RESUMO
BACKGROUND: In extramammary Paget disease (EMPD), Paget cells are sometimes detected outside the clinical border (subclinical extension). However, the spreading pattern of Paget cells in subclinical extension remains unclear. In addition, the macroscopic appearances of lesions accompanied by subclinical extension are totally unknown. OBJECTIVES: To characterize the spreading pattern of Paget cells as well as the macroscopic appearance of lesions of EMPD with subclinical extension. METHODS: Nineteen patients with primary anogenital EMPD underwent mapping biopsies and excisional surgeries; biopsy samples were then taken at the periphery of well-demarcated lesions. Samples were transparentized and subjected to whole-mount immunostaining with anticytokeratin 7 antibody to label Paget cells. The histological border was evaluated in three dimensions by two-photon microscopy. The shape and location of the histological border were compared with those of the clinical border. RESULTS: In 21 samples taken at the lesion where subclinical extension was not shown by mapping biopsy, the shape and location of the histological border were almost identical to those of the clinical border. However, two samples exhibited small foci of Paget cells outside the clinical border, showing subclinically extended satellite lesions. In the two samples taken at the lesions where subclinical extension was shown by mapping biopsy, a continuous arrangement of Paget cells extending beyond the clinical border was identified. Subclinically extended Paget cells were detected solely outside hypopigmented patches with erythema. CONCLUSIONS: In EMPD, at least two patterns of subclinical extension exist: continuous and satellite lesions. Subclinical extension might exist preferentially outside hypopigmented patches with erythema.
Assuntos
Neoplasias do Ânus/patologia , Doença de Paget Extramamária/patologia , Neoplasias Cutâneas/patologia , Neoplasias Urogenitais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Dermoscopia/métodos , Feminino , Humanos , Hipopigmentação/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Doença de Paget Extramamária/cirurgia , Fótons , Cuidados Pré-Operatórios , Neoplasias Cutâneas/cirurgiaAssuntos
Blefarite/complicações , Blefarite/tratamento farmacológico , Dermatite Atópica/complicações , Fármacos Dermatológicos/administração & dosagem , Janus Quinase 1/antagonistas & inibidores , Pirróis/administração & dosagem , Administração Tópica , Humanos , Masculino , Resultado do Tratamento , Adulto JovemAssuntos
Penfigoide Mucomembranoso Benigno , Penfigoide Bolhoso , Idoso , Autoanticorpos , Autoantígenos , Humanos , Imunoglobulina E , Laminina , MasculinoAssuntos
Obstrução das Vias Respiratórias/terapia , Epidermólise Bolhosa Adquirida/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Doenças da Laringe/terapia , Doenças Faríngeas/terapia , Obstrução das Vias Respiratórias/complicações , Epidermólise Bolhosa Adquirida/complicações , Humanos , Doenças da Laringe/complicações , Masculino , Pessoa de Meia-Idade , Doenças Faríngeas/complicações , Resultado do TratamentoRESUMO
A 79-year-old Japanese woman presented with severe recalcitrant erosions on her oral mucosa, resembling paraneoplastic pemphigus. Using indirect immunofluorescence, we detected IgA antibodies against the cell surface, and both IgG and IgA antibodies against the basement membrane zone. Immunoblotting showed that the IgG antibodies reacted weakly with bullous pemphigoid 230 and periplakin, whereas the IgA antibodies did not react with any antigen. IgA antibodies to both desmoglein (Dsg)1 and Dsg3 were detected by ELISA. IgA antibodies to desmocollin (Dsc)3 were also detected by using cDNAs for human Dsc1-3 transfected into COS-7 cells. Despite treatment with oral prednisolone, high-dose intravenous immunoglobulin and double-filtration plasmapheresis, the skin lesions remained active, and the patient died from bronchiolitis obliterans-like respiratory failure. Despite extensive investigations and postmortem examination, no underlying neoplasms were found. The complex immunopathological findings probably played an important role in the development of the patient's unusual clinical features.
