RESUMEN
The objective of the study is to develop genetic and clinical prediction models for the efficacy and hepatotoxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). Among RA patients treated with MTX, 1966 polymorphisms of 246 enzymes/transporters relevant to pharmacokinetics and pharmacodynamics were measured by the Drug Metabolism Enzymes and Transporters (DMET) microarray and direct sequencing, and clinical variables at baseline were collected. For efficacy, response criteria of the European League Against Rheumatism were used to classify patients as responders or non-responders. Hepatotoxicity was defined as elevations of aspartate aminotransferase or alanine aminotransferase ≥1.5 times the reference range upper limit. Among 166 patients, a genetic prediction model for efficacy using seven polymorphisms showed the area under the receiver operating characteristic curve (AUC) was 0.822, with 74.3% sensitivity and 76.8% specificity. A combined genetic and clinical model indicated the AUC was 0.844, with 81.5% sensitivity and 76.9% specificity. By incorporating clinical variables into the genetic model, the overall category-free net reclassification improvement (NRI) was 0.663 (P < 0.0001) and the overall integrated discrimination improvement (IDI) was 0.083 (P = 0.0009). For hepatotoxicity, a genetic prediction model using seven polymorphisms showed the AUC was 0.783 with 70.0% sensitivity and 80.0% specificity, while the combined model indicated the AUC was 0.906 with 85.1% sensitivity and 87.8% specificity (overall category-free NRI: 1.002, P < 0.0001; overall IDI: 0.254, P < 0.0001). Our genetic and clinical models demonstrated moderate diagnostic accuracy for MTX efficacy and high accuracy for hepatotoxicity. These findings should, however, be validated and interpreted with a caution until external validation.
Asunto(s)
Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Metotrexato/efectos adversos , Modelos Genéticos , Anciano , Artritis Reumatoide/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Estudios de Cohortes , Femenino , Predicción , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Bosentan, an endothelin receptor antagonist, has been widely used as a first-line medication for the treatment of pulmonary arterial hypertension (PAH). It has been shown to improve symptoms of hypertension, exercise capacity, and hemodynamics and prolong time to clinical worsening. However, liver dysfunction is a major side effect of bosentan treatment that could hamper the optimal management of patients with PAH. Previously, we demonstrated, using drug metabolism enzymes and transporters analysis, that the carbohydrate sulfotransferase 3 (CHST3) and CHST13 alleles are significantly more frequent in patients with elevated aminotransferases during therapy with bosentan than they are in patients without liver toxicity. In addition, we constructed a pharmacogenomics model to predict bosentan-induced liver injury in patients with PAH using two single-nucleotide polymorphisms and two nongenetic factors. The purpose of the present study was to externally validate the predictive model of bosentan-induced liver toxicity in Japanese patients. We evaluated five cases of patients treated with bosentan, and one presented with liver dysfunction. We applied mutation alleles of CHST3 and CHST13, serum creatinine, and age to our model to predict liver dysfunction. The sensitivity and specificity were calculated as 100% and 50%, respectively. Considering that PAH is a rare disease, multicenter collaboration would be necessary to validate our model.
