RESUMEN
BACKGROUND: Paraneoplastic cutaneous disorders (PCDs) or dermadromes are skin conditions that have an association with internal malignancies but are not themselves malignant. We report the first two cases of systemic anaplastic large cell lymphoma (s-ALCL) accompanied by erythroderma and multiple leg ulcers as PCDs. CASE 1: A 52-year-old Japanese man presented with disseminated itchy papular erythemas which he had over his entire body for the preceding 5 years that later exacerbated to erythroderma. Multiple punched-out ulcers also developed on his lower legs. Superficial lymph nodes (LNs) were swollen, and a left axillary LN biopsy demonstrated dense CD30(+) atypical large cell (ALC) infiltration. By contrast, lymphocytes infiltrating into the erythroderma and leg ulcers were CD30(-) , and T-cell receptor ß (TCRß) chain gene rearrangement was negative in skin biopsy specimens. Thus, he was diagnosed with s-ALCL. Not only his s-ALCL but also his erythroderma and leg ulcers responded well to chemotherapy. CASE 2: A 71-year-old Japanese woman presented with erythroderma that persisted for approximately 20 years after mastectomy. At her initial hospital visit, she was diagnosed with s-ALCL by biopsy of swollen left inguinal LNs. Similar to Case 1, CD30(+) ALCs were negative in skin samples with normal TCRß chain gene rearrangement. As the erythrodermic skin lesion responded well to chemotherapy for s-ALCL, it was considered a PCD. CONCLUSION: s-ALCL development may be predicted by the precedence and concurrence of intractable paraneoplastic erythrodermic and ulcerative skin lesions, as reported in our two cases.
Asunto(s)
Dermatitis Exfoliativa/complicaciones , Linfoma Anaplásico de Células Grandes/complicaciones , Síndromes Paraneoplásicos/complicaciones , Neoplasias Cutáneas/complicaciones , Anciano , Dermatitis Exfoliativa/inmunología , Dermatitis Exfoliativa/fisiopatología , Femenino , Humanos , Linfoma Anaplásico de Células Grandes/inmunología , Linfoma Anaplásico de Células Grandes/fisiopatología , Masculino , Persona de Mediana Edad , Síndromes Paraneoplásicos/inmunología , Síndromes Paraneoplásicos/fisiopatología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/fisiopatologíaRESUMEN
We report a patient with cutaneous polyarteritis nodosa, who had a 3-year history of recurrent leg and foot ulcers. Symptoms of ischaemia in the left foot, including severe pain, coldness, paraesthesia and violaceous discoloration, deteriorated abruptly, because of complete occlusion of the left anterior tibial artery. The occluded segment was revascularized by percutaneous transluminal angioplasty, resulting in a dramatic improvement in the ischaemic symptoms.
Asunto(s)
Angioplastia/métodos , Arteriopatías Oclusivas/terapia , Isquemia/terapia , Poliarteritis Nudosa/terapia , Piel/irrigación sanguínea , Arterias Tibiales/patología , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/patología , Femenino , Humanos , Isquemia/etiología , Úlcera de la Pierna/etiología , Úlcera de la Pierna/terapia , Persona de Mediana Edad , Poliarteritis Nudosa/complicaciones , Radiografía , Arterias Tibiales/diagnóstico por imagenRESUMEN
Contact hypersensitivity (CHS) is thought to be mainly associated with the activation of T helper type 1 (Th1) cells. However, there is also evidence that Th2 cells or Th2 cytokines play a role in the development of CHS. To analyze the functional contribution of Th2 cytokines interleukin (IL)-4 and IL-13, signal transducer and activator of transcription 6 (STAT6)-deficient (STAT6(-/)-) and wild-type (wt) control C57BL/6 mice were contact sensitized with 5% 2,4,6-trinitrochlorobenzene (TNCB), 0.5% 2,4-dinitrofluorobenzene, or 5% 4-ethoxyl methylene-2-phenyl-2-oxazolin-5-one, and any skin reactions were examined. Ear swelling was significantly reduced with a delayed peak response in STAT6(-/)- mice compared with wt mice.A histological analysis revealed that the infiltration of both eosinophils and neutrophils in the skin challenged after 24 h in STAT6(-/)- mice decreased substantially compared with that in wt mice. The expression of Th2 cytokines (IL-4, IL-5) in TNCB-challenged skin tissues and the supernatants from T cells stimulated by 2,4,6-trinitrobenzene sulfonate-modified spleen cells, as well as the immunoglobulin (Ig)E and IgG1 response after challenge, were also profoundly reduced in STAT6(-/)- mice, whereas the expression of interferon gamma was the same in STAT6(-/)- and wt mice after challenge. Furthermore, adoptive transfer experiments revealed that STAT6(-/)- mice induced CHS after injection of lymph node cells obtained from sensitized wt mice. Our data suggest that the STAT6 signal plays a critical role in the induction phase of CHS.
