagen vascular disease.


Assuntos
Tromboangiite Obliterante/patologia , Adulto , Artérias/patologia , Biópsia , Diagnóstico Diferencial , Feminino , Antebraço/irrigação sanguínea , Humanos , Fumar , Tromboangiite Obliterante/diagnóstico , Vasculite/diagnóstico
5.
Am J Med ; 89(4): 403-10, 1990 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-2220874

RESUMO

PURPOSE: Concerns regarding the long-term toxicity of daily cyclophosphamide (CP) therapy for the systemic vasculitides have led us to evaluate alternative approaches to treatment in an attempt to achieve comparable efficacy with less toxicity. This study sought to determine the efficacy, toxicity, and immunologic effects of glucocorticoids (GC) and intermittent high-dose intravenous CP ("pulse" CP) in the treatment of 14 patients with Wegener's granulomatosis (WG). PATIENTS AND METHODS: The diagnosis of active WG was supported by a typical clinical presentation and histopathologic findings of vasculitis, granulomatous inflammation, and tissue necrosis. GC treatment was initially provided on a daily basis and later tapered to an alternate-day schedule if vasculitis remained inactive. Pulse CP treatment was initially administered once a month for 6 months. If after 6 months remission had been attained and GC therapy had been discontinued, then pulse CP treatment was given at less frequent intervals thereafter. Treatment and evaluation were provided for participants as inpatients in a clinical research center (National Institutes of Health). RESULTS: Thirteen of 14 patients (93%) initially experienced unequivocal improvement with pulse CP therapy, and seven of 14 (50%) achieved remission within 4 months. However, treatment was associated with significant toxicity in two patients and later relapses in nine patients, so that a total of 79% either failed to achieve sustained remission or were unable to continue therapy. Three of 14 (21%) patients have achieved sustained remissions with the pulse CP protocol and one additional patient (who had a limited exacerbation of WG) continues to receive that therapy after 14 to 22 months (mean 17 months). CONCLUSIONS: The use of pulse CP and GC therapy in 14 patients with WG was associated with a high initial response rate. However, failure to respond initially to treatment, to sustain improvement, or to tolerate continued treatment was noted in 79% of patients within a period of 1 to 22 months. These observations indicate that this particular pulse CP protocol does not achieve a high degree of lasting efficacy.


Assuntos
Ciclofosfamida/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Esquema de Medicação , Feminino , Granulomatose com Poliangiite/imunologia , Granulomatose com Poliangiite/fisiopatologia , Humanos , Imunoglobulina G/análise , Injeções Intravenosas , Lorazepam/uso terapêutico , Subpopulações de Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Tietilperazina/uso terapêutico , Vasculite/tratamento farmacológico , Vômito/prevenção & controle
6.
Am J Surg Pathol ; 15(4): 315-33, 1991 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2006712

