Atualização do custo-efetividade por resposta de adalimumabe, etanercepte, guselcumabe, infliximabe, ixequizumabe, secuquinumabe e ustequinumabe no tratamento de psoríase em placas moderada a grave sob a perspectiva do Sistema de Saúde Suplementar brasileiro / An update of a cost-effectiveness per response of adalimumab, etanercept, guselcumab, infliximab, ixekizumab, secukinumab and ustekinumab for treatment of moderate to severe plaque psoriasis from the perspective of the Brazilian Supplementary Health System

Objetivo: Os agentes biológicos representam um grande avanço no tratamento da psoríase em placas moderada a grave. No entanto, variações de eficácia, segurança e custos dos tratamentos podem dificultar a escolha do agente terapêutico. Este estudo teve como objetivo atualizar o custo por resposta dos agentes biológicos disponíveis para psoríase no ROL de Procedimentos e Eventos em Saúde (ROL) da Agência Nacional de Saúde Suplementar (ANS). Métodos: Uma análise de custo por resposta foi utilizada para avaliar a razão de custo pelo desfecho Índice de Gravidade e Área da Psoríase (PASI) 90. Os resultados foram apresentados para o primeiro ano (ano I), que compreende a fase de indução e a fase manutenção até completar 52 semanas e foi realizada uma análise da efetividade do tratamento num cenário de orçamento fixo. Os custos dos tratamentos foram calculados com base nos preços de fábrica (PF18%) da Tabela da Câmara de Regulação do Mercado de Medicamentos de junho de 2021. Resultados: Para o ano I, o guselcumabe apresentou melhor resultado para custo por resposta (R$ 130.467) PASI 90, seguido por ixequizumabe, ustequinumabe, secuquinumabe, adalimumabe, infliximabe e etanercepte. No cenário com orçamento fixo, o guselcumabe demonstrou ser o agente capaz de tratar com sucesso (PASI 90) o maior número de pacientes. Atualização do custo-efetividade por resposta para psoríase em placas moderada a grave. Conclusão: Sob a perspectiva do Sistema de Saúde Suplementar do Brasil, o guselcumabe apresentou o melhor custo por resposta PASI 90, sendo, assim, a terapia com melhor custo-efetividade no tratamento da psoríase em placas moderada a grave disponível no ROL.

Objective: Biological agents represent a major advance in the treatment of moderate-to-severe plaque psoriasis. However, variations of efficiency, safety and costs of treatments make it difficult to select the drug. This study aims to update the cost per response of biological agents available in the Health Procedures and Events Roll (ROL) of the National Supplementary Health Agency (ANS). Methods: A cost-per-response analysis was used to assess the cost per outcome of Psoriasis Area and Severity Index (PASI) 90. Results were presented for the first year (I), which comprises induction and maintenance for 52 weeks and a fixed budget scenario analysis. Treatment costs were calculated based on the prices of the 2021 Medicines Market Regulation Chamber Table. Results: Analysis of year I, guselkumab showed the best result for cost per cost (R$ 130,467) PASI 90, followed by ixekizumab, ustekinumab, secukinumab, adalimumab, infliximab, and etanercept. In the fixedbudget analysis, guselkumab is the therapy capable of successfully treating (PASI 90) the largest number of patients. Conclusion: From the perspective of the Supplementary Health System in Brazil, guselkumab showed the best cost per response PASI 90, thus being the most cost-effective therapy in the treatment of moderate to severe plaque psoriasis available in the Brazilian ROL.

Mycobacterium leprae on Palatine Tonsils and Adenoids of Asymptomatic Patients, Brazil.

We investigated palatine tonsil and adenoid specimens excised from otorhinolaryngological patients in a leprosy-endemic region of Brazil. Fite-Faraco staining identified Mycobacterium spp. in 9 of 397 specimen blocks. Immunohistochemistry and molecular analysis confirmed the presence of Mycobacterium leprae, indicating that these organs can house M. leprae in persons inhabiting a leprosy-endemic region.

