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BACKGROUND: Bevacizumab, an anti-VEGF monoclonal antibody, has recently emerged as a new option for severe forms of hereditary hemorrhagic telangiectasia (HHT). Its utilization in this orphan disease has rapidly spread despite the lack of randomized trials and international guidelines. The objective of this study is to report the main clinical data (baseline characteristics, dose schedule, efficacy, adverse events and deaths) of HHT patients treated by intravenous bevacizumab in France. METHODS: Retrospective observational study of HHT patients treated with bevacizumab for a severe form of the disease in the 14 centers of the French HHT network. RESULTS: Forty-six patients (median age: 68 years) were treated between March 2009 and May 2015. Ten patients were treated for high output cardiac failure, 20 patients for severe hemorrhages and 16 for both indications. The standard protocol (6 infusions of 5mg/kg every 2 weeks) was initially used in 89% of the cases but diverse strategies were subsequently applied. A clinical improvement was noted by the referent physician for 74% of the patients with a median effect's duration of 6 months. Wound healing complications led to 2 amputations. Arthralgia/arthritis and arterial hypertension occurred in 5 patients each. One third of the patients were dead at the time of the final update, coherently with age and the poor prognosis of these highly symptomatic patients. CONCLUSION: Intravenous bevacizumab seems to provide a clinical benefice in severe HHT patients. Precautions concerning wound healing and vascular pathologies must be respected. Prospective double blinded versus placebo trials are needed.
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Bevacizumab/uso terapéutico , Telangiectasia Hemorrágica Hereditaria/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Bevacizumab/administración & dosificación , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Dipeptidyl peptidase-4 (DPP4) inhibitors are a novel therapy widespread used in type 2 diabetes mellitus. We describe 3 cases of polyarthritis which delay of appearance strongly suggests a link with DPP4 inhibitors. Three patients presented with bilateral, symmetrical, seronegative polyarthritis after introduction of DPP4 inhibitors (sitagliptine (n = 2) and vildagliptine (n = 1)). Two patients also developed xerostomia and xerostomia, and laboratory test results showed normal values of CRP and erythrocyte sedimentation rate. Joints X-rays were normal. One patient was diagnosed with primary Sjögren's syndrome and treated with hydroxychloroquine, methotrexate and prednisone, with a poor efficacy. When sitagliptine was stopped, all symptoms disappeared, leading to methotrexate and prednisone discontinuation within a month. There were no immunological abnormalities in the 2 other patients, but a chronic viral hepatitis B was found in one patient. Eventually, discontinuation of DPP4 inhibitors led to resolution of symptoms in 1 and 3 weeks for both patients. DPP4 inhibitors seemed to trigger bilateral, non-erosive, seronegative polyarthritis in our 3 patients. DPP4, also known as CD26, is expressed on many cells including lymphocytes and fibroblasts, and its inhibition may lead to immunomodulating effect as suggested by clinical and in vitro studies.
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Artritis/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Hipoglucemiantes/efectos adversos , Adamantano/efectos adversos , Adamantano/análogos & derivados , Artritis/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/enzimología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nitrilos/efectos adversos , Pirazinas/efectos adversos , Pirrolidinas/efectos adversos , Factores de Riesgo , Fosfato de Sitagliptina , Triazoles/efectos adversos , VildagliptinaRESUMEN
Imatinib is the treatment of choice for FIP1L1/PDGFRA (F/P)-associated chronic eosinophilic leukemia (F/P CEL), but its optimal dosing, duration, and possibility of discontinuation are still a matter of debate. A retrospective multicenter study was conducted with 44 F/P CEL patients identified in the French Eosinophil Network and treated with imatinib. The most frequently involved systems were skin (57%), spleen (52%), and lung (45%), and eosinophilic heart disease was observed in 15 patients (34%). Complete hematologic response (CHR) was obtained in all patients, and complete molecular response (CMR) in 95% of patients (average initial imatinib dose, 165 mg/d). For 29 patients the imatinib dose was tapered with a maintenance dose of 58 mg/d (±34 mg/d), allowing sustained CHR and CMR. None of the patients developed resistance during a median follow-up of 52.3 months (range, 1.4-97.4 mo). Imatinib was stopped in 11 patients; 6 of the patients subsequently relapsed, but 5 remained in persistent CHR or CMR (range, 9-88 mo). These results confirm that an initial low-dose regimen of imatinib (100 mg/d) followed by a lower maintenance dose can be efficient for obtaining long-term CHR and CMR. Our data also suggest that imatinib can be stopped in some patients without molecular relapse.