Asunto(s)
Bosentán/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Antagonistas de los Receptores de Endotelina/efectos adversos , Modelos Estadísticos , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Bosentán/farmacocinética , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Creatinina/sangre , Antagonistas de los Receptores de Endotelina/farmacocinética , Femenino , Humanos , Japón/epidemiología , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Mutación , Variantes Farmacogenómicas , Polimorfismo de Nucleótido Simple , Valor Predictivo de las Pruebas , Hipertensión Arterial Pulmonar/sangre , Hipertensión Arterial Pulmonar/genética , Medición de Riesgo/métodos , Sulfotransferasas/genética , Sulfotransferasas/metabolismo , Carbohidrato SulfotransferasasRESUMEN
Bosentan, an endothelin receptor antagonist, has been widely used as a first-line drug for the treatment of pulmonary arterial hypertension (PAH). In addition, bosentan is approved for patients with digital ulcers related to systemic sclerosis. Liver dysfunction is a major adverse effect of bosentan and may lead to discontinuation of therapy. The purpose of this study was to identify genomic biomarkers to predict bosentan-induced liver injury. A total of 69 PAH patients were recruited into the study. An exploratory analysis of 1936 single-nucleotide polymorphisms (SNPs) in 231 genes involved in absorption, distribution, metabolism, and elimination of multiple medications using Affimetrix DMET™ (Drug Metabolism Enzymes and Transporters) chips was performed. We extracted 16 SNPs (P < 0.05) using the Jonckheere-Terpstra trend test and multiplex logistic analysis; we identified two SNPs in two genes, CHST3 and CHST13, which are responsible for proteoglycan sulfation and were significantly associated with bosentan-induced liver injury. We constructed a predictive model for bosentan-induced liver injury (area under the curve [AUC]: 0.89, sensitivity: 82.61%, specificity: 86.05%) via receiver operating curve (ROC) analysis using 2 SNPs and 2 non-genetic factors. Two SNPs were identified as potential predictive markers for bosentan-induced liver injury in Japanese patients with pulmonary arterial hypertension. This is the first pharmacogenomics study linking proteoglycan sulfating genes to drug-induced liver dysfunction, a frequently observed clinical adverse effect of bosentan therapy. These results may provide a way to personalize PAH medicine as well as provide novel mechanistic insights to drug-induced liver dysfunction.
Asunto(s)
Antihipertensivos/efectos adversos , Pueblo Asiatico/genética , Bosentán/efectos adversos , Hipertensión Pulmonar/tratamiento farmacológico , Sulfotransferasas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipertensión Pulmonar/genética , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Adulto Joven , Carbohidrato SulfotransferasasRESUMEN
This report concerns a case of granulomatosis with polyangiitis (GPA) (Wegener's granulomatosis (WG)) with bronchus narrowing. Although nasal biopsy had been performed three times, no positive histology for GPA (WG) could be obtained. Flexible bronchoscopy revealed diffuse erythema, edema of the mucosa and stenosis of the right mainstem bronchus. Transbronchial biopsy identified granuloma with giant cells. These findings led to a diagnosis of GPA (WG). This case suggests that biopsy from the bronchus is useful for diagnosis of GPA (WG).
Asunto(s)
Biopsia/métodos , Bronquios/patología , Broncoscopía/métodos , Granulomatosis con Poliangitis/diagnóstico , Constricción Patológica/diagnóstico , Constricción Patológica/etiología , Granulomatosis con Poliangitis/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
The aim of this study was to confirm the clinical significance of serum MMP-3 measurement in the evalua- tion of disease activity and effectiveness of treatment in patients with rheumatoid arthritis (RA). MMP-3 was measured for 206 outpatients with RA during a period of 4 months, and also serially measured for RA patients treated with methotrexate(MTX) alone or together with infliximab (IFX). Serum MMP-3 was significantly correlated with CRP, SAA, and ESR. Significant correlation of serum MMP-3 was found not only with DAS28 (CRP) in female and male patients (p <0.0001 and p < 0.0051, respectively) but also with the EULAR classification criteria for the disease activity of RA. Among the items of DAS28(CRP), the strongest association of MMP-3 was found with swollen joint counts. Furthermore, MMP-3 levels increased with advances in Stage and Class of RA. MMP-3 levels gradually decreased 12 and 24 weeks after successful treatment with MTX (p=0.0188 and p=0.0179, respectively). Extent of the decrease was more prominent in patients with better response to MTX than in those with poor response. MMP-3 levels significantly decreased 6 weeks after IFX treatment and continued to decrease until 48 weeks. Significant decrease of MMP-3 level from before treatment was shown only in the good response group to IFX after 48 weeks of treatment. MMP-3 level was shown to be useful as a disease activity marker in RA patients. In addition, serial measurement of MMP-3 maybe helpful to evaluate the effect of treatments with MTX and IFX.
