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1.
Clin Exp Rheumatol ; 32(3): 324-32, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24447348

RESUMO

OBJECTIVES: Methotrexate (MTX) is the cornerstone medication in the treatment of rheumatoid arthritis (RA). We examined whether single nucleotide polymorphisms (SNPs) in enzymes of the folic acid pathway (folylpoly-gamma-glutamate synthetase [FPGS], gamma-glutamyl hydrolase [GGH], and methylenetetrahydrofolate reductase [MTHFR]) associate with significant adverse events (SigAE). METHODS: Patients (n=319) enrolled in the Veterans Affairs RA (VARA) registry taking MTX were genotyped for HLA-DRB1-SE and the following SNPs: FPGS (rs7033913, rs10760503, rs10106), GGH (12548933, rs7010484, rs4617146, rs719235, rs11988534), MTHFR (rs1801131, rs1801133). AE were abstracted from the medical record using a structured instrument. SigAE were defined as an AE leading to MTX discontinuation. Covariates included: age, gender, race, RA antibody status, tobacco, RA disease duration between diagnosis and MTX course, Charlson-Deyo comorbidity index, glucocorticoids, use of prior RA medications, and mean 4-variable disease activity score. Cox regression was performed to determine factors associated with time-to-SigAE. A p-value ≤ 0.005 established significance in the final model. RESULTS: The presence of ≥ 1 copy of the minor allele in MTHFR rs1801131 was associated with an increased hazard ratio (HR) of SigAE (HR 3.05, 95% CI 1.48-6.29, p-value 0.003 and HR 3.88, 95% CI 1.62-9.28, p-value 0.002 for heterozygotes and homozygotes for the minor allele, respectively). An interaction term, between FPGS rs7033913 heterozygotes and GGH rs11988534 homozygotes for the minor allele, had a p-value <0.0001. CONCLUSIONS: RA subjects taking MTX may have decreased time-to-SigAE with ≥ 1 copy of the minor allele in MTHFR rs1801131. Further investigation is warranted, as these SNPs may indicate susceptibility to MTX toxicity.


Assuntos
Artrite Reumatoide , Ácido Fólico/metabolismo , Metotrexato/toxicidade , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Peptídeo Sintases/genética , gama-Glutamil Hidrolase/genética , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/administração & dosagem , Antirreumáticos/toxicidade , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Feminino , Ácido Fólico/genética , Genótipo , Humanos , Masculino , Metotrexato/administração & dosagem , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Peptídeo Sintases/metabolismo , Polimorfismo de Nucleotídeo Único , Sistema de Registros , Estados Unidos , Veteranos , gama-Glutamil Hidrolase/metabolismo
2.
Clin Exp Rheumatol ; 27(4): 633-40, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19772796

RESUMO

OBJECTIVE: To evaluate the agreement among several rheumatoid arthritis (RA) response measures in a clinical setting. METHODS: 529 patients with RA were seen at 2 regular visits where the following response measures were determined: ACR-20, EULAR good or moderate (EULAR-GM), Simplified Disease Activity Index moderate (SDAI-M), Clinical DAI moderate (CDAI-M), and Patient Reported Outcomes Index-M 20 (PRO-IM-20). Each measure was modified to include a "worse" response, i.e. the inverse of the respective guidelines for a positive improvement response.Introduced for comparison was the Real-time Assessment of Disease Activity in Rheumatoid Arthritis (RADARA), a response measure that registers improvement if the patient's tender and swollen joint counts and HAQ score all improve and worsening if all three increase. Contingency tables comparing the three responses (worse, no change, and improvement) along with Cohen's kappa were calculated. RESULTS: The mean (SD) baseline characteristics of the patients included: age 66.5 (10.7) years, RA duration 12.9 (11.0) years, 91.3% male, 84.1% rheumatoid factor positive, and a Disease Activity Score-28 of 3.5 (1.3). The percentage of patients who improved/worsened were as follows: ACR-20 4.7/9.1, EULAR-GM 23.4/26.3, SDAI-M 16.1/20.6, CDAI-M 16.3/20.0, PRO-IM-20 22.5/34.4, and RADARA 7.0/11.5. Agreement (kappa) was poor to slight (

