DENISE MIYAMOTO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
14 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 14
- Bullous pemphigoid(2019) MIYAMOTO, Denise; SANTI, Claudia Giuli; AOKI, Valeria; MARUTA, Celina WakisakaBullous pemphigoid is the most frequent autoimmune bullous disease and mainly affects elderly individuals. Increase in incidence rates in the past decades has been attributed to population aging, drug-induced cases and improvement in the diagnosis of the nonbullous presentations of the disease. A dysregulated T cell immune response and synthesis of IgG and IgE autoantibodies against hemidesmosomal proteins (BP180 and BP230) lead to neutrophil chemotaxis and degradation of the basement membrane zone. Bullous pemphigoid classically manifests with tense blisters over urticarial plaques on the trunk and extremities accompanied by intense pruritus. Mucosal involvement is rarely reported. Diagnosis relies on (1) the histopathological evaluation demonstrating eosinophilic spongiosis or a subepidermal detachment with eosinophils; (2) the detection of IgG and/or C3 deposition at the basement membrane zone using direct or indirect immunofluorescence assays; and (3) quantification of circulating autoantibodies against BP180 and/or BP230 using ELISA. Bullous pemphigoid is often associated with multiple comorbidities in elderly individuals, especially neurological disorders and increased thrombotic risk, reaching a 1-year mortality rate of 23%. Treatment has to be tailored according to the patient's clinical conditions and disease severity. High potency topical steroids and systemic steroids are the current mainstay of therapy. Recent randomized controlled studies have demonstrated the benefit and safety of adjuvant treatment with doxycycline, dapsone and immunosuppressants aiming a reduction in the cumulative steroid dose and mortality.
- How can immunohistochemistry improve the diagnosis of pemphigus foliaceus?(2018) MIYAMOTO, D.; MARUTA, C.; SANTI, C.; ZOROQUIAIN, P.; DIAS, A. B.; FUKUMORI, L.; PERIGO, A.; AOKI, V.; BURNIER, M.Purpose Pemphigus foliaceus (PF) is a rare, autoimmune blistering disorder characterized by the production of autoantibodies against desmoglein 1. The mainstay for diagnosis is the demonstration of immune complex deposition by direct immunofluorescence (DIF) in fresh tissue samples. Immunohistochemistry (IHC) recognizes autoantibodies in formalin-fixed paraffin-embedded specimens, but studies regarding its use in PF are scarce. This study aims to evaluate immunoglobulin and C3 deposition using IHC in patients with confirmed PF by DIF and indirect immunofluorescence (IIF). Material and methods Six biopsies obtained from five patients with PF and six healthy individuals were included in this study. Anti-C3c, -IgG, -IgM, and -IgA antibodies were used for DIF and automated IHC. After digitalizing the slides, staining was classified as negative (0) or positive (1 = mild/2 = intense). Results DIF revealed intraepidermal intercellular deposition of IgG and C3c (n = 6), without deposits in dermal structures. IHC was positive in the intercellular spaces between keratinocytes with anti-IgG (n = 6) and anti-C3c antibodies (n = 6); no intercellular immune complexes deposition was observed in healthy individuals. In patients with PF, inflammatory cells were tagged by anti-IgG and anti-C3c (n = 6), anti-IgM (n = 1), and anti-IgA (n = 1); and immune complexes at vessel walls were detected with anti-C3c, anti-IgG, anti-IgA (n = 6), and anti-IgM (n = 5) antibodies. Adnexal positivity occurred with anti-C3c and anti-IgG (n = 6), anti-IgM (n = 1), and anti-IgA (n = 3). Healthy individuals also presented positivity in inflammatory cells with anti-IgG and anti-C3c (n = 4), anti-IgM (n = 1), and anti-IgA (n = 3); vessels were stained with anti-IgG and anti-C3c (n = 5), anti-IgM and anti-IgA (n = 4); adnexa were not represented in all samples obtained from healthy individuals. Conclusion IHC may serve as a reliable method to assess PF diagnosis. Immune deposits in dermal structures suggest their participation in autoimmune/inflammatory processes in PF. IHC may contribute to evaluate disease mechanisms, prognostic factors, and target-oriented treatment in PF. © 2017 The Authors
- Diagnostic approach of eosinophilic spongiosis(2019) MORAIS, Karina Lopes; MIYAMOTO, Denise; MARUTA, Celina Wakisaka; AOKI, ValeriaEosinophilic spongiosis is a histological feature shared by some distinct inflammatory disorders, and is characterized by the presence of intraepidermal eosinophils associated with spongiosis. Most often, isolated eosinophilic spongiosis indicates the early stages of a subjacent autoimmune bullous dermatosis, such as the pemphigus group and bullous pemphigoid. Herein, the main causes of eosinophilic spongiosis are discussed, as well as the supplementary investigation needed to elucidate its etiology. (C) 2019 Published by Elsevier Espana, S.L.U. on behalf of Sociedade Brasileira de Dermatologia.
