RESUMEN
Pemphigus and pemphigoid are autoimmune blistering diseases that affect mucosa and skin. Several clinical scoring systems, including the pemphigus disease area index (PDAI) and the bullous pemphigoid disease area index (BPDAI), have been validated for managing disease activity and severity. Current guidelines recommend that treatment response be evaluated with clinical scores and that additional second-line therapies be considered if initial treatment is insufficient for disease control. However, there have been few studies analyzing correlations between PDAI/BPDAI transitions and initial treatment effects. To investigate whether PDAI/BPDAI transitions during the treatment initiation phase correlate with initial treatment responses and whether such information can be used as a guide for necessary additional treatment, we retrospectively analyzed 67 pemphigus patients and 47 pemphigoid patients who received initial treatment at Keio University between 2012 and 2018. The clinical symptoms were evaluated weekly with PDAI/BPDAI. The patients were divided into two groups: in group A, disease was controlled only with oral corticosteroids and immunosuppressants (initial treatment), whereas in group B additional therapies were required due to insufficient responses. In pemphigus, the PDAI ratio of day 7/day 0 was significantly reduced in group A compared to group B (0.548 vs 0.761, P < 0.01) after initial treatment had started. In pemphigoid, the ratios of day 7/day 0 of BPDAI (erosion/blister) and BPDAI (urticaria/erythema) significantly decreased in group A compared to group B (0.565 vs 0.901 and 0.350 vs 0.760, respectively, P < 0.05). Receiver operating characteristic analyses on PDAI, BPDAI (erosion/blister) and BPDAI (urticaria/erythema) revealed that the cut-off values in the ratios of day 7/day 0 were 0.762, 0.675, and 0.568, respectively. Our results suggest that PDAI/BPDAI transitions during the initial phase of the treatments may be useful to predict the outcome of the treatment provided and the necessity of additional therapies to achieve disease control.
Asunto(s)
Enfermedades Autoinmunes , Penfigoide Ampolloso , Pénfigo , Urticaria , Humanos , Pénfigo/diagnóstico , Pénfigo/tratamiento farmacológico , Penfigoide Ampolloso/diagnóstico , Penfigoide Ampolloso/tratamiento farmacológico , Vesícula , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , EritemaAsunto(s)
Ictiosis Lamelar , Ictiosis , Queratodermia Palmoplantar , Humanos , Agua , Proteínas de la MembranaAsunto(s)
Linfangioma , Neoplasias Cutáneas , Dermoscopía , Humanos , Linfangioma/diagnóstico por imagenAsunto(s)
Artritis Psoriásica , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium marinum , Artritis Psoriásica/tratamiento farmacológico , Humanos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Factor de Necrosis Tumoral alfaAsunto(s)
Eosinofilia , Foliculitis , Enfermedades de la Uña , Enfermedades Cutáneas Vesiculoampollosas , Eosinofilia/diagnóstico , Eosinofilia/tratamiento farmacológico , Foliculitis/diagnóstico , Foliculitis/tratamiento farmacológico , Humanos , Enfermedades Cutáneas Vesiculoampollosas/diagnósticoAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Artritis Psoriásica/complicaciones , Productos Biológicos/uso terapéutico , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Diálisis RenalRESUMEN
Patients with disseminated superficial actinic porokeratosis (DSAP) and linear porokeratosis (LP) exhibit monoallelic germline mutations in genes encoding mevalonate pathway enzymes, such as MVD or MVK. Here, we showed that each skin lesion of DSAP exhibited an individual second hit genetic change in the wild-type allele of the corresponding gene specifically in the epidermis, indicating that a postnatal second hit triggering biallelic deficiency of the gene is required for porokeratosis to develop. Most skin lesions exhibited one of two principal second hits, either somatic homologous recombinations rendering the monoallelic mutation biallelic or C>T transition mutations in the wild-type allele. The second hits differed among DSAP lesions but were identical in those of congenital LP, suggesting that DSAP is attributable to sporadic postnatal second hits and congenital LP to a single second hit in the embryonic period. In the characteristic annular skin lesions of DSAP, the central epidermis featured mostly second hit keratinocytes, and that of the annular ring featured a mixture of such cells and naïve keratinocytes, implying that each lesion reflects the clonal expansion of single second hit keratinocytes. DSAP is therefore a benign intraepidermal neoplasia, which can be included in the genetic tumor disorders explicable by Knudson's two-hit hypothesis.