Assuntos
Artrite Reumatoide/fisiopatologia , Índice de Gravidade de Doença , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Avaliação da Deficiência , Progressão da Doença , Feminino , Nível de Saúde , Hospitais de Veteranos , Humanos , Articulações/patologia , Articulações/fisiopatologia , Masculino , Dor/fisiopatologia , Medição da Dor , Reprodutibilidade dos Testes , Resultado do Tratamento
3.
Semin Arthritis Rheum ; 49(2): 229-235, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30777365

RESUMO

OBJECTIVE: Although post-traumatic stress disorder (PTSD) is identified as a risk factor in the development of rheumatoid arthritis (RA), associations of PTSD with disease progression are less clear. To explore whether PTSD might influence disease-related measures of systemic inflammation in RA, we compared serum cytokine/chemokine (cytokine) concentrations in RA patients with and without PTSD. METHODS: Participants were U.S. Veterans with RA and were categorized as having PTSD, other forms of depression/anxiety, or neither based on administrative diagnostic codes. Multiplex cytokines were measured using banked serum. Associations of PTSD with cytokine parameters (including a weighted cytokine score) were assessed using multivariable regression, stratified by anti-CCP status and adjusted for age, sex, race, and smoking status. RESULTS: Among 1,460 RA subjects with mean (SD) age of 64 (11) years and disease duration of 11 (11) years, 91% were male, 77% anti-CCP positive, and 80% ever smokers. Of these, 11.6% had PTSD, 23.7% other depression/anxiety, and 64.7% had neither. PTSD, but not depression/anxiety, was associated with a higher cytokine score and number of high-concentration analytes in adjusted models, though this was limited to anti-CCP positive subjects. PTSD was associated with heightened expression of several individual cytokines including IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-17, IFN-γ, GM-CSF, MCP-1, and TNF-α. CONCLUSION: Anti-CCP positive RA patients with PTSD have higher serum cytokine concentrations than those without PTSD, demonstrating that systemic inflammation characteristic of RA is heightened in the context of this relatively common psychiatric comorbidity.


Assuntos
Artrite Reumatoide/complicações , Quimiocinas/sangue , Citocinas/sangue , Transtornos de Estresse Pós-Traumáticos/complicações , Veteranos , Idoso , Artrite Reumatoide/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Estresse Pós-Traumáticos/sangue
4.
Biotech Histochem ; 91(2): 77-85, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26800284

RESUMO

Serum procalcitonin (ProCT) is elevated in response to bacterial infections, whereas high sensitivity C-reactive protein (hsCRP) is a nonspecific inflammatory marker that is increased by excess adipose tissue. We examined the efficacy of ProCT and hsCRP as biomarkers of periodontitis in the saliva and serum of patients with arthritis, which is characterized by variable levels of systemic inflammation that potentially can confound the interpretation of inflammatory biomarkers. Blood and unstimulated whole saliva were collected from 33 patients with rheumatoid arthritis (RA) and 50 with osteoarthritis (OA). Periodontal status was assessed by full mouth examination and patients were categorized as having no/mild, moderate or severe periodontitis by standard parameters. Salivary and serum ProCT and hsCRP concentrations were compared. BMI, diabetes, anti-inflammatory medications and smoking status were ascertained from the patient records. Differences between OA and RA in proportionate numbers of patients were compared for race, gender, diabetes, adiposity and smoking status. Serum ProCT was significantly higher in arthritis patients with moderate to severe and severe periodontitis compared with no/mild periodontitis patients. There were no significant differences in salivary ProCT or salivary or serum hsCRP in RA patients related to periodontitis category. Most of the OA and RA patients were middle aged or older, 28.9% were diabetic, 78.3% were overweight or obese, and slightly more than half were either current or past smokers. The OA and RA groups differed by race, but not gender; blacks and males were predominant in both groups. The OA and RA groups did not differ in terms of controlled or uncontrolled diabetes, smoking status or BMI. The RA patients had been prescribed more anti-inflammatory medication than the OA patients. Our results demonstrate that circulating ProCT is a more discriminative biomarker for periodontitis than serum hsCRP in patients with underlying arthritis. Any elevation in salivary and serum hsCRP due to periodontitis apparently was overshadowed by differences among these patients in factors that influence CRP, such as the extent of inflammation between RA and OA, the extent of adipose tissue, the use of anti- inflammatory medications and smoking status. Although our study showed no differences in salivary ProCT related to severity of periodontitis, this biomarker also may be useful with further refinement.