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Artritis Reumatoide/diagnóstico , Biomarcadores/sangre , Metaloproteinasa 3 de la Matriz/metabolismo , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/enzimología , Artritis Reumatoide/metabolismo , Femenino , Humanos , Infliximab/uso terapéutico , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Resultado del TratamientoRESUMEN
The objective of this study is to clarify the characteristics and imaging results of Japanese patients with giant cell arteritis (GCA). Eight patients with biopsy-proven GCA were enrolled. Their clinical data and imaging results were retrospectively examined from their medical records. All the patients met the criteria for the classification of GCA by the American College of Rheumatology. Although the clinical manifestations are similar to those previously reported, none of the eight patients presented ocular symptoms, and half of them presented jaw claudication. Ultrasonography (US) of temporal artery showed the halo sign in all the patients. Fluorodeoxyglucose positron emission tomography (FDG-PET) was performed in four patients and indicated the presence of aortitis of the patients. US is a quick and noninvasive test to detect inflammation of temporal artery, and FDG-PET is very helpful for early diagnosis of aortitis in GCA. Awareness of the disease and appropriate imaging tests will result in diagnosis of GCA.
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Arteritis de Células Gigantes/diagnóstico , Tomografía de Emisión de Positrones , Arterias Temporales/patología , Ultrasonografía Doppler en Color , Anciano , Anciano de 80 o más Años , Aortitis/diagnóstico por imagen , Aortitis/etiología , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/patología , Femenino , Fluorodesoxiglucosa F18 , Arteritis de Células Gigantes/complicaciones , Arteritis de Células Gigantes/diagnóstico por imagen , Humanos , Japón , Estudios Retrospectivos , Arterias Temporales/diagnóstico por imagenRESUMEN
This case report describes findings in a 61-year-old woman who manifested scleritis, small pulmonary nodules, otitis media, periaortitis, and progressive epidural spinal tumor, associated with elevated serum myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) levels. She was clinically diagnosed with Wegener's granulomatosis, although vasculitis was not diagnosed due to the lack of typical histological findings. We discuss the differential diagnosis in this patient, and the association of MPO-ANCA with periaortitis or epidural spinal tumor.
Asunto(s)
Neoplasias Epidurales/complicaciones , Granulomatosis con Poliangitis/complicaciones , Fibrosis Retroperitoneal/complicaciones , Neoplasias Epidurales/patología , Femenino , Granulomatosis con Poliangitis/patología , Humanos , Inflamación/patología , Persona de Mediana Edad , Fibrosis Retroperitoneal/patología , Vértebras TorácicasRESUMEN
This study aimed to directly analyze the potential relationship of anti-nuclear antibodies (ANA) before and after the administration of TNF-α inhibitors (TNFi) with the appearance of anti-drug antibodies (ADrA) in patients with rheumatoid arthritis (RA). A total of 121 cases, viz., 38, 53, and 30 cases treated with infliximab (IFX), adalimumab (ADA), and etanercept (ETN), respectively, were enrolled. The ANA titers were measured using indirect immunefluorescence assay (IF-ANA) and multiplex flow immunoassay (ANA Screen) before and serially during the therapy. The anti-IFX antibodies (HACA) and anti-ADA antibodies (AAA) were measured with a radioimmunoassay. ADrA turned positive in 14 (36.8%) among 38 patients treated with IFX, and 16 (30.2%) among 53 treated with ADA. All of them were positive for IF-ANA before TNFi administration, while ADrA never appeared in any of the 15 patients negative for IF-ANA (< 40). IF-ANA of high titers (≥ 320 and ≥ 640) before IFX treatment showed a significant association with the appearance of HACA 52 weeks after IFX (P = 0.040 and 0.017, respectively), whereas AAA appearance was not related to IF-ANA titers before treatment. Moreover, IF-ANA of high titers before IFX treatment was significantly associated with inefficacy and discontinuation of the treatment. The positivity of anti-SS-A antibodies before therapy might be a risk factor for ADrA appearance in patients treated with IFX or ADA. The percentage of patients whose IF-ANA titers increased was significantly higher with IFX than with ADA or ETN treatments (P = 0.026 and 0.022, respectively). High ANA titers and positive ANA Screen after IFX therapy showed a significant association with HACA appearance and possibly led to treatment failure. Among the three TNFi, only IFX showed a close relationship with IF-ANA and ADrA appearance, suggesting the interaction of immunogenicity with autoimmunity as well as the advantage of ANA measurement before TNFi therapy.
Asunto(s)
Adalimumab/inmunología , Anticuerpos/inmunología , Antirreumáticos/inmunología , Artritis Reumatoide/tratamiento farmacológico , Etanercept/inmunología , Infliximab/inmunología , Adalimumab/uso terapéutico , Adulto , Anciano , Anticuerpos Antinucleares/inmunología , Antirreumáticos/uso terapéutico , Artritis Reumatoide/inmunología , Etanercept/uso terapéutico , Femenino , Humanos , Infliximab/uso terapéutico , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
A 39-year-old Japanese man presented with chest oppression in February 2017. Electrocardiogram showed ST-elevation myocardial infarction (MI), and cardiac catheterisation revealed thrombotic occlusion of the right coronary artery (RCA), which was treated with thrombectomy, and he received warfarin. Three days after discharge, he complained of chest oppression again, and re-cardiac catheterisation showed thrombi occlusion of the circumflex artery (LCX) and 90% stenosis with thrombosis in the proximal site of the anterior descending artery (LAD) and RCA. Drug eluting stent was implanted in the LAD and RCA; aspirin and prasugrel hydrochloride were added to warfarin. Before discharge, coronary computed tomography angiography (CTA) found new thrombi in the RCA, LAD, and LCX, and he was referred to our hospital on suspicion of Behçet's disease (BD). Past medical history was notable for recurrent aphthous stomatitis, a pudendal ulcer, and Crohn's disease, for which he had been taking infliximab (5 mg/kg) every 8 weeks until December 2016. Notably, his C-reactive protein (CRP) level increased before and after each MI, suggesting that the thrombi were caused by inflammation. Consequently, we concluded that his abnormalities were manifestations of vasculo-BD. After 3 days of hospitalisation, treatment with prednisolone and colchicine was started. His CRP and D-dimer levels decreased, and coronary CTA after 8 days showed disappearance of the thrombi. We tapered the prednisolone dose, and cardiovascular events have not been observed for 7 months after the treatment initiation. In summary, we report a rare case of MI associated with vasculo-BD and review the relevant literature.
Asunto(s)
Síndrome de Behçet/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/etiología , Adulto , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamiento farmacológico , Biomarcadores , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Humanos , Masculino , Infarto del Miocardio/complicaciones , Recurrencia , Trombosis/sangre , Trombosis/diagnóstico , Trombosis/etiología , Trombosis/prevención & control , Tomografía Computarizada por Rayos XAsunto(s)
Cromatografía de Gases y Espectrometría de Masas , Lupus Eritematoso Sistémico/sangre , Metabolómica/métodos , Biomarcadores/sangre , Estudios de Casos y Controles , Análisis Discriminante , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Análisis de los Mínimos Cuadrados , Lupus Eritematoso Sistémico/tratamiento farmacológico , Prednisolona/uso terapéutico , Análisis de Componente PrincipalRESUMEN
BACKGROUND: Rheumatoid factor (RF) and autoantibodies against cyclic citrullinated peptide (CCP) are markers that might help physicians diagnose rheumatoid arthritis. PURPOSE: To determine whether anti-CCP antibody more accurately identifies patients with rheumatoid arthritis and better predicts radiographic progression than does RF. DATA SOURCES: MEDLINE through September 2006 and reference lists of retrieved studies and review articles. STUDY SELECTION: Studies in any language that enrolled at least 10 participants and that examined the role of anti-CCP antibody and RF in the diagnosis or prognosis of known or suspected rheumatoid arthritis. DATA EXTRACTION: Two authors independently evaluated studies for inclusion, rated methodological quality, and abstracted relevant data. DATA SYNTHESIS: The DerSimonian-Laird random-effects method was used to summarize sensitivities, specificities, and positive and negative likelihood ratios