Asunto(s)
Carboxiliasas/genética , ADN/genética , Epidermis/patología , Mutación , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Poroqueratosis/genética , Carboxiliasas/metabolismo , Análisis Mutacional de ADN , Epidermis/enzimología , Femenino , Heterocigoto , Humanos , Linaje , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Poroqueratosis/enzimología , Poroqueratosis/patologíaAsunto(s)
Alopecia Areata/patología , Poliposis Intestinal/patología , Pólipos Intestinales/patología , Prednisolona/uso terapéutico , Administración Oral , Alopecia Areata/diagnóstico , Alopecia Areata/fisiopatología , Biopsia con Aguja , Dermoscopía/métodos , Endoscopía Gastrointestinal/métodos , Humanos , Inmunohistoquímica , Poliposis Intestinal/diagnóstico , Pólipos Intestinales/diagnóstico , Masculino , Persona de Mediana Edad , Pronóstico , Enfermedades Raras , Resultado del TratamientoRESUMEN
Human papillomavirus (HPV) has been detected in some cases of Bowen's disease, particularly on the fingers and genitalia. HPV-58 is classified as a high-risk mucosal type and accounts for a high percentage of cervical cancer in Asia. Moreover, several HPV-58 lineages, including sublineage A1, have a high prevalence in Asia. However, the nature of HPV-58-associated skin cancer is still unknown. Here, we report a case of a Japanese patient with multiple Bowen's disease on the fingers. A 33-year-old man presented with multiple reddish-brown scaly plaques on his left middle finger and right ring finger. All lesions were surgically excised, and the diagnosis of Bowen's disease was made. We performed Sanger sequencing using DNA extracted from paraffin-embedded samples and identified HPV-58 sublineage A1. Additionally, we review previous reports on HPV-58-associated skin cancers, including our case, showing a high regional prevalence in Asia. Further studies would be needed to reveal the relationship between HPV-58 lineages and carcinogenesis in the skin.
Asunto(s)
Enfermedad de Bowen/virología , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Neoplasias Cutáneas/virología , Adulto , Biopsia , Enfermedad de Bowen/diagnóstico por imagen , Enfermedad de Bowen/patología , ADN Viral/aislamiento & purificación , Dermoscopía , Dedos , Humanos , Masculino , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico por imagen , Infecciones por Papillomavirus/patología , Piel/diagnóstico por imagen , Piel/patología , Piel/virología , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patologíaRESUMEN
Nail patella syndrome is a autosomal dominant disorder caused by a genetic alteration in LMX1B. We identified a novel heterozygous in-frame indel mutation of LMX1B in a family of Nail patella syndrome. Impaired transcriptional activity but not dominant negative effect of mutant LMX1B were revealed using a transcriptional reporter assay, indicating that the mutation caused nail patella syndrome in this family via haploinsufficiency of the transcriptional activity of LMX1B.
Asunto(s)
Haploinsuficiencia , Mutación INDEL , Proteínas con Homeodominio LIM/genética , Síndrome de la Uña-Rótula/genética , Factores de Transcripción/genética , Femenino , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Síndrome de la Uña-Rótula/diagnóstico por imagen , Linaje , Dominios Proteicos/genética , RadiografíaAsunto(s)
Neoplasias de la Mama/patología , Carcinoma Basocelular/diagnóstico por imagen , Carcinoma Ductal de Mama/diagnóstico por imagen , Dermoscopía , Neoplasias Cutáneas/diagnóstico por imagen , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/secundario , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Pezones , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/secundario , Pigmentación de la PielAsunto(s)
Síndrome de Costello/genética , Enfermedades del Cabello/genética , Queratodermia Palmoplantar/genética , Mosaicismo , Nevo/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Adolescente , Biopsia , Síndrome de Costello/patología , Análisis Mutacional de ADN , Femenino , Heterocigoto , Humanos , Queratodermia Palmoplantar/patología , Mutación , Piel/patología , Secuenciación del ExomaAsunto(s)
Antibacterianos/administración & dosificación , Inmunosupresores/administración & dosificación , Minociclina/administración & dosificación , Tacrolimus/administración & dosificación , Vulvitis/tratamiento farmacológico , Administración Oral , Administración Tópica , Anciano , Esquema de Medicación , Quimioterapia Combinada/métodos , Femenino , Humanos , Pomadas , Staphylococcus epidermidis/aislamiento & purificación , Resultado del Tratamiento , Vulva/microbiología , Vulva/patología , Vulvitis/microbiología , Vulvitis/patologíaAsunto(s)
Síndrome de Bandas Amnióticas/genética , Colágeno Tipo VII/genética , Epidermólisis Ampollosa Distrófica/genética , Síndrome de Bandas Amnióticas/diagnóstico , Tobillo , Epidermólisis Ampollosa Distrófica/diagnóstico , Padre , Pruebas Genéticas , Mano/diagnóstico por imagen , Humanos , Recién Nacido , Masculino , Mutación Missense , Mutación Puntual , Radiografía , Análisis de Secuencia de ADNRESUMEN
The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs) present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes.