RESUMEN
Pigmentary mosaicism of the Ito type, also known as hypomelanosis of Ito, is a neurocutaneous syndrome considered to be predominantly caused by somatic chromosomal mosaicism. However, a few monogenic causes of pigmentary mosaicism have been recently reported. Eleven unrelated individuals with pigmentary mosaicism (mostly hypopigmented skin) were recruited for this study. Skin punch biopsies of the probands and trio-based blood samples (from probands and both biological parents) were collected, and genomic DNA was extracted and analyzed by exome sequencing. In all patients, plausible monogenic causes were detected with somatic and germline variants identified in five and six patients, respectively. Among the somatic variants, four patients had MTOR variant (36%) and another had an RHOA variant. De novo germline variants in USP9X, TFE3, and KCNQ5 were detected in two, one, and one patients, respectively. A maternally inherited PHF6 variant was detected in one patient with hyperpigmented skin. Compound heterozygous GTF3C5 variants were highlighted as strong candidates in the remaining patient. Exome sequencing, using patients' blood and skin samples is highly recommended as the first choice for detecting causative genetic variants of pigmentary mosaicism.
Asunto(s)
Hipopigmentación , Mosaicismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Humanos , Hipopigmentación/genética , Serina-Treonina Quinasas TOR/genética , Ubiquitina Tiolesterasa/genéticaRESUMEN
Some bone lesions are reported to mimic bone metastasis on imaging tests. Herein, we report a case of a 55-year-old Japanese man who presented with a skin tumor on the left lower extremity. He also had a history of recurrent generalized cutaneous blister and erosion formation since childhood. His skin lesions were diagnosed as cutaneous squamous cell carcinoma complicated by recessive dystrophic epidermolysis bullosa. Magnetic resonance imaging of the left lower extremity detected multiple focal bone lesions mimicking bone metastases in the left femur and tibia. However, bone biopsy revealed that the bone lesions were osteonecrosis without tumor cells. We suggest that cancer-induced osteonecrosis should be included in the differential diagnosis of bone lesions suspected of being metastases on magnetic resonance imaging.
Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Carcinoma de Células Escamosas/diagnóstico por imagen , Epidermólisis Ampollosa Distrófica/diagnóstico por imagen , Neoplasias Femorales/diagnóstico por imagen , Imagen por Resonancia Magnética , Osteonecrosis/diagnóstico por imagen , Neoplasias Cutáneas/diagnóstico por imagen , Tibia/diagnóstico por imagen , Biopsia , Neoplasias Óseas/secundario , Carcinoma de Células Escamosas/secundario , Diagnóstico Diferencial , Epidermólisis Ampollosa Distrófica/patología , Neoplasias Femorales/secundario , Humanos , Masculino , Persona de Mediana Edad , Osteonecrosis/patología , Valor Predictivo de las Pruebas , Neoplasias Cutáneas/patología , Tibia/patologíaRESUMEN
Animal models have enhanced our understanding of the pathogenesis of autoimmune diseases. For these models, genetically identical, inbred mice have commonly been used. Different inbred mouse strains, however, show a high variability in disease manifestation. Identifying the factors that influence this disease variability could provide unrecognized insights into pathogenesis. We established a novel Ab transfer-induced model of epidermolysis bullosa acquisita (EBA), an autoimmune disease characterized by (muco)-cutaneous blistering caused by anti-type VII collagen (COL7) autoantibodies. Blistering after anti-COL7 IgG (directed against the von Willebrand factor A-like domain 2) transfer showed clear variability among inbred mouse strains, that is, severe cutaneous blistering and inflammation in C57BL/6J and absence of skin lesions in MRL/MpJ mice. The transfer of anti-COL7 IgG into irradiated, EBA-resistant MRL/MpJ mice, rescued by transplantation with bone marrow from EBA-susceptible B6.AK-H2k mice, induced blistering. To the contrary, irradiated EBA-susceptible B6.AK-H2k mice that were rescued using MRL/MpJ bone marrow were devoid of blistering. In vitro, immune complex activation of neutrophils from C57BL/6J or MRL/MpJ mice showed an impaired reactive oxygen species release from the latter, whereas no differences were observed after PMA activation. This finding was paralleled by divergent expression profiles of immune complex-activated neutrophils from either C57BL/6J or MRL/MpJ mice. Collectively, we demonstrate that radiosensitive cells determine the varying extent of skin inflammation and blistering in the end-stage effector phase of EBA.
