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- 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.
- In situ expression of Th17 immunologic mediators in American cutaneous leishmaniasis caused by Leishmania (V.) braziliensis and Leishmania (L.) amazonensis in the Brazilian Amazon(2023) RODRIGUES, G. F.; ALCâNTARA, L. S.; BARROS, J. P. B.; LIMA, A. C. S. de; CAMPOS, M. B.; MORAES, C.; FERREIRA, A. F.; MATTA, V. L. R.; LAURENTI, M. D.; CORBETT, C. E. P.; SILVEIRA, F. T.; GOMES, C. M. C.American cutaneous leishmaniasis (ACL) presents a wide spectrum of clinical and immunopathological manifestations. In Brazil, Leishmania (L.) amazonensis[La] and Leishmania(V.)braziliensis[Lb] show the highest pathogenic potential for humans causing different clinical forms: localized cutaneous leishmaniasis (LCL : Lb/La), anergic diffuse cutaneous leishmaniasis (ADCL : La) and mucocutaneous leishmaniasis (MCL : Lb). ADCL and MCL are the most severe forms and infection leads to a cellular immune response at the hyposensitivity and hypersensitivity poles. Th17-cells are involved in the ACL pathogenesis, are derived from naïve TCD4+ cells regulated by RORγt, differentiate in presence of IL-6, TGF-β, IL- 1β, IL-23 and express IL-17. Aim of this study was to characterize the cellular immune response mediated by Th17-profile cells through in situ determination of the expression of RORγt, IL-17, IL-6, TGF-β, IL-1β, and IL-23 in the ACL clinical-immunopathological spectrum caused by L.(L.)amazonensis and L.(V.)braziliensis. Biopsies of skin and mucosal lesions from forty patients including ADCL(n=8), LCL[La](n=17), LCL[Lb](n=9) and MCL(n=6), were examined by immunohistochemistry. The immunostained cells density (cells/mm2) was determined in image analysis system using AxionVision 4.8 software (Zeiss). As the disease evolution time (DET) was different among ACL patients, the effect of DET on the expression of immunological markers was evaluated in different clinical forms and histopathological changes, using ANCOVA. Our results showed significantly increased expression of RORγt, IL-17, IL-6, IL-1β and IL-23 in patients with ACL polar forms (ADCL and MCL); higher TGF-β expression was found in ADCL. DET influenced the expression of RORγt and IL-6 in: clinical forms of ACL and in categories of parasitism. DET also affected the production of RORγt, IL-17, IL-6, TGF-β and IL-1β in types of inflammatory infiltrate, evidencing that DET had effect on the expression of Th17 profile cytokines in ACL. Together, the expression of immunological mediators of Th17 profile in the ACL spectrum, as well as the DET effect, demonstrate the participation of this cell lineage in the immunopathogenesis of ACL, mainly in the polar and more severe forms of ACL spectrum. The dubious role played by Th17-cells may favors immune response suppression and parasitic persistence in ADCL, while in MCL it contributes to an exacerbated immune response and parasite scarcity.
- Frontal fibrosing alopecia associated with lichen planus pigmentosus: A multicentre retrospective descriptive analytical study of 104 patients(2023) BRITO, Flavia Oliveira Xavier de; ALMEIDA, Rita Fernanda Cortez de; MACHADO, Carla Jorge; LEMES, Luciana Rodino; DONDA, Andre Luiz Vairo; BLANCO, Aline; SILVEIRA, Aline Lucy Galavotti; MUNCK, Andreia; LIMA, Caren dos Santos; CANELA, Carolina Porto Cotrim; FECHINE, Carolina Oliveira Costa; OBADIA, Daniel Lago; PINTO, Giselle Martins; ALVES, Lorena Dourado; DIAS, Maria Fernanda Reis Gavazzoni; BENEZ, Marcela; RIGATTI, Marcelo; KADI, Nadia El; KAKIZAKI, Priscila; MINOTTO, Renan; FRATTINI, Sidney; RAMOS, Paulo Mueller; MELO, Daniel Fernandes
- 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.