RESUMO

We report the pulmonary pathologic features in 87 open lung biopsies from 67 patients with Wegener's granulomatosis (WG) who were treated at a single institution from 1968 to 1990. At the time of open lung biopsy, 48 patients (72%) had classical WG with renal involvement; 19 (28%) had limited WG without renal involvement. The pathologic features were divided into major and minor manifestations. In the 82 specimens demonstrating no infectious organism, the three major pathologic manifestations of classical WG observed were also useful diagnostic criteria and included: (a) parenchymal necrosis, (b) vasculitis, and (c) granulomatous inflammation accompanied by an inflammatory infiltrate composed of a mixture of neutrophils, lymphocytes, plasma cells, histiocytes, and eosinophils. Parenchymal necrosis was found in 84% of biopsy specimens either as neutrophilic microabscesses (65% of specimens) or as large (67%) or small (69%) areas of geographic necrosis. Areas of geographic necrosis were usually surrounded by palisading histiocytes and giant cells. Additional granulomatous lesions consisted of microabscesses surrounded by giant cells (69%), poorly formed granulomas (59%), and scattered giant cells (79%). Sarcoid-like granulomas were uncommon (4%), and in only one specimen (1%) appeared within an inflammatory lesion of WG. Vascular changes were identified in 94% of biopsy specimens. Vascular inflammation was classified as chronic (37% arterial, 64% venous), acute (37% arterial, 29% venous), non-necrotizing granulomatous (22% arterial, 9% venous), and necrotizing granulomatous (22% arterial, 10% venous). Fibrinoid necrosis was relatively uncommon (11% arterial, 6% venous). Cicatricial changes were found in arteries in 41% of biopsy specimens and in veins in 16%. Capillaritis was present in 31% of specimens. Minor pathologic lesions were commonly observed in biopsy specimens associated with classical WG lesions, but they were usually inconspicuous and not useful diagnostic criteria. These included interstitial fibrosis (26%), alveolar hemorrhage (49%), tissue eosinophils (100%), organizing intraluminal fibrosis (70%), endogenous lipoid pneumonia (59%), lymphoid aggregates (37%), and a variety of bronchial/bronchiolar lesions including acute and chronic bronchiolitis (51% and 64%), follicular bronchiolitis (28%), and bronchiolitis obliterans (31%). These minor lesions were often found at the periphery of typical nodules of WG. However, in 15 specimens (18%) a minor pathologic feature represented the dominant or major finding: pulmonary fibrosis (six specimens, 7%), diffuse pulmonary hemorrhage (six specimens, 7%), lipoid pneumonia (one specimen, 1%), acute bronchopneumonia (one specimen, 1%), and chronic bronchiolitis, bronchiolitic obliterans with organizing pneumonia (BOOP), and bronchocentric granulomatosis (one specimen, 1%).(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Granulomatose com Poliangiite/patologia , Pulmão/patologia , Adolescente , Adulto , Idoso , Biópsia , Brônquios/patologia , Feminino , Granulomatose com Poliangiite/cirurgia , Humanos , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Pleura/patologia
7.
Surgery ; 109(3 Pt 1): 252-8, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1672048

RESUMO

We reviewed 28 patients with Takayasu's disease to determine the incidence of stroke and its relationship to the involvement of the thoracic aortic arch and its branches. We describe surgical experiences with 10 of the 28 patients who required 21 vascular surgical procedures for critical thoracic aortic arch arterial stenoses, upper and lower extremity ischemia, and renal artery stenoses. Four of the 28 patients initially had a stroke caused by occlusion of one or more thoracic aortic arch arteries. Six of the 10 patients underwent 7 bypass procedures for critical thoracic arch stenoses. All have remained free of stroke for 5 or more years. Four patients had five anastomotic stenoses or graft occlusions in late follow-up; the development of these stenoses did not relate to disease activity at the time of the operative procedure. All bypass grafts originating from the subclavian axillary artery developed anastomotic stenoses; no anastomotic stenoses occurred in bypass grafts originating from the ascending aorta. In contrast to other reports, no anastomotic false aneurysms occurred. Occlusions of major aortic arch arteries in Takayasu's disease cause stroke. Bypass of critically stenoses aortic arch arteries protects against stroke and is best performed with grafts originating from the ascending aorta. Anastomotic stenoses but not anastomotic aneurysms are common. This study suggests that aggressive surgical treatment can be performed with good results.


Assuntos
Arterite de Takayasu/cirurgia , Adulto , Aorta Torácica/fisiopatologia , Aorta Torácica/cirurgia , Transtornos Cerebrovasculares/etiologia , Seguimentos , Humanos , Estudos Prospectivos , Arterite de Takayasu/fisiopatologia , Procedimentos Cirúrgicos Vasculares/métodos
8.
Laryngoscope ; 102(12 Pt 1): 1341-5, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1453838

