NEUSA YURIKO SAKAI VALENTE
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina
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- Leprosy in transplant recipients: report of a case after liver transplantation and review of the literature(2011) TRINDADE, M. A. B.; PALERMO, M. L.; PAGLIARI, C.; VALENTE, N.; NAAFS, B.; MASSAROLLO, P. C. B.; D'ALBUQUERQUE, L. A. C.; BENARD, G.P>Leprosy still is an important public health problem in several parts of the world including Brazil. Unlike the diseases caused by other mycobacteria, the incidence and clinical presentation of leprosy seems little affected in immunosuppressed patients. We report the first case, to our knowledge, of a liver transplant patient who developed multi-bacillary leprosy. The patient presented with papules and infiltrated plaques with loss of sensation suggestive of leprosy 3.5 years after living-related liver transplantation for autoimmune hepatitis. A skin biopsy showing non-caseating macrophagic granulomas, neuritis, and intact acid-fast bacilli on Fite-Faraco stain, confirmed the diagnosis of borderline lepromatous leprosy. The donor of the liver did not show any evidence of leprosy. During follow-up, the patient presented 2 episodes of upgrading leprosy type I reactions, 1 mild before leprosy treatment, and 1 moderate 3 months after receiving standard multi-drug treatment (rifampicin, clofazimine, and dapsone). These reactions were accompanied by increase in liver function tests, especially of canalicular enzymes. This reaction occurred despite the patient's triple immunosuppression regimen. The moderate reaction was successfully treated with further immunosuppression (prednisone, 0.5 mg/kg). Currently, the patient is asymptomatic, off leprosy medication, with routine liver transplant follow-up. The dilemmas in diagnosis and management of such a case are discussed and the literature on leprosy in transplant recipients is reviewed.
- In situ immune response in human dermatophytosis: possible role of Langerhans cells (CD1a+) as a risk factor for dermatophyte infection(2019) REIS, Ana Paula Carvalho; CORREIA, Franciele Fernandes; JESUS, Thais Martins; PAGLIARI, Carla; SAKAI-VALENTE, Neusa Y.; BELDA JUNIOR, Walter; CRIADO, Paulo Ricardo; BENARD, Gil; SOUSA, Maria Gloria TeixeiraDermatophytosis is a cutaneous mycosis caused by a plethora of keratinophilic fungi, but Trichophyton rubrum is the most common etiological agent. Despite its high prevalence worldwide, little is known about the host defense mechanisms in this infection, particularly the in situ immune response. Using an immunohistochemistry approach, we investigated the density of CD1a+, factor XIIIa+ and CD68+ cells in the skin of dermatophytosis patients. Langerhans cells (CD1a+ cells) were significantly decreased in the epidermis of patients, both in affected and unaffected areas. In the dermis, however, no differences in the density of macrophages (CD68+ cells) and dermal dendrocytes (factor XIIIa+ cells) were observed. These results suggest that the decreased number of Langerhans cells may be a risk factor for development of dermatophytosis.
- Ulcers in leprosy patients, an unrecognized clinical manifestation: a report of 8 cases(2019) MIYASHIRO, Denis; CARDONA, Carolina; VALENTE, Neusa Yuriko Sakai; AVANCINI, Joao; BENARD, Gil; TRINDADE, Maria Angela BianconciniBackground Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae. It is a polymorphic disease with a wide range of cutaneous and neural manifestations. Ulcer is not a common feature in leprosy patients, except during reactional states, Lucio's phenomenon (LP), or secondary to neuropathies. Cases presentation We report eight patients with multibacillary leprosy who presented specific skin ulcers as part of their main leprosy manifestation. Ulcers were mostly present on lower limbs (eight patients), followed by the upper limbs (three patients), and the abdomen (one patient). Mean time from onset of skin ulcers to diagnosis of leprosy was 17.4 months: all patients were either misdiagnosed or had delayed diagnosis, with seven of them presenting grade 2 disability by the time of the diagnosis. Reactional states, LP or neuropathy as potential causes of ulcers were ruled out. Biopsy of the ulcer was available in seven patients: histopathology showed mild to moderate lympho-histiocytic infiltrate with vacuolized histiocytes and intact isolated and grouped acid-fast bacilli. Eosinophils, vasculitis, vasculopathy or signs of chronic venous insufficiency were not observed. Skin lesions improved rapidly after multidrug therapy, without any concomitant specific treatment for ulcers. Conclusions This series of cases highlights the importance of recognizing ulcers as a specific cutaneous manifestation of leprosy, allowing diagnosis and treatment of the disease, and therefore avoiding development of disabilities and persistence of the transmission chain of M. leprae.
- Topical Application of Imiquimod as a Treatment for Chromoblastomycosis(2014) SOUSA, Maria da Gloria Teixeira de; BELDA JR., Walter; SPINA, Ricardo; LOTA, Priscila Ramos; VALENTE, Neusa Sakai; BROWN, Gordon D.; CRIADO, Paulo Ricardo; BENARD, GilChromoblastomycosis is a subcutaneous mycosis that remains a therapeutic challenge, with no standard treatment and high rates of relapse. On the basis of our recent discoveries in mouse models, we tested the efficacy of topical applications of imiquimod to treat patients afflicted with this chronic fungal infection. We report results of treatment for the first 4 recipients of topical imiquimod, all of whom displayed a marked improvement of their lesions, both with and without concurrent oral antifungal therapy.
- Case Report: A Patient with Erythema Nodosus Leprosum and Chagas Cardiopathy: Challenges in Patient Management and Review of the Literature(2011) TRINDADE, Maria Angela B.; CARVALHO, Noemia B.; BELFORT, Elaini C.; PAGLIARI, Carla; GAKIYA, Erika; SAKAI-VALENTE, Neusa Y.; BENARD, Gil; SHIKANAI-YASUDA, Maria A.We report a patient with severe multi-bacillary leprosy complicated by recurrent episodes of erythema nodosum necrotisans that required thalidomide and/or corticosteroids during follow-up. Although the patient was from an area to which Chagas disease is endemic, this diagnosis was initially missed and was only investigated when heart failure developed in the patient. The difficulties of managing erythema nodosum necrotisans and heart failure concomitantly and those involved in excluding the diagnosis of acute myocarditis caused by reactivation of Chagas disease secondary to the immunosuppressive regimen are discussed. Other potential causes for the heart failure and possible interactions between the two diseases and their treatments are discussed. We also reviewed the literature for the association between leprosy and Chagas disease, both of which are highly endemic in Brazil. This case emphasizes the importance of searching for subclinical co-infections in leprosy patients because reactions frequently develop during specific. treatment in these patients, and these reactions require prolonged therapy with immunosuppressive drugs.
- Severe type 1 upgrading leprosy reaction in a renal transplant recipient: a paradoxical manifestation associated with deficiency of antigen-specific regulatory T-cells?(2017) VIEIRA, Ana Paula; TRINDADE, Maria Angela Bianconcini; PAULA, Flavio Jota de; SAKAI-VALENTE, Neusa Yurico; DUARTE, Alberto Jose da Silva; LEMOS, Francine Brambate Carvalhinho; BENARD, GilBackground: Due to its chronic subclinical course and large spectrum of manifestations, leprosy often represents a diagnostic challenge. Even with proper anti-mycobacteria treatment, leprosy follow up remains challenging: almost half of leprosy patients may develop reaction episodes. Leprosy is an infrequent complication of solid organ transplant recipients. This case report illustrates the challenges in diagnosing and managing leprosy and its reactional states in a transplant recipient. Case presentation: A 53-year-old man presented 34 months after a successful renal transplantation a borderline-tuberculoid leprosy with signs of mild type 1 upgrading reaction (T1R). Cutaneous manifestations were atypical, and diagnosis was only made when granulomatous neuritis was found in a cutaneous biopsy. He was successfully treated with the WHO recommended multidrug therapy (MDT: rifampicin, dapsone and clofazimine). However he developed a severe T1R immediately after completion of the MDT but no signs of allograft rejection. T1R results from flare-ups of the host T-helper-1 cell-mediated immune response against Mycobacterium leprae antigens in patients with immunologically unstable, borderline forms of leprosy and has been considered an inflammatory syndrome in many aspects similar to the immune reconstitution inflammatory syndromes (IRS). The T1R was successfully treated by increasing the prednisone dose without modifying the other immunosuppressive drugs used for preventing allograft rejection. Immunological study revealed that the patient had a profound depletion of both in situ and circulating regulatory T-cells and lack of expansion of the Tregs upon M. leprae stimulation compared to T1R leprosy patients without iatrogenic immunosuppression. Conclusions: Our case report highlights that leprosy, especially in the transplant setting, requires a high degree of clinical suspicion and the contribution of histopathology. It also suggests that the development of upgrading inflammatory syndromes such as T1R can occur despite the sustained immunosuppressors regimen for preventing graft rejection. Our hypothesis is that the well-known deleterious effects of these immunosuppressors on pathogen-induced regulatory T-cells contributed to the immunedysregulation and development T1R.
- Development of Type 2, But Not Type 1, Leprosy Reactions is Associated with a Severe Reduction of Circulating and In situ Regulatory T-Cells(2016) VIEIRA, Ana Paula; TRINDADE, Maria Angela Bianconcini; PAGLIARI, Carla; AVANCINI, Joao; SAKAI-VALENTE, Neusa Yurico; DUARTE, Alberto Jose da Silva; BENARD, GilLeprosy is frequently complicated by the appearance of reactions that are difficult to treat and are the main cause of sequelae. We speculated that disturbances in regulatory T-cells (Tregs) could play a role in leprosy reactions. We determined the frequency of circulating Tregs in patients with type 1 reaction (T1R) and type 2 reaction (T2R). The in situ frequency of Tregs and interleukin (IL)-17, IL-6, and transforming growth factor beta (TGF)-beta-expressing cells was also determined. T2R patients showed markedly lower number of circulating and in situ Tregs than T1R patients and controls. This decrease was paralleled by increased in situ IL -17 expression but decreased TGF-beta expression. Biopsies from T1R and T2R patients before the reaction episodes showed similar number of forkhead box protein P3 + (FoxP3+) and IL-17+ cells. However, in biopsies taken during the reaction, T2R patients showed a decrease in Tregs and increase in IL-17+ cells, whereas T1R patients showed the opposite: Tregs increased but IL-17+ cells decreased. We also found decreased expansion of Tregs upon in vitro stimulation with Mycobacterium leprae and a trend for lower expression of FoxP3 and the immunosuppressive molecule cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in T2R Tregs. Our results provide some evidence to the hypothesis that, in T2R, downmodulation of Tregs may favor the development of T-helper -17 responses that characterize this reaction.