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BACKGROUND: Pulmonary hypertension (PH) complicating systemic sclerosis (SSc)-related interstitial lung disease (ILD) is usually associated with a poor prognosis. However, data are either lacking or scarce on prognostic factors in this condition. The objectives of this study were to compare the survival of patients with ILD-associated PH (PH-ILD) or pulmonary arterial hypertension (PAH) and to determine whether the severity of PH has prognostic value in SSc-associated PH-ILD. METHODS: Consecutive patients with SSc and PH-ILD (n = 47) or PAH (n = 50) confirmed by right-sided heart catheterization were included in a cross-sectional analysis. PH was classified as mild (mean pulmonary arterial pressure [mPAP] ≤ 35 mm Hg) or moderate to severe (mPAP > 35 mm Hg). RESULTS: As compared with patients with PAH, subjects with PH-ILD were younger, were more frequently men with a history of smoking, had more frequently diffuse SSc, less frequently anticentromere antibodies, and a lower FVC/diffusing capacity of lung for carbon monoxide (DLCO) ratio. They had a worse prognosis than patients with PAH (3-year survival of 47% vs 71%, respectively; P = .07). Patients with mild PH-ILD had similar poor outcomes when compared with those with moderate to severe PH-ILD. Pericardial effusion (hazard ratio [HR], 2.44; P = .04) and lower DLCO (HR, 0.96; P = .01) were the only independent factors predictive of a poor survival in the PH-ILD group. CONCLUSIONS: Patients with SSc with PH-ILD had a different phenotype and a worse prognosis than those with SSc and PAH. Lower DLCO and presence of pericardial effusion were predictive of a poor outcome in PH-ILD, whereas mPAP seemed to have no prognostic significance.
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Hipertensión Pulmonar/mortalidad , Hipertensión Pulmonar/fisiopatología , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/fisiopatología , Esclerodermia Sistémica/mortalidad , Esclerodermia Sistémica/fisiopatología , Adulto , Anciano , Anticuerpos Antinucleares/sangre , Presión Sanguínea/fisiología , Monóxido de Carbono/metabolismo , Comorbilidad , Estudios Transversales , Hipertensión Pulmonar Primaria Familiar , Femenino , Humanos , Hipertensión Pulmonar/epidemiología , Pulmón/metabolismo , Enfermedades Pulmonares Intersticiales/epidemiología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Esclerodermia Sistémica/epidemiología , Índice de Severidad de la Enfermedad , Tasa de SupervivenciaRESUMEN
BACKGROUND: Systemic lupus erythematosus (SLE) affects women of child-bearing age. Combined oral contraceptives can worsen the course and increase the risk of thrombosis. The objectives of this study were to provide an alternative contraception and thus evaluate the gynecological tolerability of pregnane progestins (PPs) in SLE patients. Systemic lupus erythematosus disease activity and vascular tolerance were also reported. STUDY DESIGN: We used two PP with antigonadotropic potencies, chlormadinone acetate (CMA, 10 mg/day) and cyproterone acetate (CPA, 50 mg/day), administered orally for contraception in 187 SLE patients observed for 46±34.6 months (mean±S.E.), i.e., 6854 women-months. RESULTS: The gynecological tolerability was satisfactory: breakthrough bleeding was reported in 17.7% patients using CPA and 12.6% patients using CMA. No pregnancy was observed in the women followed in this cohort study. One deep vein thrombosis, one myocardial infarction, and one tibial posterior arterial occlusion were observed, giving an incidence for venous thromboembolism of 1.39/year×1000 women (95% CI 0-4.12) and for macroarterial disease an incidence of 2.79/year×1000 women (95% CI 0-6.65). Disease activity was less than before progestins. CONCLUSIONS: Pregnane progestin contraception is effective and well tolerated, thus providing SLE patients an excellent contraceptive alternative to the currently used methods.
