RESUMEN
Bullous pemphigoid (BP) is the most common autoimmune bullous disease: it most commonly affects individuals over 70 years old and impacts severely on their quality of life. BP represents a paradigm for an organ-specific autoimmune disease and is characterized by circulating IgG autoantibodies to hemidesmosomal components: BP180 and BP230. While the crucial role of these autoantibodies in triggering BP inflammatory cascade is fully acknowledged, many ancillary etiological mechanisms need to be elucidated yet. Cutaneous melanoma is due to a malignant transformation of skin melanocytes, that produce and distribute pigments to surrounding keratinocytes. Melanoma is the most fatal skin cancer because of its increasing incidence and its propensity to metastasize. Several data such as: i) reported cases of concomitant melanoma and BP; ii) results from association studies; iii) BP onset following immune check-point inhibitors therapy; iv) expression of BP antigens in transformed melanocytes; and vi) circulating autoantibodies to BP antigens in melanoma patients suggest an intriguing, although unproven, possible association between melanoma and BP. However, a possible causative link is still debated and the putative pathogenetic mechanism underlying this association is unclear. This review aims to describe and discuss the possible relationship between BP and melanoma and give an overview of the speculations for or against this association. Of note, if demonstrated, this association could unwrap considerations of clinical relevance that represent new research frontiers.
Asunto(s)
Autoanticuerpos , Autoantígenos , Melanoma , Penfigoide Ampolloso , Humanos , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/etiología , Melanoma/inmunología , Melanoma/etiología , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Autoantígenos/inmunología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/etiología , Colágeno Tipo XVII , Colágenos no Fibrilares/inmunología , Melanocitos/inmunología , Melanocitos/patología , Animales , Relevancia ClínicaAsunto(s)
Autoanticuerpos , Enfermedades del Colágeno , Penfigoide Ampolloso , Humanos , Penfigoide Ampolloso/diagnóstico , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/tratamiento farmacológico , Enfermedades del Colágeno/patología , Enfermedades del Colágeno/diagnóstico , Diagnóstico Diferencial , Autoanticuerpos/sangre , Femenino , Piel/patología , Piel/inmunología , Piel/efectos de los fármacos , Anciano , Biopsia , Masculino , Valor Predictivo de las Pruebas , Autoantígenos/inmunología , LamininaAsunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Linagliptina , Penfigoide Ampolloso , Humanos , Linagliptina/efectos adversos , Linagliptina/uso terapéutico , Penfigoide Ampolloso/mortalidad , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Masculino , Anciano , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Anciano de 80 o más Años , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Factores de Riesgo , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Anticuerpos Monoclonales Humanizados , Dermatitis Atópica , Penfigoide Ampolloso , Humanos , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/diagnóstico , Penfigoide Ampolloso/inducido químicamente , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/diagnóstico , Penfigoide Ampolloso/inmunología , Anticuerpos Monoclonales Humanizados/efectos adversos , Masculino , Femenino , Resultado del Tratamiento , Persona de Mediana Edad , AncianoRESUMEN
Acquired hemophilia A, a rare condition resulting in spontaneous bleeding without prior bleeding disorders, arises due to autoantibody-mediated inhibition of coagulation factor VIII and is typically associated with autoimmune, neoplastic, drug, or obstetric factors. We present the case of a 31-year-old woman with bullous pemphigoid, managed with corticosteroids since 2013, who presented spontaneous hemorrhagic manifestations. Upon admission, laboratory tests revealed hypochromic microcytic anemia, prolonged activated partial thromboplastin time, and a factor VIII level < 1%, indicative of acquired hemophilia A. Further assessments showed elevated Ristocetin cofactor activity, von Willebrand factor antigen, and a factor VIII inhibitor level of 665 BU. This underscores the importance of considering acquired hemophilia A in autoimmune dermatological conditions like bullous pemphigoid, highlighting the association between autoimmune disorders and coagulation abnormalities, particularly in cases of spontaneous hemorrhagic events.
Asunto(s)
Hemofilia A , Penfigoide Ampolloso , Humanos , Femenino , Hemofilia A/complicaciones , Penfigoide Ampolloso/diagnóstico , Adulto , Hemorragia/etiología , Factor VIII/inmunología , Tiempo de Tromboplastina Parcial , Corticoesteroides/administración & dosificación , Glucocorticoides/administración & dosificación , Autoanticuerpos/sangreAsunto(s)
Antineoplásicos Fitogénicos , Neoplasias Endometriales , Paclitaxel , Penfigoide Ampolloso , Humanos , Femenino , Penfigoide Ampolloso/inducido químicamente , Penfigoide Ampolloso/tratamiento farmacológico , Neoplasias Endometriales/tratamiento farmacológico , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Anciano , Persona de Mediana EdadRESUMEN
The majority of dermatitis cases in adults result from chronic or relapsing atopic dermatitis in childhood. Adult-onset atopic dermatitis, also known as idiopathic chronic eczematous eruption of aging (CEEA), is a phenomenon seen in adults 50 years and older with no prior history of atopic dermatitis. CEEA is often a diagnosis of exclusion after ruling out more serious causes of dermatitis including bullous pemphigoid (BP), allergic conditions, and hematologic malignancies. This report details the case of a 67-year-old woman with no history of atopy who presented with a persistent, eczematous dermatitis not responsive to traditional therapy, consistent with CEEA, but was later identified as BP.