- Therapeutic Activity of a Topical Formulation Containing 8-Hydroxyquinoline for Cutaneous Leishmaniasis(2023) LIMA, Sarah Kymberly Santos de; CAVALLONE, italo Novaes; SERRANO, Dolores Remedios; ANAYA, Brayan J.; LALATSA, Aikaterini; LAURENTI, Marcia Dalastra; LAGO, Joao Henrique Ghilardi; SOUZA, Dalete Christine da Silva; MARINSEK, Gabriela Pustiglione; LOPES, Beatriz Soares; MARI, Renata de Britto; PASSERO, Luiz Felipe Domingues; MICHNIAK-KOHN, Bozena B.Cutaneous leishmaniasis exhibits a wide spectrum of clinical manifestations; however, only a limited number of drugs are available and include Glucantime (R) and amphotericin B, which induce unacceptable side effects in patients, limiting their use. Thus, there is an urgent demand to develop a treatment for leishmaniasis. Recently, it was demonstrated that 8-hydroxyquinoline (8-HQ) showed significant leishmanicidal effects in vitro and in vivo. Based on that, this work aimed to develop a topical formulation containing 8-HQ and assess its activity in experimental cutaneous leishmaniasis. 8-HQ was formulated using a Beeler base at 1 and 2% and showed an emulsion size with a D-50 of 25 and 51.3 mu m, respectively, with a shear-thinning rheological behaviour. The creams were able to permeate artificial Strat-M membranes and excised porcine skin without causing any morphological changes in the porcine skin or murine skin tested. In BALB/c mice infected with L. (L.) amazonensis, topical treatment with creams containing 1 or 2% of 8-HQ was found to reduce the parasite burden and lesion size compared to infected controls with comparable efficacy to Glucantime (R) (50 mg/kg) administered at the site of the cutaneous lesion. In the histological section of the skin from infected controls, a diffuse inflammatory infiltrate with many heavily infected macrophages that were associated with areas of necrosis was observed. On the other hand, animals treated with both creams showed only moderate inflammatory infiltrate, characterised by few infected macrophages, while tissue necrosis was not observed. These histological characteristics in topically treated animals were associated with an increase in the amount of IFN-gamma and a reduction in IL-4 levels. The topical use of 8-HQ was active in decreasing tissue parasitism and should therefore be considered an interesting alternative directed to the treatment of leishmaniasis, considering that this type of treatment is non-invasive, painless, and, importantly, does not require hospitalisation, improving patient compliance by allowing the treatment to be conducted.
- Prevalence and incidence of canine visceral leishmaniasis and its clinical-immunological features in an endemic area of the Brazilian Amazon(2023) CARNEIRO, Liliane A.; LIMA, Luciana V.; CAMPOS, Marliane B.; SANTOS, Thiago Vasconcelos dos; RAMOS, Patricia K.; LAURENTI, Marcia D.; SILVEIRA, Fernando T.Background: A cohort study for 2 years period analysed the prevalence, incidence and clinical-immunological features of canine Leishmania (L.) chagasi-infection in 316 mongrel dogs in a visceral leishmaniasis-endemic area in Para State, Brazil.Objective/Methods: Diagnosis of infection was performed by the indirect fluorescent antibody test (IFAT-IgG), the leishmanin skin test (LST) and a parasite search (from the popliteal lymph node aspiration) at the beginning of the study and at 6, 12 and 24 months intervals.Results: IFAT/LST revealed three immune profiles of infection: (I) IFAT((+))/LST(-) (81), (II) IFAT((-))/LST(+) (17) and (III) IFAT((+))/LST(+) (13). Prevalence of profiles I, II and III were 25.6, 5.4 and 4.1%, and an overall prevalence 35.1%. Incidence of profiles I, II and III were 5.4, 0.3 and 0.0%, and an overall incidence 5.7% dogs per month. Incidence at the age ranges <1 year, >= 1 year, <7 years and >= 7 years evidenced a highest rate in the age range <1 year (6.6% dogs per month). Parasitological diagnosis was positive in 19% dogs at the prevalence (85.7% profile I), and in 11% at the incidence (100% profile I). The clinical picture of 179 infected dogs showed 145 (81%) of profile I (82% subclinical); 21 (11.7%) of profile II (100% subclinical); and 13 (7.3%) of profile III (84.6% subclinical). Conversion from subclinical to sick dogs was higher (p < 0.05) in profile I (40.2%) than in profiles II (5.8%) and III (9%). Immunological conversion showed that only 3.2% of profile I dogs (prevalence) converted to LST(+) (two at the end of the first 6 months and 1 after 24 months), while 82.3% of profile II dogs converted to IFAT((+)) (11 in the first 6 months, whereas three after 12 months). A 100% death rate was observed in dogs from profile I alone.Conclusion: These results reinforce the need of adopting preventive strategies against CVL as early as in the first semester of the dog's life.