- Paraneoplastic pemphigus: a clinical, laboratorial, and therapeutic overview(2019) MARUTA, Celina Wakisaka; MIYAMOTO, Denise; AOKI, Valeria; CARVALHO, Ricardo Comes Ribeiro de; CUNHA, Breno Medeiros; SANTI, Claudia GiuliParaneoplastic pemphigus is a rare and severe autoimmune blistering disease characterized by mucocutaneous lesions associated with benign and malignant neoplasms. Diagnostic criteria include the presence of chronic mucositis and polymorphic cutaneous lesions with occult or confirmed neoplasia; histopathological analysis exhibiting intraepidermal acantholysis, necrotic keratinocytes, and vacuolar interface dermatitis; direct immunofluorescence with intercellular deposits (IgG and C3) and at the basement membrane zone (IgG); indirect immunofluorescence with intercellular deposition of IgG (substrates: monkey esophagus and simple, columnar, and transitional epithelium); and, autoreactivity to desmogleins 1 and 3, desmocollins 1, 2, and 3, desmoplakins I and II, envoplakin, periplakin, epiplakin, plectin, BP230, and alpha-2-macroglobulin-like protein 1. Neoplasias frequently related to paraneoplastic pemphigus include chronic lymphocytic leukemia, non-Hodgkin lymphoma, carcinomas, Castleman disease, thymoma, and others. Currently, there is no standardized treatment for paraneoplastic pemphigus. Systemic corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, rituximab, cyclophosphamide, plasmapheresis, and intravenous immunoglobulin have been used, with variable outcomes. Reported survival rates in 1, 2, and 5 years are 49%, 41%, and 38%, respectively.
- Recurrent erythema multiforme: A therapeutic proposal for a chronic disease(2021) OLIVEIRA, Natasha Favoretto Dias de; MIYAMOTO, Denise; MARUTA, Celina Wakisaka; AOKI, Valeria; SANTI, Claudia GiuliRecurrent erythema multiforme is a chronic relapsing disease that represents a therapeutic challenge. Our objective was to retrospectively evaluate the clinical-epidemiological characteristics and therapeutic response of patients with recurrent erythema multiforme and suggest a therapeutic protocol. We included patients with recurrent erythema multiforme diagnosed between January 2000 and December 2019. Clinical symptoms and a positive serology for herpes simplex virus were the inclusion criteria to initiate acyclovir in monotherapy or a combined treatment with dapsone, thalidomide, or immunosuppressants in refractory cases. Thirty-five patients were included and 71.4% were female. The median disease onset age was 35.7 years and the mean follow-up was 7.58 years. The skin was the most affected site (91.4%). Herpes simplex virus immunoglobulin (Ig)G serology was positive in 91.1% of cases. Acyclovir treatment was used in 33 of 35 patients, and complete remission was achieved in 22 of 33 after the first therapeutic course; 16 of 22 relapsed and required a second acyclovir cycle. Combined treatment with dapsone was required in nine of 33 due to partial response to acyclovir; thalidomide was an adjuvant drug in four of 33 due to adverse effects to dapsone. After the first cycle of acyclovir with or without combined therapy, 19 of 33 patients relapsed and received 2-6 additional cycles. Our results suggest that recurrent erythema multiforme presents a good response to acyclovir in monotherapy or in combined therapy with dapsone or thalidomide in the majority of patients. We propose a long-term therapeutic protocol to enable disease remission.
- Increased serum levels of vascular endothelial growth factor in pemphigus foliaceus patients with erythroderma(2017) MIYAMOTO, D.; SOTTO, M. N.; OTANI, C. S. V.; FUKUMORI, L. M. I.; PEREIRA, N. V.; SANTI, C. G.; MARUTA, C. W.; BURNIER, M. N. N.; REBEIS, M. M.; AOKI, V.Background Erythroderma is a clinical skin syndrome shared by patients with cutaneous disorders of distinct aetiologies as a result of the combined actions of chemokines, adhesion molecules, and cytokines, such as vascular endothelial growth factor (VEGF). Objective To evaluate the profile of serum levels of VEGF and soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) in pemphigus foliaceus (PF) patients with erythroderma. Methods We conducted a retrospective study, which included (i) a chart review of all PF patients from the Autoimmune Blistering Clinic, University of Sao Paulo, Brazil, from January 1991 to December 2014, together with an evaluation of demographic variables, hospitalization duration and complications and (ii) analysis of the circulating VEGF and sVEGFR-1 levels in PF patients with erythroderma by ELISA. The controls included patients with pemphigus vulgaris or psoriasis. Results We observed higher serum VEGF levels in PF patients during erythroderma than during the non-erythrodermic phase. PF patients showed increased serum levels of sVEGFR-1 during the erythrodermic phase in comparison to controls. Interestingly, the sVEGFR-1 and antidesmoglein-1 levels were positively correlated during the non-erythrodermic period. Conclusion Erythroderma, which represents one clinical form of PF, implies more severe outcomes. The circulating levels of VEGF, a potent endothelial activator, are increased in PF patients with erythroderma; this result suggests the contribution of the blood vessel endothelium to the pathogenesis of this clinical syndrome. Interestingly, our findings showed a positive correlation between the sVEGFR-1 and antidesmoglein-1 antibody levels, indicating a suppressive response to VEGF augmentation during the erythrodermic phase of PF.
