RESUMEN
BACKGROUND: The histological characteristic of hypertensive leg ulcers (HLU) is the presence of "arteriolosclerosis." The pertinence of performing a skin biopsy to diagnose HLU is questionable, as cutaneous arteriolosclerosis may be related to patient comorbidities. The objective here was to evaluate the frequency of arteriolosclerosis in skin leg biopsies performed in patients without ulcer and in control patients with HLU. METHODS: We performed a retrospective study between January 2013 and July 2014. Patients were included if they had undergone a deep skin biopsy on the lower limbs, in the absence of any leg ulcer. Controls were patients with typical HLU. RESULTS: Fifty-eight patients and 6 controls were included. Hypertension was present in 25 patients (43%). Arteriolosclerosis, defined as fibrous endarteritis, was present in 35 out of 58 patients (60%) and in all of the controls. No hyalinosis or hyperplastic proliferative arteriolosclerosis was observed in the patients or controls. Only age was an independent factor associated with the presence of cutaneous arteriolosclerosis (p &x#3c; 0.0001). CONCLUSION: Cutaneous arteriolosclerosis is significantly and independently associated with age. Thus, skin biopsy seems not to be necessary for the diagnosis of HLU but only for a differential diagnosis.
Asunto(s)
Arterioloesclerosis/patología , Hipertensión/complicaciones , Isquemia/patología , Úlcera de la Pierna/patología , Enfermedades Cutáneas Vasculares/patología , Piel/irrigación sanguínea , Piel/patología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Arterioloesclerosis/complicaciones , Biopsia , Estudios de Casos y Controles , Endarteritis/complicaciones , Endarteritis/patología , Femenino , Humanos , Isquemia/diagnóstico , Isquemia/etiología , Úlcera de la Pierna/diagnóstico , Úlcera de la Pierna/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades Cutáneas Vasculares/complicacionesRESUMEN
Histiocytoses are a group of heterogeneous diseases that mostly comprise Langerhans cell histiocytosis (LCH) and non-LCH. The association of LCH with non-LCH is exceptional. We report 23 patients with biopsy-proven LCH associated with Erdheim-Chester disease (ECD) (mixed histiocytosis) and discuss the significance of this association. We compare the clinical phenotypes of these patients with those of 56 patients with isolated LCH and 53 patients with isolated ECD. The average age at diagnosis was 43 years. ECD followed (n = 12) or was diagnosed simultaneously with (n = 11) but never preceded LCH. Although heterogeneous, the phenotype of patients with mixed histiocytosis was closer to that of isolated ECD than to that of isolated LCH (principal component analysis). LCH and ECD improved in response to interferon alpha-2a treatment in only 50% of patients (8 of 16). We found the BRAF(V600E) mutation in 11 (69%) of 16 LCH lesions and in 9 (82%) of 11 ECD lesions. Eight patients had mutations in both ECD and LCH biopsies. Our findings indicate that the association of LCH and ECD is not fortuitous and suggest a link between these diseases involving the BRAF(V600E) mutation.
Asunto(s)
Enfermedad de Erdheim-Chester/genética , Predisposición Genética a la Enfermedad/genética , Histiocitosis de Células de Langerhans/genética , Mutación Missense , Proteínas Proto-Oncogénicas B-raf/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Análisis Mutacional de ADN , Enfermedad de Erdheim-Chester/tratamiento farmacológico , Enfermedad de Erdheim-Chester/patología , Femenino , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Histiocitosis de Células de Langerhans/patología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND & AIMS: The development of vaccines and other strategies to prevent hepatitis C virus (HCV) infection is limited by rapid viral evasion. HCV entry is the first step of infection; this process involves several viral and host factors and is targeted by host-neutralizing responses. Although the roles of host factors in HCV entry have been well characterized, their involvement in evasion of immune responses is poorly understood. We used acute infection of liver graft as a model to investigate the molecular mechanisms of viral evasion. METHODS: We studied factors that contribute to evasion of host immune responses using patient-derived antibodies, HCV pseudoparticles, and cell culture-derived HCV that express viral envelopes from patients who have undergone liver transplantation. These viruses were used to infect hepatoma cell lines that express different levels of HCV entry factors. RESULTS: By using reverse genetic analyses, we identified altered use of host-cell entry factors as a mechanism by which HCV evades host immune responses. Mutations that alter use of the CD81 receptor also allowed the virus to escape neutralizing antibodies. Kinetic studies showed that these mutations affect virus-antibody interactions during postbinding steps of the HCV entry process. Functional studies with a large panel of patient-derived antibodies showed that this mechanism mediates viral escape, leading to persistent infection in general. CONCLUSIONS: We identified a mechanism by which HCV evades host immune responses, in which use of cell entry factors evolves with escape from neutralizing antibodies. These findings advance our understanding of the pathogenesis of HCV infection and might be used to develop antiviral strategies and vaccines.
Asunto(s)
Anticuerpos Neutralizantes/inmunología , Hepacivirus/genética , Hepatitis C/genética , Internalización del Virus , Línea Celular Tumoral , Hepacivirus/inmunología , Hepatitis C/inmunología , Humanos , Masculino , Mutación , Trasplantes/virologíaRESUMEN
Hypertrophic pseudo tumoral herpetic lesion is an uncommon presentation in immunocompromized hosts that can be refractory to established therapies. We describe bipolar anal and tonsilar herpetic tumoral lesions related to acyclovir-resistant HSV-2 in a human immunodeficiency virus-infected patient. Treatment with valacyclovir, cidofovir, and thalidomide failed and surgical excision was required.