Asunto(s)
Enfermedades de los Párpados/patología , Dermatosis Facial/patología , Calentamiento Global , Esporotricosis/patología , Clima , Enfermedades de los Párpados/microbiología , Dermatosis Facial/microbiología , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Sporothrix/crecimiento & desarrolloRESUMEN
Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering skin disease that specifically involves oral mucosa. It was recently shown that a very small number of patients with PV show no mucous membrane involvement although they have circulating autoantibodies directed against both desmoglein (Dsg)1 and Dsg3 that are associated with histopathological suprabasal acantholysis. These cases are classed as cutaneous-type PV. We report here a case of cutaneous-type PV that occurred in a 50-year-old man. Clinical examination revealed numerous tense and spreading blisters and erosions over the patient's entire body, similar to the classic mucocutaneous-type PV. Interestingly, none of the previously reported patients with cutaneous PV had shown skin features like those of mucocutaneous PV, whereas the present case clearly demonstrated very typical clinical features similar to those in mucocutaneous PV.
Asunto(s)
Pénfigo/patología , Piel/patología , Autoanticuerpos/análisis , Técnica del Anticuerpo Fluorescente Directa , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Inmunoglobulina G/análisis , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Pénfigo/tratamiento farmacológico , Pénfigo/inmunología , Prednisolona/uso terapéutico , Piel/inmunologíaRESUMEN
The rare presence of proliferative nodules in cases of giant congenital naevus can, in some cases, be potentially misdiagnosed as neonatal melanoma. We report here a case of multiple, proliferative nodules found in a giant congenital naevus lesion in a female neonatal patient diagnosed with neurocutaneous melanosis. Our initial clinical observations of this case suggested the possibility of primary cutaneous neonatal melanoma or skin metastasis from a melanoma in the meninges or elsewhere in the central nervous system. However, histological examination revealed no sign of melanoma, abnormal mitosis, necrosis or any malignant change. Pagetoid arrays of naevus cells in the junctional zone and myxoid changes present in a significant portion of the dermis led to the diagnosis of proliferative nodules. Distinct histological patterns seen in the proliferative nodules in our neonatal patient were useful to differentiate between benign pigmented nodular lesions in a giant congenital naevus and malignant melanoma, and reduced the chance of misdiagnosis.
Asunto(s)
Nevo Pigmentado/patología , Anomalías Cutáneas/patología , Neoplasias Cutáneas/patología , Piel/patología , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Nevo Pigmentado/congénito , Resultado del TratamientoRESUMEN
We report a patient with epidermodysplasia verruciformis (EV) who had severe generalized verrucous skin lesions for 50 years without any immunological abnormality. Microscopic examination showed two histopathological features, including seborrhoeic keratosis and common warts. The detected human papilloma virus (HPV) types were found to be HPV 3, 50, 5, and 76, using a degenerate PCR method. EV and generalized verrucosis are distinguished by slight differences in clinical symptoms or HPV types, so there should be no apparent differential points common to both diseases. Therefore, we propose that an abnormal susceptibility specific to HPV, which is the most characteristic feature in EV, should be regarded as a differential point in these two diseases.
Asunto(s)
Epidermodisplasia Verruciforme/clasificación , Dermatosis del Pie/clasificación , Dermatosis de la Pierna/clasificación , Papillomaviridae , Infecciones por Papillomavirus/clasificación , Antivirales/uso terapéutico , Calcitriol/análogos & derivados , Calcitriol/uso terapéutico , ADN Viral/análisis , Epidermodisplasia Verruciforme/patología , Epidermodisplasia Verruciforme/virología , Etretinato/uso terapéutico , Dermatosis del Pie/tratamiento farmacológico , Dermatosis del Pie/patología , Humanos , Inmunocompetencia , Dermatosis de la Pierna/tratamiento farmacológico , Dermatosis de la Pierna/patología , Masculino , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/tratamiento farmacológico , Infecciones por Papillomavirus/patología , Reacción en Cadena de la Polimerasa , Verrugas/clasificación , Verrugas/tratamiento farmacológico , Verrugas/patologíaRESUMEN
Oral lichen planus (LP) is a severe, painful form of LP, and is often resistant to topical corticosteroid therapy. Recently, open trials demonstrated that topical tacrolimus therapy was effective for the treatment of chronic erosive oral LP. We report two cases with severe recalcitrant erosive oral LP, who dramatically benefited from topical tacrolimus therapy. In case 1, a 64-year-old man presented with a 5-month history of painful erosions on his entire lower lip and buccal mucosa. Physical and histological examination confirmed a diagnosis of LP. He experienced rapid relief from pain and a dramatic improvement was obtained within 5 weeks of topical tacrolimus treatment. No significant irritation was observed and blood tacrolimus level was kept within a safe level (2.5 ng/mL). In case 2, a 68-year-old man developed painful erosions on his right lower lip and buccal mucosa 2 months before his arrival at our hospital. Histopathological analysis confirmed a diagnosis of oral LP. He experienced a rapid dramatic improvement of both lesions within 4 weeks of the start of tacrolimus application. No significant irritation or recurrence was observed. Thus, topical tacrolimus is suggested as a well-tolerated, effective therapy for oral LP.