from 37 studies of anti-CCP antibody and 50 studies of RF. The pooled sensitivity, specificity, and positive and negative likelihood ratios for anti-CCP antibody were 67% (95% CI, 62% to 72%), 95% (CI, 94% to 97%), 12.46 (CI, 9.72 to 15.98), and 0.36 (CI, 0.31 to 0.42), respectively. For IgM RF, the values were 69% (CI, 65% to 73%), 85% (CI, 82% to 88%), 4.86 (CI, 3.95 to 5.97), and 0.38 (CI, 0.33 to 0.44). Likelihood ratios among IgM RF, IgG RF, and IgA RF seemed to be similar. Results from studies of patients with early rheumatoid arthritis were similar to those from all studies. Three of 4 studies found that risk for radiographic progression was greater with anti-CCP antibody positivity than with IgM RF positivity. LIMITATIONS: Many studies had methodological limitations. Studies of RF were heterogeneous and had wide ranges of sensitivity and specificity. CONCLUSIONS: Anti-CCP antibodies are more specific than RF for diagnosing rheumatoid arthritis and may better predict erosivedisease.
Asunto(s)
Artritis Reumatoide/diagnóstico , Autoanticuerpos/sangre , Péptidos Cíclicos/inmunología , Factor Reumatoide/sangre , Biomarcadores/sangre , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Funciones de Verosimilitud , Pronóstico , Sensibilidad y EspecificidadRESUMEN
Regarding viral infection of intestinal mucosa, there have been only a few studies on limited diseases, targeting a few herpes family viruses. In this study, we analyzed 12 kinds of DNA viruses including 8 species of herpes family viruses in the gastrointestinal mucosa of patients with hematologic malignancies, inflammatory bowel diseases, collagen diseases, or other miscellaneous forms of gastroenteritis using the multiplex virus PCR assay, which we recently developed. The virus PCR assay yielded positive results in 63 of 102 patients; Epstein-Barr virus (EBV) was the most frequently detected, followed by cytomegalovirus (CMV), human herpes virus 6 (HHV-6), HHV-7, parvovirus B19, and herpes simplex virus type 1. The frequencies of viral detection in the 4 diseases were similar involving these 6 viruses. Regarding CMV colitis, the multiplex virus PCR assay was superior to the immunohistopathologic method in detecting CMV. All viruses were more efficiently detected in the mucosa than in the blood in individual patients. These results suggest that CMV, EBV, and HHV-6 were commonly detected in the gastrointestinal mucosa of patients with these 4 diseases, and our multiplex virus PCR assay was useful for the early diagnosis of gastrointestinal virus infection, especially CMV colitis.
RESUMEN
Purpose To evaluate the incidence of fragility fractures associated with high-dose glucocorticoid therapy in patients with systemic rheumatic disease. METHODS: A retrospective study of patients who were treated with high-dose prednisolone (> 0.8 mg/kg) for systemic rheumatic disease at Kobe University Hospital from April 1988 to March 2012. The primary outcome was a major osteoporotic fracture (defined as a clinical vertebral, hip, forearm, or proximal humerus fracture) after high-dose glucocorticoid therapy. For postmenopausal women and men over 40 of age, the patient's fracture risk at the beginning of high-dose glucocorticoid therapy was assessed by the World Health Organization's Fracture Risk Assessment Tool (FRAX®). Results Of 229 patients (median age: 49 years), 57 suffered a fragility fracture during the observation period (median observation period: 1558 days). Of 84 premenopausal patients, 5 suffered a fracture. In contrast, of 86 postmenopausal female, 36 suffered a fracture. Fragility fractures were far more frequent than predicted by the FRAX® score. Patients with FRAX® scores over 8.3% had a particularly high risk of fracture. Conclusions Fragility fractures associated with high-dose glucocorticoid therapy are common among postmenopausal women. Extreme care should be taken especially for postmenopausal women when high-dose glucocorticoid therapy is required.
