Artigos e Materiais de Revistas Científicas - LIM/53
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A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.
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- Human interleukin-36γ plays a crucial role in cytokine induction during Sporothrix brasiliensis and S. schenckii infection in keratinocytes and PBMCs(2024) KISCHKEL, Brenda; SANTOS, Jessica C. dos; LOPES-BEZERRA, Leila; TABORDA, Carlos P.; JOOSTEN, Leo A. B.Cytokines of the interleukin (IL)-1 superfamily including the different IL-36 isoforms, have been reported as mediators of acute and chronic inflammation in human skin diseases, such as psoriasis. Here, we demonstrated for the first time that Sporothrix schenckii and S. brasiliensis, the fungi that cause subcutaneous infection sporotrichosis, can induce the expression of IL-36 alpha, IL-36 gamma and IL-36Ra in human keratinocytes and primary peripheral blood mononuclear cells (PBMCs). Specifically, IL-36 gamma was differentially expressed by keratinocytes stimulated with Sporothrix yeasts when compared to the commensal microorganism Staphylococcus epidermidis. The exposure of keratinocytes to 24 h or 7-days culture supernatant of PBMCs stimulated with Sporothrix induced higher IL-36 gamma production compared to direct stimulation of keratinocytes with the live fungus. We identified that IL-36 gamma mRNA expression in keratinocytes is increased in the presence of IL-17, TNF, IL-113 and IL-1 alpha and these cytokines may act synergistically to maintain IL-36 gamma production. Lastly, using a cohort of 164 healthy individuals, we showed that individuals carrying variants of the IL36G gene (rs11690399 and rs11683399) exhibit increased IL-36 gamma production as well as increased innate cytokine production after Sporothrix exposure. Importantly, stimulation of PBMCs with recombinant IL-36 gamma increased the production of IL-113 and IL-6, while IL-36Ra were able to decrease the concentration of these cytokines. Our findings contribute to the understanding of the pathogenesis of sporotrichosis and suggest that IL-36 gamma may be involved in maintaining the cytokine loop that leads to tissue destruction by exacerbating the immune response in sporotrichosis. Of high interest, we present the IL-36 signalling pathway as a potential new therapeutic target.
- Areata-Like Lupus as a Clinical Manifestation of Cutaneous Lupus Erythematosus(2022) MORAIS, K. L.; SECCHIN, P.; ANZAI, A.; VERUSSA, M. J. M. C.; MUNCK, A.; FECHINE, C. O. C.; VALENTE, N. Y. S.; ROMITI, R.Introduction: Lupus erythematosus (LE) is a chronic autoimmune disease that frequently causes hair loss and scalp lesions. Hair loss can be scarring and nonscarring, diffuse, or patchy. The nonscarring patchy alopecia is usually related to systemic LE (SLE) and may simulate alopecia areata (AA), reason why it is named areata-like lupus. Our case was diagnosed with areata-like lupus but did not meet criteria for SLE. Case Report: A 63-year-old woman presented with irregular nonscarring patchy alopecia in the temporal and frontoparietal scalp. Trichoscopy showed exclamation mark hairs, vellus hairs, and sparse yellow dots. Histology revealed epidermal vacuolar interface dermatitis, lymphohistiocytic infiltrate around the bulbs of anagen follicles, and eccrine glands. Direct immunofluorescence showed deposits of C3, IgA, and IgG in the basement membrane zone. Discussion: Patients with cutaneous LE can also manifest as nonscarring patchy alopecia that is clinically similar to AA, despite the absence of systemic manifestations. Areata-like lupus is secondary to the lupus autoimmune infiltrate that affects the skin including the hair follicles. Trichoscopy, histology, and direct immunofluorescence are important to differentiate this form of alopecia from AA, which is believed to have a higher incidence in lupus patients.
