The first report of leukocytoclastic vasculitis induced by once-weekly subcutaneous semaglutide.

INTRODUCTION: Leukocytoclastic vasculitis (LCV) is a small vessel vasculitis involving arterioles, capillaries and postcapillary venules. LCV is generally confined to the skin, with extracutaneous manifestations occurring less frequently. LCV has multiple potential etiologies. Indeed, histological LCV can be found in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, immune complex vasculitis, vasculitis associated with systemic diseases (i.e. sarcoidosis, Sjögren's syndrome, rheumatoid arthritis, and systemic lupus erythematosus), or in vasculitis associated with cancer, infections, sepsis and use of certain medications. LCV can also be idiopathic in up to 50% of cases. CASE REPORT: Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist used for management of type 2 diabetes mellitus (T2DM), obesity and overweight associated with one or more weight-related comorbidities. A case of drug-induced LCV has already been described with the use of once-daily oral semaglutide. Herein, we describe the first case of skin-limited LCV induced by once-weekly subcutaneous semaglutide in a 73-year-old man with T2DM, who experienced the complete resolution of the skin lesions shortly after the discontinuation of semaglutide therapy. CONCLUSION: Future prospective studies, adverse event reporting and post-marketing surveillance will certainly contribute to establishing if LCV represents a less rare than expected side effect of both oral and subcutaneous semaglutide formulations.

Nosso sistema imune de cada dia e os agrotóxicos de hoje / Our everyday immune system and today's pesticides

O uso massivo dos agrotóxicos nas lavouras deu-se a partir de 1950 com a "Revolução Verde", como resultado da busca por aumento da produtividade e modernização dos campos agrícolas. Diante disso, na década de 1960, foi criado o Programa Nacional de Defensivos Agrícolas (PNDA), que veio para facilitar a introdução dos agroquímicos, colaborando para que, a partir de 2008, o Brasil passasse a ser o país com maiores percentuais de uso destes produtos. Essas substâncias geram efeitos deletérios sobre a resposta imune dos indivíduos expostos, principalmente relacionada aos macrófagos, células B, T e NK. Isso afeta a capacidade de fagocitose, apresentação de antígenos e produção de anticorpos, além de induzir a geração de radicais livres de oxigênio e disfunção mitocondrial, resultando em estresse oxidativo e danos ao DNA celular, apoptose em excesso, mutação no ciclo celular, desordem de regulação e, consequentemente, imunodeficiência. Dessa forma, o desenvolvimento de doenças imunomediadas, como asma e doença pulmonar obstrutiva crônica (DPOC), está estreitamente ligado aos agrotóxicos, uma vez que esses variados mecanismos de toxicidade ao sistema imune induzem, dentre outras, manifestações respiratórias, tais como tosse, sibilo, irritação e inflamação. Além disso, estes pesticidas estão relacionados com doenças não imunomediadas ao alterar a função normal dos hormônios da tireoide, andrógenos e estrógenos. A fim de avaliar estes impactos, o presente estudo consiste em uma revisão integrativa da literatura e, diante da crescente utilização descontrolada dos agrotóxicos, assume grande relevância, refletindo a necessidade de maior atuação da vigilância epidemiológica, ambiental e da saúde do trabalhador.

Beginning in the 1950s, massive pesticide use began in what is called the "Green Revolution", a quest for increased agricultural productivity and modernization. In the 1960s, the Brazilian National Program of Agricultural Defense was created to facilitate the introduction of agrochemicals, leading the country to become one of the world's largest pesticide users by 2008. These substances have deleterious effects on the immune response of exposed individuals, mainly related to macrophages and B, T, and NK cells. This affects phagocytosis and antigen and antibody production, inducing production of oxygen free radicals and mitochondrial dysfunction, which results in oxidative stress and cellular DNA damage, excess apoptosis, cell cycle mutations, regulatory disorders, and, consequently, immunodeficiency. Thus, the development of immune-mediated diseases, such as asthma and chronic obstructive pulmonary disease (COPD), is closely linked to pesticides, since these varied mechanisms of toxicity to the immune system induce respiratory manifestations, such as cough, wheezing, irritation and inflammation. Pesticide use is also related to non-immune-mediated diseases because exposure alters the normal function of thyroid hormones, androgens, and estrogens. To evaluate their impact, the present study performed an integrative review of the literature, which, due to the growing and uncontrolled use of pesticides, is of great relevance and demonstrates the need for greater epidemiological, environmental, and worker health surveillance.