Asunto(s)
Dermatitis por Contacto/inmunología , Transducción de Señal/inmunología , Transactivadores/fisiología , Animales , Antígenos de Superficie/química , Recuento de Células , Citocinas/biosíntesis , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Dermatitis por Contacto/etiología , Dermatitis por Contacto/genética , Dermatitis por Contacto/patología , Dinitrofluorobenceno/inmunología , Células Epidérmicas , Epidermis/inmunología , Eritrocitos/inmunología , Citometría de Flujo , Hipersensibilidad Tardía/genética , Hipersensibilidad Tardía/inmunología , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Irritantes/inmunología , Células de Langerhans/citología , Células de Langerhans/inmunología , Células de Langerhans/metabolismo , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/metabolismo , Activación de Linfocitos/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Oxazoles/inmunología , Cloruro de Picrilo/inmunología , Factor de Transcripción STAT6 , Ovinos , Linfocitos T/inmunología , Antígenos Thy-1/biosíntesis , Transactivadores/deficiencia , Transactivadores/genéticaRESUMEN
Bleomycin has a chemical toxicity capable of inducing superoxide radicals, which are suggested to play an important part in bleomycin-induced pulmonary fibrosis. We have recently established a mouse model for scleroderma induced by repeated local injections of bleomycin. In this study, we examined the inhibitory effect of superoxide dismutase on the development of dermal sclerosis induced by bleomycin using this mouse model. PC-superoxide dismutase, which is a lecithinized superoxide dismutase with high tissue accumulation and long half-life in blood, was administered (3000 U per kg; dissolved in 5% mannitol) 3 h before the injection of bleomycin in C3H mice for 3 wk. Systemic PC-superoxide dismutase markedly inhibited the development of dermal sclerosis, which was also accompanied by a decrease in the number of infiltrating mast cells and eosinophils. Furthermore, the hydroxyproline content in the skin was significantly reduced, as compared with mice treated with bleomycin only or bleomycin and 5% mannitol. In a separate experiment, after the development of dermal sclerosis following treatment with bleomycin for 3 wk, PC-superoxide dismutase was administered for 2 wk. Histologic examination again revealed a reduction of dermal sclerosis, followed by a significant associate in the number of both mast cells and eosinophils. The hydroxyproline content in the skin was not significantly decreased, however, even after injections of high amounts of PC-superoxide dismutase (30,000 U per kg). These results support the involvement of oxygen free radicals in bleomycin-induced dermal sclerosis, and also indicate that administration of superoxide dismutase may be effective in the therapeutic approach in systemic sclerosis.
Asunto(s)
Bleomicina , Esclerodermia Localizada/inducido químicamente , Superóxido Dismutasa/farmacología , Animales , Modelos Animales de Enfermedad , Hidroxiprolina/análisis , Inyecciones Intravenosas , Manitol/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Fosfatidilcolinas , Esclerodermia Localizada/prevención & control , Esclerodermia Sistémica/terapia , Piel/química , Superóxido Dismutasa/uso terapéuticoRESUMEN
We have established a mouse model for scleroderma induced by repeated local injections of bleomycin (BLM). Daily injection of BLM at a dose of >10 microg per ml for 4 wk induced histologic changes of dermal sclerosis, but not fibrosis, with thickened and homogenous collagen bundles and cellular infiltrates in BALB/C mice, whereas clinical signs of scleroderma were not apparent. In addition, lung fibrosis was also induced preceding the cutaneous changes. Sclerotic changes were not found in other sites of the skin distant from the injection site. Dermal sclerosis could also be induced by injecting BLM only every other day. The sclerotic changes of the dermis were sustained after ceasing BLM applications for at least 6 wk. Mast cells gradually increased in number as the sclerotic changes developed. Marked degranulation of mast cells was observed with elevated histamine release. The amount of hydroxyproline in skin was significantly increased at 4 wk of BLM treatment as compared with that in untreated or phosphate-buffered saline-treated mice. Anti-nuclear antibody was detected in serum of BLM-treated mice. Transforming growth factor-beta1 mRNA was detected at an early phase, while transforming growth factor-beta2 mRNA was strongly expressed at 4 wk when the sclerotic features were prominent. These results suggest that dermal sclerosis induced by BLM closely resembles systemic sclerosis both histologically and biochemically. Our mouse model can provide a powerful tool of inducing dermal sclerosis to examine the pathogenesis and the therapeutic approach of scleroderma.