RESUMEN
Thioredoxin (TRX) is an oxidative stress-inducible biological antioxidant that is highly expressed in the synoviocytes of rheumatoid arthritis (RA) patients. There is much evidence that oxidative stress plays a key role in the inflammation and destruction of RA joints; the functional relationship between TRX and RA remains unknown, however. We therefore investigated the role played by TRX in the inflammatory and joint-damaging processes of RA using a murine model in which arthritis was induced by administering a mixture of anti-type II collagen monoclonal antibodies (mAb) and lipopolysaccharide (LPS). In Wt mice mAb/LPS injection induced neutrophil infiltration, cartilage destruction, and chondrocyte apoptosis within the joints, all of which were dramatically suppressed in TRX transgenic (TRX-Tg) mice. Moreover, the 8-hydoxy-2'-deoxyguanosine (8-OHdG) expression seen in Wt mice after mAb/LPS injection was almost completely inhibited in TRX-Tg mice. The administration of recombinant TRX also suppressed mAb/LPS-induced joint swelling in Wt mice. Taken together, these results suggest that TRX protects against arthritis and is a plausible candidate with which to develop novel therapies for the treatment of RA.
Asunto(s)
Artritis Reumatoide/prevención & control , Articulaciones/efectos de los fármacos , Articulaciones/patología , Tiorredoxinas/uso terapéutico , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Apoptosis/efectos de los fármacos , Artritis Reumatoide/patología , Desoxiguanosina/análogos & derivados , Desoxiguanosina/biosíntesis , Modelos Animales de Enfermedad , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Ratones , Ratones Transgénicos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tiorredoxinas/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Giant cell arteritis (GCA), a type of systemic arteritis, is rare in Japan. We herein report a case of acute myeloid leukemia (AML) complicated by GCA that manifested during chemotherapy for AML. A 77-year-old woman with severe back pain was diagnosed with AML. She achieved complete remission with the resolution of her back pain following induction chemotherapy. However, she developed a headache and fever after consolidation chemotherapy. A diagnosis of GCA was made based on a biopsy of the temporal artery and arterial imaging. GCA should therefore be included in the differential diagnosis in AML patients complicated with a headache and fever of unknown origin.
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Antiinflamatorios/uso terapéutico , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dolor de Espalda/etiología , Arteritis de Células Gigantes/inducido químicamente , Leucemia Mieloide Aguda/tratamiento farmacológico , Prednisolona/uso terapéutico , Anciano , Biopsia , Diagnóstico Diferencial , Femenino , Arteritis de Células Gigantes/diagnóstico , Arteritis de Células Gigantes/tratamiento farmacológico , Humanos , Japón , Leucemia Mieloide Aguda/diagnóstico , Inducción de Remisión , Índice de Severidad de la Enfermedad , Resultado del TratamientoAsunto(s)
Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnóstico , Enfermedades del Colágeno/complicaciones , Enfermedades del Colágeno/diagnóstico , Fiebre de Origen Desconocido/etiología , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Artritis Reumatoide , Síndrome de Behçet , Dermatomiositis , Diagnóstico Diferencial , Arteritis de Células Gigantes , Humanos , Lupus Eritematoso Sistémico , Enfermedad de Still del Adulto , Arteritis de TakayasuRESUMEN
We describe two cases of IgG4-related disease associated with skin manifestations with IgG4-positive plasma cells. The first patient was a 52-year-old woman with a 3-year history of IgG4-related sialadenitis who presented with pruritic, indurated erythematous lesions on the auricle, postauricular and submandibular regions and neck. A skin biopsy showed infiltration of IgG4-positive plasma cells in the subcutaneous tissue. The second patient was a 53-year-old woman with IgG4-related lesions in the ocular adnexal tissues and nasal cavity who presented with pruritic, indurated erythema on the cheek and submandibular region. Histopathological examination of a skin biopsy revealed a dense, patchy infiltrate comprised of lymphocytes, IgG4-positive plasma cells and eosinophils around blood vessels and sweat glands in the entire dermis and subcutis. The skin lesions in these cases were considered to be skin manifestations of IgG4-related disease. The findings of these two cases together with the three reported cases of IgG4-related disease with skin manifestations in the literature suggest that IgG4-related skin lesions may appear on the scalp, face, neck, auricle and postauricular regions during the course of IgG4-related disease.