- Nanostructured Lipid Carriers as Robust Systems for Lupeol Delivery in the Treatment of Experimental Visceral Leishmaniasis(2023) JESUS, Jessica Adriana; SILVA, Thays Nicolli Fragoso da; SOUSA, Ilza Maria Oliveira; FERREIRA, Aurea Favero; LAURENTI, Marcia Dalastra; COSTA, Paulo Cardoso da; FERREIRA, Domingos de Carvalho de; PASSERO, Luiz Felipe DominguesLeishmaniasis is a neglected tropical disease that affects millions of people around the world. Available therapy causes severe side effects, has unacceptable prices for some specific formulations, and the existence of drug-resistant parasites limits the use of the currently available arsenal of antiparasitic drugs. Therefore, natural products serve as one of the main sources to develop new and effective alternative drugs against leishmaniasis. In this sense, the present study evaluated the potential of the triterpene Lupeol (Lu) entrapped in nanostructured lipid carriers (NLCs) for the treatment of experimental visceral leishmaniasis. The therapeutic efficacy of Lu or Lu entrapped in NLC (Lu-NLC) was investigated in golden hamsters infected with Leishmania (Leishmania) infantum. Lu-NLC presented a mean particle size of 265.3 +/- 4.6 nm, a polydispersity index of <0.25 and a zeta potential of -37.2 +/- 0.84 mV; the efficacy of encapsulation was 84.04 +/- 0.57%. Studies on hamsters showed that Lu-NLC (5 mg/kg) administered intraperitoneally for 10 consecutive days caused a reduction of 99.9% in the number of parasites in the spleen and liver compared to the untreated infected control. On the contrary, Lu-treated animals (5 mg/kg) had 94.4 and 90.2% less parasites in the spleen and liver, respectively, than the infected group. Additionally, a significant preservation of splenic and hepatic tissues was observed in animals treated with Lu-NLC or Lu. Furthermore, Lu-NLC-treated animals produced high levels of anti-Leishmania IgG2 isotype. These data indicate that NLC potentialized Lu efficacy in experimental visceral leishmaniasis. This work suggests that Lu and nanoformulations carrying this compound may be considered as an important tool to be included in the alternative therapy of leishmaniasis.
