RESUMO
INTRODUCTION: Mucous membrane pemphigoid (MMP) refers to a heterogeneous group of rare, chronic, inflammatory, mucous membrane-dominated, sub-epithelial blistering diseases that manifest with a varying constellation of oral, ocular, cutaneous, genital, nasopharyngeal, esophageal, and laryngeal lesions. MMP can progress to scarring in affected areas, which may lead to devastating complications including ocular involvement leading to blindness as well as laryngeal involvement leading to airway obstruction. MATERIALS AND METHODS: A retrospective chart review was conducted for patients that were followed in two tertiary academic centers between 2009 through 2017 for upper aerodigestive tract manifestations of MMP. Patients with significant underlying skin involvement suggestive of bullous pemphigoid as well as MMP with isolated ocular involvement were excluded. RESULTS: Twenty-seven patients were diagnosed with MMP and followed in two tertiary referral medical centers. The most common site of initial presentation was the oral cavity, and all patients had oral cavity involvement at some point. Two-thirds of our patients had complete remission or remission with intermittent relapses disease. Patients with mild to moderate disease showed excellent response to topical steroid treatment. For more severe disease, high-dose prednisone was insufficient, as in most cases relapse occurred at some point of time during tapering down. CONCLUSIONS: MMP is a rare autoimmune disorder that may present with a wide spectrum of head and neck manifestations and, potentially, catastrophic sequelae. This work highlights the experience of two tertiary centers with MMP in an attempt to draw attention to this unusual disorder.
Assuntos
Penfigoide Mucomembranoso Benigno , Penfigoide Bolhoso , Vesícula , Humanos , Mucosa , Penfigoide Mucomembranoso Benigno/complicações , Penfigoide Mucomembranoso Benigno/diagnóstico , Penfigoide Mucomembranoso Benigno/tratamento farmacológico , Estudos RetrospectivosRESUMO
Cucurbits represent an attractive model to explore the dynamics of fruit set, whose regulation is not fully understood, despite its importance for yield determination. A fertilized ovary must integrate signals from distant plant parts and 'decide' whether to set fruit, or remain inhibited and later senesce. Here, we set out to characterize first-fruit inhibition (FFI), that is, the inhibitory effect of the first fruit on subsequent development of younger ovaries during pollination-induced and parthenocarpic fruit set. After the first fertilized ovaries set fruit, younger fertilized ovaries remained in a temporary state of inhibition. Such ovaries preserved their size and green color, and if the older fruit were removed within a 1-week reversibility window, they set fruit. The FFI effect was documented in both fertilized and parthenocarpic ovaries. We compared the gene expression profiles of pollinated ovaries (committed to set fruit) with respect to those affected by FFI, and to non-pollinated ovaries (undergoing senescence). The three fates of the ovaries were characterized by wide changes in gene expression, with several specific transcripts being up- or down-regulated in response to pollination, and to the presence of inhibitory fruit. Metabolic profiling was undertaken and integrated with the transcriptomic data in order to characterize early physiological changes that occur in post-anthesis ovaries in parthenocarpic and non-parthenocarpic genotypes. The combined results are discussed with respect to current models of fruit set and specifically with regard to FFI. Moreover, these metabolome and transcriptome data provide a valuable resource for studying ovary development and fruit set.
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Cucumis sativus/genética , Regulação da Expressão Gênica de Plantas , Transcriptoma , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/fisiologia , Regulação para Baixo , Flores/genética , Flores/crescimento & desenvolvimento , Flores/fisiologia , Frutas/genética , Frutas/crescimento & desenvolvimento , Frutas/fisiologia , PolinizaçãoRESUMO
Despite recent advances in our understanding of the pathogenesis of ectodermal dysplasias (EDs), the molecular basis of many of these disorders remains unknown. In the present study, we aimed at elucidating the genetic basis of a new form of ED featuring facial dysmorphism, scalp hypotrichosis and hypodontia. Using whole exome sequencing, we identified 2 frameshift and 2 missense mutations in TSPEAR segregating with the disease phenotype in 3 families. TSPEAR encodes the thrombospondin-type laminin G domain and EAR repeats (TSPEAR) protein, whose function is poorly understood. TSPEAR knock-down resulted in altered expression of genes known to be regulated by NOTCH and to be involved in murine hair and tooth development. Pathway analysis confirmed that down-regulation of TSPEAR in keratinocytes is likely to affect Notch signaling. Accordingly, using a luciferase-based reporter assay, we showed that TSPEAR knock-down is associated with decreased Notch signaling. In addition, NOTCH1 protein expression was reduced in patient scalp skin. Moreover, TSPEAR silencing in mouse hair follicle organ cultures was found to induce apoptosis in follicular epithelial cells, resulting in decreased hair bulb diameter. Collectively, these observations indicate that TSPEAR plays a critical, previously unrecognized role in human tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway.
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Displasia Ectodérmica/genética , Morfogênese/genética , Proteínas/genética , Receptor Notch1/biossíntese , Animais , Diferenciação Celular/genética , Análise Mutacional de DNA , Displasia Ectodérmica/patologia , Mutação da Fase de Leitura/genética , Regulação da Expressão Gênica no Desenvolvimento , Folículo Piloso/crescimento & desenvolvimento , Humanos , Camundongos , Linhagem , Receptor Notch1/genética , Transdução de Sinais/genética , Dente/crescimento & desenvolvimento , Dente/metabolismoRESUMO
OBJECTIVE: This study aimed to present our experience in treating laryngeal pemphigoid (LP) patients, including disease course, treatment and treatment response, and to search for predictors of response to treatment. STUDY DESIGN: A retrospective cohort study. METHODS: The medical records of all patients with LP from March 2013 to August 2020 were reviewed. Potential relationships between disease severity and response to treatment and demographics, diagnosis, extent of laryngeal and extra-laryngeal involvement, comorbidities, immunostaining, and serology profile were explored. RESULTS: Eight patients were included in the study (seven females, one male, mean age 79 years, mean follow-up 22 months). Diagnoses included mucous membrane pemphigoid (MMP, n = 5), bullous pemphigoid (BP, n = 3). Two patients achieved complete laryngeal remission, four achieved partial remission, and two had no remission. The time to achieve laryngeal disease control was longer than for extra-laryngeal disease (P = 0.02). Potential associations were found between the absence of immunoglobulin G (IgG)-type auto-antibodies deposits in the basement membrane zone and a laryngeal disease that responded to topical corticosteroids and between the presence of BP180-C-terminal IgG auto-antibodies and a resistant rapidly progressive laryngeal disease. CONCLUSIONS: LP has a spectrum of severity, variable response and is more resistant to treatment. The absence of IgG-type auto-antibodies may indicate a response to topical corticosteroids. Based on our limited observation, the presence of IgG-type auto-antibodies that target BP180-C-terminal domain may indicate a more severe scarring disease. Early recognition of these "high-risk patients" will allow early initiation of advanced systemic treatment that may prevent the irreversible effects of scarring.
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Doenças da Laringe , Penfigoide Bolhoso , Feminino , Humanos , Masculino , Idoso , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/tratamento farmacológico , Estudos Retrospectivos , Cicatriz , Autoanticorpos , Imunoglobulina G , Corticosteroides/uso terapêuticoRESUMO
Human papillomavirus (HPV) is ubiquitously distributed in the population worldwide and its most frequent clinical presentation is cutaneous warts. Despite various treatment options currently available, many patients experience persistent and refractory disease. We sought to evaluate the clinical effectiveness and safety profile of intralesional HPV 9-valent vaccine for the treatment of recalcitrant warts. A retrospective study was performed for all cases of cutaneous warts treated with intralesional 9-valent HPV vaccine between January 2017 and March 2021. Epidemiologic, clinical, and treatment data, including safety and effectiveness scores, were reviewed. Our cohort was composed of 20 patients: 13 adults and seven children. Twelve patients (60%) displayed a complete response whereas 8 patients (40%) showed a partial response. Older age was associated with a better response to treatment, while a history of laser therapy was associated with a worse prognosis. Adverse events were local, transient, and negligible. No systemic adverse effects were reported. Intralesional 9-valent HPV vaccine may be considered for the treatment of recalcitrant cutaneous warts. Controlled studies are required to confirm these results.
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Infecções por Papillomavirus , Vacinas contra Papillomavirus , Verrugas , Adulto , Criança , Humanos , Verrugas/tratamento farmacológico , Vacinas contra Papillomavirus/efeitos adversos , Papillomavirus Humano , Infecções por Papillomavirus/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Injeções IntralesionaisRESUMO
BACKGROUND: Gain-of-function mutations in CARD14 have recently been shown to be involved in the pathogenesis of psoriasis and pityriasis rubra pilaris (PRP). Those mutations were found to activate the NF-kB signaling pathway. OBJECTIVE: Zebrafish is often used to model human diseases in general, and in skin disorders more particularly. In the present study, we aimed to examine the effect of CARD14 overexpression in zebrafish with the aim to validate this model for future translational applications. METHODS: We used light microscopy, scanning electron microscopy, histological analysis and whole mount in situ hybridization as well as real-time PCR to ascertain the effect of CARD14 overexpression in the developing zebrafish. RESULTS: Overexpression of human CARD14 had a marked morphological and developmental effect on the embryos. Light microscopy demonstrated a characteristic cutaneous pattern including a granular surface and a spiky pigment pattern. In situ hybridization revealed keratinocytes of uneven size and shape. Scanning electron microscopy showed aberrant production of actin microridges and a rugged keratinocyte cell surface, reminiscent of the human hyperkeratotic phenotype. Developmentally, overexpression of CARD14 had a variable effect on anterior-posterior axis symmetry. Similar to what has been observed in humans with psoriasis or PRP, NF-kB expression was higher in CARD14-overexpressing embryos compared to controls. CONCLUSIONS: Overexpression of CARD14 results in a distinct cutaneous pattern accompanied by hyperactivation of the NF-kB pathway, suggesting that the zebrafish represents a useful system to model CARD14-associated papulosquamous diseases.