Asunto(s)
Bleomicina/toxicidad , Modelos Animales de Enfermedad , Esclerodermia Sistémica/inducido químicamente , Animales , Autoanticuerpos/biosíntesis , Colágeno/biosíntesis , Femenino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Esclerodermia Sistémica/metabolismo , Esclerodermia Sistémica/patología , Factor de Crecimiento Transformador beta/fisiologíaAsunto(s)
Bleomicina , Colágeno Tipo I/metabolismo , Mastocitos/fisiología , Esclerodermia Localizada/inducido químicamente , Esclerodermia Localizada/metabolismo , Animales , Línea Celular , Colágeno Tipo I/genética , Femenino , Ratones , Ratones Mutantes , ARN Mensajero/metabolismo , Valores de Referencia , Esclerodermia Localizada/patología , Piel/metabolismo , Piel/patologíaAsunto(s)
Bleomicina , Interferón gamma/uso terapéutico , Esclerodermia Sistémica/inducido químicamente , Esclerodermia Sistémica/tratamiento farmacológico , Animales , Femenino , Hidroxiprolina/antagonistas & inhibidores , Hidroxiprolina/metabolismo , Ratones , Ratones Endogámicos BALB C , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/patología , Esclerodermia Sistémica/metabolismo , Esclerodermia Sistémica/patología , Piel/metabolismo , Piel/patologíaRESUMEN
A familial case of multiple minute digitate hyperkeratoses is reported. Hundreds of tiny, spiked, keratotic papules were scattered on the trunk and limbs. Microscopically, the lesions showed digitiform orthohyperkeratosis with tenting of the epidermis. Neither atypical epidermal cells nor a dermal infiltrate were observed. This disease has three types: familial, sporadic and postinflammatory. We have analysed the histopathological features of all the cases reported to date. While the familial and sporadic types are similar, the lesions in the postinflammatory type are composed of parakeratotic columns with an invaginated epidermis. Although morphological analysis may not provide any clues to pathogenetic differences, it seems reasonable to assume that the postinflammatory type is an entity different from the other two forms.
Asunto(s)
Queratosis/genética , Anciano , Salud de la Familia , Femenino , Humanos , Queratosis/clasificación , Queratosis/patología , LinajeRESUMEN
Recent studies have demonstrated the evidence of the crucial role of transforming growth factor-beta (TGF-beta) in the pathogenesis of tissue fibrosis; however, its precise role has not been fully elucidated. Administration of anti-TGF-beta antibody is shown to be effective for inhibiting lung fibrosis induced by bleomycin in an experimental animal model. We have recently established a mouse model for scleroderma by repeated injections of bleomycin. In this study, we examined whether the suppression of TGF-beta leads to the improvement of dermal sclerotic lesion by using this model. We induced dermal sclerosis in C3H mice by subcutaneous injections of bleomycin (100 microg/ml) for 3 weeks, and separate groups of mice were also injected with bleomycin with either anti-TGF-beta antibody (10 microg/ml) or control normal rabbit serum for 3 weeks. Thus treated skins were harvested and analyzed for histological sclerosis, serum cytokine, and influx of mast cells and eosinophils, both of which are known to release fibrogenic cytokines or several mediators responsible for tissue fibrosis. The result showed that anti-TGF-beta antibody caused a significant reduction in cutaneous sclerosis characterized by histological features and hydroxyproline contents. Examination of tissue sections also revealed a significant suppression of influx of mast cells and eosinophils. Serum interleukin-4 (IL-4) and IL-6 levels determined by enzyme-linked immunosorbent assay exhibited a significant reduction after anti-TGF-beta antibody treatment. Our results suggest that administration of an antibody against TGF-beta is useful in preventing experimental dermal sclerosis induced by bleomycin and raises a possibility of the therapeutic approach of anti-TGF-beta antibody in scleroderma.