- Chromoblastomycosis: New Perspective on Adjuvant Treatment with Acitretin(2023) JR, Walter Belda; PASSERO, Luiz Felipe Domingues; CARVALHO, Caroline Heleno Chagas de; MOJICA, Paula Celeste Rubiano; VALE, Pablo AndradeChromoblastomycosis (CBM) is a neglected human disease, caused by different species of pigmented dematiaceous fungi that cause granulomatous and suppurative dermatosis. This infection is difficult to treat and there are limited therapeutic options, including terbinafine, itraconazole, and tioconazole. Classic treatment is administered for a long period of time, but some patients do not respond properly, and therefore, such therapeutic approaches possess low cure rates. Therefore, it is vital to develop new strategies for the treatment of CBM. In this regard, it has been observed that the association of immunomodulatory molecules such as glucan with therapy carried out with antifungal drugs improves cutaneous lesions in comparison to treatment with antifungal drugs alone, suggesting that drug association may be an interesting and significant approach to incorporate into CBM therapy. Thus, the aim of this work was to associate classical antifungal therapy with the adjuvants imiquimod and acitretin. In the present case, we reported a patient with extensive CBM caused by Fonsaecae pedrosoi, that affected an extensive area of the right leg, that was left without treatment for 11 years. He was treated with a classical combination of itraconazole and terbinafine via the oral route plus topical imiquimod and oral acitretin, as an adjuvant therapy. After five months of treatment, a significant regression of verrucous plaques was observed, suggesting that the use of these adjuvants combined with the classical antifungal drugs, intraconazole plus terbinafine, can reduce treatment time and rapidly improve the patient's quality of life. This result confirms that the use of coadjuvant drugs may be effective in the treatment of this infectious disease.
- New Immunological Markers in Chromoblastomycosis-The Importance of PD-1 and PD-L1 Molecules in Human Infection(2023) CAVALLONE, Italo N.; JR, Walter Belda; CARVALHO, Caroline Heleno C. de; LAURENTI, Marcia D.; PASSERO, Luiz Felipe D.The pathogenesis of chromoblastomycosis (CBM) is associated with Th2 and/or T regulatory immune responses, while resistance is associated with a Th1 response. However, even in the presence of IFN-gamma, fungi persist in the lesions, and the reason for this persistence is unknown. To clarify the factors associated with pathogenesis, this study aimed to determine the polarization of the cellular immune response and the densities of cells that express markers of exhaustion in the skin of CBM patients. In the skin of patients with CBM, a moderate inflammatory infiltrate was observed, characterized primarily by the occurrence of histiocytes. Analysis of fungal density allowed us to divide patients into groups that exhibited low and high fungal densities; however, the intensity of the inflammatory response was not related to mycotic loads. Furthermore, patients with CBM exhibited a significant increase in the number of CD4+ and CD8+ cells associated with a high density of IL-10-, IL-17-, and IFN-gamma-producing cells, indicating the presence of a chronic and mixed cellular immune response, which was also independent of fungal load. A significant increase in the number of PD-1+ and PD-L1+ cells was observed, which may be associated with the maintenance of the fungus in the skin and the progression of the disease.
- 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.
- First report of putative Leishmania RNA virus 2 (LRV2) in Leishmania infantum strains from canine and human visceral leishmaniasis cases in the southeast of Brazil(2023) REGO, Felipe Dutra; SILVA, Eduardo Sergio da; LOPES, Valeriana Valadares; TEIXEIRA-NETO, Rafael Goncalves; BELO, Vinicius Silva; JR, Antonio Augusto Fonseca; PEREIRA, Diego Andrade; PENA, Heber Paulino; LAURENTI, Marcia Dalastra; V, Gabriela Araujo; MATTA, Vania Lucia Ribeiro da; CHOUMAN, Islam Hussein; BURRIN, Thaina Bergantin; SANDOVAL, Carmen M.; BARROUIN-MELO, Stella Maria; PINHO, Flaviane Alves de; ANDRADE, Helida Monteiro de; NUNES, Ramon Vieira; GONTIJO, Celia Maria Ferreira; SOCCOL, Vanete Thomaz; KLOCEK, Donnamae; GRYBCHUK, Danyil; MACEDO, Diego Henrique; MONTE-NETO, Rubens Lima do; YURCHENKO, Vyacheslav; SOARES, Rodrigo PedroBACKGROUND Leishmania RNA virus 1 (LRV1) is commonly found in South American Leishmania parasites belonging to the subgenus Viannia, whereas Leishmania RNA virus 2 (LRV2) was previously thought to be restricted to the Old-World pathogens of the subgenus Leishmania. OBJECTIVES In this study, we investigated the presence of LRV2 in strains of Leishmania (L.) infantum, the causative agent of visceral leishmaniasis (VL), originating from different hosts, clinical forms, and geographical regions. METHODS A total of seventy-one isolates were screened for LRV2 using semi-nested reverse transcription-polymerase chain reaction (RT-PCR) targeting the RNA-dependent RNA polymerase (RdRp) gene. FINDINGS We detected LRV2 in two L. infantum isolates (CUR268 and HP-EMO) from canine and human cases, respectively. MAIN CONCLUSIONS To the best of our knowledge, this is the first detection of LRV2 in the New World.