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Antagonistas de Andrógenos/administración & dosificación , Acetato de Clormadinona/administración & dosificación , Anticoncepción/métodos , Acetato de Ciproterona/administración & dosificación , Lupus Eritematoso Sistémico/fisiopatología , Adolescente , Adulto , Antagonistas de Andrógenos/efectos adversos , Anticuerpos Antifosfolípidos/sangre , Distribución de Chi-Cuadrado , Acetato de Clormadinona/efectos adversos , Estudios de Cohortes , Acetato de Ciproterona/efectos adversos , Femenino , Humanos , Estudios Longitudinales , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Persona de Mediana Edad , Estudios Prospectivos , Trombosis de la Vena/etiología , Trombosis de la Vena/prevención & control , Adulto JovenRESUMEN
The FIP1L1-PDGFRA (F/P) fusion gene, which was identified as a recurrent molecular finding in hypereosinophilic syndrome (HES), lead to a constitutively increased tyrosine kinase activity of the fusion protein. Despite data obtained in animals or cell lines models, the mechanisms underlying the predominant eosinophil lineage targeting and the cytotoxicity of eosinophils in this leukemia remain unclear. To define more precisely intrinsic molecular events associated with F/P gene, we performed a proteomic analysis comparing F/P+ eosinophils (F/P-Eos) and eosinophils from healthy donors (C-Eos). Using 2D-DIGE and mass spectrometry techniques, we identified 41 proteins significantly overexpressed between F/P-Eos and C-Eos. Among them, 17.8% belonged to the oxidoreductase family. We further observed a down-expression of peroxiredoxin-2 (PRX-2) and an overexpression of src-homology-2 domain containing tyrosine phosphatase (SHP-1), enzymes regulating PDGFR downstream pathways, and especially intracellular reactive oxygen species (ROS) production. This profile, confirmed in immunoblot analysis, appears specific to F/P-Eos compared to controls and patients with idiopathic HES. In this clonal disorder possibly involving a pluripotent hematopoietic stem cell, we postulate that the well documented relationships between PDGFRA downstream signals and intracellular ROS levels might influence the phenotype of this leukemia.
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Eosinófilos , Síndrome Hipereosinofílico/metabolismo , Proteínas de Fusión Oncogénica/metabolismo , Proteoma/análisis , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Transducción de Señal/fisiología , Factores de Escisión y Poliadenilación de ARNm/metabolismo , Adulto , Anciano , Animales , Línea Celular , Bases de Datos de Proteínas , Eosinófilos/química , Eosinófilos/metabolismo , Femenino , Humanos , Síndrome Hipereosinofílico/genética , Síndrome Hipereosinofílico/fisiopatología , Masculino , Espectrometría de Masas/métodos , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Oxidación-Reducción , Peroxirredoxinas/genética , Peroxirredoxinas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Electroforesis Bidimensional Diferencial en Gel/métodos , Factores de Escisión y Poliadenilación de ARNm/genéticaRESUMEN
Hypereosinophilic syndrome (HES) is characterized by chronic unexplained eosinophilia with organ involvement. The concept of HES as a single disease entity is being challenged by the recent identification of multiple underlying molecular mechanisms. HES can directly affect the eosinophil lineage (often linked to a fusion gene FIP1L1-PDGFRA, and corresponding in this case to chronic eosinophilic leukemia), or the lymphoid lineage, where eosinophilia is secondary to expansion of a T cell subset overproducing interleukin-5, a cytokine involved in eosinophilopoiesis. These recent discoveries have legitimized the use of tyrosine kinase inhibitors such as imatinib, which, by inhibiting PDGFRA, have transformed the prognosis of chronic eosinophilic leukemia, and also the use of monoclonal anti-IL-5 antibodies, which are promising treatment for steroid-dependent HES.