Asunto(s)
Células de la Médula Ósea/inmunología , Trasplante de Médula Ósea/métodos , Dermatitis/inmunología , Epidermólisis Ampollosa Adquirida/inmunología , Animales , Autoanticuerpos/inmunología , Vesícula/inmunología , Células de la Médula Ósea/efectos de la radiación , Colágeno Tipo VII/inmunología , Modelos Animales de Enfermedad , Redes Reguladoras de Genes/inmunología , Humanos , Inmunoglobulina G/inmunología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ratones Endogámicos MRL lpr , Ratones Noqueados , Microscopía Electrónica de Transmisión , Microscopía Fluorescente , Neutrófilos/inmunología , Neutrófilos/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Conejos , Especies Reactivas de Oxígeno/inmunología , Especies Reactivas de Oxígeno/metabolismo , Especificidad de la Especie , Transcriptoma/inmunologíaRESUMEN
"Nagashima-type" palmoplantar keratosis (NPPK) is an autosomal recessive nonsyndromic diffuse palmoplantar keratosis characterized by well-demarcated diffuse hyperkeratosis with redness, expanding on to the dorsal surfaces of the palms and feet and the Achilles tendon area. Hyperkeratosis in NPPK is mild and nonprogressive, differentiating NPPK clinically from Mal de Meleda. We performed whole-exome and/or Sanger sequencing analyses of 13 unrelated NPPK individuals and identified biallelic putative loss-of-function mutations in SERPINB7, which encodes a cytoplasmic member of the serine protease inhibitor superfamily. We identified a major causative mutation of c.796C>T (p.Arg266(∗)) as a founder mutation in Japanese and Chinese populations. SERPINB7 was specifically present in the cytoplasm of the stratum granulosum and the stratum corneum (SC) of the epidermis. All of the identified mutants are predicted to cause premature termination upstream of the reactive site, which inhibits the proteases, suggesting a complete loss of the protease inhibitory activity of SERPINB7 in NPPK skin. On exposure of NPPK lesional skin to water, we observed a whitish spongy change in the SC, suggesting enhanced water permeation into the SC due to overactivation of proteases and a resultant loss of integrity of the SC structure. These findings provide an important framework for developing pathogenesis-based therapies for NPPK.
Asunto(s)
Queratodermia Palmoplantar/genética , Mutación , Serpinas/genética , Adolescente , Adulto , Alelos , Pueblo Asiatico/genética , Niño , Preescolar , Exoma , Femenino , Humanos , Queratodermia Palmoplantar/patología , Masculino , Persona de Mediana Edad , Linaje , Adulto JovenRESUMEN
Bullous pemphigoid (BP) and epidermolysis bullosa acquisita are subepidermal autoimmune blistering diseases mediated by autoantibodies against type XVII collagen (Col17) and Col7, respectively. For blister formation, Fc-mediated events, such as infiltration of inflammatory cells in the skin, complement activation, and release of proteases at the dermal-epidermal junction, are essential. Although in the neonatal passive transfer mouse model of BP, tissue destruction is mediated by Fcγ receptors (FcγRs) I and III, the passive transfer model of epidermolysis bullosa acquisita completely depends on FcγRIV. To clarify this discrepancy, we developed a novel experimental model for BP using adult mice. Lesion formation was Fc mediated because γ-chain-deficient mice and mice treated with anti-Col17 IgG, depleted from its sugar moiety at the Fc portion, were resistant to disease induction. By the use of various FcγR-deficient mouse strains, tissue destruction was shown to be mediated by FcγRIV, FcγRIII, and FcγRIIB, whereas FcγRI was not essential. Furthermore, anti-inflammatory mediators in already clinically diseased mice can be explored in the novel BP model, because the pharmacological inhibition of FcγRIV and depletion of granulocytes abolished skin blisters. Herein, we extended our knowledge about the importance of FcγRs in experimental BP and established a novel BP mouse model suitable to study disease development over a longer time period and explore novel treatment strategies in a quasi-therapeutic setting.
Asunto(s)
Colágeno Tipo VII/inmunología , Modelos Animales de Enfermedad , Penfigoide Ampolloso/inmunología , Receptores de IgG/inmunología , Animales , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Fluorescente , Colágenos no Fibrilares/inmunología , Penfigoide Ampolloso/patología , Colágeno Tipo XVIIRESUMEN
In autoimmune bullous dermatoses (AIBD), autoantibodies induce blisters on skin or mucous membranes, or both. Mechanisms of continued autoantibody production and blistering have been well characterized using AIBD animal models. Mechanisms leading to the initial autoantibody production, however, have not been investigated in detail. Epidermolysis bullosa acquisita (EBA) is an AIBD associated with autoantibodies to type VII collagen (COL7). The majority of EBA patients' sera recognize the noncollagenous domain 1, including the von Willebrand factor A-like domain 2 (vWFA2). In experimental EBA induced by immunization with GST-COL7, disease manifestation depended on the genetic background, a Th1 polarization, and the GST-tag. In this model, nude mice neither produced autoantibodies nor blisters. It has remained uncertain which APC and T cell subsets are required for EBA induction. We established a novel EBA model by immunization with vWFA2 fused to intein (lacking the GST-tag). All tested mouse strains developed autoantibodies, but blisters were exclusively observed in mice carrying H2s. In immunized mice, CD4 T cells specific for vWFA2 were detected, and their induction required presence of B cells, dendritic cells, and macrophages. Anti-vWFA2 autoantibodies located at the lamina densa bound to the dermal side of salt-split skin and induced blisters when transferred into healthy mice. Absence of CD8 T cells at time of immunization had no effect, whereas depletion of CD4 T cells during the same time period delayed autoantibody production and blisters. Collectively, we demonstrate the pathogenic relevance of Abs targeting the vWFA2 domain of COL7 and show the requirement of APC-induced CD4 T cells to induce experimental EBA.
Asunto(s)
Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Células Dendríticas/inmunología , Epidermólisis Ampollosa Adquirida/inmunología , Macrófagos/inmunología , Animales , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Autoinmunidad/inmunología , Biomarcadores de Tumor/inmunología , Proteínas de Unión al Calcio , Colágeno Tipo VII/inmunología , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Proteínas de la Matriz Extracelular/inmunología , Humanos , Immunoblotting , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Microscopía Fluorescente , Estructura Terciaria de Proteína , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa InversaAsunto(s)
Ácido Ascórbico/análogos & derivados , Dermatitis Alérgica por Contacto/diagnóstico , Dermatosis Facial/diagnóstico , Inmunosupresores/uso terapéutico , Pruebas del Parche , Crema para la Piel/efectos adversos , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Ácido Ascórbico/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Eritema/inducido químicamente , Etanercept/uso terapéutico , Dermatosis Facial/inducido químicamente , Femenino , Humanos , Metotrexato/uso terapéutico , Crema para la Piel/químicaRESUMEN
BACKGROUND: Cutaneous plasmacytosis and systemic plasmacytosis are rare entities arising primarily in patients of Japanese descent. The origin and exact pathogenesis are poorly understood. OBJECTIVE: We sought to determine clinicopathologic features of cutaneous and systemic plasmacytosis. METHODS: We describe the clinicopathologic features of 6 patients with cutaneous plasmacytosis with or without systemic involvement (male:female = 3:1; mean age: 49.7 years; median age: 50.5 years; age range: 29-64 years). RESULTS: Patients presented clinically with multiple, red-brown infiltrated plaques and flat tumors, mainly located on the trunk. Histology revealed in all cases the presence of clusters of mature plasma cells within the dermis. Lymphoid follicles with reactive germinal centers were seen in 3 cases. Five cases showed the expected polyclonal expression of immunoglobulin light chain by the plasma cells, but monoclonality was observed in 1 case, thus showing overlapping features with cutaneous marginal zone lymphoma. One patient revealed overlapping features with multicentric Castleman disease. LIMITATIONS: This was a retrospective study on a relatively small number of patients. CONCLUSIONS: Despite typical clinical presentation, some of our patients presented with histopathologic and immunohistochemical features that deviated from the conventional appearance. Our observation confirms and expands previous observations of this elusive entity, suggesting that the spectrum of clinicopathologic presentations may be wider than previously recognized.