- Prevalence of HIV-1 infection and associated characteristics in a Brazilian indigenous population: a cross-sectional study(2023) SCHNAUFER, Erica C. S.; BARBOSA, Marcelo S.; MARQUES, Michele F. R.; BRITO, Gabriel T.; FERREIRA, Tiago S.; RIBEIRO, Anny D. C.; VALIENTE, Anna C.; MACHADO, Indianara R.; GONCALVES, Crhistinne C. M.; TANAKA, Tayana S. O.; GUIMARAES, Monick L.; RIBEIRO, Suzana M.; CRODA, Julio; SIMIONATTO, SimoneBackground Despite significant progress in the areas of prevention, diagnosis, and treatment, HIV continues to result in a substantial number of fatalities on a global scale each year. Gaining insights from epidemiological data can prove instrumental in the development of health promotion strategies, particularly within vulnerable populations, such as indigenous groups. Consequently, our study aimed to investigate the prevalence of HIV infection within the indigenous population residing in the second-largest region of Brazil. Additionally, we sought to explore the subtypes of HIV-1 and detect any drug-resistance mutations present within this population.Methods In this cross-sectional study, we aimed to evaluate the prevalence of HIV-1 infection and explore its associated characteristics within the indigenous population residing in the villages of Jaguapiru and Bororo, located in the Dourados area of Mato Grosso do Sul (MS), Brazil. Blood samples were collected for rapid HIV screening, serological tests, nucleic acid amplification, and HIV subtyping. Additionally, the HIV-1 viral load and CD4+ T lymphocyte count of the people living with HIV (PLHIV) were assessed at the time of recruitment and 24 weeks later.Findings Out of the 2190 invited individuals, 1927 (88%) were included in this study. The average age of the participants was 34.2 (& PLUSMN;13.8) years, with a majority of 74% being female. Moreover, 68.44% of the participants identified themselves as belonging to the Guarani-Kaiowa ethnic group. HIV seroprevalence was 0.93% (18/1927), and 73.22% (1411/1927) were unaware of their serological status. The prevalence of HIV-1 was higher in single indigenous people [10/617 (1.62%)], who received government benefits [14/1021 (1.37%)], had less than five years of formal education [11/685 (1.61%)], had sexual intercourse with users of injectable drugs [2/21 (9.52%)], with history of sexually transmitted infections (STIs) [10/62 (16.2%)] and incarceration [3/62 (4.84%)]. Of 18 positive samples, 44.4% (8/ 18) were successfully amplified, and HIV-1 subtype C was prevalent. Furthermore, we identified HIV-1 drug resistance mutations in four patients, specifically from the classes of Protease Inhibitor, Nucleoside Reverse Transcriptase Inhibitor, and Non-Nucleoside Reverse Transcriptase Inhibitor. Notably, three of these patients exhibited a high viral load even after 24 weeks of undergoing antiretroviral therapy. Out of the 18 PLHIV, 66.66% (12/18) had a viral load below 1000 copies/mL, while 50% (9/18) had a CD4+ T lymphocytes count greater than 350 cells/mL after 24 weeks of treatment.Interpretation Despite the concerted efforts to control HIV infection, the prevalence observed in the indigenous popu-lation under study surpassed that reported in other Brazilian indigenous groups. This disparity highlights the dispro-portionate impact of the disease on this particular group. The detection of drug-resistance mutations further emphasizes the critical need to expand diagnostic coverage, closely monitor treatment strategies, and maintain ongoing molecular surveillance. These measures are imperative for enhancing HIV management within this vulnerable population. Funding This study was partially funded by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Fundacao de Apoio ao Desenvolvimento do Ensino, Ciencia e Tecnologia do Estado de Mato Grosso do Sul (FUN-DECT), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Secretaria do Estado de Saude (SES) of Governo do Estado de Mato Grosso do Sul, and Universidade Federal da Grande Dourados (UFGD). Copyright & COPY; 2023 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
- 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.