- TOLL-LIKE RECEPTORS (TLR) 2 AND 4 EXPRESSION OF KERATINOCYTES FROM PATIENTS WITH LOCALIZED AND DISSEMINATED DERMATOPHYTOSIS(2015) OLIVEIRA, Cristiane Beatriz de; VASCONCELLOS, Cidia; SAKAI-VALENTE, Neusa Y.; SOTTO, Mirian Nacagami; LUIZ, Fernanda Guedes; BELDA JUNIOR, Walter; SOUSA, Maria da Gloria Teixeira de; BENARD, Gil; CRIADO, Paulo RicardoThere are few studies on the role of innate immune response in dermatophytosis. An investigation was conducted to define the involvement of Toll-Like Receptors (TLRs) 2 and 4 in localized (LD) and disseminated (DD) dermatophytosis due to T. rubrum. Fifteen newly diagnosed patients, eight patients with LD and seven with DD, defined by involvement of at least three body segments were used in this study. Controls comprised twenty skin samples from healthy individuals undergoing plastic surgery. TLR2 and TLR4 were quantified in skin lesions by immunohistochemistry. A reduced expression of TLR4 in the lower and upper epidermis of both LD and DD patients was found compared to controls; TLR2 expression was preserved in the upper and lower epidermis of all three groups. As TLR4 signaling induces the production of inflammatory cytokines and neutrophils recruitment, its reduced expression likely contributed to the lack of resolution of the infection and the consequent chronic nature of the dermatophytosis. As TLR2 expression acts to limit the inflammatory process and preserves the epidermal structure, its preserved expression may also contribute to the persistent infection and limited inflammation that are characteristic of dermatophytic infections.
- Case Report: Leprosy and Tuberculosis Co-Infection: Clinical and Immunological Report of Two Cases and Review of the Literature(2013) TRINDADE, Maria Angela B.; MIYAMOTO, Denise; BENARD, Gil; SAKAI-VALENTE, Neusa Y.; VASCONCELOS, Dewton de M.; NAAFS, BernardA review of the records of patients seen between 2004 and 2011 at the Dermatology Clinic of the Sao Paulo University Medical School showed that only two leprosy patients had been co-infected with tuberculosis (TB). One patient showed a type 1 leprosy reaction during the first 3 months of treatment of pleural TB and in the other patient, pulmonary TB was diagnosed during the first 3 months of treatment of a type 1 leprosy reaction. Both patients showed normal cellular immune response tests, including those of the interferon-gamma (IFN-gamma)/interleukin 12 (IL-12) axis. Although both mycobacterial infections are endemic in developing countries like Brazil, the co-infection has hardly been reported in the last decade. There is no suitable explanation for this observation. The reports on the interaction between the two mycobacteria are highly speculative: some studies suggest that leprosy, especially the anergic form, would predispose to TB, whereas other investigations suggested an antagonism between the two diseases.
- Recurrent and disseminated pityriasis versicolor: A novel clinical form consequent to Malassezia-host interaction?(2017) ROMERO-SANDOVAL, Karina; COSTA, Anderson Alves; SOUSA, Maria Gloria Teixeira; FURUCHO, Celia Regina; VALENTE, Neusa; CRIADO, Paulo R.; AOKI, Valeria; BENARD, GilPityriasis versicolor is a superficial fungal infection caused by Malassezia spp. The aim of this study is to propose the definition of a new clinical entity: the recurrent and disseminated pityriasis versicolor (RDPV). All patients with RDPV were enrolled over an eight-month period. Clinical and epidemiological data were obtained, Malassezia (M.) species were isolated in cultures and identified by phenotypic and molecular characterization, skin biopsies were taken from active lesions, serum levels of immunoglobulin E were obtained and therapeutic schemes were evaluated. A total of 16 patients were included (11 male, 5 female). The most frequently isolated species were M. japonica (n = 3) and M. furfur (n = 3). This is the first study that isolates M. japonica in patients with pityriasis versicolor; interestingly, those were recalcitrant patients. Seven patients (43.8%) had no cure with any of the proposed treatments; among those, 5 (71.4%) had increased serum IgE levels. The most effective treatment was itraconazole 200 mg daily for 28 days. The RDPV has very different features from the classic form, including a poor response to treatment, and the isolation of different Malassezia species; therefore, we propose a hypothesis for the definition of a new clinical condition (RDPV), which could be a result of the interaction Malassezia-host.