Linear verrucous epidermal nevus with oral manifestations: report of two cases.

Linear verrucous epidermal nevi (LVEN) are characterized by verrucous papules often coalescing into well-demarcated skin-colored or brown plaques following the lines of Blaschko. We present two new cases of LVEN with oral mucosa involvement and briefly discuss this very rare finding. In both cases, oral biopsies showed hyperkeratosis, acanthosis, and papillomatosis. Although several treatment modalities have been reported for the cutaneous lesions, there is no consensus for the management of oral lesions so far.

Patch-type granuloma annulare: a case report

Granuloma annulare (GA) is a benign, self-limited condition which the etiology remains unknown. It is clinically characterized as annularly, erythematous papules on the extremities. Histologically, it shows as palisading granulomas with central degenerated collagen and mucin deposits. The patient in this case report had a rare GA variant named patch-type GA. It appeared as asymptomatic erythematous macules with central clarification on the upper portion of thighs. Histopathology was compatible with interstitialtype GA. We highlight that a high index of suspicion is necessary to make the diagnosis of patch-type GA and confirmation can only be achieved through histopathology study. (AU)

O granuloma anular (GA) é uma condição benigna, autolimitada e de etiologia desconhecida. Clinicamente é caracterizado por pápulas eritematosas anulares nas extremidades. Do ponto de vista histológico, observa-se a formação de granulomas com colágeno degenerado em sua porção central e depósito de mucina. O paciente deste caso clínico foi diagnosticado com uma variante rara de granuloma anular, na sua forma macular. A lesão se apresentava como máculas eritematosas assintomáticas na porção superior das coxas. Nos cortes histológicos, o quadro era compatível com GA do tipo intersticial. Neste trabalho enfatiza-se a necessidade de um elevado índice de suspeição clínica para o diagnóstico de GA macular e a confirmação só poderá ser alcançada através do estudo histopatológico. (AU)

Dermatologic manifestations of infective endocarditis

Abstract Despite advances in diagnosis and treatment, infective endocarditis still shows considerable morbidity and mortality rates. The dermatological examination in patients with suspected infective endocarditis may prove very useful, as it might reveal suggestive abnormalities of this disease, such as Osler’s nodes and Janeway lesions. Osler’s nodes are painful, purple nodular lesions, usually found on the tips of fingers and toes. Janeway lesions, in turn, are painless erythematous macules that usually affect palms and soles. We report a case of infective endocarditis and highlight the importance of skin examination as a very important element in the presumptive diagnosis of infective endocarditis.

Dermatologic manifestations of infective endocarditis.

Despite advances in diagnosis and treatment, infective endocarditis still shows considerable morbidity and mortality rates. The dermatological examination in patients with suspected infective endocarditis may prove very useful, as it might reveal suggestive abnormalities of this disease, such as Osler's nodes and Janeway lesions. Osler's nodes are painful, purple nodular lesions, usually found on the tips of fingers and toes. Janeway lesions, in turn, are painless erythematous macules that usually affect palms and soles. We report a case of infective endocarditis and highlight the importance of skin examination as a very important element in the presumptive diagnosis of infective endocarditis.

Colecistite alitiásica aguda: revisão de literatura / Acute acalculous cholecystitis: literature review