Assuntos
Membrana Basal/imunologia , Caderinas de Desmossomos/imunologia , Imunoglobulina A/imunologia , Neoplasias Bucais/imunologia , Síndromes Paraneoplásicas/imunologia , Penfigoide Bolhoso/imunologia , Idoso , Desmocolinas/imunologia , Desmogleína 1/imunologia , Desmogleína 3/imunologia , Evolução Fatal , Feminino , Humanos , Imunoglobulina G/imunologiaRESUMO
BACKGROUND: Pemphigus is a potentially fatal autoimmune epidermal bullous disorder. Various treatment modalities have been described to treat pemphigus. In cases where the disease fails to respond to conventional therapy, rituximab has been shown to be effective. OBJECTIVE: To study the efficacy of rituximab in the treatment of resistant or severe pemphigus in Indian patients. METHODS: Patients with pemphigus were treated with intravenous rituximab 1000 mg in adults or 375 mg/m(2) body surface area in children by two doses, 15 days apart in this open labelled pilot study. Anti-desmoglein1 (anti-Dsg1) antibodies and anti-desmoglein3 (anti-Dsg3) antibodies were measured at the start of therapy and at the end of the follow-up period. The outcome was studied in terms of control of disease activity (CD), complete remission (CR), partial remission (PR) and time to disease control (TDC) as defined by the consensus statement from the International Pemphigus Committee. RESULTS: A total of 9 (90%) of 10 patients responded to the treatment. Three (30%) had CR of disease and were off all treatment. Four (40%) patients had CR and were on low dose oral prednisolone. Two (20%) patients had PR and were on low dose prednisolone. One patient died of sepsis. The mean TDC was 8 weeks. Response to treatment showed good correlation with index values of anti-Dsg1 antibody. Infusion-related angioedema and sepsis were seen as complications due to rituximab administration. CONCLUSION: Rituximab is effective in treating resistant and severe pemphigus in Indian patients. Acute complications can occur during rituximab infusion and require close monitoring.
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Pênfigo/diagnóstico , Pênfigo/tratamento farmacológico , Adolescente , Adulto , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos/efeitos adversos , Criança , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Índia , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Medição de Risco , Rituximab , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Oral mucosal lesions develop in pemphigus vulgaris, but not in pemphigus foliaceus. This clinical phenomenon is explained by the 'desmoglein (Dsg) compensation theory'. Dsg3 and Dsg1 are major autoantigens for pemphigus vulgaris and pemphigus foliaceus, respectively. Dsg3 is overexpressed and Dsg1 is weakly expressed on the oral mucosa. Thus, on the oral mucosa, suppression of Dsg3 function by anti-Dsg3 autoantibodies is not compensated by weakly expressed Dsg1 in pemphigus vulgaris, while suppression of Dsg1 function by anti-Dsg1 autoantibodies is perfectly compensated by richly expressed Dsg3 in pemphigus foliaceus. OBJECTIVES: We present five Japanese patients with pemphigus who deviate from this theory, i.e. all patients showed oral lesions (three also had cutaneous lesions) and reacted only with Dsg1, but not with Dsg3, by enzyme-linked immunosorbent assay. METHODS: To confirm whether the unique clinical phenotypes in our patients were due to a different immunological profile from that in classical pemphigus, we examined the reactivity of the patient sera by immunoprecipitation-immunoblotting analysis using five Dsg1/Dsg2 domain-swapped molecules. RESULTS: The sera of two patients who had only oral lesions tended to react with the extracellular (EC) 5 domain of Dsg1, the domain that is considered nonpathogenic in classical pemphigus foliaceus. Sera of three patients with mucocutaneous lesions reacted with EC1 domain or with both EC1 and EC2 domains of Dsg1, like classical pemphigus foliaceus. CONCLUSIONS: These results indicate that antigenic diversity of anti-Dsg1 antibodies in these patients may cause the unique oral mucosal and cutaneous lesions, although further studies are required to elucidate the pathomechanisms.