Efeito da exposição à hidroquinona na resposta imune adaptativa induzida pela vacina contra a influenza / Effects of hydroquinone exposure on the adaptive immune response induced by the influenza vaccine

A gripe é causada pelo vírus Influenza e é um problema de saúde pública mundial, que pode levar a problemas sérios em idosos e crianças. O Brasil implantou a vacinação anual contra influenza a partir de 1999, como ação preventiva contra a doença. A vacina é produzida pelo Instituto Butantan e contém três cepas diferentes do vírus Influenza fragmentado para induzir resposta imune adaptativa, com produção de anticorpos específicos e neutralizantes. A literatura tem mostrado que a exposição à xenobióticos com potencial imunossupressor pode comprometer a eficácia de imunizações ativas, como a imunização contra a gripe. Nosso grupo de pesquisa tem mostrado que a exposição à hidroquinona (HQ), um composto tóxico presente em altas concentrações na fumaça do cigarro, prejudica a resposta imune inata e adquirida. Assim, este trabalho avaliou o efeito da exposição à HQ sobre a resposta imune à vacinação contra influenza. Camundongos machos da linhagem C57BL/6 foram diariamente expostos à HQ (2500 ppm) ou PBS, por 1 hora, por nebulização, por um período de 8 semanas. Durante este período, foram imunizados nas semanas 6 e 8 do início das exposições, pela injeção i.m. de 100µL da vacina. Os parâmetros tóxicos e imunológicos foram avaliados 7, 35 e 70 dias após a segunda dose da vacina. A exposição à HQ não alterou o peso corpóreo dos animais e nem causou alterações morfológicas no pulmão, fígado e rins (histologia por H&E); reduziu a frequência de hemácias (11%), hematócrito (14%), hemoglobina (14%) e volume celular (4%); causou estresse oxidativo no baço (citometria de fluxo); aumentou a área dos folículos de células B no baço e linfonodomegalia (histologia por H&E). Em conjunto, os dados aqui obtidos mostram que a exposição à HQ afetou mecanismos envolvidos na gênese da imunidade ativa contra influenza. Assim, os dados deste trabalho mostram mecanismos tóxicos ainda não descritos para a HQ, e ressalta a HQ como um poluente ambiental que deve ser considerado nas avaliações de risco

The flu is a health problem worldwide which is caused by the Influenza virus and may result in severe illness in infants and the elderly. The annually vaccination against influenza was implemented in Brazil in 1999 as a preventive measure. The vaccine is produced by Butantan Institute and contains three different strains of the inactivated Influenza virus which induce the adaptive immune response along with production of specific and neutralizing antibodies. The literature has shown that exposure to immunosuppressive xenobiotics may compromise the efficacy of active immunizations, such as influenza. Our research group has shown that exposure to hydroquinone (HQ), a toxic constituent of cigarette smoke, impairs both innate and adaptive immune response. Thus, the aim of this work was to evaluate the effects of HQ on the immune response induced by the influenza vaccine. Male C57BL/6 mice were daily exposed to HQ (2500 ppm) or PBS by nebulization, for 1 hour, for 8 weeks. During the exposure period, the animals were vaccinated on weeks 6 and 8 with 100µL of the vaccine. Toxicologic and immunological parameters were assessed 7, 35 and 70 days after boost administration. HQ exposure did not alter body weight and did not cause morphological alterations in the lungs, liver and kidneys (H&E staining); reduced the frequency of erythrocytes (11%), hematocrit (14%), hemoglobin (14%) and cellular volume (4%) and caused oxidative stress on the spleen (Flow Cytometry); increased the area of B cell follicles in the spleen and increased the size of draining lymph nodes (H&E staining). Altogether, these data show that HQ exposure affected mechanisms involved in the genesis of the adaptive immune response. Thus, the data presented in this work show toxic mechanisms of HQ that have not yet been described, and it also points out HQ as an environmental pollutant which should be considered on risk assessments

Exogenous ochronosis: case report and literature review / Ocronose exógena: relato de caso e revisão de literatura