Asunto(s)
Hipergammaglobulinemia/diagnóstico , Células Plasmáticas/patología , Enfermedades de la Piel/diagnóstico , Adulto , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Piel/patologíaRESUMEN
Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease of the elderly associated with considerable morbidity and mortality. As unspecific immunosuppressants are still the mainstay of BP therapy, several animal models, based on the passive transfer of autoantibodies or immune cells, have been developed to obtain a better understanding of the pathogenesis of BP and evaluate novel therapeutic interventions. We describe in this study an experimental model inducing BP by immunization of immunocompetent mice with a recombinant form of the immunodominant 15th noncollagenous domain of murine BP180 (type XVII collagen). The homologous noncollagenous 16A domain of human BP180 has previously been identified as an immunodominant region in human BP. Immunization of female SJL/J mice with the murine peptide led to clinical disease within 14 wk in 56% of mice. In contrast, none of the other strains developed blisters despite the presence of autoantibodies. The clinical disease manifested for at least 8 wk without further manipulation. This novel immunization-induced model reflects key immunopathological characteristics of human BP, including binding of complement-fixing autoantibodies along the dermal-epidermal junction, elevated total IgE serum levels, and infiltration of skin lesions with eosinophilic granulocytes. The use of immunocompetent mice and the induction of sustained clinical disease not requiring additional interventions make this immunization-induced mouse model most suitable to further explore the pathogenesis of BP and novel therapeutic interventions for this and other autoantibody-mediated diseases.
Asunto(s)
Autoantígenos/administración & dosificación , Tolerancia Inmunológica , Colágenos no Fibrilares/administración & dosificación , Penfigoide Ampolloso/inmunología , Vacunas de Virosoma/toxicidad , Animales , Autoantígenos/genética , Autoantígenos/inmunología , Sitios de Unión de Anticuerpos , Quimiotaxis de Leucocito/genética , Quimiotaxis de Leucocito/inmunología , Activación de Complemento/genética , Activación de Complemento/inmunología , Modelos Animales de Enfermedad , Eosinófilos/inmunología , Eosinófilos/patología , Epidermis/inmunología , Epidermis/metabolismo , Epidermis/patología , Femenino , Tolerancia Inmunológica/genética , Inmunización Secundaria/efectos adversos , Inmunoglobulina G/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Neutrófilos/inmunología , Neutrófilos/patología , Colágenos no Fibrilares/genética , Colágenos no Fibrilares/inmunología , Penfigoide Ampolloso/genética , Penfigoide Ampolloso/patología , Vacunas de Subunidad/genética , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/toxicidad , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/toxicidad , Vacunas de Virosoma/administración & dosificación , Vacunas de Virosoma/inmunología , Colágeno Tipo XVIIRESUMEN
BACKGROUND/AIM: The decrease of skin elasticity on the cheek is a major concern to woman. The Cutometer has been widely used to evaluate skin elasticity and its change with aging. Cutometer parameters derived from one suction have been traditionally used to evaluate skin elasticity, and few reports describe the use of multiple suctions to obtain parameters to assess the skin elasticity of the cheek. To find the most suitable Cutometer parameter that reflects age-related changes in the elasticity of cheek skin using multiple suctions. METHODS: The cheeks of 32 healthy Japanese women (mean age, 42.3 years) were assessed using the Cutometer MPA580 by measuring the skin mechanical parameters R0-R9, F2 and F3. Parameters F2 and F3 were obtained by the multiple suction method. The relationship between age and these parameters were then examined. RESULTS: Significant negative correlations were found between the age of subjects and R2, R3, R7, R8 and F3. Of these, the correlation coefficient was best between age and F3 (r = -0.641), followed R8 (r = -0.603). CONCLUSION: Although R parameters have been used to evaluate skin elasticity, our study showed that F3 parameters derived from multiple suctions appear to be suitable for evaluating the elasticity of cheek skin, since this parameter is less influenced by environmental factors compared with R parameters.
Asunto(s)
Mejilla/patología , Diagnóstico por Imagen de Elasticidad/métodos , Envejecimiento de la Piel/patología , Piel/patología , Adulto , Fenómenos Biomecánicos , Técnicas Cosméticas , Elasticidad , Femenino , Humanos , Persona de Mediana Edad , Fenómenos Fisiológicos de la PielRESUMEN
Our Research Group for Rare and Intractable Skin Diseases operates within the Project for Research on Intractable Diseases of the Ministry of Health, Labour, and Welfare of Japan and is conducting research on eight rare intractable skin diseases. Five of these are monogenic disorders (epidermolysis bullosa, congenital ichthyoses, oculocutaneous albinism, pseudoxanthoma elasticum, and hereditary angioedema), and for a sixth [generalized pustular psoriasis (GPP)], genetic predisposing factors are important. This review introduces our activities for raising public awareness of these six intractable hereditary skin diseases and summarizes our recent achievements in clarifying the situation of medical treatments for these diseases in Japan. We note our current progress in elucidating the pathogeneses of these diseases and in developing new treatment methods, and we discuss our progress in establishing clinical practice guidelines. A nationwide survey on epidermolysis bullosa and a clinical survey on congenital ichthyoses are progressing. The Angioedema Activity Score and the Angioedema Quality-of-Life Questionnaire, the latter of which is a quality-of-life evaluation tool, have been established for hereditary angioedema. Registries of patients with oculocutaneous albinism and pseudoxanthoma elasticum have been created, and the registry for the latter has achieved its target of 170 cases. For GPP, the results of our survey on clinical practice were published in 2021. Information regarding all six of these hereditary skin diseases has been disseminated to academic societies, medical professionals, patients, and the general public.
RESUMEN
Pemphigus vulgaris is an autoimmune disease caused by IgG antibodies against desmoglein 3 (Dsg3). Previously, we isolated a pathogenic mAb against Dsg3, AK23 IgG, which induces a pemphigus vulgaris-like phenotype characterized by blister formation. In the present study, we generated a transgenic mouse expressing AK23 IgM to examine B-cell tolerance and the pathogenic role of IgM. Autoreactive transgenic B cells were found in the spleen and lymph nodes, whereas anti-Dsg3 AK23 IgM was detected in the cardiovascular circulation. The transgenic mice did not develop an obvious pemphigus vulgaris phenotype, however, even though an excess of AK23 IgM was passively transferred to neonatal mice. Similarly, when hybridoma cells producing AK23 IgM were inoculated into adult mice, no blistering was observed. Immunoelectron microscopy revealed IgM binding at the edges of desmosomes or interdesmosomal cell membranes, but not in the desmosome core, where AK23 IgG binding has been frequently detected. Furthermore, in an in vitro dissociation assay using cultured keratinocytes, AK23 IgG and AK23 IgM F(ab')(2) fragments, but not AK23 IgM, induced fragmentation of epidermal sheets. Together, these observations indicate that antibodies must gain access to Dsg3 integrated within desmosomes to induce the loss of keratinocyte cell-cell adhesion. These findings provide an important framework for improved understanding of B-cell tolerance and the pathophysiology of blister formation in pemphigus.