- Small fiber neuropathy and intractable scalp pruritus in dermatomyositis patients(2023) CIRINO, P. V.; HORDINSKY, M.; MCADAMS, B.; ROMITI, R.Background: Scalp pruritus is a common symptom in Dermatomyositis (DM) patients. There are indications that small nerve fibers neuropathy could be involved in this symptom, however the etiology of scalp pruritus is not fully understood. Objectives: To assess epidermal nerve fiber (ENF) density of dermatomyositis patients with scalp pruritus by biopsy by confocal microscopy and immunohistochemistry with subsequent imaging analysis. Methods: DM patients with severe scalp pruritus from the dermatology outpatient clinic were compared to healthy volunteers. Two 4-mm scalp skin biopsies were obtained above the right ear in the parietal region and below the occipital protuberance in the occipital region. Biopsy specimens were incubated with primary antibodies to protein gene product (PGP 9.5), calcitonin gene–related peptide (CGRP), substance P (SP) were used to visualize nerve fibers (ENF) and collagen IV was used to label the epidermal basement membrane. The number of ENFs per millimeter was counted and recorded as the mean of ± SD of counts in 16 images at two micrometer increments/sections, two from each of the samples. ENF densities were compared between groups and a multiple linear regression model was applied to associated factors with ENF density. Results: Fifteen DM patients with severe scalp pruritus and 12 healthy volunteers were included in the study. The mean number of ENF/mm in occipital region of DM group was 16.0 ± 13.9 while the control group in the same region was 99.8 ± 33.1. In parietal region the number of ENF/mm of DM group was 18.0 ± 20.7 while in control group was 50.4 ± 17.4 (p < 0.001). Conclusion: DM patients with pruritus could have some impairment of small nerve fiber density that could explain their recalcitrant scalp pruritus.
- Correlation of clinical, histopathologic, and direct immunofluorescence findings in lesional and nonlesional scalp of frontal fibrosing alopecia and lichen planopilaris – An observational study(2023) DOCHE, I.; VALENTE, N.; SOTTO, M. N.; RIVITTI-MACHADO, M. C.; AOKI, V.; GERLERO, P.; HORDINSKY, M. K.
- Skin innate immune response against fungal infections and the potential role of trained immunity(2024) BOMBASSARO, Amanda; FIGUEIREDO, Julia Marcondes; TABORDA, Carlos P.; JOOSTEN, Leo A. B.; VICENTE, Vania A.; QUEIROZ-TELLES, Flavio; MEIS, Jacques F.; KISCHKEL, BrendaFungal skin infections are distributed worldwide and can be associated with economic and social traits. The immune response related to skin cells is complex and its understanding is essential to the comprehension of each cell's role and the discovery of treatment alternatives. The first studies of trained immunity (TI) described the ability of monocytes, macrophages and natural killer (NK) cells to develop a memory-like response. However, the duration of TI does not reflect the shorter lifespan of these cells. These conclusions supported later studies showing that TI can be observed in stem and haematopoietic cells and, more recently, also in non-immune skin cells such as fibroblasts, highlighting the importance of resident cells in response to skin disorders. Besides, the participation of less studied proinflammatory cytokines in the skin immune response, such as IL-36 gamma, shed light into a new possibility of inflammatory pathway blockade by drugs. In this review, we will discuss the skin immune response associated with fungal infections, the role of TI in skin and clinical evidence supporting opportunities and challenges of TI and other inflammatory responses in the pathogenesis of fungal skin infections.
- Sensitive Scalp and Trichodynia: Epidemiology, Etiopathogenesis, Diagnosis, and Management(2023) SOUZA, Emilly Neves; ANZAI, Alessandra; FECHINE, Carolina Oliveira Costa; VALENTE, Neusa Yuriko Sakai; ROMITI, RicardoSensitive scalp (SSc) is considered a sensitive skin on the scalp, with its particularities. Although it is not rare in the dermatological practice and the term is commonly present in personal care products, this entity is poorly investigated in the medical literature. The etiopathogenesis is still uncertain, and the sensitivity may be associated with hair loss. Clinical manifestations are subjective symptoms of pruritus, burning, pain, pricking, and/or trichodynia, often with scalp erythema. SSc can be triggered by several factors (endogenous or exogenous). The diagnosis is guided by the anamnesis, and there are still no specific trichoscopic features. Trigeminal trophic syndrome and postherpetic neuralgia are the main differential diagnosis to be considered. We organized the therapeutical approach in three steps: scalp care, topical and systemic treatment.