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Síndrome Hipereosinofílico/tratamiento farmacológico , Síndrome Hipereosinofílico/genética , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Citocinas/metabolismo , Humanos , Interleucina-5/antagonistas & inhibidores , Proteínas de Fusión Oncogénica/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Subgrupos de Linfocitos T/inmunología , Factores de Escisión y Poliadenilación de ARNm/genéticaAsunto(s)
Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/virología , Infecciones por Citomegalovirus/complicaciones , Adalimumab , Adulto , Anticuerpos Monoclonales Humanizados , Antivirales/uso terapéutico , Azatioprina/uso terapéutico , Infecciones por Citomegalovirus/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Ganciclovir/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéuticoRESUMEN
OBJECTIVE: Rituximab, a chimeric monoclonal antibody directed against the CD20 antigen expressed by B cells, is now considered an effective second-line therapy in various systemic diseases. We describe here the effects of rituximab in patients with relapsing polychondritis. METHODS: This was a retrospective study of 9 patients with relapsing polychondritis who received different regimens of rituximab in addition to their ongoing therapies. Clinical, laboratory, physiologic, and radiologic indicators were used to assess disease activity. We also examined their corticosteroid doses and any change in immunosuppressive agents. We then compared disease activity in the 6 months preceding rituximab administration and at 6 and 12 months after. RESULTS: At 6 months, 2 patients showed partial improvement, 4 were stable, and 3 had worsened disease; however, no patient had complete remission. At 12 months (after exclusion of the 3 patients whose disease had worsened at 6 months), 2 patients remained stable and 4 had worsened disease; however, there were no partial or complete remissions. B cells were counted in 8 patients during the first 6 months after treatment, and B cell depletion was observed in all of the patients. CONCLUSION: Although we cannot rule out the possibility that rituximab had a small effect, our patients' clinical courses did not improve significantly with this treatment.
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Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Policondritis Recurrente/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales de Origen Murino , Antirreumáticos/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inmunosupresores/uso terapéutico , Depleción Linfocítica , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rituximab , Resultado del TratamientoRESUMEN
Hypereosinophilia (>0.5x10(9)/L) is a common clinical finding that can be secondary to a large variety of diseases (helminth infections, allergic diseases, drug reactions, specific organ disease, malignancies, systemic diseases). When a complete evaluation of a chronic hypereosinophilia fails to reveal an underlying disease, the diagnosis of hypereosinophilic syndrome (HES) or Churg-Strauss syndrome (CSS) is suggested.