Assuntos
Artrite Reumatoide/metabolismo , Proteína C-Reativa/análise , Calcitonina/sangue , Osteoartrite/metabolismo , Periodontite/metabolismo , Precursores de Proteínas/sangue , Saliva/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saliva/metabolismo , Estados Unidos , Veteranos
5.
Am J Surg Pathol ; 19(2): 161-72, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7832276

RESUMO

While no cutaneous lesion is specific for Wegener's granulomatosis (WG), several histopathologic entities, including leukocytoclastic vasculitis and necrotizing granulomatous inflammation, are characteristic. This report details the histopathologic features of 75 cutaneous biopsies from 46 patients with WG. Biopsies were subdivided into histologic groups that included leukocytoclastic vasculitis (31%), granulomatous inflammation (GI) (19%), nonspecific ulceration (4%), superficial dermal and epidermal necrosis without inflammation (2.7%), erythema nodosum (2.7%), granuloma annulare (1%), chronic inflammation (31%), and acute inflammatory lesions without vasculitis (9%). No convincing example of granulomatous vasculitis was observed. The histopathologic subgroups were correlated with clinical features, and the results were compared with those from a control group of 82 WG patients with no skin involvement. We found that the histopathologic subgroups of leukocytoclastic vasculitis and granulomatous inflammation correlated with different clinical courses. Patients with leukocytoclastic vasculitis developed WG at an earlier age (median age, 30 years) than did the control group (median age, 45 years). Leukocytoclastic vasculitis developed shortly after onset of WG (median, 15 months vs. 35 months for patients with nonspecific chronic inflammation). All lesions occurred during active disease. Active disease with leukocytoclastic vasculitis was associated with a mean erythrocyte sedimentation rate twice that of active disease in the same patient when leukocytoclastic vasculitis was absent. The patients with leukocytoclastic vasculitis had more rapidly progressive and widespread WG than patients with granulomatous skin lesions or patients without skin lesions. A marked excess of joint and musculoskeletal symptoms and renal disease was seen in patients with leukocytoclastic vasculitis. Patients with granulomatous inflammation also developed WG at an early age (median age, 30 years) when compared with the control group. Cutaneous granulomatous lesions also developed shortly after presentation (median, 12 months). Only 64% of granulomatous biopsies were from patients with active disease. These patients frequently had neither renal nor pulmonary manifestations of WG, and their disease progressed at a slower rate than that of the patients with leukocytoclastic vasculitis. These findings suggest that the cutaneous lesions characteristic of WG may correlate with the activity, distribution, and course of the disease.


Assuntos
Granulomatose com Poliangiite/patologia , Dermatopatias/patologia , Adolescente , Adulto , Idoso , Granuloma/patologia , Humanos , Pessoa de Meia-Idade , Úlcera Cutânea/patologia
6.
Rheum Dis Clin North Am ; 21(4): 1041-58, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8592736

RESUMO

Takayasu's arteritis (TA) is a chronic disease characterized by inflammation of large vessels. Individuals of any race, gender, or age may be affected by TA, but it is most common in young Asian females. Current data provide increasing support for an autoimmune basis for TA, but the cause remains unknown. Parameters of disease activity and imaging studies evaluating disease progression are imperfect. Treatment is aimed at controlling disease with minimal morbidity. Appropriate timing of improved surgical techniques is invaluable in the management of TA.


Assuntos
Arterite de Takayasu , Feminino , Antígenos HLA/análise , Humanos , Incidência , Mortalidade , Gravidez , Complicações Cardiovasculares na Gravidez , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/etiologia , Arterite de Takayasu/terapia
7.
Best Pract Res Clin Rheumatol ; 15(2): 203-23, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11469818

RESUMO

Vasculitis is a process that results from the inflammation of blood vessels and can occur de novo or secondary to a variety of diseases or drugs. Clinical presentation depends on the size and distribution of vessels involved. Anti-neutrophil cytoplasmic antibodies (ANCA) have been shown to have variable sensitivity in making the diagnosis of specific vasculitic syndromes, therefore histological confirmation may be necessary. Angiography is a useful tool in evaluating disease of large and medium-sized vessels that are inaccessible or potentially dangerous to biopsy. New imaging modalities are becoming more useful in diagnosing vessel wall changes, particularly in large-vessel vasculitides. In clinical practice it is not always possible to classify or apply a specific label to a patient with vasculitis, but for appropriate patient management it is important to define the extent and severity of disease and to exclude underlying secondary causes.