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Hipergammaglobulinemia/complicaciones , Inmunoglobulina G , Enfermedades de la Piel/complicaciones , Corticoesteroides/uso terapéutico , Párpados , Femenino , Humanos , Hipergammaglobulinemia/tratamiento farmacológico , Persona de Mediana Edad , Células Plasmáticas/patología , Sialadenitis/complicaciones , Sialadenitis/patología , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/patologíaRESUMEN
OBJECTIVE: To clarify the role of platelet-derived microparticles (PDMP), which are small vesicles with thrombotic and immunological properties, in systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis/polymyositis (PM/DM), and mixed connective tissue disease (MCTD). METHODS: Plasma levels of PDMP were measured by ELISA, and compared among patients with one of the 4 diseases. Association of PDMP levels with clinical characteristics and medication of the patients was also examined. RESULTS: PDMP levels were higher in patients with MCTD and SSc than in controls. Multiple linear regression analysis revealed that patients with Raynaud's phenomenon (RP) showed higher PDMP levels than those without. PDMP levels in individual patients did not fluctuate significantly over several months. CONCLUSION: PDMP level is associated with MCTD, SSc, and RP, and could be a novel marker for RP.
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Plaquetas/química , Micropartículas Derivadas de Células/metabolismo , Enfermedades del Tejido Conjuntivo/sangre , Adulto , Dermatomiositis/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Mixta del Tejido Conjuntivo/sangre , Polimiositis/sangre , Enfermedad de Raynaud/sangre , Esclerodermia Sistémica/sangreRESUMEN
BACKGROUND: Rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) have been studied extensively as prognostic markers of rheumatoid arthritis (RA). However, despite the fact that matrix metalloproteinase-3 (MMP-3) is linked to RA activity, few studies have evaluated MMP-3 as prognostic marker. OBJECTIVE: To evaluate the performance of MMP-3 as predictor of joint destruction in RA treated with non-biological disease modifying anti-rheumatic drugs. METHODS: In a retrospective study of 58 early to moderate stage RA patients who consulted the Department of Clinical Pathology and Immunology, Kobe University Hospital between May 2002 and April 2009, we evaluated the performance of MMP-3 and other biomarkers as predictors of joint destruction, by comparing them between radiographically progressive and non-progressive group. RESULTS: Serum levels of RF at entry and ACPA, but not MMP-3 at entry, were significantly higher for the progressive group. Ratios of patients with MMP-3 levels higher than healthy control were not significantly different for the two groups. However, cutoff values determined through receiver operating characteristic analysis showed that the ratio of patients with elevated RF was significantly higher in the progressive group (p=0.001), while MMP-3 (p=0.092), ACPA (p=0.052), CRP (p=0.056), and ESR (p=0.069) tended to be more elevated in the progressive group. Multiple logistic regression analysis using the cutoff value identified MMP-3 positive and RF positive, but not ACPA, CRP or ESR, as significant factors for radiographic progression (OR 16.79 [95% CI: 1.34-414.19]). CONCLUSION: MMP-3 can be a useful marker for prediction of joint destruction.