RESUMO

Wegener's granulomatosis (WG) is a multisystem inflammatory disease characterized by vasculitis, granuloma formation, and necrosis. Among 158 patients treated at the National Institutes of Health during the past 24 years, 145 (92%) had an otolaryngologic manifestation of their disease and 25 (16%) had subglottic stenosis (SGS). SGS varied from asymptomatic to life-threatening. Sixteen (80%) of 20 patients with fixed SGS required surgical intervention, including manual dilations, carbon-dioxide laser resections, and laryngotracheoplasty (LTP). LTP was performed with and without microvascular reconstruction. Thirteen of the patients required tracheostomy and all 13 were ultimately decannulated. Five patients who repeatedly failed dilations and/or endoscopic laser surgery underwent LTP. Since 1987, two patients have undergone LTP with microvascular free flaps. Both patients were subsequently decannulated. The authors' experience demonstrates that management of SGS in WG is complex, requiring individualized frequent multimodality interventions to achieve satisfactory results. Microvascular laryngotracheal reconstruction should be considered in the surgical armamentarium for patients with persistent stenoses.


Assuntos
Granulomatose com Poliangiite/cirurgia , Laringoestenose/cirurgia , Estenose Traqueal/cirurgia , Adolescente , Adulto , Cartilagem/transplante , Criança , Terapia Combinada , Dilatação , Feminino , Glote , Glucocorticoides/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Laringoestenose/tratamento farmacológico , Laringe/cirurgia , Terapia a Laser , Masculino , Pessoa de Meia-Idade , Reoperação , Retalhos Cirúrgicos/métodos , Traqueia/cirurgia , Estenose Traqueal/tratamento farmacológico , Traqueostomia
9.
Adv Exp Med Biol ; 336: 411-4, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8296645

RESUMO

One hundred and six patients with Wegener's granulomatosis (WG) were studied for the presence of antineutrophil cytoplasmic antibodies (ANCA). In 53 patients serial ANCA determinations were obtained. C-ANCA positivity was a sensitive (88%) marker of active WG. However, changes in serial titers were temporally concordant with a change in disease status in only 55% of patients. Furthermore, a rise in c-ANCA titer preceded clinical exacerbation of disease in only 24% of patients who had been in remission or had low grade, smoldering disease. A rise in c-ANCA titer alone should not be considered a priori evidence of impending relapse, and does not justify modification of immunosuppressive therapy.


Assuntos
Autoanticorpos/sangue , Granulomatose com Poliangiite/imunologia , Imunoglobulina G/sangue , Anticorpos Anticitoplasma de Neutrófilos , Humanos , Prognóstico
10.
Rev Inst Med Trop Sao Paulo ; 42(1): 27-36, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10742724

RESUMO

Treatment with indinavir has been shown to result in marked decreases in viral load and increases in CD4 cell counts in HIV-infected individuals. A randomized double-blind study to evaluate the efficacy of indinavir alone (800 mg q8h), zidovidine alone (200 mg q8h) or the combination was performed to evaluate progression to AIDS. 996 antiretroviral therapy-naive patients with CD4 cell counts of 50-250/mm3 were allocated to treatment. During the trial the protocol was amended to add lamivudine to the zidovudine-containing arms. The primary endpoint was time to development of an AIDS-defining illness or death. The study was terminated after a protocol-defined interim analysis demonstrated highly significant reductions in progression to a clinical event in the indinavir-containing arms, compared to the zidovudine arm (p<0. 0001). Over a median follow-up of 52 weeks (up to 99 weeks), percent reductions in hazards for the indinavir plus zidovudine and indinavir groups compared to the zidovudine group were 70% and 61%, respectively. Significant reductions in HIV RNA and increases in CD4 cell counts were also seen in the indinavir-containing groups compared to the zidovudine group. Improvement in both CD4 cell count and HIV RNA were associated with reduced risk of disease progression. All three regimens were generally well tolerated.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Indinavir/uso terapêutico , Zidovudina/uso terapêutico , Adulto , Protocolos Clínicos , Intervalos de Confiança , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Infecções por HIV/sangue , Inibidores da Protease de HIV/uso terapêutico , Humanos , Masculino , RNA Viral/efeitos dos fármacos , Carga Viral
14.
Curr Opin Rheumatol ; 4(1): 16-22, 1992 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1543658

RESUMO

Wegener's granulomatosis is a clinicopathologic syndrome of unknown etiology characterized by granulomatous vasculitis of the upper and lower respiratory tracts and by glomerulonephritis. Virtually any organ system can be affected, and many patients present with unusual features of disease. During the period covered by this review, several articles reported atypical manifestations of Wegener's granulomatosis, including diffuse pulmonary infiltrates, lymphadenopathy, diffuse pulmonary hemorrhage, and overlap with giant cell arteritis. Unusual features of upper airway, eye, gastrointestinal, nervous system, and genitourinary tract disease were also described, and less common histopathologic features of pulmonary and nasal disease were characterized.