Asunto(s)
Dermatitis Atópica , Penfigoide Ampolloso , Humanos , Penfigoide Ampolloso/diagnóstico , Femenino , Anciano , Dermatitis Atópica/diagnóstico , Diagnóstico DiferencialRESUMEN
Background and Objectives: Dapsone (DP) is employed in the management of various skin conditions, including autoimmune bullous diseases to non-enzymes (n-eAIBDs). This study aimed to assess the advantages and safety profile of DP treatment in n-eAIBDs patients. The evaluation focused on clinical remission, reduction in glucocorticosteroid (GCS) usage, and adverse incidents during a 12-month observation in a dermatology department at a Central European university. Materials and Methods: Our retrospective study included forty-one patients who met the inclusion criteria, comprising nineteen with pemphigus vulgaris, nine with pemphigus foliaceus, four with bullous pemphigoid, and nine with mucous membrane pemphigoid, including one patient with Brunsting-Perry pemphigoid. Patients received 25-50 mg/day of DP along with oral GCSs for a year, with a subsequent dose reduction where feasible. Results: The mean decreases in prednisone-equivalent dosages across all groups after 2, 6, and 12 months of DP treatment were 45.66%, 65.77%, and 63.03%, respectively. Throughout the 12-month observation period, 21.62% of patients experienced a relapse, while the remaining patients attained either complete or partial remission with minimal therapy. Adverse incidents were observed in 29.27% of patients; these were mild or moderate, and no severe negative effects were observed. Conclusions: DP is an effective and affordable choice to support the treatment of n-eAIBDs, but it may not be sufficient for long-term management in certain patients with severe n-eAIBDs.
Asunto(s)
Enfermedades Autoinmunes , Dapsona , Humanos , Estudios Retrospectivos , Masculino , Dapsona/uso terapéutico , Femenino , Persona de Mediana Edad , Anciano , Enfermedades Autoinmunes/tratamiento farmacológico , Adulto , Enfermedades Cutáneas Vesiculoampollosas/tratamiento farmacológico , Resultado del Tratamiento , Anciano de 80 o más Años , Penfigoide Ampolloso/tratamiento farmacológicoAsunto(s)
Antineoplásicos Inmunológicos , Ciclosporina , Melanoma , Nivolumab , Penfigoide Ampolloso , Humanos , Penfigoide Ampolloso/inducido químicamente , Penfigoide Ampolloso/diagnóstico , Nivolumab/efectos adversos , Nivolumab/administración & dosificación , Melanoma/tratamiento farmacológico , Ciclosporina/efectos adversos , Ciclosporina/administración & dosificación , Ciclosporina/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Masculino , Inmunosupresores/efectos adversos , Inmunosupresores/administración & dosificación , Anciano , FemeninoRESUMEN
Bullous pemphigoid (BP), although a rare disease, is the most frequent subepidermal autoimmune disorder. Treatment with gliptins, used for type 2 diabetes, was reported as associated with BP onset. To identify HLA alleles that may reflect a higher susceptibility to BP in the Italian population, we analysed 30 patients affected by idiopathic bullous pemphigoid (IBP) and 86 gliptin-associated BP (GABP) patients. A significant association between HLA-DQB1*03:01 allele and IBP and GABP patients was found. Of note, both IBP and GABP were significantly associated with one of the following haplotypes: DRB1*11:01, DRB3*02:02, DQA1*05:05, DQB1*03:01 or DRB1*11:04, DRB3*02:02, DQA1*05:05 and DQB1*03:01. These data identify, for the first time, potential markers of susceptibility to BP in the Italian population, especially when associated with gliptin intake.
Asunto(s)
Alelos , Predisposición Genética a la Enfermedad , Haplotipos , Penfigoide Ampolloso , Humanos , Penfigoide Ampolloso/genética , Penfigoide Ampolloso/inducido químicamente , Italia , Femenino , Masculino , Anciano , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Cadenas beta de HLA-DQ/genética , Persona de Mediana Edad , Frecuencia de los Genes , Anciano de 80 o más AñosAsunto(s)
Hospitalización , Cobertura del Seguro , Penfigoide Ampolloso , Humanos , Penfigoide Ampolloso/economía , Penfigoide Ampolloso/epidemiología , Estudios Retrospectivos , Estudios Transversales , Hospitalización/estadística & datos numéricos , Femenino , Masculino , Anciano , Cobertura del Seguro/estadística & datos numéricos , Anciano de 80 o más Años , Persona de Mediana EdadAsunto(s)
Penfigoide Ampolloso , Escabiosis , Anciano , Humanos , Penfigoide Ampolloso/diagnóstico , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/patología , Penfigoide Ampolloso/complicaciones , Escabiosis/complicaciones , Escabiosis/diagnóstico , Escabiosis/tratamiento farmacológico , Escabiosis/patologíaAsunto(s)
Penfigoide Ampolloso , Neoplasias Cutáneas , Humanos , Penfigoide Ampolloso/complicaciones , Penfigoide Ampolloso/patología , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/patología , Femenino , Carcinoma de Apéndice Cutáneo/patología , Carcinoma de Apéndice Cutáneo/complicaciones , Anciano , Masculino , Anciano de 80 o más AñosRESUMEN
The 16th non-collagenous domain (NC16A) of BP180 is the main antigenic target of autoantibodies in bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP). Commercially available assays detect serum autoantibodies against NC16A in the majority of BP (80%-90%) and in approximately 50% of MMP patients. However, a standardized test system for detecting antibodies against other regions of BP180 is still lacking. Moreover, anti-BP180 autoantibodies have been found in neurological conditions such as multiple sclerosis and Parkinson disease. This study aimed at identifying primary epitopes recognized by BP autoantibodies on the BP180 ectodomain. Serum samples of 51 BP and 30 MMP patients both without anti-NC16A reactivity were included along with 44 multiple sclerosis and 75 Parkinson disease sera. Four overlapping His-tagged proteins covering the entire BP180 ectodomain (BP180(ec)1-4) were cloned, expressed, purified and tested for reactivity by immunoblot. IgG antibodies to BP180(ec)3 were detected in 98% of BP, 77% of MMP and 2% of normal human sera. Only weak reactivity was detected for neurological diseases against BP180(ec)1, BP180(ec)2 and BP180(ec)4, in 3%, 11% and 7% of tested multiple sclerosis sera, respectively. 8% of Parkinson disease sera reacted with BP180(ec)2 and 9% with BP180(ec)4. In conclusion, this study successfully identified epitopes recognized by BP autoantibodies outside the NC16A domain in pemphigoid diseases. These findings contribute to a better understanding of the immune response in BP and MMP with potential implications for a future diagnostic assay for NC16A-negative pemphigoid patients.
Asunto(s)
Autoanticuerpos , Autoantígenos , Colágeno Tipo XVII , Esclerosis Múltiple , Colágenos no Fibrilares , Enfermedad de Parkinson , Penfigoide Benigno de la Membrana Mucosa , Penfigoide Ampolloso , Humanos , Enfermedad de Parkinson/inmunología , Enfermedad de Parkinson/sangre , Colágenos no Fibrilares/inmunología , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/sangre , Autoantígenos/inmunología , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/sangre , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Penfigoide Benigno de la Membrana Mucosa/inmunología , Penfigoide Benigno de la Membrana Mucosa/sangre , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Epítopos/inmunología , Dominios Proteicos , Femenino , Masculino , AncianoRESUMEN
Bullous pemphigoid (BP) is a type 2 inflammation- and immunity-driven skin disease, yet a comprehensive understanding of the immune landscape, particularly immune-stromal crosstalk in BP, remains elusive. Herein, using single-cell RNA sequencing (scRNA-seq) and in vitro functional analyzes, we pinpoint Th2 cells, dendritic cells (DCs), and fibroblasts as crucial cell populations. The IL13-IL13RA1 ligand-receptor pair is identified as the most significant mediator of immune-stromal crosstalk in BP. Notably, fibroblasts and DCs expressing IL13RA1 respond to IL13-secreting Th2 cells, thereby amplifying Th2 cell-mediated cascade responses, which occurs through the specific upregulation of PLA2G2A in fibroblasts and CCL17 in myeloid cells, creating a positive feedback loop integral to immune-stromal crosstalk. Furthermore, PLA2G2A and CCL17 contribute to an increased titer of pathogenic anti-BP180-NC16A autoantibodies in BP patients. Our work provides a comprehensive insight into BP pathogenesis and shows a mechanism governing immune-stromal interactions, providing potential avenues for future therapeutic research.
