Asunto(s)
Penfigoide Ampolloso , Humanos , Colágenos no Fibrilares , Autoantígenos , Prurito , Biomarcadores , Quimiocinas , AutoanticuerposAsunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Hipohidrosis/inducido químicamente , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Adenocarcinoma del Pulmón/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Humanos , Hipohidrosis/diagnóstico , Hipohidrosis/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Piel/patologíaRESUMEN
Antimalarials are usually recommended for the first-line systemic treatment of cutaneous lupus erythematosus. Alopecia in patients with discoid lupus erythematosus (DLE) is sometimes a refractory condition in spite of topical therapies. We herein described a case of DLE on the scalp with a pathological change of a xanthomatous reaction, which was successfully treated with hydroxychloroquine (HCQ). A 34-year-old woman presented with hair loss to the parietal region. She had been diagnosed with systemic lupus erythematosus (SLE) four years previously. Treatment with 30 mg/day of prednisolone (PSL) had been initiated, and the dose was gradually reduced. At 10 mg/day of PSL, she had noticed her hair loss. Physical examination revealed some small erythematous lesions to the parietal region with accompanying hair loss. Pathological findings of the erythematous lesion on her head revealed thickening of the basement membrane zone, the interface dermatitis with vacuolar degeneration, and both superficial perivascular and perifollicular infiltration of inflammatory cells in the dermis. In addition, there was an infiltrate of xanthomatous cells detected in the papillary dermis, which were positive for CD68 and CD163. The patient started treatment with HCQ at a dose of 200 mg/day. The skin lesions completely resolved within five months after initiation of HCQ without increase in the dose of PSL. Xanthomatous reactions are rarely recognized in lupus erythematosus. The chronic epithelial injury in DLE could be implicated in triggering the secondary reactive process of a xanthomatous reaction. We believe that the reaction seen in our patient was a secondary change to pathological alteration due to SLE. However, as yet unrecognized factors may play a role in the development of a xanthomatous reaction in DLE.
Asunto(s)
Alopecia/tratamiento farmacológico , Antirreumáticos/administración & dosificación , Hidroxicloroquina/administración & dosificación , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Adulto , Alopecia/etiología , Alopecia/patología , Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Femenino , Humanos , Lupus Eritematoso Cutáneo/complicaciones , Receptores de Superficie Celular , Piel/patologíaRESUMEN
An entire, female, mixed-breed cat of unknown age was presented with a 6-week history of lethargy, anorexia and vomiting. There was an increase in the number of white blood cells in the blood, including neutrophils and eosinophils; moderate anaemia; ascites; and possible mesenteric peritonitis. Exploratory laparotomy revealed firm, multifocal small nodules in the mesentery. As the nodules were surgically unresectable, they were biopsied. Histologically, the nodules were composed of thin trabeculae of dense collagen fibres mixed with plump fibroblasts and numerous eosinophils, consistent with feline gastrointestinal eosinophilic sclerosing fibroplasia. Bacteria were not detected on histological examination of the nodules and cytology of the ascites. Remission of disease occurred following treatment with prednisolone and ciclosporin A for 22 days and antibiotics for 40 days. After remission, ciclosporin A was administered for 236 days and then discontinued. Eosinophilia also resolved after treatment with ciclosporin A. The cat is still alive and in good condition on day 689. This report describes what may be an atypical case of feline gastrointestinal eosinophilic sclerosing fibroplasia, lacking involvement of the gastrointestinal tract, and was apparently cured by treatment that involved ciclosporin A.