- Evaluation of a diagnostic algorithm for mastocytosis in skin biopsies and CD25 expression in skin mast cells of 49 patients followed up at a Tertiary Hospital in Sao Paulo, Brazil(2024) VIEIRA, Marina L.; SAMORANO, Luciana P.; PINCELLI, Marcella S.; RIVITTI-MACHADO, Maria C. da M.; OLIVEIRA, Zilda N. P. de
- Imiquimod chemoprophylaxis for field cancerization in xeroderma pigmentosum patients-A prospective study(2023) ROCHA, Lilian Kelly Faria Licariao; FERREIRA, Paula; GIANOTTI, Marcelo A.; AVANCINI, Joao; MENCK, Carlos F. M.; CASTRO, Ligia P.; OLIVEIRA, Zilda Najjar Prado de; RIVITTI, Maria C.; SAMORANO, Luciana P.; PEREIRA, Naiura Vieira; FESTA NETO, Cyro
- Can COVID-19 impact the natural history of paracoccidioidomycosis? Insights from an atypical chronic form of the mycosis(2023) SOUZA, Cesar Augusto Tomaz de; PONCE, Cesar Cilento; KLAUTAU, Gisele Burlamaqui; MARQUES, Nathan Costa; QUEIROZ, Wladimir; PATZINA, Rosely Antunes; BENARD, Gil; LINDOSO, Jose Angelo LaulettaParacoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides spp. It can occur as an acute/subacute form (A/SAF), a chronic form (CF) and rarely as a mixed form combining the features of the two aforementioned forms in an immunocompromised patient. Here, we report a 56-year-old male patient with CF-PCM who presented with atypical manifestations, including the development of an initial esophageal ulcer, followed by central nervous system (CNS) lesions and cervical and abdominal lymphatic involvement concomitant with severe SARS-CoV-2 infection. He was HIV-negative and had no other signs of previous immunodeficiency. Biopsy of the ulcer confirmed its mycotic etiology. He was hospitalized for treatment of COVID-19 and required supplemental oxygen in the intensive unit. The patient recovered without the need for invasive ventilatory support. Investigation of the extent of disease during hospitalization revealed severe lymphatic involvement typical of A/SAF, although the patient`s long history of high-risk exposure to PCM, and lung involvement typical of the CF. Esophageal involvement is rare in non-immunosuppressed PCM patients. CNS involvement is also rare. We suggest that the immunological imbalance caused by the severe COVID-19 infection may have contributed to the patient developing atypical severe CF, which resembles the PCM mixed form of immunosuppressed patients. Severe COVID-19 infection is known to impair the cell-mediated immune response, including the antiviral response, through T-lymphopenia, decreased NK cell counts and T-cell exhaustion. We hypothesize that these alterations would also impair antifungal defenses. Our case highlights the potential influence of COVID-19 on the course of PCM. Fortunately, the patient was timely treated for both diseases, evolving favorably.
- Fast and cost-effective protocol to produce Paracoccidioides spp. antigens(2023) FERNANDES-BERALDO, Karolina Rosa; FREITAS-XAVIER, Roseli Santos de; PARDINI-VICENTINI, AdrianaIntroduction. The existing methods for Paracoccidioides spp. antigen production are problematic in terms of standardization, specificity, stability, repeatability, and reproducibility.Objective. To optimize the methodology for Paracoccidioides spp. antigen production and evaluate its applicability in paracoccidioidomycosis immunodiagnosis.Materials and methods. The antigens were obtained from Paracoccidioides lutzii isolates (01, 66, and 8334), Paracoccidioides brasiliensis sensu stricto (113), and Paracoccidioides restripiensis (B-339). These fungi were grown at 36 degrees C +/- 1 degrees C, on modified Fava-Netto agar, according to Freitas et al. (2018). Paracoccidioides lutzii antigens were obtained after 5, 10, and 20 days of culture, whereas P. brasiliensis and P. restripiensis antigens were obtained after 10 days. Antigens were evaluated in natura, 10 and 20 times concentrated. Antigenic capacity was evaluated using a double immunodiffusion assay against serum samples from patients with paracoccidioidomycosis, histoplasmosis, and aspergillosis, and random blood donors.Results. Cross-reactivity between Paracoccidioides spp. antigens was observed when P. brasiliensis, P. restrepiensis antigens, and P. lutzii antigens were evaluated with the polyclonal antibodies against P. lutzii and P. brasiliensis, respectively. No cross-reactivity was obtained for polyclonal antibodies against Histoplasma capsulatum, Aspergillus fumigatus, and random blood donors. The proposed protocol allowed stable, repeatable, and reproducible genus-specific antigen production at a low cost and in a short cultivation time.Conclusion. The proposed protocol allowed us to obtain genus-specific antigens that can be developed and reproduced in all laboratories in Brazil and South America, where paracoccidioidomycosis is a neglected disease, contributing to an early diagnosis, especially in endemic regions, regardless of the species.
- Vaccine development for pathogenic fungi: current status and future directions(2023) CHECHI, Jessica L.; COSTA, Felipe A. C. da; FIGUEIREDO, Julia M.; SOUZA, Cassia M. de; VALDEZ, Alessandro F.; ZAMITH-MIRANDA, Daniel; CAMARA, Aline C.; TABORDA, Carlos P.; NOSANCHUK, Joshua D.Introduction: Fungal infections are caused by a broad range of pathogenic fungi that are found worldwide with different geographic distributions, incidences, and mortality rates. Considering that there are relatively few approved medications available for combating fungal diseases and no vaccine formulation commercially available, multiple groups are searching for new antifungal drugs, examining drugs for repurposing and developing antifungal vaccines, in order to control deaths, sequels, and the spread of these complex infections.Areas covered: This review provides a summary of advances in fungal vaccine studies and the different approaches under development, such as subunit vaccines, whole organism vaccines, and DNA vaccines, as well as studies that optimize the use of adjuvants. We conducted a literature search of the PubMed with terms: fungal vaccines and genus of fungal pathogens (Cryptococcus spp. Candida spp. Coccidioides spp. Aspergillus spp. Sporothrix spp. Histoplasma spp. Paracoccidioides spp. Pneumocystis spp. and the Mucorales order), a total of 177 articles were collected from database.Expert opinion: Problems regarding the immune response development in an immunocompromised organism, the similarity between fungal and mammalian cells, and the lack of attention by health organizations to fungal infections are closely related to the fact that, at present, there are no fungal vaccines available for clinical use.
- Prevalence of psoriasis and other autoimmune skin diseases in a recently contacted indigenous community in the Auaris region, Yanomami Indigenous Territory, Brazil(2023) ROMITI, Ricardo; MARTINS, Luciana P. F.; SANTANA, Yago R. T.; TIMBO, Renata V.; KURIZKY, Patricia S.; BARROSO, Daniel H.; ANDRADE, Rafael R. De; GOMES, Ciro M.; GRIFFITHS, Christopher E. M.
- Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique(2023) ORFALI, Raquel Leao; LORENZINI, Daniel; BRESSAN, Aline; TANAKA, Anber Ancel; CERQUEIRA, Ana Maria Mosca de; HIRAYAMA, Andre da Silva; RAMOS, Andrea Machado Coelho; PROENCA, Carolina Contin; SILVA, Claudia Marcia de Resende; LACZYNSKI, Cristina Marta Maria; CARNEIRO, Francisca Regina; DUARTE, Gleison; HANS FILHO, Gunter; GONCALVES, Heitor de Sa; MELO, Ligia Pessoa de; AZULAY-ABULAFIA, Luna; WEBER, Magda Blessmann; RIVITTI-MACHADO, Maria Cecilia; ZANIBONI, Mariana Colombini; OGAWA, Marilia; PIRES, Mario Cezar; IANHEZ, Mayra; FELIX, Paulo Antonio Oldani; BONAMIGO, Renan; TAKAOKA, Roberto; LAZZARINI, Rosana; CESTARI, Silmara; MAYOR, Silvia Assumpcao Soutto; CESTARI, Tania; OLIVEIRA, Zilda Najjar Prado de; SPULS, Phyllis I.; GERBENS, Louise A. A.; AOKI, ValeriaThis publication is an update of the ""Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology"" published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript. (c) 2023 Sociedade Brasileira de Dermatologia.