Assuntos
Vasculite/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/sangue , Angiografia Cerebral , Humanos , Imageamento por Ressonância Magnética , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Vasculite/sangue , Vasculite/classificação , Vasculite/etiologia
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.
J Clin Rheumatol ; 6(6): 309-12, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19078490

RESUMO

To determine if odontoid erosions are a marker for more severe cervical spine disease in rheumatoid arthritis (RA), 25 patients with RA were enrolled and had radiographs of the cervical spine including lateral and open mouth odontoid (OMO) views. The presence of odontoid erosions and of anterior atlantoaxial subluxation (AAS) was noted. Lateral cervical spine views were available for 19 patients, 11 of whom demonstrated odontoid erosions. Seven of 22 patients who had OMO views available demonstrated odontoid erosions. In only 3 of the 15 patients could odontoid erosions be seen on both views. Anterior AAS was present in 6 of 25 patients, 5 of whom had odontoid erosions. Anterior AAS was seen more commonly in patients with odontoid erosions. We propose that if erosions are present, patients should be more closely monitored for AAS and neurologic signs. OMO views are not as sensitive but are complementary to lateral cervical spine views in the detection of odontoid erosions.

11.
Ear Nose Throat J ; 68(6): 426, 428-9, 1989 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2663438

RESUMO

From the extensive morphological studies performed, otosclerosis appears to be ubiquitous, and in many instances subclinical. Despite reports of the efficacy of fluoride for this condition, at present its use should be regarded as experimental.


Assuntos
Fluoretos/uso terapêutico , Otosclerose/tratamento farmacológico , Humanos
13.
J Rheumatol ; 24(11): 2134-8, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9375872

RESUMO

OBJECTIVE: To prospectively evaluate the prevalence and clinical spectrum of cryoglobulinemia in a population infected with the hepatitis C virus (HCV). METHODS: Inpatients and outpatients at the Veterans Affairs (VA) Medical Center were recruited for study. Sixty-nine patients with HCV and 68 anti-HCV negative, age and sex matched controls were evaluated for the prevalence of cryoglobulinemia. Clinical and laboratory profiles were obtained in all patients and rheumatologic complaints were sought in 58 anti-HCV positive patients. RESULTS: Twenty-nine (42%) of 69 anti-HCV positive patients and no controls had cryoglobulinemia (p < 0.001). A history of intravenous drug abuse and excessive alcohol ingestion was more prevalent in the anti-HCV positive group compared to controls, (p < 0.001 and p = 0.02, respectively), but was unrelated to the presence or absence of cryoglobulinemia. Of 58 anti-HCV positive patients evaluated for rheumatologic complaints, 12 (21%) reported symptoms; 9 (41%) of 22 with cryoglobulinemia and 3 (8%) of 36 without cryoglobulinemia (p < 0.01). No patient had vasculitis. Antinuclear antibody (ANA) and rheumatoid factor (RF) were evaluated in 19 anti-HCV positive patients with cryoglobulinemia. About one-half were positive for ANA or RF, fewer than 50% of whom had rheumatologic symptoms. Nineteen of the 29 patients with cryoglobulinemia were available for followup after one year. Ten of 19 revealed only trace (< 5%) cryoglobulinemia; 7 were type III, one type I, and none were type II. The character of the remaining 2 cryoglobulins was unknown. Twenty-five liver biopsy specimens were available for review; there were no histological differences between patients with and without cryoglobulinemia. CONCLUSION: The prevalence of HCV related cryoglobulinemia at a VA hospital was 42% and was most often of the type III variety. Although mild rheumatologic symptoms were common in HCV infected patients with cryoglobulinemia, no specific syndrome denoted its presence. The absence of any specific rheumatologic disease in this cohort implies that the pathogenesis of diseases such as essential mixed cryoglobulinemia is multifactorial and that low levels of type III cryoglobulinemia in HCV infected patients are not specific for the diagnosis.