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Eosinofilia/diagnóstico , Síndrome Hipereosinofílico/diagnóstico , Síndrome de Churg-Strauss/complicaciones , Síndrome de Churg-Strauss/patología , Síndrome de Churg-Strauss/terapia , Eosinofilia/etiología , Eosinofilia/terapia , Femenino , Humanos , Síndrome Hipereosinofílico/complicaciones , Síndrome Hipereosinofílico/terapia , MasculinoRESUMEN
OBJECTIVE: To describe characteristics and outcomes of vasculitides associated with malignancies. METHODS: The requirement for inclusion in this retrospective, 10-year study was development of vasculitis in patients with a progressing malignancy. Malignancies secondary to immunosuppressants used to treat vasculitis were excluded. The main characteristics of vasculitides were analyzed and compared according to the type of malignancy. RESULTS: Sixty patients were included (male/female sex ratio 2.53, mean age 62.4 years). Mean followup duration was 45.2 months. Vasculitides were cutaneous leukocytoclastic (45%), polyarteritis nodosa (36.7%), Wegener's granulomatosis (6.7%), microscopic polyangiitis (5%), and Henoch-Schönlein purpura (5%). Malignancies were distributed as follows: hematologic in 63.1%, myelodysplastic syndrome (MDS) in 32.3%, lymphoid in 29.2%, and solid tumor in 36.9%. Vasculitides were diagnosed concurrently with malignancy in 38% of the cases. Manifestations of vasculitides were fever (41.7%), cutaneous involvement (78.3%), arthralgias (46.7%), peripheral neuropathy (31.7%), renal involvement (23.3%; 11.7% glomerulonephritis, 11.7% microaneurysms, 6.7% renal insufficiency), and antineutrophil cytoplasmic antibody (20.4%). Vasculitis treatments were corticosteroids (78.3%) and immunosuppressant(s) (41.7%). Vasculitis was cured in 65% of patients, but 58.3% died, with 1 death secondary to vasculitis. Independent of subtype, patients with vasculitides associated with MDS more frequently had renal manifestations (P = 0.02) and steroid dependence (P = 0.04) and achieved complete remission less often (P = 0.04) than patients with vasculitides associated with other malignancies. Patients with vasculitides associated with a solid tumor more frequently had peripheral neurologic involvement (P = 0.05). Patients with vasculitides associated with lymphoid malignancy had less frequent arthralgias (P = 0.01) and renal involvement (P = 0.02). CONCLUSION: Vasculitides occurring during malignancies present distinctive features according to the vasculitis subtype and nature of the malignancy.
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Neoplasias Pulmonares/complicaciones , Linfoma/complicaciones , Síndromes Mielodisplásicos/complicaciones , Vasculitis/etiología , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias Gastrointestinales/complicaciones , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/etiología , Humanos , Inmunosupresores/uso terapéutico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Poliarteritis Nudosa/tratamiento farmacológico , Poliarteritis Nudosa/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias Urogenitales/complicaciones , Vasculitis/tratamiento farmacológico , Vasculitis Leucocitoclástica Cutánea/tratamiento farmacológico , Vasculitis Leucocitoclástica Cutánea/etiologíaRESUMEN
INTRODUCTION: Vulvar involvement in Crohn's disease is uncommon. We report here a rare case of Crohn's disease affecting only the vulva and perineum. CASE: A 55-year-old women had been followed at another hospital since 1995 for histology-proved Crohn's disease affecting only the vulvoperineal area. Treatment with infliximab led to a relapse in 2001. The patient was hospitalized because of a new vulvar and perineal flare-up, with major vulvar edema, aphthoid vulvar and perineal erosions and fissures. Findings from upper endoscopy and colonoscopy were normal. A biopsy sample of the ulcerated tissue showed inflammatory infiltration including histiocytes and macrophages. No microorganisms were found. The initial course was favorable, with systemic corticosteroid therapy and azathioprine. Clinical relapse during the corticosteroid tapering necessitated infliximab. DISCUSSION: Vulvar localizations of Crohn's disease are uncommon. They may precede gastrointestinal involvement by many years or very rarely be isolated, as here. Typical clinical appearance includes edema and ulcerations. Other causes of granulomatous vulvar and perineal lesions must be ruled out. There is no consensus for its treatment. This case indicates that infliximab, which is used in fistulized Crohn's disease, can be useful for vulvar and perineal involvement. Physicians must recognize that on rare occasions vulvar involvement is possible without any gastrointestinal localization.