A colecistite alitiásica aguda (CAA) trata-se de uma inflamação da vesícula biliar sem a evidência de cálculos biliares. É estimado que ocorra em 2-15% de todos os casos de colecistite aguda e geralmente se associa a condições de saúde críticas, como pós-operatório, trauma recente grave e queimaduras. A etiologia da CAA é multifatorial e sua patofisiologia ainda permanece pouco compreendida. Os principais mecanismos de doença propostos incluem lesão por isquemia-reperfusão, resposta inflamatória sistêmica e estase biliar. O diagnóstico, que costuma ser difícil, é baseado em dados clínicos, laboratoriais, radiológicos e peroperatórios. As manifestações costumam ser inespecíficas, tais como dor em quadrante superior direito, febre, náusea, vômitos, icterícia, leucocitose e função hepática alterada. Os achados de imagem na ultrassonografia (US) e tomografia computadorizada (TC) incluem aumento da espessura da parede e do volume da vesícula biliar, barro biliar, fluido pericolecístico e presença de gás intramural. A combinação de pelo menos três desses achados é necessária para o diagnóstico de CAA. A sensibilidade e especificidade dos métodos de imagem são variáveis, entretanto, considera-se que a TC é superior à US. O tratamento de escolha é colecistectomia, com crescente preferência para utilização da via percutânea. O tratamento clínico associado inclui melhora dos parâmetros hemodinâmicos com drogas vasoativas e medicamentos antimicrobianos. A taxa de mortalidade costuma ser alta (10-67%), independentemente do tratamento instituído. Tal fato é atribuído às condições mórbidas pré-existentes que costumam acompanhar o quadro e contribuem para a rápida progressão da doença para gangrena e perfuração. (AU)

Acalculous cholecystitis (AC) is an acute infiamatory disease of the gallbladder without the evidence of biliary stones. It accounts for 2-15% of all cases of acute cholecystitis and is generally associated with critically ill patients, post-operatory, recente trauma and burns. AC etiology is multifactorial and still obscure. The main mechanisms include ischemia/ reperfusion lesions, systemic infiamatory reaction and biliary stasis. The diagnosis may be difficult, being based on clinical, labaratorial, radiographic and peroperatory features. Clinical manifestations, although inespefics, are right hypochondrial pain, fever, nausea, vomit, jaundice, leukocytosis and high liver enzymes. Ultrasound and tomography aspects are thickening of the gallbladder wall with pericholecystic fluid, biliary sludge and emphysematous cholecystitis. The combination of three or more of those aspects is necessary to confirm the diagnosis of AC. The sensibility and specificity of the radiological exams are insconstant, but the tomography is considered superior to ultrasound. The definitive therapy is cholecystectomy. Associated clinical approach include the use of vasoactive drugs and antibiotics. Mortality is high (10-67%), mainly because of the comobidity diseases. (AU)

In vitro antimicrobial activity of Brazilian medicinal plant extracts against pathogenic microorganisms of interest to dentistry.

This study evaluated the susceptibility of oral pathogenic microorganisms Candida albicans, Streptococcus mutans, Staphylococcus aureus, and Aggregatibacter actinomycetemcomitans to Brazilian medicinal plant extracts of Schinus terebinthifolius (aroeira), Croton campestris (velame), Lafoensia pacari (pacari), Centaurium erythraea (centáurea), Stryphnodendron adstringens (barbatimão), and Anacardium humile (cajuzinho-docerrado), as compared to standardized antimicrobial agents (nystatin, chloramphenicol and tetracycline hydrochloride). Ethanol, hexane and butane fractions from stem barks, rinds, leaves, and/or roots were extracted and tested. Antimicrobial diffusion agar test and MIC were performed according to CLSI. After 24 h of incubation at 37 °C, the diameter of inhibition zones and spectrophotometer readings were measured and compared. The results were reported as means ± standard deviation (M ± SD). With the exception of five extracts that showed no antimicrobial activity, all the extracts tested showed antimicrobial activity, in different levels. This study suggests that extracts from the plants tested could be an alternative therapeutic option for infectious conditions of the oral cavity, such as denture stomatitis, dental caries, and periodontitis.

Perspectivas da medicina personalizada em Dermatologia / Perspectives of personalized medicine in Dermatology

A medicina personalizada preconiza a utilização de dados contidos no genótipo de um indivíduo com vistas a classificar ou predizer, com melhor acurácia, certas condições/reações patológicas, com o intuito de fornecer uma abordagem individual para aquele determinado paciente. O objetivo deste trabalho é discutir a mudança de paradigmas proporcionada pela genômica e o consequente surgimento da medicina personalizada, além de pontuar sua relevância e suas aplicações, com ênfase para a Dermatologia. Paralelamente, visa-se discutir quais são as principais expectativas que o clínico deve ter em mente para a utilização dessas novas ferramentas no futuro.