Assuntos
Crioglobulinemia/complicações , Crioglobulinemia/epidemiologia , Hepatite C/epidemiologia , Biópsia , Feminino , Seguimentos , Hepacivirus/isolamento & purificação , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/patologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Interferon-alfa/uso terapêutico , Masculino , Estudos Prospectivos , Doenças Reumáticas/diagnóstico
14.
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
15.
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
16.
Arthritis Rheum ; 38(5): 608-13, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7748215

RESUMO

OBJECTIVE: To determine the efficacy of low-dose methotrexate (MTX) plus prednisone in the treatment of Wegener's granulomatosis (WG). METHODS: An open-label study of weekly low-dose MTX plus prednisone for the treatment of WG was performed. Forty-two patients who did not have immediately life-threatening disease were enrolled into the study. Outcome was determined by clinical characteristics and pathologic, laboratory, and radiographic findings. RESULTS: Weekly administration of MTX and prednisone resulted in remission of disease in 30 of the 42 patients (71%). The median time to remission was 4.2 months. The estimated median time to relapse for all patients in whom remission was achieved was 29 months. Eight patients who had relapses were treated with a second course of MTX plus prednisone, and a second remission was induced in 6 of the 8 (75%). CONCLUSION: Weekly low-dose MTX was shown in this study to be an acceptable alternative form of therapy for selected patients with WG who do not have immediately life-threatening disease or who have developed serious cyclophosphamide-associated toxicity.


Assuntos
Granulomatose com Poliangiite/tratamento farmacológico , Metotrexato/administração & dosagem , Prednisona/administração & dosagem , Administração Oral , Adulto , Idoso , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/mortalidade , Humanos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Infecções Oportunistas/epidemiologia , Prednisona/efeitos adversos , Estudos Prospectivos , Recidiva , Indução de Remissão , Fatores de Tempo
17.
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
18.
J Pediatr ; 122(1): 26-31, 1993 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8419611

RESUMO

We prospectively studied and compared clinical features, treatment, course of illness, and long-term morbidity and mortality rates for Wegener granulomatosis in 23 childhood-onset patients with those of 135 adult-onset patients who were studied concurrently. Treatment was usually provided with glucocorticoids and cyclophosphamide. The mean follow-up period was 8.7 years for childhood-onset and 7.6 years for adult-onset Wegener granulomatosis. Most aspects of Wegener granulomatosis were similar in childhood-onset and adult-onset patients. Permanent morbidity from disease occurred in 86% of both groups. However, some features were significantly different. Wegener granulomatosis in childhood-onset patients was complicated five times more often by subglottic stenosis and twice as often by nasal deformity. Treatment-related permanent morbidity occurred in 22% of childhood-onset patients and 45% of adult-onset patients. After similar periods of cyclophosphamide therapy and follow-up, cyclophosphamide-related malignancies were less likely (0% vs 11%) to have developed in childhood-onset patients. Although 89% of patients treated with glucocorticoids and cyclophosphamide had remission, prolonged delay in achieving remission and relapses led in both patient groups to freedom from active disease for approximately 50% of the total patient-years. As a result, morbidity was substantial and has led to comparative studies of alternative therapies.


Assuntos
Granulomatose com Poliangiite/fisiopatologia , Adolescente , Adulto , Fatores Etários , Criança , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Oftalmopatias/fisiopatologia , Feminino , Seguimentos , Glomerulonefrite/fisiopatologia , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Laringoestenose/fisiopatologia , Pneumopatias/fisiopatologia , Masculino , Doenças Nasais/fisiopatologia , Infecções Oportunistas , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Estudos Prospectivos , Indução de Remissão , Taxa de Sobrevida , Resultado do Tratamento
19.
Am J Respir Crit Care Med ; 151(3 Pt 1): 795-9, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7881673