- Histopathological characteristics of cutaneous lesions caused by Leishmania Viannia panamensis in Panama(2018) GONZÁLEZ, Kadir; DIAZ, Rosendo; FERREIRA, Aurea F.; GARCÍA, Víctor; PAZ, Héctor; CALZADA, José E.; RUÍZ, Michelle; LAURENTI, Márcia; SALDAñA, AzaelABSTRACT Cutaneous leishmaniasis (CL) is an endemic disease in the Republic of Panama, caused by Leishmania (Viannia) parasites, whose most common clinical manifestation is the presence of ulcerated lesions on the skin. These lesions usually present a chronic inflammatory reaction, sometimes granulomatous, with the presence of lymphocytes, plasma cells and macrophages. This study describes the histopathological characteristics found in the skin lesions of patients with CL caused by Leishmania (V.) panamensis in Panama. We analyzed 49 skin biopsy samples from patients with clinical suspicion of CL, by molecular tests (PCR for subgenus Viannia and HSP-70) and by Hematoxylin-Eosin staining. Samples were characterized at the species level by PCR-HSP-70/RFLP. From the 49 samples studied, 46 (94%) were positive by PCR and were characterized as Leishmania (V.) panamensis. Of these, 48% were positive by Hematoxylin-Eosin staining with alterations being observed both, in the epidermis (85%) and in the dermis (100%) of skin biopsies. The inflammatory infiltrate was characterized according to histopathological patterns: lymphohistiocytic (50%), lymphoplasmacytic (61%) and granulomatous (46%) infiltration, being the combination of these patterns frequently found. The predominant histopathological characteristics observed in CL lesions caused by L. (V.) panamensis in Panama were: an intense inflammatory reaction in the dermis with a combination of lymphohistiocytic, lymphoplasmacytic and granulomatous presentation patterns and the presence of ulcers, acanthosis, exocytosis and spongiosis in the epidermis.
- Expression of HMGCS2 in intestinal epithelial cells is downregulated in inflammatory bowel disease associated with endoplasmic reticulum stress(2023) MARTIN-ADRADOS, Beatriz; WCULEK, Stefanie K. K.; FERNANDEZ-BRAVO, Sergio; TORRES-RUIZ, Raul; VALLE-NOGUERA, Ana; GOMEZ-SANCHEZ, Maria Jose; HERNANDEZ-WALIAS, Jose Carlos; FERREIRA, Frederico Moraes; CORRALIZA, Ana Maria; SANCHO, David; ESTEBAN, Vanesa; RODRIGUEZ-PERALES, Sandra; CRUZ-ADALIA, Aranzazu; NAKAYA, Helder I. I.; SALAS, Azucena; BERNARDO, David; CAMPOS-MARTIN, Yolanda; MARTINEZ-ZAMORANO, Elena; MUNOZ-LOPEZ, Diego; MORAL, Manuel Gomez del; CUBERO, Francisco Javier; BLUMBERG, Richard S. S.; MARTINEZ-NAVES, EduardoIntroductionThe Unfolded Protein Response, a mechanism triggered by the cell in response to Endoplasmic reticulum stress, is linked to inflammatory responses. Our aim was to identify novel Unfolded Protein Response-mechanisms that might be involved in triggering or perpetuating the inflammatory response carried out by the Intestinal Epithelial Cells in the context of Inflammatory Bowel Disease. MethodsWe analyzed the transcriptional profile of human Intestinal Epithelial Cell lines treated with an Endoplasmic Reticulum stress inducer (thapsigargin) and/or proinflammatory stimuli. Several genes were further analyzed in colonic biopsies from Ulcerative Colitis patients and healthy controls. Lastly, we generated Caco-2 cells lacking HMGCS2 by CRISPR Cas-9 and analyzed the functional implications of its absence in Intestinal Epithelial Cells. ResultsExposure to a TLR ligand after thapsigargin treatment resulted in a powerful synergistic modulation of gene expression, which led us to identify new genes and pathways that could be involved in inflammatory responses linked to the Unfolded Protein Response. Key differentially expressed genes in the array also exhibited transcriptional alterations in colonic biopsies from active Ulcerative Colitis patients, including NKG2D ligands and the enzyme HMGCS2. Moreover, functional studies showed altered metabolic responses and epithelial barrier integrity in HMGCS2 deficient cell lines. ConclusionWe have identified new genes and pathways that are regulated by the Unfolded Protein Response in the context of Inflammatory Bowel Disease including HMGCS2, a gene involved in the metabolism of Short Chain Fatty Acids that may have an important role in intestinal inflammation linked to Endoplasmic Reticulum stress and the resolution of the epithelial damage.
- Rational evaluation of patients with COVID-19-related hair loss(2022) REZENDE, Hudson Dutra; MINARI, Gabriela; CUNHA, Marcele; DINATO, Sandra; DIAS, Maria Fernanda Reis Gavazzoni; ROMITI, Ricardo
- International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis(2022) HUIZEN, Astrid M. van; MENTING, Stef P.; GYULAI, Rolland; IVERSEN, Lars; KRAAIJ, Gayle E. van der; MIDDELKAMP-HUP, Maritza A.; WARREN, Richard B.; I, Phyllis SpulsIMPORTANCE A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. Objective To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Design, Setting, and Participants Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). Main Outcomes and Measures In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Results Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. Conclusions and Relevance In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.
- Generalized pustular psoriasis: A global Delphi consensus on clinical course, diagnosis, treatment goals and disease management(2023) PUIG, Lluis; CHOON, Siew Eng; GOTTLIEB, Alice B. B.; MARRAKCHI, Slaheddine; PRINZ, Joerg C.; ROMITI, Ricardo; TADA, Yayoi; BREDOW, Dorothea von; GOODERHAM, MelindaBackgroundGeneralized pustular psoriasis (GPP) is a rare and highly heterogeneous skin disease, characterized by flares of neutrophilic pustules and erythema. As a rare disease with few clinical studies and no standardized management approaches, there is a paucity of knowledge regarding GPP. ObjectivesConduct a Delphi panel study to identify current evidence and gain advanced insights into GPP. MethodsA systematic literature review was used to identify published literature and develop statements categorized into four key domains: clinical course and flare definition; diagnosis; treatment goals; and holistic management. Statements were rated on a Likert scale by a panel of dermatologists in two rounds of online questionnaires; the threshold for consensus was agreement by >= 80%. ResultsTwenty-one panellists reached consensus on 70.9%, 61.8%, 100.0% and 81.8% of statements in the 'clinical course and flare definition', 'diagnosis', 'treatment goals' and 'holistic management of GPP' domains, respectively. There was clear consensus on GPP being phenotypically, genetically and immunologically distinct from plaque psoriasis. Clinical course is highly variable, with an extensive range of complications. Clinical and histologic features supporting GPP diagnosis reached high levels of agreement, and although laboratory evaluations were considered helpful for diagnosis and monitoring disease severity, there was uncertainty around the value of individual tests. All acute and long-term treatment goals reached consensus, including rapid and sustained clearance of pustules, erythema, scaling and crust, clearance of skin lesions and prevention of new flares. Potential triggers, associated comorbidities and differential diagnoses achieved low rates of consensus, indicating that further evidence is needed. ConclusionsGlobal consensus between dermatologists was reached on clinically meaningful goals for GPP treatment, on key features of GPP flares and on approaches for assessing disease severity and multidisciplinary management of patients. On this basis, we present a management algorithm for patients with GPP for use in clinical practice.