Isolation and characterization of gingival fibroblasts positive for alkaline phosphatase in patients with chronic periodontitis and drug-induced gingival hyperplasia / Isolamento e caracterização de fibroblastos gengivais positivos para fosfatase alcalina de pacientes portadores de periodontite crônica e hiperplasia gengival medicamentosa

Purpose: To investigate the expression of alkaline phosphatase (ALP) activity in gingival fibroblasts from individuals with chronic periodontitis (CP) and drug-induced gingival hyperplasia (DGH) induced by diphenylhydantoin. Methods: Gingival fragments were obtained from 13 patients (8 women and 5 men, from 22 to 74 years of age), with 4 fragments from clinically normal gingiva (NG), 5 from biopsy of periodontal pockets with CP, and 4 from DGH induced by diphenylhydantoin. Using an enzymatic digestion procedure, gingival cell suspensions containing ALP-positive fibroblasts were prepared without affecting ALP activity. Cytochemistry and histochemistry analyses were performed. Results: Fibroblasts from NG presented low levels of ALP when compared to CP and DGH, which showed elevated and intermediate levels of ALP, respectively. Little cell proliferation was observed for fibroblasts from CP and DGH as compared to NG. However, the quantity of cells recovered from the subcultures was similar to the quantity recovered from the initial cell culture for the three sources. Conclusion: The expression of ALP is increased in CP and DGH, and fibroblasts in CP and DGH show low proliferation. This suggests that periodontal inflammation and diphenylhydantoin may influence ALP expression and human gingival fibroblast expansion. Other studies are necessary to better assess the importance of ALP in the development and progression of CP and DGH.

Objetivo: Investigar a expressão da atividade de fosfatase alcalina (ALP) em fibroblastos gengivais de sujeitos com periodontite crônica (PC) e hiperplasia gengival medicamentosa (HGM) induzida por difenilhidantoína. Metodologia: Os fragmentos gengivais foram obtidos de 13 pacientes (8 mulheres e 5 homens, 22 a 74 anos), sendo 4 fragmentos procedentes de gengiva clinicamente normal (GN), 5 de biópsias de bolsas periodontais com PC e 4 de HGM induzida pela difenilhidantoína. Através de digestão enzimática, suspensões de células gengivais foram preparadas contendo fibroblastos ALP-positivos sem afetar a atividade da enzima ALP. Análises citoquímica e histoquímica foram realizadas. Resultados: Fibroblastos de GN apresentaram fraca positividade para ALP quando comparados com PC e HGM. PC e HGM exibiram níveis elevados e intermediários, respectivamente, de ALP. Observou-se menor proliferação celular na cultura de células em PC e HGM que em GN. Entretanto, a quantidade de células recuperadas das sub-culturas foi similar à quantidade recuperada na cultura inicial para as três linhagens. Conclusões: A expressão de ALP na PC e na HGM encontra-se aumentada e ocorre baixa proliferação de fibroblastos na PC e na HGM. Isto sugere que a inflamação periodontal e a difenilhidantoína podem influenciar a expressão de ALP e a multiplicação de fibroblastos gengivais humanos. Outros estudos são necessários para melhor avaliar a importância de ALP no desenvolvimento e na progressão de PC e HGM.

Experimental oral chronic infection induced by actinomyces israelii and propionibacterium acnes

The purpose of this study was to evaluate an experimental animal model of oral chronic infection induced by Actinomyces israelii and propionibacterium acnes in mice. Swiss/NIH mice (n=100), 21 days of age, male and female were divided into two groups of 45 animals. A. israelii (n=45) and P. acnes (n=45) were inoculated in the anterior mandibular paraperiosteal periodontal tissue associated with sodium alginate gel particles. The animals were evaluated clinically and microscopically at 1,3,7,15,21,30 and 45 days after inoculation. Actinomycotic and propioni lesions were induced in all animals. In control mice (n=10), no lesions were noted; however, differences in the clinical and histopathological evoluations of actinomycosis and propioni lesions were observed and are discussed in this study. Microorganisms entrapped in alginate gel provided a prolonged bacterial irritation, and chronic histopathologic features similar to those seen in human actinomycosis could be detected.

Antimicrobial activity of a propolis adhesive formulation on different oral pathogens

Recent studies have shown that propolis has appreciable antibacterial, antifungal and antiviral actions, as well as cytostatic and antitumoral activity. In light of these studies, the antimicrobial activity of a new adhesive formulation containing propolis was evaluated in this in vitro study. Susceptibility of the oral strains tested (Candida albicans, Candida tropicalis, Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, Actinomyces israelli, Actinobacillus actinomycetemcomitans) was evaluated using the agar diffusion method with different concentrations of propolis (5, 10, 15 and 20%). All of the assayed bacteria and fungi species were susceptible to propolis, with minimum inhibitory concentrations (MIC) ranging from 1.75 to 14.0 ãfg/ml. The positive results suggest that propolis in this sustained release formulation should be further tested as an alternative therapy of infectious conditions of the oral cavity, such as denture stomatitis and periodontitis. However, in vivo studies of the effect of this new adhesive formulation of propolis are needed to determine its possible effects on the oral mucosa.

Infecção oral crônica experimental induzida por actinomyces israelii e propionibacterium acnes / Experimental oral chronic infection induced by actinomyces israelii and propionibacterium acnes

The purpose of this study was to evaluate an experimental animal model of oral chronic infection induced by Actinomyces israelii and propionibacterium acnes in mice. Swiss/NIH mice (n=100), 21 days of age, male and female were divided into two groups of 45 animals. A. israelii (n=45)and P. acnes (n=45) were inoculated in the anterior mandibular paraperiosteal periodontal tissue associated with sodium alginate gel particles. The animals were evaluated clinically and microscopically at 1,3,7,15,21,30 and 45 days after inoculation. Actinomycotic and propioni lesions were induced in all animals. In control mice (n=10), no lesions were noted; however, differences in the clinical and histopathological evoluations of actinomycosis and propioni lesions were observed and are discussed in this study. Microorganisms entrapped in alginate gel provided a prolonged bacterial irritation, and chronic histopathologic features similar to those seen in human actinomycosis could be detected.

Sympathetic nerve blocks in mandibular herpes zoster and postherpetic neuralgia.

Sympathetic blocks have been indicated for the diagnosis and treatment of painful neuropathic conditions, such as herpes zoster (HZ) and postherpetic neuralgia (PHN). The purpose of this article is to report a case of mandibular HZ and PHN in an HIV-positive patient, and discuss the efficacy of sympathetic nerve blocks for pain relief and prevention of PHN.

Sialoadenites: revisão de literatura sobre a etiologia, o diagnóstico e o tratamento / Sialadenitis: literature review regarding the etiology, diagnosis and treatment

As sialoadenites constituem um conjunto de doenças inflamatórias das glândulas salivares caracterizadas geralmente por edema e sintomatologia dolorosa. O processo inflamatório, que pode ser tanto agudo quanto crônico, acomete principalmente idosos, porém esta condição também é relatada em todas as idades. A sialoadenite tem sido tradicionalmente considerada como uma infecção bacteriana retrógrada ascendente via ducto salivar em direção ao parênquima glandular, no entanto, a inflamação pode ter origem a partir de diversas causas, infecciosas ou não. As sialoadenites causam considerável morbidade para o paciente e, portanto, requerem avaliação cuidadosa com o intuito de se prover um tratamento adequado. O objetivo deste trabalho é discutir a etiologia, as características clínicas, o diagnóstico e as formas atuais de tratamento das condições inflamatórias das glândulas salivares maiores.