Asunto(s)
Desmogleína 3/química , Inmunoglobulina G/química , Inmunoglobulina M/química , Pénfigo/inmunología , Secuencia de Aminoácidos , Animales , Linfocitos B/citología , Vesícula/inmunología , Adhesión Celular , Citometría de Flujo/métodos , Hibridomas/metabolismo , Inmunoglobulina M/metabolismo , Queratinocitos/citología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Fluorescente/métodos , Microscopía Inmunoelectrónica/métodos , Modelos Genéticos , Datos de Secuencia MolecularRESUMEN
BACKGROUND: Early excision is the only strategy to reduce melanoma mortality, but unnecessary excision of benign lesions increases morbidity and healthcare costs. OBJECTIVE: To assess accuracy in melanoma detection based on number-needed-to-excise (NNE) values over a 10-year period. METHODS: Information was retrieved on all histopathologically confirmed cutaneous melanomas or melanocytic nevi that were excised between 1998 and 2007 at participating clinics. NNE values were calculated by dividing the total number of excised lesions by the number of melanomas. Analyses included changes in NNE over time, differences in NNE between specialized clinical settings (SCS) versus non-specialized clinical settings (NSCS), and patient factors influencing NNE. RESULTS: The participating clinics contributed a total of 300,215 cases, including 17,172 melanomas and 283,043 melanocytic nevi. The overall NNE values achieved in SCS and NSCS in the 10-year period were 8.7 and 29.4, respectively. The NNE improved over time in SCS (from 12.8 to 6.8), but appeared unchanged in NSCS. Most of the effect on NNE in SCS was due to a greater number of excised melanomas. Higher NNE values were observed in patients younger than 40 years and for lesions located on the trunk. LIMITATIONS: No data concerning the use of dermatoscopy and digital monitoring procedures were collected from the participating centers. CONCLUSION: Over the 10-year study period, accuracy in melanoma detection improved only in specialized clinics maybe because of a larger use of new diagnostic techniques such as dermatoscopy.
Asunto(s)
Melanoma/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adulto , Anciano , Dermoscopía , Humanos , Melanoma/patología , Melanoma/cirugía , Persona de Mediana Edad , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/patología , Nevo Pigmentado/cirugía , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Adulto JovenRESUMEN
Grover's disease is an acquired dermatosis of unknown cause histopathologically characterized by the presence of acantholysis. We report an 83-year-old Japanese man who showed multiple pruritic papular lesions distributed bilaterally along Blaschko lines, necessitating the exclusion of segmental Darier's disease. No mutations in ATP2A2, ATP2C1 or keratin 5 genes were found both in the lesional skin and in peripheral leukocytes, suggesting that putative pathogenesis of Grover's disease is distinct from those of other acantholytic dermatoses. Electron microscopy revealed poorly developed tonofibrils in the basal cells, and the structure of desmosomes appeared normal, with an increase in the number of desmosomes in the spinous layer, indicating compensation of defective desmosomal function. Impairment of desmosomal plaque proteins linking tonofilaments to desmosomal cadherins may thus account for acantholysis. The unusual bilateral mosaic arrangement in our patient may offer valuable clues to the genetic basis of Grover's disease.
Asunto(s)
Acantólisis/genética , Acantólisis/patología , Ictiosis/genética , Ictiosis/patología , Anciano de 80 o más Años , Pueblo Asiatico , ATPasas Transportadoras de Calcio/genética , Análisis Mutacional de ADN , Desmosomas/ultraestructura , Diagnóstico Diferencial , Humanos , Queratina-5/genética , Masculino , Microscopía Electrónica/métodos , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/genética , Enfermedades de la Piel/patologíaRESUMEN
BACKGROUND/AIMS: The interpretation of patch test reactions may vary between examiners. As test results are graded, an issue also arises when differing degrees of erythema are placed in the same grade. The purpose of this study was to quantitatively evaluate the degree of erythema in patch tests using image analysis and to study the usefulness of this method by comparing it with visual grading. METHODS: A total of 121 Japanese patients were patch tested with various materials. At 48 h, digital photographs of the patch test areas were taken, in addition to a visual evaluation by dermatologists. Digital images of the areas were converted to erythema index (EI) images using image processing and both EI and ΔEI (the difference between the patch test site and adjacent normal skin) values of the patch test sites were compared with the corresponding visual grades. RESULTS: An excellent linear correlation (r=0.95) was found between ΔEI and visual grades, although EI also significantly correlated with visual grades. There were significant differences (P<0.0001-0.05) between the mean ΔEI values of any two adjacent visual grades. CONCLUSION: ΔEI values derived from image processing appear to be suitable for the quantitative evaluation of erythema in patch tests. This method may be helpful in overcoming the subjectiveness of visual evaluation and for training non-experts in patch testing.