- In vitro activity of sanitizers against mono- and polymicrobial biofilms of C. parapsilosis and S. aureus(2023) CASTRO, Vitor de Paula; THOMAZ, Danilo Yamamoto; VIEIRA, Kayro de Lima; LOPES, Leonardo Guedes; ROSSI, Flavia; NEGRO, Gilda M. B. Del; BENARD, Gil; PIRES, Regina HelenaThe emergence of disinfectant-resistant microorganisms poses a significant threat to public health. These resilient pathogens can survive and thrive in hospital settings despite routine disinfection practices, leading to persistent infections and the potential for outbreaks. In this study, we investigated the impact of 11 different commercial sanitizers at various concentrations and exposure times on biofilms consisting of clinical and nosocomial environmental isolates of Candida parapsilosis and Staphylococcus aureus. Among the sanitizers tested, 0.5% and 2.0% chlorhexidine (CLX), 10% polyvinyl pyrrolidone (PVP-I), a disinfectant based on quaternary ammonium compound (QAC), 2% glutaraldehyde, and 0.55% orthophthalaldehyde (OPA) demonstrated efficacy against both C. parapsilosis and S. aureus in monospecies and mixed biofilms. Analysis showed that 0.5% CLX and 10% PVP-I had fungicidal and bactericidal activity against all biofilms. However, the sanitizer based on QAC and 0.55% OPA proved to be bacteriostatic and fungicidal against both monospecies and mixed biofilms. In mixed biofilms, despite the last four sanitizers exerting fungicidal action, the reduction of fungal cells was approximately 4 log(10) CFU/mL compared to monospecies biofilms, showing that the interaction provided more resistance of the yeast to the sanitizer. Formation of mixed biofilms in hospital settings can create an ecological niche that enhances the survival of pathogens against routine sanitization procedures. Therefore, effective sanitization practices, including regular cleaning with effective sanitizers, should be implemented to prevent C. parapsilosis/S. aureus biofilm formation in healthcare settings.
- Human peripheral blood age-associated (CD11c+Tbet+) B cells: No association with age(2023) PINTO, Thalyta Nery Carvalho; SILVA, Cibele Cristine Berto Marques da; PINTO, Regina Maria Carvalho; DUARTE, Alberto Jose da Silva; BENARD, Gil; FERNANDES, Juliana Ruiz
- Mutational signatures and increased retrotransposon insertions in xeroderma pigmentosum variant skin tumors(2023) CORRADI, Camila; VILAR, Juliana B.; BUZATTO, Vanessa C.; SOUZA, Tiago A. de; CASTRO, Ligia P.; MUNFORD, Veridiana; VECCHI, Rodrigo De; GALANTE, Pedro A. F.; ORPINELLI, Fernanda; MILLER, Thiago L. A.; BUZZO, Jose L.; SOTTO, Mirian N.; SALDIVA, Paulo; OLIVEIRA, Jocelanio W. de; CHAIBUB, Sulamita C. W.; SARASIN, Alain; MENCK, Carlos F. M.This manuscript describes the genetic alterations found in the skin tumors of XP-V patients deficient in translesion synthesis. The alterations include mutation signatures and retrotransposition insertions, which provide mechanistic information about DNA polymerase eta functions. Xeroderma pigmentosum variant (XP-V) is an autosomal recessive disease with an increased risk of developing cutaneous neoplasms in sunlight-exposed regions. These cells are deficient in the translesion synthesis (TLS) DNA polymerase eta, responsible for bypassing different types of DNA lesions. From the exome sequencing of 11 skin tumors of a genetic XP-V patients' cluster, classical mutational signatures related to sunlight exposure, such as C>T transitions targeted to pyrimidine dimers, were identified. However, basal cell carcinomas also showed distinct C>A mutation spectra reflecting a mutational signature possibly related to sunlight-induced oxidative stress. Moreover, four samples carry different mutational signatures, with C>A mutations associated with tobacco chewing or smoking usage. Thus, XP-V patients should be warned of the risk of these habits. Surprisingly, higher levels of retrotransposon somatic insertions were also detected when the tumors were compared with non-XP skin tumors, revealing other possible causes for XP-V tumors and novel functions for the TLS polymerase eta in suppressing retrotransposition. Finally, the expected high mutation burden found in most of these tumors renders these XP patients good candidates for checkpoint blockade immunotherapy.