Assuntos
Granulomatose com Poliangiite/diagnóstico , Oftalmopatias/etiologia , Gastroenteropatias/etiologia , Arterite de Células Gigantes/etiologia , Granulomatose com Poliangiite/etiologia , Humanos , Pneumopatias/etiologia , Doenças do Sistema Nervoso/etiologia , Doenças Respiratórias/etiologia
15.
Curr Opin Rheumatol ; 3(1): 8-14, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2043454

RESUMO

Wegner's granulomatosis is a clinicopathologic syndrome of unknown etiology characterized by granulomatous vasculitis of the upper and lower respiratory tracts and glomerulonephritis. During the period covered by this review several articles were published describing the clinical and pathologic features of Wegner's granulomatosis. Specifically, two large series are discussed reviewing the pulmonary manifestations of the disease and the histopathology of the head and neck disease associated with Wegner's granulomatosis. The majority of publications related to Wegner's granulomatosis concern anti-neutrophil cytoplasmic antibodies and their role in the diagnosis, management, and pathogenesis of Wegner's granulomatosis. In the period covered by this article, no new reports on the therapy of Wegner's granulomatosis were reviewed. However, two articles that address the efficacy of cyclophosphamide pulse therapy in Wegner's granulomatosis have recently been published with conflicting conclusions. The data from these articles are mentioned but will be reviewed in more detail in a subsequent article.


Assuntos
Granulomatose com Poliangiite/patologia , Ciclofosfamida/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/imunologia , Humanos
16.
Am Rev Respir Dis ; 134(1): 149-66, 1986 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2873770

RESUMO

The granulomatous vasculitides frequently involve the lung. These syndromes include Wegener's granulomatosis, allergic angiitis and granulomatosis, and the polyangiitis overlap syndrome. Although not a true systemic vasculitis, necrotizing sarcoid granulomatosis also represents a type of pulmonary vasculitis. It is clear that many infectious agents can cause a picture in the lung that can be confused with granulomatous vasculitis and that an infectious process must be ruled out before a diagnosis of pulmonary vasculitis can be established. Pulmonary vasculitis can be associated with the hypersensitivity vasculitides, and pulmonary hemorrhage can be secondary to pulmonary capillaritis. Therapy of the hypersensitivity vasculitides consists of removing the offending antigen and instituting a limited course of corticosteroids. If the vasculitis is secondary to an underlying disease, such as lymphoma, therapy should be directed at the primary disease. Combination therapy with cyclophosphamide and corticosteroids is effective in the systemic vasculitides and the 5-yr survival rate is approximately 90%.


Assuntos
Pneumopatias , Vasculite , Corticosteroides/uso terapêutico , Azatioprina/uso terapêutico , Síndrome de Behçet/classificação , Clorambucila/uso terapêutico , Doenças do Tecido Conjuntivo/classificação , Ciclofosfamida/uso terapêutico , Ciclosporinas/uso terapêutico , Combinação de Medicamentos/uso terapêutico , Granuloma/classificação , Granulomatose com Poliangiite/classificação , Hemorragia/classificação , Humanos , Pneumopatias/classificação , Pneumopatias/tratamento farmacológico , Granulomatose Linfomatoide/classificação , Infecções Respiratórias/classificação , Sulfametoxazol/uso terapêutico , Síndrome , Arterite de Takayasu/classificação , Trimetoprima/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol , Vasculite/classificação , Vasculite/tratamento farmacológico , Vasculite Leucocitoclástica Cutânea/classificação
17.
Arthritis Rheum ; 35(11): 1322-9, 1992 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1445449

