RESUMEN
Pemphigus vegetans is a rare type of pemphigus characterized by vegetative lesions primarily localized to the intertriginous area. Despite its unique clinical presentation, the underlying pathomechanism remains unclear owing to the rarity of the disease. We report a case of pemphigus vegetans with antibodies against desmoglein 1 and desmocollins 1-3. Furthermore, immunohistochemical analyses were performed to address the pathogenesis of this disease. A 73-year-old man presented with multiple vegetative plaques with erythema on the trunk, groins, and extremities. Mucosal lesions were not observed. Laboratory examinations revealed mild leukocytosis with eosinophilia. A histopathological examination of the skin lesion showed epidermal hyperplasia and intraepidermal abscesses with marked infiltration of neutrophils and eosinophils, and infiltration of lymphocytes and eosinophils into the upper derms. Bacterial culture of the skin tissue was positive for Staphylococcus aureus. Direct immunofluorescence showed deposits of IgG and C3 on keratinocyte surfaces in the epidermis. Autoantibodies against desmoglein 1 and autoantibodies against desmocollin 1, desmocollin 2, and desmocollin 3 were detected by enzyme-linked immunosorbent assays. The diagnosis of pemphigus vegetans was made. Initiation of prednisolone (1.0 mg/kg/day) gradually improved his skin symptoms. We performed immunohistochemical analyses of the lesional skin, which revealed infiltration of CD3-positive, CD4-positive, and CD68-positive cells in the upper dermis, but CD20- or CD56-positive cells were negative. In addition, the present case showed more prominent infiltration of IL-17A- and IL-22-positive cells in the upper dermis than in pemphigus foliaceus, a type of pemphigus with autoantibodies against desmoglein 1. Furthermore, these cells co-expressed CD3 and CD68. We hypothesized that IL-22 and IL-17A produced by T cells and macrophages and their dysregulation might be involved in the pathogenesis of pemphigus vegetans. Additionally, skin colonization and/or infection with Staphylococcus aureus could potentially contribute to the pathogenesis of the disease.
Asunto(s)
Autoanticuerpos , Autoantígenos , Linfocitos B , Colágeno Tipo XVII , Inmunoglobulina A , Inmunoglobulina G , Colágenos no Fibrilares , Penfigoide Benigno de la Membrana Mucosa , Humanos , Autoanticuerpos/inmunología , Inmunoglobulina A/inmunología , Penfigoide Benigno de la Membrana Mucosa/inmunología , Penfigoide Benigno de la Membrana Mucosa/diagnóstico , Colágenos no Fibrilares/inmunología , Inmunoglobulina G/inmunología , Autoantígenos/inmunología , Linfocitos B/inmunología , Femenino , Masculino , AncianoAsunto(s)
Anticuerpos Monoclonales Humanizados , Penfigoide Ampolloso , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/complicaciones , Anticuerpos Monoclonales Humanizados/uso terapéutico , Penfigoide Ampolloso/tratamiento farmacológico , Resultado del Tratamiento , Masculino , Femenino , LamininaRESUMEN
IgA pemphigus is an autoimmune bullous disease caused by anti-keratinocyte cell surface IgA autoantibodies. Mucous membrane involvement is rare in IgA pemphigus. We report a case of IgA pemphigus with oral mucosal lesions, in which acantholysis was pathologically confirmed. A 31-year-old woman presented with skin erythema with small pustules and oral mucosal erosions. Histopathological examination of the erosions on her oral mucosa and papules on her back revealed acantholysis and intraepidermal infiltration of neutrophils. Direct immunofluorescence tests showed intercellular deposition of IgA, but not IgG, mainly in the lower, but not entire, layer of the epidermis. C3 was linearly present in the basement membrane zone (BMZ), but not in the intercellular space. Enzyme-linked immunosorbent assay revealed that both anti-desmoglein (Dsg) 3 IgA and IgG were positive. Neither IgA nor IgG against desmocollin 1-3 were detected. This case was clinically and histologically compatible with IgA pemphigus, but immunologically anti-BMZ autoimmunity was additionally observed. IgA pemphigus is classified into two major types: subcorneal pustular dermatosis type and intraepidermal neutrophilic dermatosis type. This case was not typical in terms of rarely observed oral lesions and predominant deposition of IgA in the lower layer of the epidermis. Instead, this case could be considered a rare subtype of IgA pemphigus, IgA-pemphigus vulgaris. Oral lesions in IgA pemphigus may be clinical clue of having anti-Dsg3 IgA that cannot be routinely examined.
Asunto(s)
Autoanticuerpos , Desmogleína 1 , Desmogleína 3 , Pénfigo , Recurrencia , Humanos , Pénfigo/inmunología , Pénfigo/sangre , Pénfigo/diagnóstico , Pénfigo/patología , Desmogleína 3/inmunología , Desmogleína 1/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Femenino , Masculino , Persona de Mediana Edad , Piel/patología , Piel/inmunologíaRESUMEN
Pathogenic variants in ABCA12 are important causative genetic defects for autosomal recessive congenital ichthyoses (ARCI), which include congenital ichthyosiform erythroderma (CIE), harlequin ichthyosis, and lamellar ichthyosis. In addition, pathogenic variants in ABCA12 are known to cause a localized nevoid form of CIE due to recessive mosaicism. We previously reported siblings who carried an ABCA12 variant but did not show a "congenital" phenotype. They were considered to have pityriasis rubra pilaris (PRP). Here, we present a further patient with ABCA12 variants whose phenotype was not congenital ichthyosis, in an independent family. Notably, these three patients had geographic unaffected areas. Such areas are not usually found in patients with ARCI who have ABCA12 variants, suggesting mild phenotypes for these patients. Interestingly, the histological features of the ichthyotic lesions in these patients resembled those of PRP. All three patients had homozygous pathogenic missense variants in ABCA12. Our findings expand the phenotypic spectrum of patients with ABCA12 variants.
Asunto(s)
Eritrodermia Ictiosiforme Congénita , Ictiosis Lamelar , Ictiosis , Pitiriasis Rubra Pilaris , Humanos , Pitiriasis Rubra Pilaris/genética , Ictiosis Lamelar/genética , Eritrodermia Ictiosiforme Congénita/genética , Eritrodermia Ictiosiforme Congénita/patología , Fenotipo , Mutación , Transportadoras de Casetes de Unión a ATP/genéticaAsunto(s)
Dermatitis Herpetiforme , Inhibidores de la Dipeptidil-Peptidasa IV , Pénfigo , Humanos , Pénfigo/diagnóstico , Pénfigo/tratamiento farmacológico , Desmocolinas , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Autoanticuerpos , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas , Dermatitis Herpetiforme/diagnóstico , Dermatitis Herpetiforme/tratamiento farmacológicoAsunto(s)
Dermatosis Bullosa IgA Lineal , Psoriasis , Anomalías Cutáneas , Enfermedades de la Piel , Humanos , Dermatosis Bullosa IgA Lineal/inducido químicamente , Dermatosis Bullosa IgA Lineal/diagnóstico , Pemetrexed/efectos adversos , Nivolumab/efectos adversos , Vesícula/inducido químicamente , Psoriasis/tratamiento farmacológico , Inmunoglobulina AAsunto(s)
Autoanticuerpos , Desmogleína 3 , Linfoma Folicular , Síndromes Paraneoplásicos , Pénfigo , Humanos , Pénfigo/inmunología , Pénfigo/diagnóstico , Pénfigo/patología , Pénfigo/complicaciones , Linfoma Folicular/complicaciones , Linfoma Folicular/diagnóstico , Linfoma Folicular/inmunología , Linfoma Folicular/patología , Linfoma Folicular/tratamiento farmacológico , Síndromes Paraneoplásicos/inmunología , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/etiología , Síndromes Paraneoplásicos/patología , Desmogleína 3/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Masculino , Piel/patología , Piel/inmunología , Femenino , Persona de Mediana Edad , AncianoRESUMEN
Introduction: Inflammatory epidermolysis bullosa acquisita (EBA) is characterized by a neutrophilic response to anti-type VII collagen (COL7) antibodies resulting in the development of skin inflammation and blistering. The antibody transfer model of EBA closely mirrors this EBA phenotype. Methods: To better understand the changes induced in neutrophils upon recruitment from peripheral blood into lesional skin in EBA, we performed single-cell RNA-sequencing of whole blood and skin dissociate to capture minimally perturbed neutrophils and characterize their transcriptome. Results: Through this approach, we identified clear distinctions between circulating activated neutrophils and intradermal neutrophils. Most strikingly, the gene expression of multiple C-type lectin receptors, which have previously been reported to orchestrate host defense against fungi and select bacteria, were markedly dysregulated. After confirming the upregulation of Clec4n, Clec4d, and Clec4e in experimental EBA as well as in lesional skin from patients with inflammatory EBA, we performed functional studies in globally deficient Clec4e-/- and Clec4d-/- mice as well as in neutrophil-specific Clec4n-/- mice. Deficiency in these genes did not reduce disease in the EBA model. Discussion: Collectively, our results suggest that while the upregulation of Clec4n, Clec4d, and Clec4e is a hallmark of activated dermal neutrophil populations, their individual contribution to the pathogenesis of EBA is dispensable.