Asunto(s)
Inmunosupresores/uso terapéutico , Liquen Plano Oral/tratamiento farmacológico , Tacrolimus/uso terapéutico , Administración Tópica , Anciano , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Recurrencia , Tacrolimus/administración & dosificaciónRESUMEN
Defensins are small cationic proteins that harbor broad-spectrum microbicidal activity against bacteria, fungi and viruses. This study examines the effects on pathogens of the epidermis engineered to express human beta-defensin 3 (HBD3) to combat bacterial infections. First, we examined the localization of HBD3 in the epidermis and observed HBD3 in the intercellular spaces and lamellar bodies of the upper epidermal layers. This result showed HBD3 expressed and assembled in the outer layers of the epidermis was suspected to counter the invading microorganisms. Next, we established a keratinocyte cell line that stably expressed HBD3 and found that the culture medium showed antibacterial activity. Furthermore, we prepared an epidermal sheet of these cells with the HBD3 gene and grafted this onto a dermal wound on a nude rat. The HBD3 engineered epidermis demonstrated significant antimicrobial activity. Skin ulcers without epidermis are constantly exposed to invading microorganisms. Biopsy samples of re-epithelizing epidermis from patients with skin ulcers were collected, and HBD3 mRNA level measured in the epidermis. The epidermal samples from the ulcer skin expressed 2.5 times higher levels of HBD3 transcript than those in the control skin. These results, taken together, indicate that the therapeutic introduction of the HBD3 gene into somatic cells may provide a new gene therapy strategy for intractable infectious diseases.
Asunto(s)
Antiinfecciosos/metabolismo , Infecciones Bacterianas/prevención & control , Epidermis/inmunología , Terapia Genética/métodos , Úlcera Cutánea/terapia , Cicatrización de Heridas , beta-Defensinas/genética , Animales , Infecciones Bacterianas/inmunología , Línea Celular , Medios de Cultivo Condicionados , Expresión Génica , Humanos , Queratinocitos/metabolismo , ARN Mensajero/análisis , Ratas , Ratas Endogámicas , Trasplante de Piel , Úlcera Cutánea/inmunología , Úlcera Cutánea/microbiología , beta-Defensinas/metabolismoRESUMEN
We describe two patients with psoriasis vulgaris who subsequently developed a subepidermal blistering disease which disclosed IgG and C3 at the basement membrane zone in direct immunofluorescence. The first case was a 75-year-old Japanese man with herpetiform lesions. Histopathology showed neutrophil infiltration. IgG antibodies bound to the dermal side of the salt-split skin. Immunoblot analysis identified a 200-kD antigen in dermal extracts. The second case was a 70-year-old Japanese man. Histopathology showed eosinophil infiltration. IgG antibodies bound to the epidermal side of salt-split skin. Immunoblot analysis identified a 180-kD bullous pemphigoid (BP) antigen in epidermal extracts. We review the clinical and pathological features of psoriatic patients who presented a subepidermal blistering disease in which antigens were detected by immunoblot analysis; i.e., anti-p200 pemphigoid (14 cases) or BP (12 cases). There were few distinct clinical differences between two diseases. However, neutrophils were predominant in anti-p200 pemphigoid, while eosinophils were predominant in BP. After blister formation, ciclosporin was used effectively in addition to systemic steroids in the treatment of anti-p200 pemphigoid. On the other hand, ciclosporin was not used in the treatment of BP with psoriasis.
Asunto(s)
Autoantígenos/inmunología , Penfigoide Ampolloso/inmunología , Psoriasis/inmunología , Psoriasis/patología , Anciano , Autoantígenos/análisis , Biopsia con Aguja , Técnica del Anticuerpo Fluorescente Indirecta , Estudios de Seguimiento , Humanos , Immunoblotting , Inmunohistoquímica , Inmunosupresores/uso terapéutico , Masculino , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/patología , Psoriasis/tratamiento farmacológico , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
CD4+ T cells differentiate into at least two distinct subsets, Th1 and Th2, that are characterized by their cytokine-producing profiles. In this study, we attempted to delineate whether and how CD4+ T-cell responses could be skewed in one direction or another. BALB/c mice were immunized with chicken ovalbumin (OVA) emulsified with either incomplete or complete Freund's adjuvant (IFA or CFA). When lymph node cells were assessed on day 7, antigen specific proliferation was similarly observed both in the mice immunized with IFA and CFA. In contrast, on day 28 there was a less significant response in the mice primed with IFA than in those primed with CFA. ELISA analyses revealed more Th1 predominant cytokine production by T cells immunized with OVA+CFA rather than in IFA, which resulted in balanced IFN-gamma and IL-4 production. Flow cytometric analyses of intracellular cytokines confirmed that T cells from mice primed with CFA produced Th1 cytokines more predominantly. When lymph node dendritic cells (DC) were compared for their co-stimulatory molecule expression, priming with CFA and IFA similarly upregulated CD80 and CD86 expression by lymph node DC, and no significant differences were observed in CD40, 54, 80 and 86 expression between the DC harvested from IFA and CFA immunized mice. In addition, both priming with IFA and CFA similarly induced IL-12 production by DC. Thus, although the reason(s) for the preferential induction of a Th1/Th2 response remains unknown, these results indicate that a relatively Th1/Th2 skewed response is differentially induced by different types of adjuvants, and induction of a Th1 skewed response may be responsible for long lasting cellular immunity.
Asunto(s)
Adyuvante de Freund/inmunología , Inmunización/métodos , Células TH1/citología , Células Th2/citología , Animales , Linfocitos T CD4-Positivos/citología , Diferenciación Celular/fisiología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Femenino , Adyuvante de Freund/administración & dosificación , Adyuvante de Freund/clasificación , Inyecciones Subcutáneas , Interleucina-12/biosíntesis , Ganglios Linfáticos/citología , Ratones , Ratones Endogámicos BALB C , Células TH1/inmunología , Células Th2/inmunologíaRESUMEN
Langerhans cells (LC) are professional antigen-presenting cells of dendritic cell (DC) lineage and are critical for the induction of primary immune responses in skin. Following antigenic stimulation, LC migrate to regional lymph nodes and induce antigen-specific activation of T cells. After primary expansion, the majority of T cells undergo Fas/Fas ligand (FasL)-mediated apoptotic cell death, thereby suppressing their excessive expansion. Although recent investigations have indicated an immunoregulatory function for DC, whether LC could be involved in Fas/FasL-mediated suppression of activated T cells is still unclear. In this study, we found that LC express FasL after activation triggered through CD40 molecules on their surface, but not by stimulation with LPS or IFN-gamma. The functional significance of FasL expression by LC was demonstrated using two different assays for apoptosis induced in Jurkat cells. The apoptosis in Jurkat cells was completely blocked by anti-FasL blocking antibody, suggesting a Fas/FasL-mediated mechanism. These results indicate a new feedback mechanism to down-regulate T cell activation by LC through the interaction of the TNF receptor/ligand superfamily, CD40/CD40L and Fas/FasL.