Asunto(s)
Dermatitis por Contacto/patología , Dermoscopía/métodos , Eritema/patología , Pruebas del Parche/métodos , Índice de Severidad de la Enfermedad , Adulto , Colorimetría/métodos , Eritema/inducido químicamente , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Persona de Mediana EdadRESUMEN
Blastomycosis-like pyoderma (BLP) is a type of chronic pyoderma characterized histologically by specific epidermal changes namely: pseudoepitheliomatous hyperplasia and intraepithelial abscesses. These epidermal changes are also seen in blastomycosis (referred to as deep dermatophytosis in North America). Here, we describe the case of a 53-year-old male with prurigo nodularis, diabetes, and chronic lymphocytic leukemia who presented with multiple yellowish-red colored papules that coalesced to form a vegetating plaque. In addition to the typical features of BLP, spores with budding were seen histopathologically in a biopsy specimen. Cultures of a skin specimen grew Staphylococcus epidermidis and Trichophyton rubrum. Antibiotic therapy was effective but failed to eliminate the lesion until antifungal therapy using terbinafine was administered concurrently. Past reports suggest that BLP is mainly caused by bacterial infection, but our case suggests that fungal infection can also be involved as the causative organism in BLP.
Asunto(s)
Blastomicosis/patología , Dermatomicosis/patología , Piodermia/patología , Enfermedades Cutáneas Bacterianas/patología , Infecciones Estafilocócicas/patología , Tiña/patología , Antibacterianos/uso terapéutico , Antifúngicos/uso terapéutico , Blastomicosis/complicaciones , Blastomicosis/microbiología , Dermatomicosis/complicaciones , Dermatomicosis/tratamiento farmacológico , Dermatomicosis/microbiología , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Piodermia/complicaciones , Piodermia/microbiología , Enfermedades Cutáneas Bacterianas/complicaciones , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Enfermedades Cutáneas Bacterianas/microbiología , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/aislamiento & purificación , Tiña/complicaciones , Tiña/tratamiento farmacológico , Tiña/microbiología , Resultado del Tratamiento , Trichophyton/aislamiento & purificaciónRESUMEN
Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome (OMIM 308205) is an extremely rare X-linked oculocutaneous genetic disorder characterized by follicular keratotic papules, total to subtotal alopecia, and photophobia. Previous reports depicted the histopathological features of affected skin lesions, represented by marked follicular plugging and hypoplastic pilosebaceous structures. However, past studies provided limited pathological information of pilosebaceous unit anomaly. Here, we report a 3-year-old boy's case with this uncommon condition. In this case, scalp biopsy samples were processed by both vertical and transverse sectioning techniques, which enabled a more detailed and quantitative pathological analysis of pilosebaceous structures. In vertical slices, miniaturized anagen hair follicles with characteristic follicular plugs were observed. A transverse section identified abortive sebaceous glands in hair follicles, a finding rarely observed in vertical sections. In addition, a transverse slice demonstrated that the number of total hair follicles was not significantly decreased compared with the average hair follicle density in Asians, suggesting that the pilosebaceous hypoplasia might arise from impaired maturation, not from initiation defect, during hair follicle morphogenesis. This study provides a more comprehensive pathological insight into pilosebaceous anomaly in IFAP syndrome and substantiats the usefulness of the combination of vertical and transverse sectioning approaches in the pathological examination of congenital hypotrichosis, including IFAP syndrome.
Asunto(s)
Anomalías Múltiples/patología , Alopecia/patología , Hipotricosis/patología , Ictiosis Ligada al Cromosoma X/patología , Fotofobia/patología , Preescolar , Humanos , Masculino , Microtomía/métodos , SíndromeRESUMEN
Nephrogenic systemic fibrosis (NSF) is a fibrotic disease that presents with a history of renal dysfunction. The differential diagnosis generally includes scleromyxedema, systemic sclerosis, and morphea. Especially, scleromyxedema can be extremely difficult to distinguish microscopically. Although the fibrocytes in NSF are often positive for CD34 and procollagen-I, this is not specific for NSF. We identified positive iron staining in the skin of a patient with NSF and investigated whether this was a specific feature among 9 patients with NSF reported in Japan. We found that 6 of 9 patients showed positive iron staining in the dermal fibrocytes. The amount of iron deposition seemed to have no correlation with the degree of fibrosis or duration of the skin lesions but correlated with apparent history of the use of gadolinium-based contrast agents. As controls, skin biopsies from patients with scleromyxedema, morphea, and systemic sclerosis were evaluated by iron staining. None of these control patients showed iron deposition, indicating that positive iron staining may be specific to NSF and can be a useful tool for NSF diagnosis.