- Epidermolysis bullosa acquisita(2022) MIYAMOTO, Denise; GORDILHO, Juliana Olivieri; SANTI, Claudia Giuli; PORRO, Adriana MariaEpidermolysis bullosa acquisita is a rare autoimmune disease, characterized by the synthesis of anti-collagen VII autoantibodies, the main component of hemidesmosome anchoring fibrils. The antigen-antibody binding elicits a complex inflammatory response, which culminates in the loss of dermo-epidermal adhesion of the skin and/or mucous membranes. Skin fragility with bullae, erosions, and milia in areas of trauma characterizes the mechanobullous form of the disease. In the inflammatory form of epidermolysis bullosa acquisita, urticarial inflammatory plaques with tense bullae, similar to bullous pemphigoid, or mucosal lesions can determine permanent scars and loss of functionality in the ocular, oral, esophageal, and urogenital regions. Due to the similarity of the clinical findings of epidermolysis bullosa acquisita with other diseases of the pemphigoid group and with porphyria cutanea tarda, the diagnosis is currently confirmed mainly based on the clinical correlation with histopathological findings (pauci-inflammatory subepidermal cleavage or with a neutrophilic infiltrate) and the demonstration of the presence of anti-collagen VII IgG in situ by direct immunofluorescence, or circulating anti-collagen VII IgG through indirect immunofluorescence and/or ELISA. There is no specific therapy for epidermolysis bullosa acquisita and the response to treatment is variable, usually with complete remission in children and a worse prognosis in adults with mucosal involvement. Systemic corticosteroids and immunomodulators (colchicine and dapsone) are alternatives for the treatment of mild forms of the disease, while severe forms require the use of corticosteroid therapy associated with immunosuppressants, intravenous immunoglobulin, and rituximab. (C) 2022 Sociedade Brasileira de Dermatologia.
- Considerations on Immunization and Immunosuppression of Patients With Autoimmune Blistering Diseases During COVID-19 Pandemic in Brazil: Case Report(2022) MIYAMOTO, Denise; SANTI, Claudia Giuli; MARUTA, Celina Wakisaka; AOKI, ValeriaAutoimmune blistering diseases comprise a rare group of potentially life-threatening dermatoses. Management of autoimmune disorders poses a challenge in terms of achieving disease control and preventing adverse events. Treatment often requires an individualized approach considering disease severity, age, comorbidities, and infectious risk especially in the context of the ongoing COVID-19 pandemic. Knowledge regarding SARS-CoV-2 infection is still evolving and no specific antiviral therapy is available yet. We report four patients with active disease that required adjustment of treatment during the pandemic to discuss the use of immunosuppressants and immunobiologics, weighing potential risks and benefits of each therapy modality and vaccination status.
- How Coronavirus Disease 2019 Changed Dermatology Practice in 1 Year Around the World from 11 Countries(2021) SUN, Qisi; MCMAHON, Devon E.; UGWU-DIKE, Pearl O.; SUN, Qiuning; TANG, Keyun; ZHANG, Hanlin; SUCHONWANIT, Poonkiat; OH, Choon Chiat; CHONG, Alvin H.; WILLEMS, Anneliese; GALVAN, Cristina; DODIUK-GAD, Roni P.; FANTINI, Fabrizio; RECALCATI, Sebastiano; AVANCINI, Joao; MIYAMOTO, Denise; SANCHES, Jose A.; RABOOBEE, Noufal; BRAVO, Francisco; FREEMAN, Esther E.
- Pseudomonas aeruginosa as an uncommon agent of infectious panniculitis(2022) YENDO, Tatiana Mina; PANTE, Cristina de Castro; MIYAMOTO, DenisePseudomonas aeruginosa is a Gram-negative bacillus that frequently causes septicemia, abscesses and infections in skin wounds. Panniculitis caused by this microorganism is unusual and there are few well-documented cases, none of them in a patient with systemic lupus erythematosus. The present report describes an immunosuppressed patient with systemic lupus erythematosus who developed panniculitis caused by Pseudomonas aeruginosa, with a review of the literature on this rare presentation. (C) 2022 Sociedade Brasileira de Dermatologia.