Asunto(s)
Esclerodermia Sistémica/prevención & control , Factor de Crecimiento Transformador beta/inmunología , Animales , Anticuerpos/uso terapéutico , Basófilos/citología , Bleomicina , Recuento de Células , Modelos Animales de Enfermedad , Eosinófilos/citología , Femenino , Interleucina-4/sangre , Interleucina-6/sangre , Recuento de Leucocitos , Mastocitos/citología , Ratones , Ratones Endogámicos C3H , Esclerodermia Sistémica/inducido químicamente , Piel/citologíaRESUMEN
OBJECTIVE: Previously, we established a mouse model of scleroderma induced by repeated subcutaneous bleomycin injections. In this model, increased numbers of mast cells were observed in the lesional skin of dermal sclerosis, and degranulation of mast cells was prominent prior to the increase of mast cell numbers. Mast cells have been suggested to play an important role in tissue fibrosis. In this study, we investigated whether dermal sclerosis is also induced by bleomycin administration in genetically mast cell deficient WBB6F1-W/W(V) mice. METHODS: Bleomycin was subcutaneously injected every day in WBB6F1-W/W(V) and their normal littermate WBB6F1-+/+ mice for 4 weeks, and mice were analyzed for histological sclerosis, mast cell number, plasma histamine level, and hydroxyproline content. RESULTS: Four weeks' injections of bleomycin effected histological dermal sclerosis in both mast cell deficient and control strains; however, at 1 week, dermal sclerosis was induced only in WBB6F1-+/+ mice. Mast cells gradually increased in number around or on the edge of sclerotic lesions in WBB6F1-+/+ mice, as the dermal sclerosis developed. Hydroxyproline content of the skin of WBB6F1-+/+ mice was higher than that of WBB6F1-W/Wv mice at 1 week, but was not statistically significant. After 2 weeks' treatment with bleomycin, the hydroxyproline content of the skin was similar in both strains. The number of infiltrating macrophages and CD4+ T cells also gradually increased in both strains; however, the difference did not reach significance during the course of bleomycin treatment. CONCLUSION: These results show that mast cell is not necessary for inducing dermal sclerosis by bleomycin, and other types of inflammatory cells such as infiltrating macrophages or T lymphocytes may play a role in triggering induction of dermal sclerosis via fibrogenic cytokines. However, mast cell releasing mediators or cytokines may play a role in accelerating formation of dermal sclerosis, in particular, at an early phase of the sclerotic process, and not merely as a result of sclerosis.
Asunto(s)
Modelos Animales de Enfermedad , Mastocitos/citología , Ratones Mutantes , Esclerodermia Sistémica/tratamiento farmacológico , Esclerodermia Sistémica/genética , Animales , Antibióticos Antineoplásicos , Biopsia , Bleomicina , Recuento de Células , Femenino , Fibrosis , Histamina/sangre , Hidroxiprolina/análisis , Interleucina-4/sangre , Ratones , Esclerodermia Sistémica/inducido químicamente , Esclerosis , Piel/química , Piel/patología , Factor de Necrosis Tumoral alfa/análisisRESUMEN
We report a case of direct skin invasion by Hodgkin's disease from a left supraclavicular lymph node. Clinical and pathological presentations mimicked infectious disease such as scrofuloderma. The nodule later developed a fistula following a biopsy that never healed despite numerous antibiotic treatments. Ten months later, other nodules with spontaneous fistula formation appeared on the anterior neck. A diagnosis of Hodgkin's disease was then made. Subsequent COPP cytostatic therapy remarkably improved the skin lesions and lymph nodes achieving complete remission.
Asunto(s)
Enfermedad de Hodgkin/patología , Neoplasias Cutáneas/secundario , Tuberculosis Cutánea/patología , Anciano , Diagnóstico Diferencial , Humanos , Masculino , Invasividad NeoplásicaRESUMEN
Systemic sclerosis (SSc) is a connective tissue disorder with an unknown etiology. There are currently no effective therapies for SSc. (In this study, working with a bleomycin(BLM)-induced scleroderma model mice, we performed two transfections of human hepatocyte growth factor (HGF) cDNA into the skeletal muscle and showed that this treatment not only helped to prevent the dermal sclerosis simultaneously injected BLM but also improved the symptoms of dermal sclerosis induced by BLM 4 weeks previously.) RT-PCR, ELISA and an immunohistochemical analysis revealed that both mRNA and protein of human HGF as well as murine HGF were enhanced in the skin, lung, muscle and the serum after two transfections of human HGF cDNA. These analyses also revealed that this treatment significantly reduced both the expression of the TGF-beta1 mRNA and the production of TGF-beta1 on macrophage-like cells that infiltrated the dermis and the fibroblastic cells in BLM-induced scleroderma. Furthermore, HGF-gene transfection both prevented and ameliorated the symptoms of not only dermal sclerosis but also of lung fibrosis induced by a subcutaneous BLM injection. These results indicated that gene therapy by the transfection of the human HGF cDNA may thus be a useful therapy for SSc and lung fibrosis involved with SSc.