CELINA WAKISAKA MARUTA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Dermatologia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina
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- Analysis of the reactivity of indirect immunofluorescence in patients with pemphigus foliaceus and pemphigus vulgaris using rat bladder epithelium as a substrate(2011) ORTOLAN, Damaris G.; SOUZA, Danielle P. G.; AOKI, Valeria; SANTI, Claudia G.; GABBI, Tatiana V. B.; ICHIMURA, Ligia M. F.; MARUTA, Celina W.OBJECTIVES: To evaluate the reactivity of indirect immunofluorescence using rat bladder epithelium as a substrate in patients with pemphigus foliaceus and pemphigus vulgaris from the Department of Dermatology, University of Sao Paulo Medical School, Brazil. METHODS: Thirty-two patients (8 male and 24 female) from the Department of Dermatology, University of Sao Paulo Medical School, were selected. Three had mucosal pemphigus vulgaris, 20 had mucocutaneous pemphigus vulgaris, and 9 had pemphigus foliaceus. Patients' sera were tested by indirect immunofluorescence performed on human foreskin and rat bladder epithelium and by ELISA assays utilizing baculovirus-expressed recombinant desmoglein 3 and desmoglein 1. RESULTS: No patients with mucosal pemphigus vulgaris, 5 of 20 patients with mucocutaneous pemphigus vulgaris (25%) and 4 of 9 patients with pemphigus foliaceus (44%) had positive indirect immunofluorescence using rat bladder epithelium as a substrate. CONCLUSION: Indirect immunofluorescence using rat bladder epithelium as a substrate is recommended whenever a diagnosis of paraneoplastic pemphigus is considered. The identification of a subset of pemphigus foliaceus and pemphigus vulgaris patients that recognizes desmoplakins by this laboratory tool is critical to avoid the misdiagnosis of paraneoplastic pemphigus.
- Histopathological and clinical evaluation of chronic spontaneous urticaria patients with neutrophilic and non-neutrophilic cutaneous infiltrate(2018) MARTINS, Cintia Freitas; MORAIS, Karina Lopes; FIGUEROA, Pamela; DIAS, Natasha Favoretto; VALENTE, Neusa Sakai; MARUTA, Celina Wakisaba; CRIADO, Paulo RicardoBackground: Chronic urticaria has an expressive prevalence in general population, especially in adults, and is defined by the presence of intermittent hives for six weeks or longer. Our study aims to characterize the histological patterns of chronic spontaneous urticaria, based on the inflammatory cell infiltrate, and correlate them to laboratory exams. Methods: It was performed a retrospective analysis of laboratory, histopathology and direct immunofluorescence data of 93 patients with chronic urticaria. For histopathological analysis, cell count was performed in four fields at high magnification (x400) for each specimen. The resulting cell count medians were submitted to statistical analysis and, then, were correlated to laboratorial findings. Results: We found a female predominance (76.34%) of chronic urticaria cases, and an average age of 42.5 years (SD +/- 15). Two histological groups were distinctive: 1) chronic urticaria with predominance of neutrophils or eosinophils - N (%) = 39 (42.4%) - and 2) chronic urticaria with predominance of lymphocytes - N (%) = 53 (57.6%). There was not significant correlation between histological groups and laboratorial tests. Moreover, direct immunofluorescence was positive in 21 (33,87%) from 62 patients. Conclusions: There is not enough scientific evidence to support neutrophilic urticaria as a solid, separate entity.
- Laryngeal involvement in pemphigus vulgaris: a proposed classification(2012) MAHMOUD, A.; MIZIARA, I. D.; COSTA, K. C.; SANTI, C. G.; MARUTA, C. W.; AOKI, V.Objective: (1) To investigate the incidence of laryngeal involvement in a large series of patients with pemphigus vulgaris, using endoscopic examination, (2) to describe the lesions, and (3) to establish a classification of laryngeal involvement in pemphigus vulgaris based on the location of the lesions. Study design: Prospective study. Methods: A total of 40 sequentially treated pemphigus vulgaris patients, diagnosed using clinical, histological and immunofluorescence criteria, were evaluated for laryngeal manifestations using endoscopic examination. The results were used to establish a graded classification of laryngeal involvement according to the location of the lesions. Results: Active laryngeal lesions (ulcers or blisters) were found in 16 patients (40 per cent). Of these, 37.5 per cent were classified as grade I, 20 per cent as grade II, 20 per cent as grade III and 17.5 per cent as grade IV. Conclusion: Laryngeal involvement is common in pemphigus vulgaris and must be considered at the point of diagnosis. Grade I lesions are the most frequent.
- 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.