Exogenous ochronosis is a rare, cosmetically disfiguring condition, resulting from the longterm use of topical hydroquinone in treatment of melasma. It manifests as gray-brown or blue-black macules in hydroquinone-exposed regions. The exact incidence of ochronosis is unknown. High rates have been reported in the South African population, and it is rare in the United States. We report the case of a patient who developed exogenous ochronosis while using topical hydroquinone. It is necessary to recognize this disorder at the earliest stage and discontinue hydroquinone immediately, as its treatment is difficult. Sun exposure facilitates the formation of exogenous ochronosis and must be strictly avoided, although it is a practical problem in the tropical climate of Brazil, particularly for those who work outdoors.

Ocronose exógena é uma condição rara, cosmeticamente desfigurante, devido ao uso tópico indiscriminado de hidroquinona para tratamento do melasma. Manifesta-se como máculas marrom-acinzentadas ou preto-azuladas em áreas cutâneas do uso de hidroquinona. A exata incidência de ocronose Exógena é desconhecida. Altos índices têm sido relatados em populações sul-africanas, sendo rara nos Estados Unidos. Relatamos um caso de uma paciente que desenvolveu ocronose Exógena durante uso de hidroquinona para tratamento do melasma. É necessário o reconhecimento dessa patologia no seu estágio precoce e imediata descontinuação da droga, pois seu tratamento é difícil. A exposição solar é um fator precipitante e deve ser estritamente evitada, embora isso seja difícil no clima tropical do Brasil, especialmente para aqueles que trabalham ao ar livre.

Aplicação da dermatoscopia no auxílio diagnóstico da ocronose exógena / Use of dermoscopy for diagnosis of exogenous ochronosis

A ocronose exógena consiste em hiperpigmentação crônica de áreas previamente tratadas com agentes tópicos como: a hidroquinona, a resorcina, os antimaláricos e o fenol. O diagnóstico precoce permite suspender prontamente o agente causador, uma vez que as opções terapêuticas disponíveis são escassas e com resultados insatisfatórios. Reportam-se três casos de ocronose exógena na face, diagnosticados pela dermatoscopia. O estudo dermatoscópico evidenciou estruturas amorfas de coloração cinza-enegrecido, algumas obliterando as aberturas foliculares. O exame histopatológico corroborou o diagnóstico.

Exogenous ochronosis consists of chronic hyperpigmentation of areas previously treated with topical agents such as hydroquinone, resorcinol, antimalarials and phenol. Early diagnosis allows to promptly suspend the causative agent and it is imperative since the available therapeutic options are scarce and have presented so far unsatisfactory results. Three cases of exogenous ochronosis on the face which were diagnosed with the use of dermoscopy are presented. Dermatoscopy showed blackish-gray amorphous structures, some obliterating the follicular openings. Histopathological examination confirmed the diagnosis.

Ocronose exógena induzida por hidroquinona: relato de quatro casos / Exogenous ochronosis hydroquinone induced: a report of four cases

A ocronose exógena é uma dermatose, aparentemente pouco frequente, caracterizada por hiperpigmentação negro-azulada fuliginosa, localizada na região onde foi aplicado o agente causador. Pode ser causada por uso de medicamentos sistêmicos, os antimaláricos e de uso tópico, como fenol, resorcinol, benzeno, ácido pícrico e a hidroquinona - que é um composto fenólico, com propriedade despigmentante, muito utilizado em formulações dermatológicas para o tratamento de melasma e outras hiperpigmentações. A fisiopatogenia deste processo ainda não está esclarecida e as abordagens terapêuticas são insatisfatórias. Relatam-se quatro casos de pacientes do sexo feminino que, após uso de preparados contendo hidroquinona, desenvolveram hiperpigmentação acentuada na face, caracterizadas no exame dermatológico e histopatológico como ocronose. Enfatiza-se a possibilidade de casos de ocronose exógena estarem sendo diagnosticados erroneamente, como falha de tratamento de melasma, e também para os riscos do uso indiscriminado de formulações, contendo hidroquinona, muitas vezes, sem acompanhamento médico.