- Access to psoriasis treatment in Brazil and Chile: A cross-sectional multicentre Global Healthcare Study on Psoriasis(2023) MAUL, Julia-Tatjana; FROEHLICH, Fabienne; MAUL, Lara Valeska; STUNNENBERG, Rieka; VALENZUELA, Fernando; CRUZ, Claudia De La; VERA-KELLET, Cristian; ARMIJO, Daniela; CESAR, Wagner G.; CARVALHO, Andre; DIDASKALU, Johannes Alexander; GRAF, Nicole; EGEBERG, Alexander; WU, Jashin J.; THYSSEN, Jacob P.; ROMITI, Ricardo; GRIFFITHS, Christopher E. M.Background Sufficient data on access to systemic treatment for patients with psoriasis living in Latin America (LA) including Brazil and Chile are lacking. Understanding the availability and limiting factors of access to treatments can help to improve patient care and decrease long-term healthcare costs. Objectives In association with the Global Psoriasis Atlas, this cross-sectional survey study analysed the availability and insurance reimbursement of systemic treatments for adult patients with psoriasis in Brazil and Chile. Methods A multicentre, cross-sectional Global Healthcare Study on Psoriasis was performed in Brazil and Chile in 2020. For each eligible adult patient with psoriasis, doctors and nurses completed a 48-item questionnaire about clinical aspects of psoriasis including the Psoriasis Area Severity Index (PASI), body surface area (BSA) score and the Dermatology Life Quality Index (DLQI), as well as the availability of systemic treatments and insurance reimbursement status. Between-country differences were compared with Wilcoxon rank sum tests for continuous variables, and a chi(2)-test or Fisher's exact test, where appropriate, for categorical variables. The median and interquartile range (IQR) was calculated for non-normal distributed data. Results A total of 1424 patients with psoriasis from 43 centres [27 centres in Brazil (n = 826) and 16 in Chile (n = 598)], were included with a mean (SD) age of 49.1 (16.3) and 49.2 (15.1) years, respectively. Unstratified analyses revealed that patients with psoriasis in Chile had more severe disease than those in Brazil [PASI 11.6 vs. 8.4 (P < 0.001) and BSA 14.7 vs. 12.0 (P = 0.003), respectively]. For patients with moderate-to-severe psoriasis, defined as PASI and/or BSA >= 10, systemic nonbiologic drugs were available (81.2% in Brazil and 65.3% in Chile, P <= 0.001), but only 37.0% of patients in Brazil and 27.3% in Chile received biologics (P = 0.01). Lack of availability and/or lack of insurance reimbursement for biologic drugs for patients with moderate-to-severe psoriasis was reported for 22.2% (50 of 225) in Brazil and 67.9% (148 of 218) in Chile (P < 0.001). Patients with no access to biologic therapies due to lack of availability/insurance reimbursement had a median PASI of 9.15 (IQR 3.00-14.25) in Brazil and 12.0 (IQR 5.00-19.00) in Chile (P = 0.007), as well as a median BSA of 7.0 (IQR 3.00-15.00) and 12.0 (IQR 5.00-22.50) (P = 0.002), and median DLQI of 11.0 (6.00-15.00) and 21.0 (6.50-25.00) (P = 0.007), respectively. Conclusions Chilean patients had significantly more severe psoriasis compared with Brazilian patients in our study. While nonbiologic treatments for moderate-to-severe psoriasis were available in both LA countries, there is a high need for improvement in access to more effective psoriasis treatments including biologics. Our results highlight a significant gap between treatment recommendations in international psoriasis guidelines and real-world situations in Brazil and Chile.