- Cutaneous metastases from solid neoplasms - Literature review(2023) SOUZA, Bruno de Castro e; MIYASHIRO, Denis; PINCELLI, Marcella Soares; SANCHES, Jose AntonioCutaneous metastases from solid tumors are uncommon events in clinical practice. Most of the time, the patient already has the diagnosis of a malignant neoplasm when the cutaneous metastasis is detected. However, in up to one-third of cases, cutaneous metastasis is identified before the primary tumor. Therefore, its identification may be essential for starting treatment, although it is usually indicative of poor prognosis. The diagnosis will depend on clinical, histopathological, and immunohistochemical analysis. Sometimes the identification of the primary site is difficult; however, a thorough analysis using imaging tests and constant surveillance is important. (c) 2023 Sociedade Brasileira de Dermatologia.
- Significance of Aspergillus spp. isolation in defining cases of COVID-19 Associated Pulmonary Aspergillosis - CAPA(2023) COCIO, Tiago Alexandre; SIQUEIRA, Lumena Pereira Machado; RICILUCA, Katie Cristina Takeuti; GIMENES, Viviane Mazo Favero; ANDRADE, Tania Sueli de; BENARD, Gil; MARTINEZ, Roberto; BOLLELA, Valdes RobertoCOVID-19-Associated Pulmonary Aspergillosis (CAPA) is a relatively common complica-tion in patients with severe forms of the disease caused by the SARS-CoV-2 virus. Diag-nosing and confirming CAPA is challenging. In this study, Aspergillus spp. isolation in respiratory specimens from patients with COVID-19 was evaluated for identifying cases of CAPA. In 2020-2021, 17 Aspergillus spp. were isolated from 15 COVID-19 patients admit-ted to a university hospital in Brazil. Patient records were retrospectively reviewed to obtain clinical-epidemiological data and other markers of Aspergillus spp. infection and then compared with the ECMM/ISHAM criteria for defining CAPA. Probable CAPA was defined in 5/10 patients, who had Aspergillus spp. isolated from Bronchoalveolar Lavage (BAL) or a positive galactomannan blood test. Additionally, anti-Aspergillus antibodies were detected in two of these patients, during active or follow-up phases of CAPA. In another seven patients with Aspergillus spp. isolated from tracheobronchial aspirate or sputum, CAPA was presumed, mainly due to deterioration of clinical conditions and new lung imaging suggestive of fungal infection. Antifungal agents to control CAPA, particu-larly voriconazole, were used in 9/15 cases. In cases of probable CAPA and remaining patients, clinical conditions and comorbidities were similar, with lethality being high, at 60% and 71%, respectively. The number of CAPA cases defined by scientific criteria was lower than that assumed in the clinical context. This was largely due to the lack of BAL collection for fungal culture and the non-intensive use of other markers of invasive asper-gillosis. The isolation of Aspergillus spp. in different respiratory specimens should alert clinicians to the diagnosis of CAPA.