RESUMO

OBJECTIVE: To identify alternatives to daily low-dose cyclophosphamide (CYC) in the treatment of Wegener's granulomatosis (WG). METHODS: An open-label pilot study of weekly low-dose methotrexate (MTX) plus glucocorticoids (GC) for treatment of patients with WG was performed. Twenty-nine patients who did not have immediately life-threatening disease were included. Outcome was determined by clinical characteristics, pathologic findings, course of illness, laboratory and radiographic findings, and successful withdrawal of GC therapy. RESULTS: Weekly administration of MTX (at a mean stable dosage of 20 mg) and GC resulted in marked improvement in 76% of the 29 patients. Remission was achieved in 69% of the patients, 7% improved but had intermittent smoldering disease that precluded total withdrawal of GC, and 17% had progressive disease within 2-6 months of starting the study treatment. Two patients who initially achieved remission later had relapses after GC was discontinued. Of those who remain in remission (mean followup time 14.5 months), 72% have not required GC for a mean period of 10 months. CONCLUSION: Although standard therapy for WG (daily CYC and GC) has dramatically improved outcome in this often-fatal disease, treatment morbidity has led to attempts to identify effective interventions that have less toxicity. Weekly low-dose MTX was shown in this study to be a feasible alternative to CYC in patients whose illness was not immediately life-threatening or in whom prior CYC treatment was ineffective or produced serious toxicity. Although these results are preliminary, they are encouraging and justify further studies in which MTX, CYC, and other alternative therapeutic approaches are compared concurrently.


Assuntos
Glucocorticoides/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Metotrexato/uso terapêutico , Adulto , Idoso , Anticorpos Anticitoplasma de Neutrófilos , Autoanticorpos/análise , Quimioterapia Combinada , Feminino , Granulomatose com Poliangiite/sangue , Granulomatose com Poliangiite/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Recidiva , Indução de Remissão , Falha de Tratamento
18.
Arthritis Rheum ; 36(3): 365-71, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8452581

RESUMO

OBJECTIVE: To assess the correlation and prognostic value of antineutrophil cytoplasmic antibody (cANCA) titers with disease activity in patients with Wegener's granulomatosis (WG). METHODS: One hundred six patients with WG had serum ANCA determinations; 72 had serial titers obtained routinely at 1-3-month intervals. One hundred twelve subjects (19 of whom were healthy donors) served as controls. All serum samples were tested for cANCA by an indirect immunofluorescence technique. A prospective analysis of disease activity and cANCA values was performed. Disease activity was assessed according to clinical, laboratory, radiographic, and histopathologic findings. RESULTS: Positivity for cANCA was a sensitive (88%) marker of active WG. However, changes in serial titers temporally correlated with a change in disease status in only 64% of patients. Furthermore, an increase in the cANCA titer preceded clinical exacerbation of disease in only 24% of patients who had been in remission or had low-grade, smoldering disease. CONCLUSION: A rise in cANCA titer alone should not be considered adequate evidence of an impending clinical exacerbation, and therefore does not justify initiating or increasing immunosuppressive therapy.


Assuntos
Autoanticorpos/análise , Granulomatose com Poliangiite/imunologia , Imunoglobulina G/análise , Anticorpos Anticitoplasma de Neutrófilos , Biomarcadores , Ciclofosfamida/uso terapêutico , Reações Falso-Positivas , Imunofluorescência , Seguimentos , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/patologia , Humanos , Valor Preditivo dos Testes , Prednisona/uso terapêutico , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade
19.
Arthritis Rheum ; 37(4): 578-82, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7908520