Exogenous ochronosis is an infrequent dermatosis characterized as a dark blue hyperpigmentation localized where the causing agent was applied. It may be caused by the use of systemic medication such as antimalarials and by the use of topic substances such as phenol, resorcinol, benzene, or hydroquinone, which is a fenolic compound with depigmentation action, largely used in the treatment of melasma and other hyperpigmentation. The physiopathology of this process is not well clear up to this moment, and the therapeutic measures are not satisfactory either. Here we present four cases of female patients that developed hyperpigmentation on their faces after the use of hydroquinone containing compounds, characterized clinically and histological as ochronosi. We emphasize the possibility of exogenous ochronosis cases being misdiagnosed as a melasma treatment failure. We also emphasize the risks of the indiscriminated use of hydroquinone containing compounds, used, in many instances, without medical prescription.

Predictors of Topical Steroid Misuse among Patrons of Pharmacies in Pretoria

The misuse of topical steroids; i.e. the usage of these products for skin lightening; is a widespread phenomenon among African men and women. Studies have reported prevalence rates of 18.5to 70 among participants. Though women constitute the majority of users; people of various age groups; socioeconomic status; employment and marital status practise skin lightening. Besides topical steroid products; other commonly used products include preparations containing hydroquinone or mercury derivatives. The misuse of these products is associated with skin problems such as cellulitis; contact eczema; bacterial and fungal infections; Cushing's syndrome; acne; skin atrophy and pigmentation disorders. Although these effects are well documented; it seems that there is little wareness of them among the general public. Other less commonly reported problems include delaying the diagnosis of leprosy; and erythrodermic psoriasis. Data on the misuse and side effects of topical steroids have been gathered primarily from prescriptions; despite the fact that these products could be obtained over the counter; shared between relatives or friends; or come from other informal sources. Moreover; we found no community-based study that investigated the prevalence of the misuse of topical steroid products in South Africa. This survey was therefore conducted to examine the misuse of topical steroid products for skin lightening; among patrons of pharmacies in Pretoria and to determine the potential predictors of misuse.Methods: The aim of this study was to examine the misuse of topical steroid products for skin lightening by patrons of pharmacies in Pretoria and to determine the potential predictors of misuse. Exit interviews were conducted at 21 randomly selected pharmacies by trained interviewers using a structured questionnaire. A total of 1 228 patrons were approached; of which 225 gave verbal consent to be interviewed.Results: Of the 225 participants; 83 were female; 50.7 were 20-40 years old; 56 were employed; and 53.3 were married. The majority of participants (75.1) were black Africans. About half of them (50.2) had high school education. The prevalence of topical steroid misuse for skin lightening was 35.5. A logistic regression analysis revealed that being a black female African and initially being advised to use the products by a friend were the only parameters that significantly correlated with topical steroid misuse.Conclusion: In conclusion; the prevalence of the misuse of topical steroid products among the respondents was 35.5. The following predictors were associated with topical steroid misuse: being a black female African; not being aware of the side effects of these products; and initially being advised to use the products by a friend. In a logistic regression model; the last two predictors were the only parameters that significantly correlated with topical steroid misuse. (SA Fam Pract 2006; 48(1): 14)

Exogenous ochronosis

La ocronosis exógena es una condición que se caracteriza por tener hiperpigmentación de la cara secundario al uso crónico de cremas blanqueadores que contienen hidroquinona. Histopatológicamente se ve una colección de glóbulos amarillo-marrón (ocronóticos) en la dermis papilar. Se reportan dos casos de ocronosis exógena y se hace un repaso de la literatura

Monomethyl ether of hydroquinone as possible cause of chemical vitiligo in patients with melasma

Melasma, in Iraq, is a common upsetting dermatological problem among young females. Chemical vitiligo could be seen as a complication following treatment with bleaching depigmenting agents. In this study four patients with melasma were reported to develop chemical vitiligo following topical therapy with 10% monomethyl ether of hydroquinone [Leucodinine B] ointment