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Enfermedad de Crohn , Perineo , Enfermedades de la Vulva , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Biopsia , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/patología , Femenino , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Humanos , Infliximab , Persona de Mediana Edad , Perineo/patología , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Recurrencia , Factores de Tiempo , Resultado del Tratamiento , Enfermedades de la Vulva/diagnóstico , Enfermedades de la Vulva/patologíaRESUMEN
Aseptic abscesses (AA) are characterized by deep, sterile, round lesions consisting of neutrophil that do not respond to antibiotics but improve dramatically with corticosteroids. We report the clinical, laboratory, and radiologic characteristics and the associated conditions of 29 patients from the French Register on AA plus 1 patient from the Netherlands.The mean age of patients at AA diagnosis was 29 years (SD = 14). The main clinical manifestations of AA were fever (90%), abdominal pain (67%), and weight loss (50%). Duration of symptoms was 4.7 months on average until abscesses were discovered. The abscesses involved the spleen in 27/29 patients (93%; the thirtieth patient had a personal history of splenectomy after a trauma). In 7 they were unifocal and in the others they were multifocal, involving in addition the abdominal lymph nodes in 14 (48%), liver in 12 (40%), lung in 5 (17%), pancreas in 2 (7%), and brain in 2 (7%). They were not splenic in 3, including 2 with abdominal lymph nodes and 1 with superficial lymph nodes and testicle and lung involvement. Twenty-two patients (70%) had elevated white blood cell and neutrophil count; antineutrophil cytoplasmic autoantibodies with a perinuclear, cytoplasmic or atypical pattern (negative for antiproteinase 3 and negative for antimyeloperoxidase except for 1) were positive in 21% of the 24 patients tested. Twenty-one patients had inflammatory bowel disease (IBD), which preceded the occurrence of abscesses in 7, was concomitant in 7, and appeared secondarily in 7. Six patients had neutrophilic dermatosis (20%), 3 had relapsing polychondritis as an associated condition, and 3 others had monoclonal gammopathy of undetermined significance. Three patients had no associated condition. Splenectomy was performed in 15 (52%) patients. All patients received steroid therapy. Thirteen (43%) were given additional immunosuppressive therapy, 1 immediately and the others after a relapse, of whom 3 were also treated by anti-tumor necrosis factor-alpha agents. Mean follow-up was 7 years. Eighteen (60%) patients experienced 1 or several relapses, but there was no death related to AA. Relapses occurred on immunosuppressive therapy in 2 patients and off immunosuppressive therapy in the others while corticosteroids were being tapered. We surveyed the literature and analyzed 19 additional cases. AA is an emergent and probably underrecognized entity. It represents an apparently noninfectious inflammatory disorder involving neutrophils that responds to corticosteroid therapy. AA mainly affects patients with IBD but also affects those with other conditions, or with no other apparent disease.
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Absceso/complicaciones , Enfermedades Inflamatorias del Intestino/complicaciones , Dolor Abdominal/etiología , Absceso/terapia , Adolescente , Adulto , Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Niño , Femenino , Fiebre/etiología , Humanos , Inmunosupresores/uso terapéutico , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Recurrencia , Esplenectomía , Enfermedades del Bazo/complicaciones , Enfermedades del Bazo/terapia , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Pérdida de PesoRESUMEN
BACKGROUND: Superficial venous thrombophlebitis (SVT), often perceived as benign, can coexist with hypercoagulable states. Predisposing risk factors for SVT are similar to those observed for deep venous thrombosis. Association of eosinophilia with SVT is a rare situation that can reveal neoplasia, malignant blood disorders, or vasculitis, but it has never been described in hypereosinophilic syndrome (HES). We herein describe the clinical and biological features, outcome, and response to therapy of 3 patients with SVT associated with eosinophilia that revealed HES. OBSERVATIONS: Superficial venous thrombophlebitis was the initial manifestation of HES in all 3 patients. The mean eosinophil count at diagnosis was 2.4 x 10(3)/muL. All patients received corticosteroids and anticoagulants as the initial treatment, with marked improvement of SVT and return of the eosinophil count to reference limits. All patients experienced relapse and remained dependent on corticosteroid therapy. Two patients received interferon alfa with dramatic regression of SVT, allowing a decrease in the dose of corticosteroids. CONCLUSIONS: We report, to our knowledge, the first 3 cases of SVT related to HES. Superficial venous thrombophlebitis was difficult to treat, with dependence on corticosteroid therapy and partial efficacy of anticoagulant and antiplatelet therapy. Interferon alfa was effective in preventing relapse of SVT related to HES. Mechanisms implied in this thrombogenesis are multiple and remain speculative.