RESUMO

OBJECTIVE: To identify the role of methotrexate (MTX) in the treatment of persistent or recurrent Takayasu arteritis that is refractory to treatment with glucocorticoids (GC) alone. METHODS: An open-label pilot study of weekly low-dose MTX+GC treatment was performed. Outcome was evaluated according to clinical characteristics, laboratory abnormalities, findings on routinely performed angiographic studies, and ability to withdraw GC and MTX therapy. Eighteen patients entered the study; 2 dropped out, and 16 were followed up for a mean period of 2.8 years (range 1.3-4.8 years). RESULTS: Weekly administration of MTX (mean stable dose of 17.1 mg) and GC resulted in remissions in 13 of 16 patients (81%). However, 7 patients (44%) had relapses as GC was tapered to or near discontinuation. Retreatment again led to remission, and 3 of 7 patients in this group have successfully stopped GC therapy. Of those patients who achieved remission, 8 (50%) have sustained remissions of 4-34 months (mean 18 months), and 4 of this group have not required GC or MTX therapy for 7-18 months (mean 11.3 months). Three patients experienced disease progression in spite of treatment. CONCLUSION: About half of all Takayasu arteritis patients have chronic active disease for which GC therapy alone does not provide sustained remissions that allow withdrawal of treatment. Weekly low-dose MTX is an effective means of inducing remission and minimizing GC therapy and toxicity in most of these patients. Further long-term studies will be required to assess the durability of remission and the need for maintenance MTX therapy in this subset of Takayasu arteritis patients.


Assuntos
Glucocorticoides/administração & dosagem , Metotrexato/administração & dosagem , Arterite de Takayasu/tratamento farmacológico , Adolescente , Adulto , Esquema de Medicação , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Projetos Piloto , Recidiva , Indução de Remissão , Arterite de Takayasu/complicações
20.
Ann Intern Med ; 116(6): 488-98, 1992 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-1739240

RESUMO

OBJECTIVE: To prospectively study the clinical features, pathophysiology, treatment and prognosis of Wegener granulomatosis. DESIGN: Of the 180 patients with Wegener granulomatosis referred to the National Institute of Allergy and Infectious Diseases during the past 24 years, 158 have been followed for 6 months to 24 years (a total of 1229 patient-years). MEASUREMENTS: Characteristics of clinical presentation, surgical pathology, course of illness, laboratory and radiographic findings, and the results of medical and surgical treatment have been recorded in a computer-based information retrieval system. SETTING: The Warren Magnuson Clinical Center of the National Institutes of Health. MAIN RESULTS: Men and women were equally represented; 97% of patients were white, and 85% were more than 19 years of age. The mean period of follow-up was 8 years. One hundred and thirty-three patients (84%) received "standard" therapy with daily low-dose cyclophosphamide and glucocorticoids. Eight (5.0%) received only low-dose cyclophosphamide. Six (4.0%) never received cyclophosphamide and were treated with other cytotoxic agents and glucocorticoids. Ten patients (6.0%) were treated with only glucocorticoids. Ninety-one percent of patients experienced marked improvement, and 75% achieved complete remission. Fifty percent of remissions were associated with one or more relapses. Of 99 patients followed for greater than 5 years, 44% had remissions of greater than 5 years duration. Thirteen percent of patients died of Wegener granulomatosis, treatment-related causes, or both. Almost all patients had serious morbidity from irreversible features of their disease (86%) or side effects of treatment (42%). CONCLUSIONS: The course of Wegener granulomatosis has been dramatically improved by daily treatment with cyclophosphamide and glucocorticoids. Nonetheless, disease- and treatment-related morbidity is often profound. Alternative forms of therapy have not yet achieved the high rates of remission induction and successful maintenance that have been reported with daily cyclophosphamide treatment. Despite continued therapeutic success with cyclophosphamide, our long-term follow-up of patients with Wegener granulomatosis has led to increasing concerns about toxicity resulting from prolonged cyclophosphamide therapy and has encouraged investigation of other therapeutic regimens.


Assuntos
Ciclofosfamida/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Prednisona/uso terapêutico , Adolescente , Adulto , Idoso , Biópsia , Criança , Ciclofosfamida/efeitos adversos , Quimioterapia Combinada , Feminino , Seguimentos , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Infecções Oportunistas/epidemiologia , Prednisona/efeitos adversos , Recidiva , Indução de Remissão , Resultado do Tratamento
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