Asunto(s)
Ligando de CD40/fisiología , Células de Langerhans/fisiología , Glicoproteínas de Membrana/biosíntesis , Animales , Anticuerpos Monoclonales/inmunología , Apoptosis , Células Cultivadas , Células Dendríticas/fisiología , Proteína Ligando Fas , Femenino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Receptor fas/fisiologíaRESUMEN
Monocyte chemoattractant protein (MCP)-1 is a chemotactic cytokine for monocytes, memoryT cells and dendritic cells (DC). However, the precise role of MCP-1 in a variety of immunological responses remains unclear. In the present study, we analyzed contact hypersensitivity (CHS) using human MCP-1 transgenic mice (hMCP-1Tgm) that constitutively produce high levels of hMCP-1 in the sera. Following 2,4-dinitrofluorobenzene (DNFB) sensitization, enhancement of CHS was demonstrated in Tgm as compared with that in non-Tgm. Anti-hMCP-1 antibodies significantly inhibited the CHS in Tgm. A prominent accumulation of B7-1+I-Ad+ Langerhans' cells (LC) bearing haptens was detected in draining lymph nodes (DLN) of Tgm 24 h after DNFB or fluorescein isothiocyanate (FITC) sensitization. Similar results were obtained with BALB/c mice administrated recombinant (r) hMCP-1. Langerhans' cells (LC) in the epidermal sheets of Tgm increased in size and expressed high levels of I-Ad and B7-1 12 h after FITC application compared with those of non-Tgm. After 18 h, the number of LC in the epidermis was reduced in Tgm. It was also shown that the B7-1 expression on LC of BALB/c mice was augmented after culture with rhMCP-1. These findings demonstrate that MCP-1 not only accelerates LC migration from epidermis into the DLN after sensitization with haptens but also up-regulates the I-Ad and B7-1 expressions, which results in the enhanced T cell activation and CHS.
Asunto(s)
Quimiocina CCL2/inmunología , Dermatitis por Contacto/inmunología , Animales , Antígeno B7-1/inmunología , División Celular , Movimiento Celular , Células Cultivadas , Quimiocina CCL2/genética , Células Dendríticas/inmunología , Dinitrofluorobenceno/inmunología , Dinitrofluorobenceno/farmacología , Haptenos/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos , Queratinocitos/citología , Queratinocitos/inmunología , Cinética , Ganglios Linfáticos/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Transgénicos , Monocitos/inmunología , Linfocitos T/citología , Regulación hacia ArribaRESUMEN
Dendritic cells (DC) are bone marrow derived cells with strong antigen presenting capacity and can induce primary immune responses by activating naive T cells. Cells of this lineage are called as professional antigen presenting cells (APC), because of their primary function as APC. Since the demonstration of IgE bound epidermal Langerhans cells (LC) in atopic dermatitis (AD) patients, a role of IgE bearing DC as a regulator of IgE mediated allergic reactions is emphasized. Indeed, IgE molecules on DC are functional. DC can take up, process and present IgE bound antigens to T cells more efficiently by means of their surface IgE receptor, FcepsilonRI. In addition to its role as an antigen focusing molecule, DC FcepsilonRI may have another function to induce co-stimulatory signals to T cells, by which Th2 type T cell activation is preferentially induced. Thus, this receptor could serve as an amplifying factor for T cell mediated allergic reactions.
Asunto(s)
Células Dendríticas/metabolismo , Hipersensibilidad/inmunología , Inmunoglobulina E/metabolismo , Receptores de IgE/fisiología , Linfocitos T/metabolismo , Animales , Células Dendríticas/inmunología , Humanos , Inmunidad Celular , Inmunoglobulina E/inmunología , Linfocitos T/inmunologíaRESUMEN
In this study, we examined the relative amounts of mRNA expressed in normal versus psoriatic epidermis, using in situ hybridization with a biotinylated oligonucleotide poly d(T) probe. The hybridization image was analyzed by Laser Scanning Confocal Microscopy (LSCM). In normal human skin, hybridization signals were detected homogeneously throughout the epidermis, mostly in nucleus. These signals disappeared following RNase T2 or RNase A treatment, indicating that the target for this probe is RNA; by implication, mRNA. In psoriatic lesions, the overall signal intensity was significantly elevated, especially in the basal/suprabasal layers. Moreover, those signals were most prominent in the cytoplasm, not in the nucleus. In contrast, the signals of uninvolved epidermis adjacent to the psoriatic lesions were indistinguishable from those of normal skin in both signal intensity and hybridization profile. Our data are consistent with the notion that one of the characteristic features of psoriasis is an elevated (or uncontrolled) synthesis of mRNA and proteins.