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Síndrome Hipereosinofílico/complicaciones , Tromboflebitis/etiología , Adulto , Glucocorticoides/uso terapéutico , Humanos , Síndrome Hipereosinofílico/sangre , Síndrome Hipereosinofílico/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Interferón-alfa/uso terapéutico , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Pronóstico , Tromboflebitis/sangre , Tromboflebitis/tratamiento farmacológicoRESUMEN
INTRODUCTION: Primary retroperitoneal synovial sarcoma is a rare malignant neoplasm that typically arises in young adults. We report here an unusual presentation of this tumor during hemorrhagic shock and retroperitoneal hematoma. CASE: A 31-year-old man was admitted complaining of acute violent pain of the right lower abdominal quadrant. Physical examination was normal. The computed tomography scan showed a heterogeneous retroperitoneal mass near the iliac bifurcation, with a diameter of 3 cm and spontaneous contrast. The tumor ruptured shortly afterwards and the patient underwent emergency surgery for hemorrhagic shock and retroperitoneal hematoma. No metastases were observed. Although six cycles of doxorubicin and ifosfamide led to initial clinical and tomographic remission, relapse occurred 17 months later. DISCUSSION: Only 20 cases of primary retroperitoneal synovial sarcoma have been described. They are most often discovered following abdominal pain or anemia. Tumor rupture with retroperitoneal hematoma has not previously been reported. Surgical ablation remains the basis for management of this tumor, and survival appears to depend on its quality. Prognosis is poor. Our case is original by the tumor's location and mode of discovery.
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Doxorrubicina/uso terapéutico , Neoplasias Retroperitoneales/diagnóstico por imagen , Sarcoma Sinovial/diagnóstico por imagen , Choque Hemorrágico/etiología , Adulto , Antibióticos Antineoplásicos/uso terapéutico , Humanos , Masculino , Neoplasias Retroperitoneales/tratamiento farmacológico , Neoplasias Retroperitoneales/patología , Sarcoma Sinovial/tratamiento farmacológico , Sarcoma Sinovial/patología , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Takayasu's arteritis (TA) is a chronic large vessel vasculitis. The physiopathology of TA has not been completely elucidated, but it appears to be multifactorial and to mainly involve cellular immunity. The pathologic sequence could implicate stimulation from an antigen that triggers heat shock protein (HSP)-65 expression in aortic tissue which, in turn, induces MHC class I-related chain A (MICA). T-cells and natural killer (NK) cells expressing NKG2D receptors could recognize MICA, resulting in acute inflammation. Pro-inflammatory cytokines released from these infiltrating cells induce matrix metalloproteinases and amplify the inflammatory response, inducing more MHC antigen and costimulatory molecule expression on vascular cells and, thus, recruiting more mononuclear cells. Alpha-beta T-cells then infiltrate and specifically recognize one or a few autoantigens presented by a shared epitope associated with specific MHC on the dendritic cells (DC). These DC simultaneously cooperate to some extent with B-cells and determine a humoral immunity mainly constituted by anti-endothelial cell autoantibodies that could trigger complement-dependent cytotoxicity against endothelial cells. The use of corticosteroids and of other immunosuppressive agents can bring TA into remission in most patients. A better understanding of the immunological mechanisms responsible for the vascular injury has led to trials of anti-TNF-alpha agents with encouraging results. In the near future, new drugs specifically designed to target some of the mechanisms described above may be able to expand the physician's therapeutic arsenal in TA.