Asunto(s)
Eosinofilia/veterinaria , Enfermedades Gastrointestinales/veterinaria , Animales , Biopsia/veterinaria , Enfermedades de los Gatos , Gatos , Femenino , MesenterioRESUMEN
BACKGROUND: Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a commonly occurring condition related to systemic autoimmune disease. It is characterized histopathologically by a distinct pattern of granulomatous inflammation in the presence or absence of leukocytoclastic vasculitis. The properties of granulomatous cells in PNGD are still uncertain. OBJECTIVE: We sought further investigation on the phenotype of the infiltrated cells in PNGD from two patients with systemic lupus erythematosus (SLE) and reviewed the previous published reports in order to provide a comprehensive summary on the clinical features of PNGD in SLE. METHODS: The immunohistochemical features of granulomatous cells in PNGD associated with SLE were analyzed. Immunohistochemical studies were performed on sections from our two cases using antibodies against CD68, CD163, CD15, Factor XIIIa, myeloperoxidase and neutrophil elastase. The clinical characteristics of the SLE patients who developed PNGD were also evaluated. We included all cases retrieved through a PubMed search with the key words PNGD and SLE. RESULTS: Cutaneous lesions consisted of erythematous plaques distributed on the face and upper limbs in both cases. The infiltrated cells were mainly positive for CD68 and CD163, a phenotype suggestive of M2 macrophages. Some mature neutrophils and lymphocytes were also present. A review of the literature of PNGD associated with SLE revealed a predominance in females, high prevalence of lupus nephritis and a good response to systemic steroids, with frequent skin lesions relapses during tapering of the treatment. LIMITATIONS: This study examined only two cases; the pathogenesis of the disease remains to be clarified. CONCLUSION: PNGD lesions were abundantly infiltrated by M2 macrophages, suggesting that they may have a role in this condition. SLE accompanied by PNGD might be associated with lupus nephritis and frequent relapses of skin lesions.
Asunto(s)
Dermatitis/etiología , Granuloma/etiología , Lupus Eritematoso Sistémico/complicaciones , Piel/patología , Adulto , Antígenos CD/inmunología , Antígenos de Diferenciación Mielomonocítica/inmunología , Dermatitis/patología , Femenino , Granuloma/patología , Humanos , Macrófagos/patología , Neutrófilos/patología , Receptores de Superficie Celular/inmunología , Factores SexualesAsunto(s)
Artritis/patología , Granuloma/patología , Proteína Adaptadora de Señalización NOD2/genética , Sinovitis/patología , Uveítis/patología , Artritis/genética , Preescolar , Diagnóstico Diferencial , Granuloma/genética , Humanos , Masculino , Mutación , Sarcoidosis , Sinovitis/genética , Uveítis/genéticaRESUMEN
BACKGROUND: During perioperative fasting, lipid metabolism gradually increases, resulting in free fatty acids (FFA) and/or ketone bodies. Suppression of surgical stress by remifentanil may allow the safe administration of glucose infusions, avoiding both hyperglycemia and ketogenesis. The effects of glucose infusion on glucose and lipid metabolism were therefore investigated in patients undergoing minor surgery with remifentanil anesthesia. METHODS: Thirty-four patients were randomized 1 : 1 to receive no glucose (0G group) or low-dose glucose (0.1 g/kg/h for 1 h followed by 0.05 g/kg/h for 1 h; LG group). The concentrations of glucose, adrenocorticotropic hormone (ACTH), 3-methylhistidine (3-MH), insulin, cortisol, FFA, creatinine (Cr), and ketone bodies were measured before anesthetic induction, 1 and 2 h after glucose infusion, at the end of surgery, and the next morning. RESULTS: The concentrations of cortisol and ACTH decreased during surgery in both groups when compared with the concentrations before anesthesia and at the end of surgery (P < 0.05). Glucose and insulin concentrations were significantly higher in the LG than in the 0G group at 1 and 2 h after infusion. No patient experienced hyperglycemia. The concentrations of FFA and ketone bodies were lower in the LG than in the 0G group during surgery, but there were no significant between group differences in 3-MH/Cr. CONCLUSION: Infusion of low-dose glucose attenuated fat catabolism without causing hyperglycemia, indicating that infusion of low-dose glucose during remifentanil-induced anesthesia may be safe for patients.