RESUMO

The risk factors and clinical and laboratory parameters in Pneumocystis carinii pneumonia in patients with Wegener's granulomatosis have not been well characterized. We undertook a retrospective chart review of all patients with a diagnosis of Wegener's granulomatosis and P. carinii pneumonia who were followed at the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. The chart review focused on clinical, laboratory, and roentgenologic evidence of P. carinii pneumonia. Eleven cases of P. carinii pneumonia were diagnosed in some 180 patients with Wegener's granulomatosis, for an overall incidence of approximately 6%. All patients developed P. carinii pneumonia either during the initial course of treatment or during therapy for recurrent Wegener's granulomatosis. All patients were receiving daily glucocorticoids and a second immunosuppressive therapy. Lymphocytopenia was noted in all patients, with a mean +/- SEM total lymphocyte count of 303 +/- 69 cells/microL. All patients tested (10 of 11) were seronegative for human immunodeficiency virus (HIV) infection. Eight presented with worsening chest roentgenograms compared with baseline, whereas three presented with normal chest roentgenograms. We conclude that P. carinii is a common opportunistic pathogen in patients with Wegener's granulomatosis receiving immunosuppressive therapy. Therapeutic immunosuppression (daily glucocorticoids and immunosuppressive agents) and the resultant lymphocytopenia, as well as the lymphocyte and monocyte functional abnormalities caused by glucocorticoids, may be the most likely factors predisposing to P. carinii pneumonia in patients with Wegener's granulomatosis. Based on our data, all patients with Wegener's granulomatosis should be given chemoprophylaxis against P. carinii while they are receiving daily glucocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Terapia de Imunossupressão/efeitos adversos , Infecções Oportunistas/complicações , Pneumonia por Pneumocystis/complicações , Feminino , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/epidemiologia , Pneumonia por Pneumocystis/epidemiologia , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Estudos Retrospectivos , Fatores de Risco
20.
Ann Intern Med ; 120(11): 919-29, 1994 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-7909656

RESUMO

OBJECTIVE: To evaluate prospectively the clinical features, angiographic findings, and response to treatment of patients with Takayasu arteritis. DESIGN: 60 patients with Takayasu arteritis were studied at the National Institute of Allergy and Infectious Diseases between 1970 and 1990 and were followed for 6 months to 20 years (median follow-up, 5.3 years). MEASUREMENTS: Data on clinical features, angiographic and laboratory findings, disease course, and response to therapy were all recorded and stored in a computer-based retrieval system. SETTING: The Warren Magnuson Clinical Center of the National Institutes of Health. RESULTS: In our series of patients, Takayasu arteritis was more common in Asian persons compared with persons from other racial groups. Females (97%) were most frequently affected. The median age at disease onset was 25 years. Juveniles had a delay in diagnosis that was about four times that of adults. The clinical presentation ranged from asymptomatic to catastrophic with stroke. The most common clinical finding was a bruit. Hypertension was most often associated with renal artery stenosis. Only 33% of all patients had systemic symptoms on presentation. Sixty-eight percent of patients had extensive vascular disease; stenotic lesions were 3.6-fold more common than were aneurysms (98% compared with 27%). The erythrocyte sedimentation rate was not a consistently reliable surrogate marker of disease activity. Surgical bypass biopsy specimens from clinically inactive patients showed histologically active disease in 44% of patients. Although clinically significant palliation usually occurred after angioplasty or bypass of severely stenotic vessels, restenosis was common. Medical therapy was required for 80% of patients, whereas 20% had monophasic self-limiting disease. Immunosuppressive treatment with glucocorticoids alone or in combination with a cytotoxic agent failed to induce remission in one fourth of patients; about half of those who achieved remission later relapsed. CONCLUSIONS: In North America, Takayasu arteritis is a rare disease. It is heterogeneous in presentation, progression, and response to therapy. Current laboratory markers of disease activity are insufficiently reliable to guide management. Most patients require repeated and, at times, prolonged courses of therapy. Although mortality was low, substantial morbidity occurred in most patients.


Assuntos
Arterite de Takayasu/diagnóstico , Arterite de Takayasu/terapia , Adolescente , Adulto , Angiografia , Criança , Diagnóstico Diferencial , Feminino , Antígenos HLA , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Complicações Cardiovasculares na Gravidez/terapia , Estudos Prospectivos , Estatística como Assunto , Arterite de Takayasu/diagnóstico por imagem , Arterite de Takayasu/imunologia , Resultado do Tratamento
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