- Generalized pustular psoriasis in Brazil: A public claims database study(2022) DUARTE, G. V.; CARVALHO, A. V. Esteves de; ROMITI, R.; GASPAR, A.; MELO, T. Gomes de; SOARES, C. P.; AGUIRRE, A. R.Background: Generalized pustular psoriasis (GPP) is a rare and severe phenotype of psoriasis characterized by sudden outbreak of widespread coalescent sterile pustules associated with a spectrum of systemic symptoms. Objective: We aimed to describe the epidemiology and treatment of GPP in Brazil from the public health care system perspective. Methods: This was a retrospective public claims database study, using outpatient and inpatient databases, with information from January 2018 to August 2020, based on records of health resource utilization by patients with GPP. Outpatient treatment regimens and fatal inpatient outcomes were described. Results: In total, 1458 outpatients of all ages were identified, of whom 53% were women. We estimated the GPP prevalence in Brazil to be between 0.7 and 0.9 per 100,000. Acitretin was the most commonly dispensed drug. Of all the outpatients, 769 outpatients could be tracked in the inpatient database, and 151 had hospital admissions during the study period. Of them, 5.3% had a fatal outcome during hospitalization. A primary skin condition or an infection was the most frequent hospitalization cause. Limitation: The International Classification of Diseases codes for GPP and psoriasis have not been previously validated in this context. Conclusion: GPP is a rare disease in Brazil and affects individuals of all ages and both sexes. Hospitalizations and disease-related deaths highlight the need for its prompt diagnosis, close medical follow-up, and effective treatment. © 2021 American Academy of Dermatology, Inc.
- Chronic exposure to cigarette smoke transiently worsens the disease course in a mouse model of pulmonary paracoccidioidomycosis(2022) BUCCHERI, Renata; DUARTE-NETO, Amaro Nunes; SILVA, Flaviano Luiz Batista; HADDAD, Gabrielle Carvalho; SILVA, Leandro Buffoni Roque da; AZEVEDO NETTO, Raymundo; LEDESMA, Felipe Lourenço; TABORDA, Carlos Pelleschi; BENARD, GilABSTRACT Paracoccidioidomycosis (PCM) may present as an acute/subacute clinical form, characterized by a progressive disease arising from the airborne initial infection, or, most often, as an asymptomatic or subclinical infection that may manifest later during an individual’s life, the chronic form. Epidemiological studies show the existence of a strong association between smoking and the development of the chronic form. Current evidence demonstrates that cigarette smoke (CS) has immunosuppressive properties that could be implicated in the increasing susceptibility to the chronic form of PCM. To address this issue, we developed a murine model of a non-progressive pulmonary form of PCM that was exposed to CS at a magnitude that mimicked a moderate smoker. The chronic CS exposure started after 2 weeks and lasted up until 20 weeks post-infection, with the aim of mimicking human natural history, since it is estimated that individuals from endemic areas are infected early in life. The control group consisted of infected but not CS-exposed mice. We assessed the lung fungal burden (colony forming units [CFU]) and the area affected by the granulomatous inflammatory response, fungal dissemination to spleen and liver, and, by immunohistochemistry, the presence of CD4 and CD8 lymphocytes, CD68 and MAC-2 macrophages, and IFN-γ, IL-10 and TNF expressing cells within the granulomatous response. We detected a CS effect as early as 2 weeks after exposure (four weeks post-infection) when the lung CFU of exposed animals was significantly higher than in their non-exposed counterparts. At 12 weeks, the CS-exposed animals presented a more severe disease, as witnessed by the persistent higher lung fungal load (although it did not reach statistical significance [ p = 0.054]), greater dissemination to other organs, greater affected area of the lung, decreased IFN-γ/IL-10 ratio, and higher TNF expression within the granulomas, compared with CS-non-exposed mice. The number of CD4 and CD8 lymphocytes infiltrating the granulomas was similar between both mice groups, but there was a decrease in the number of MAC-2+ macrophages. No difference was noted in the CD68+ macrophage number. However, the follow-up in week 20 showed that the immunological effects of exposure to CS ceased, with both CS and NCS mice showing the same infectious features, i.e., a trend for resolution of the infection. In conclusion, we show that chronic CS-exposure alters the course of the disease in an experimental model of subclinical pulmonary PCM, confirming the epidemiological link between CS-exposure and the chronic form of PCM. However, we also show that this effect is transitory, being detected between 4- and 12-weeks post-infection but not thereafter. The possible immune mechanisms that mediate this effect and the reasons for its transitory effect are discussed.