Asunto(s)
Fibroblastos/metabolismo , Hierro/análisis , Dermopatía Fibrosante Nefrogénica/diagnóstico , Piel/patología , Anciano , Antígenos CD34/análisis , Antígenos CD34/biosíntesis , Colorantes , Diagnóstico Diferencial , Femenino , Ferrocianuros , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Dermopatía Fibrosante Nefrogénica/metabolismo , Piel/metabolismo , Adulto JovenRESUMEN
We report a 46,XY boy with a mild focal dermal hypoplasia phenotype who had both wild-type and mutated copies of the PORCN gene and was, therefore, mosaic for the mutation. He had cutaneous syndactyly, hydronephrosis, and nail dystrophy. Small whitish depigmented spots, which were slightly depressed from the skin surface, were distributed linearly on the trunk and arms. Aside from these findings, streaks of brown-pigmented macules were seen on the dorsal aspect of the legs. Both the linear arrangement of the whitish spots and the streaks of pigmented macules followed the lines of Blaschko. The phenotype of the patient, who did not exhibit cribriform atrophy, telangiectasia or fat herniation, seemed to be much milder than that of typical female patients with focal dermal hypoplasia. Analysis of the genomic DNA extracted from the peripheral lymphocytes revealed a transition 129G>A within exon 1 of PORCN, which leads to a nonsense mutation W43X. The percentage of peripheral lymphocytes carrying a mutation was estimated to be 50% by the subcloning and sequencing of individual clones of the PCR product amplified across the mutation. This patient's case history provides further molecular evidence supporting the concept that "male focal dermal hypoplasia" does exist and that typical features such as telangiectasia and fat herniation are sometimes absent.
Asunto(s)
Hipoplasia Dérmica Focal/genética , Disgenesia Gonadal 46 XY/genética , Proteínas de la Membrana/genética , Mosaicismo , Aciltransferasas , Secuencia de Bases , Niño , Codón sin Sentido , Exones , Humanos , MasculinoRESUMEN
Psoriasis is an intractable inflammatory skin disorder characterized by scaly erythema and plaques. The Psoriasis Area and Severity Index (PASI) is widely used to score disease severity, but evaluation is subjective, and an objective biomarker would be useful. The stratum corneum (SC), which can be non-invasively harvested, may reflect psoriasis-associated changes in epidermal keratinocytes, such as the upregulation of the calprotectin proteins S100A8 and S100A9. The aim of this study was to examine the availability of S100A8/A9 protein levels in SC as a biomarker of psoriasis disease activity. Fifty-three patients with psoriasis, 30 with psoriasis vulgaris (PsV), and 23 with psoriatic arthritis (PsA) participated. SC cells from lesional and non-lesional skin were collected by tape-stripping. S100A8/A9 levels in serum and in SC were quantified by enzyme-linked immunosorbent assay and compared with PASI score before and after treatment initiation or switching. Atopic dermatitis (AD) patients and disease-free individuals were used as controls. Expression of S100A8/A9 in SC of lesional skin of psoriasis patients was significantly higher than in non-lesional skin or AD skin. There was no significant difference of SC S100A8/A9 levels between PsV and PsA patients. The S100A8/A9 levels in SC of psoriasis patients were significantly positively correlated with the PASI score. When patients' skin lesions cleared (PASI clear) in response to treatment, expression of S100A8/A9 in SC was no longer detectable. S100A8/A9 protein levels in SC may be available as an objective, non-invasive biomarker of psoriasis activity to complement PASI scoring.