Asunto(s)
Ácidos Grasos no Esterificados/sangre , Glucosa/farmacología , Complicaciones Intraoperatorias/sangre , Cuerpos Cetónicos/sangre , Piperidinas/efectos adversos , Hormona Adrenocorticotrópica/sangre , Adulto , Androstanoles/efectos adversos , Creatina/sangre , Femenino , Glucosa/administración & dosificación , Humanos , Hidrocortisona/sangre , Hiperglucemia/prevención & control , Infusiones Intravenosas , Insulina/sangre , Complicaciones Intraoperatorias/prevención & control , Metabolismo de los Lípidos , Masculino , Metilhistidinas/sangre , Persona de Mediana Edad , Remifentanilo , Rocuronio , Método Simple Ciego , Tiamilal/efectos adversosRESUMEN
NLR family pyrin domain containing 3 (NLRP3) is a cytoplasmic pattern recognition receptor that regulates innate immune responses by forming a protein complex, the inflammasome. It leads to production of proinflammatory cytokine productions such as interleukin 1ß (IL-1ß). We and others demonstrated that an induction of activated NLRP3 also induced cell death. However, little is known about the characteristics and mechanisms of the cell death and its involvement in the pathogenesis of inflammatory conditions. In this study, we established cell lines in which NLRP3 was induced by doxycycline using a tetracycline-inducible expression (Tet-on) system. Using this system, the expression of NLRP3 mutants in cryopyrin-associated periodic syndrome (CAPS) patients was sufficient for the induction of necrotic cell death without lipopolysaccharide stimulation or generation of mature IL-1ß. We also found that CA074-Me, a cathepsin B inhibitor, blocked cell death before oligomerization of apoptosis-associated speck-like protein containing a CARD (ASC), whereas Z-VAD-fmk, a pan-caspase inhibitor, blocked the cell death after the oligomerization. Silencing of the ASC gene (Pycard) by small hairpin RNA treatment inhibited the NLRP3 mutant-induced cell death, but silencing of the caspase-1 gene (Casp1) did not. Taken together, these results indicated that ASC was indispensable for NLRP3-mediated programmed necrotic cell death, and that this type of cell death was distinct from 'pyroptosis', which requires caspase-1. Finally, we demonstrated in an in vivo model that the programmed necrotic cell death induced by activated NLRP3 could cause neutrophil infiltration, indicating a possible role of cell death in neutrophil infiltration of skin lesions in CAPS patients.
Asunto(s)
Apoptosis , Proteínas Portadoras/metabolismo , Proteínas del Citoesqueleto/metabolismo , Inflamación , Necrosis , Clorometilcetonas de Aminoácidos/farmacología , Animales , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis , Proteínas Adaptadoras de Señalización CARD , Proteínas Portadoras/genética , Caspasa 1/química , Caspasa 1/genética , Caspasa 1/metabolismo , Inhibidores de Caspasas/farmacología , Proteínas del Citoesqueleto/antagonistas & inhibidores , Proteínas del Citoesqueleto/genética , Dipéptidos/farmacología , Doxiciclina/farmacología , Humanos , Interleucina-1beta/metabolismo , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR , Neutrófilos/citología , Neutrófilos/inmunología , Neutrófilos/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismoRESUMEN
We report the first case of 68-year-old Japanese woman with metastatic HER2-positive extramammary Paget's disease that showed the validity of trastuzumab monotherapy. We administered trastuzumab at a loading dose of 8 mg/kg i.v., followed by a 6 mg/kg maintenance dose every three weeks according to a protocol for HER2-positive metastatic breast cancers and a near-complete response was achieved after the tenth infusion. The patient experienced a moderate headache and flushing during the first infusion, but had no advanced effects during subsequent infusions with ibuprofen and d-chlorpheniramine maleate. Given the dramatic response, the patient has had 17 infusions of trastuzumab with no disease progression. Thus, trastuzumab has few side effects and is well tolerated for elderly patients. It may become a new choice of the adjubant therapy of this disease.
RESUMEN
BACKGROUND: Malignant melanomas clinically and/or histologically associated with melanocytic nevi have been reported worldwide. Approximately 20% of malignant melanomas in Caucasians, most of which are found on the trunk and proximal extremities, develop in association with pre-existing melanocytic nevi. In Japan, however, over half of all melanomas are acral lentiginous melanomas (ALMs) on the hands and feet; melanomas on sun-exposed areas are seen less frequently in Japanese people than in Caucasians. As ALMs are not usually accompanied by melanocytic nevi and there have been no reviews of the literature or statistical data regarding Japanese cases of melanomas with melanocytic nevi, dermatologists in Japan have few opportunities to see melanomas associated with pre-existing melanocytic nevi. METHODS: Here we report a case of a superficial spreading melanoma that was formed on a melanocytic nevus on the trunk, and we review for the first time the case reports from the Japanese literature. RESULTS AND CONCLUSIONS: With regard to the reported cases, melanomas associated with melanocytic nevi were mainly superficial spreading melanomas and nodular melanomas on the trunk or extremities; ALMs were rarely associated with nevi, indicating a trend similar to that observed in Caucasians. These findings suggest that the low frequency of associations between melanomas and melanocytic nevi in Japan reflects racial differences in the frequencies of each type of melanoma.