Asunto(s)
Quimiocina CCL17 , Células Dendríticas , Fibroblastos , Penfigoide Ampolloso , Análisis de la Célula Individual , Células Th2 , Humanos , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/genética , Análisis de la Célula Individual/métodos , Fibroblastos/metabolismo , Fibroblastos/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Quimiocina CCL17/genética , Quimiocina CCL17/metabolismo , Células Th2/inmunología , Autoanticuerpos/inmunología , Transcriptoma , Interleucina-13/metabolismo , Interleucina-13/genética , Interleucina-13/inmunología , Colágenos no Fibrilares/inmunología , Colágenos no Fibrilares/genética , Colágenos no Fibrilares/metabolismo , Inflamación/inmunología , Inflamación/genética , Inflamación/metabolismo , Perfilación de la Expresión Génica/métodos , Masculino , Femenino , Autoantígenos/inmunología , Autoantígenos/metabolismo , Autoantígenos/genética , Colágeno Tipo XVII , Células Mieloides/metabolismo , Células Mieloides/inmunología , Células del Estroma/metabolismo , Células del Estroma/inmunologíaRESUMEN
Background: Pemphigoid diseases constitute a group of autoimmune blistering disorders characterized by subepithelial blistering. The association between pemphigoid diseases and both end-stage kidney disease (ESKD) and its treatment is notable. However, there is limited evidence about the management of pemphigoid diseases in patients with ESKD. This systematic review compiled case reports and relevant studies, summarized the underlying mechanisms of pemphigoid diseases in patients with ESKD, and summarized the efficacy of various therapies. Methods: A systematic search of PubMed and Embase was performed for articles published between 1982 to June 2, 2024. Results: Fifty-three case reports and eight relevant studies were included. Triggers for pemphigoids in patients with ESKD included materials used to treat ESKD, immune dysregulation of patients with ESKD, and rejection of renal allograft. Treatment for these patients included removing triggers, as well as administering of corticosteroids, mycophenolate mofetil (MMF), tetracyclines, rituximab, methotrexate, dapsone, azathioprine, cyclosporine, intravenous immunoglobin (IVIG), plasmapheresis, and Janus kinase inhibitors. Conclusion: Removing triggers is the most effective strategy. Despite their suboptimal efficacy, corticosteroids remain the most commonly used agents in this patient population. MMF, tetracyclines, and rituximab are less used but with benefits. There are significant adverse effects associated with methotrexate treatment. Other treatment may also be beneficial and require further investigation. These findings may enable clinicians to optimize the therapeutic approach for these patients.
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Fallo Renal Crónico , Penfigoide Ampolloso , Humanos , Penfigoide Ampolloso/terapia , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/etiología , Penfigoide Ampolloso/inmunología , Fallo Renal Crónico/terapia , Fallo Renal Crónico/etiología , Fallo Renal Crónico/complicaciones , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversosRESUMEN
Aims/Background Indeterminate cell histiocytosis is a rare proliferative histiocytic disease with an unknown aetiology, which shares immunophenotypic features of both Langerhans cells and macrophages. There is a relationship between indeterminate cell histiocytosis and cancer, while there are no reports about indeterminate cell histiocytosis and bullous pemphigoid. In this study, we reported the rare case of a patient with primary cutaneous indeterminate cell histiocytosis who had been diagnosed with oesophagal cancer and later developed bullous pemphigoid. The objective of this clinical case report is to analyse the association between solid tumours and indeterminate cell histiocytosis and focus on the coexistence of indeterminate cell histiocytosis and bullous pemphigoid in a patient with cancer. Case Presentation This study presented the case of a 75-year-old man who exhibited annular erythema lesions of variable size and papules scattered over his chest, abdomen, and limbs, along with four bullae on his thigh, persisting for 1.5 months. The patient also had a 9-month history of oesophageal cancer treated with radical radiotherapy. Histopathology and immunohistochemistry confirmed cutaneous indeterminate cell histiocytosis. Bullae and blisters developed on the lower limbs 38 days after treatment. A diagnosis of bullous pemphigoid was established based on clinical and histopathological features and results of direct immunofluorescence and enzyme-linked immunosorbent assay. Results Histopathological examination of the abdominal lesion revealed an accumulation of mononuclear cells in the dermis, with infiltration of eosinophils and lymphocytes in the superficial dermal layer. The histology of the blister on the thigh indicated the formation of an old subepidermal blister, with slurry and eosinophils present within the blister, and infiltration of eosinophils, lymphocytes, as well as histiocytoid cells in the superficial dermal layer. Immunohistochemical staining was positive for CD1a, S100, and CD68, and negative for CD207. Histopathological examination of blisters and bullae on the lower limbs revealed a subepidermal blister with infiltration of a large number of eosinophils within the blister and the dermis beneath it. Direct immunofluorescence showed that immunoglobulin Gs (IgGs) were linearly deposited in the basal membrane zone. Conclusion The coexistence of oesophageal carcinoma, indeterminate cell histiocytosis, and bullous pemphigoid in a single patient represents a rare case that warrants consideration of possible underlying mechanisms.