- Trichosporon inkin as an Emergent Pathogen in Patients With Severe Pemphigus(2015) ALMEIDA JUNIOR, Joao Nobrega de; OLIVEIRA, Renata Buccheri de; DUARTE, Amaro; MOTTA, Adriana Lopes; ROSSI, Flavia; FIGUEIREDO, Dulce Sachiko Yamamoto de; NEGRO, Gilda Maria Barbaro Del; AOKI, Valeria; MARUTA, Celina Wakisaka; SANTI, Claudia Giuli; BENARD, GilIMPORTANCE To our knowledge, these are the first reports of bloodstream infections by Trichosporon inkin in patients with pemphigus. OBSERVATIONS Trichosporon inkin, a novel organism causing bloodstream infection, was detected in 2 patients with pemphigus. An elderly man with pemphigus foliaceus died despite treatment with liposomal amphotericin B, 3mg/kg/d, and a young girl with pemphigus vulgaris responded to treatment with voriconazole, 8mg/kg/d, for 24 days. One of the T inkin isolates had a minimal inhibitory concentration of 2mg/L against amphotericin B, suggesting resistance to the drug. CONCLUSIONS AND RELEVANCE Delayed suspicion of invasive infection by T inkin may result in a poor outcome in patients with severe forms of pemphigus. This opportunistic infection is highly refractory to conventional potent antifungal treatment.
- Evaluation of D-dimer serum levels among patients with chronic urticaria, psoriasis and urticarial vasculitis(2013) CRIADO, Paulo Ricardo; ANTINORI, Lidi Che Leon; MARUTA, Celina Wakisaka; REIS, Vitor Manoel Silva dosBACKGROUND: It has been demonstrated that neutrophils, eosinophils and monocytes, under appropriated stimulus, may express tissue factor and therefore, activate the extrinsic pathway of coagulation. We performed a transversal and case-control study of patients with chronic urticaria and patients with psoriasis, in our outpatient clinic to evaluate the production of D-dimer. OBJECTIVE: To evaluate D-dimer serum levels in patients with chronic urticaria and its possible correlation with disease activity. PATIENTS AND METHODS: The study was conducted from October 2010 until March 2011. We selected 37 consecutive patients from our Allergy Unit and Psoriasis Unit, and divided them into three groups for statistical analysis: (i) 12 patients with active chronic urticaria (CU); (ii) 10 patients with chronic urticaria under remission and (iii) 15 patients with psoriasis (a disease with skin inflammatory infiltrate constituted by neutrophils, lymphocytes and monocytes). Another five patients with urticarial vasculitis were allocated in our study, but not included in statistical analysis. The serum levels of D-dimer were measured by Enzyme Linked Fluorescent Assay (ELFA), and the result units were given in ng/ml FEU. RESULTS: Patients with active chronic urticaria had the highest serum levels of D-dimer (p<0.01), when compared to patients with CU under remission and the control group (patients with psoriasis). CONCLUSIONS: Patients with active chronic urticaria have higher serum levels of D-dimer, when compared to patients with chronic urticaria under remission and patients with psoriasis. We found elevated serum levels of D-dimer among patients with urticarial vasculitis.
- Up-regulation of chemokine C-C ligand 2 (CCL2) and C-X-C chemokine 8 (CXCL8) expression by monocytes in chronic idiopathic urticaria(2012) SANTOS, J. C.; BRITO, C. A. de; FUTATA, E. A.; AZOR, M. H.; ORII, N. M.; MARUTA, C. W.; RIVITTI, E. A.; DUARTE, A. J. S.; SATO, M. N.The disturbed cytokinechemokine network could play an important role in the onset of diseases with inflammatory processes such as chronic idiopathic urticaria (CIU). Our main objectives were to evaluate the relation between proinflammatory chemokine serum levels from CIU patients and their response to autologous skin test (ASST) and basophil histamine release (BHR). We also aimed to assess the chemokine secretion by peripheral blood mononuclear cells (PBMC) upon polyclonal stimulus and to evaluate chemokine CC ligand 2/C-X-C chemokine 8 (CCL2/CXCL8) and Toll-like receptor-4 (TLR-4) expression in monocytes. We observed significantly higher serum levels of the CXCL8, CXCL9, CXCL10 and CCL2 in CIU patients compared to the healthy group, regardless of the BHR or ASST response. The basal secretion of CCL2 by PBMC or induced by Staphylococcus aureus enterotoxin A (SEA) was higher in CIU patients than in the control group, as well as for CXCL8 and CCL5 secretions upon phytohaemagglutinin stimulation. Also, up-regulation of CCL2 and CXCL8 mRNA expression was found in monocytes of patients upon SEA stimulation. The findings showed a high responsiveness of monocytes through CCL2/CXCL8 expression, contributing to the creation of a proinflammatory environment in CIU.
- 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
- IgA pemphigus: Case series with emphasis on therapeutic response(2014) MORENO, Ana Carulina L.; SANTI, Claudia G.; GABBI, Tatiana V. B.; AOKI, Valeria; HASHIMOTO, Takashi; MARUTA, Celina W.
- 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.