RESUMEN
Diagnosis of major hypereosinophilia (>1500 x 10(9)/L) is complex because the possible causes cover the entire range of medical specialties. History and clinical condition will usually suggest parasitic or allergic diseases or drug reactions. When workups for them are negative, rarer causes must be suspected: specific organ diseases (chronic eosinophilic pneumonia, bullous pemphigoid, etc.), solid tumor, clonal blood disorders, or vasculitis. When the condition is prolonged and unexplained, hypereosinophilic syndrome is diagnosed. A rare disorder, its prognosis depends on largely on its cardiac effects. It is usually associated with heterogeneous hematologic conditions, mainly myeloproliferative and lymphocytic disease. The myeloproliferative or primary variant sometimes follows chromosomal deletions that cause a fusion between the Fip1-like1 (FIP1L1) and platelet-derived growth factor receptor (PDGFR) genes, thus increasing the tyrosine kinase activity of the latter. Imatinib mesylate, a tyrosine kinase inhibitor, is usually effective in this situation. In the lymphocytic variant, hypereosinophilia is secondary to a primitive Th2 lymphocyte expansion that causes overproduction of interleukin 5 (IL-5). Corticosteroids are the first-line therapy. Mepolizumab, an anti-IL-5 monoclonal antibody, currently being evaluated, seems promising. Despite recent progress, about 40% of the cases of hypereosinophilic syndrome remain unexplained.
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Eosinofilia/diagnóstico , Eosinofilia/etiología , Síndrome Hipereosinofílico/diagnóstico , Síndrome Hipereosinofílico/etiología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Enfermedad Crónica , Diagnóstico Diferencial , Eosinofilia/terapia , Humanos , Síndrome Hipereosinofílico/diagnóstico por imagen , Síndrome Hipereosinofílico/tratamiento farmacológico , Síndrome Hipereosinofílico/genética , Enfermedad Iatrogénica , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/diagnóstico , Pronóstico , Eosinofilia Pulmonar/diagnóstico , Enfermedades Reumáticas/complicaciones , Enfermedades de la Piel/complicaciones , Tomografía Computarizada por Rayos XRESUMEN
Leuconostoc spp. is a variety of streptococcus that can cause disease in humans, most notably those with HIV infection or other causes of immunodepression. We report the case of a patient who had Leuconostoc osteomyelitis in an area of lymphedema.
Asunto(s)
Infecciones por Bacterias Grampositivas/diagnóstico , Leuconostoc , Osteomielitis/diagnóstico , Tibia/microbiología , Infecciones por Bacterias Grampositivas/diagnóstico por imagen , Humanos , Inmunocompetencia , Linfedema/complicaciones , Masculino , Persona de Mediana Edad , Osteomielitis/diagnóstico por imagen , Radiografía , Tibia/diagnóstico por imagenRESUMEN
This retrospective study concerned 18 female and 23 male patients with cardiac sarcoidosis (CS). The average age at CS diagnosis was 38 years. CS was observed in white (73% of cases) and in black or Caribbean patients (27% of cases). All patients had extracardiac histologic proof of sarcoid tissue. In 63% of cases, the CS arose during the follow-up of systemic sarcoidosis. Systemic sarcoidosis was not specific except for a high frequency of neurosarcoidosis. Revealing cardiac signs were clinical in 63% of cases and electrical in 22%. In most patients these signs were associated with an abnormal echocardiography (77%) and/or a defect on thallium-201 or sestamibi imaging (75%). Thirty-nine patients received steroid therapy (initial dose mostly equal to 1 mg/kg per day), associated in 13 cases with another immunosuppressive treatment. In 26% of cases the immunosuppressive treatment was associated with a specific cardiac treatment. In the long-term follow-up (average follow-up, 58 mo), 87% of the cases showed an improvement, and 54% were cured from a clinical and laboratory point of view (electrocardiogram, 24-hour monitoring, echocardiography, radionuclide imaging). There was no sudden death. Two patients worsened, which can be explained in 1 case by very late treatment and in the other case by lack of treatment, except for a pacemaker. Our experience leads us to treat CS with corticosteroids as soon as possible and to use another immunosuppressive treatment where there is an insufficient therapeutic response or where there are contraindications to corticosteroids.