Hand-foot syndrome due to hepatitis C therapy

SUMMARY INTRODUCTION Direct-acting antivirals are new drugs for chronic hepatitis C treatment. They are usually safe and well tolerated, but can sometimes cause serious adverse effects and there is no consensus on how to treat or prevent them. We described a case of hand-foot syndrome due to hepatitis C virus interferon-free therapy. METHODS We report the case of a 49-year-old man with compensated liver cirrhosis due to chronic hepatitis C genotype 1, treatment-naïve, who started viral treatment with sofosbuvir, simeprevir and ribavirin for 12 weeks. RESULTS At the sixth week of treatment he had anemia, requiring a lower dose of ribavirin. At the tenth week, he had erythematous, pruritic, scaly and flaky lesions on hands and feet, which showed a partial response to oral antihistamines and topical corticosteroids. It was not necessary to discontinue antiviral treatment, but in the first week after the end of treatment, there was worsening of injuries, including signs of secondary infection, that required hospitalization, antibiotics and oral corticosteroid, with progressive improvement. Biopsy of the lesions was consistent with pharmacodermia. The patient had sustained a virological response, despite the side effect. He had a history of pharmacodermia one year ago attributed to the use of topiramate, responsive to oral corticosteroid. CONCLUSION Interferon-free therapies can rarely lead to severe adverse reactions, such as skin lesions. Patients receiving ribavirin combinations and those who had a history of pharmacodermia or skin disease may be more susceptible. There is no consensus on how to prevent skin reactions in these patients.

RESUMO INTRODUÇÃO Antivirais de ação direta são as novas drogas utilizadas no tratamento da hepatite C crônica. São geralmente seguros, com boa tolerância, mas eventualmente podem causar efeitos adversos graves, e não há consenso sobre como tratá-los ou preveni-los. Descrevemos um caso de síndrome mão-pé secundária à terapia livre de interferon para hepatite C crônica. Materiais e métodos Relatamos o caso de um paciente de 49 anos com cirrose hepática compensada secundária à hepatite C crônica, genótipo 1, virgem de tratamento, que iniciou terapia com sofosbuvir, simeprevir e ribavirina por 12 semanas. Resultados Na sexta semana de tratamento, apresentou anemia, sendo necessária redução de dose da ribavirina. Na 20a semana, apresentou lesões eritematosas e descamativas, com prurido em mãos e pés, que teve resposta parcial ao uso de anti-histamínico oral e corticoide tópico. Não foi necessário descontinuar os antivirais, mas na primeira semana após o término do tratamento, houve piora das lesões, com sinais de infecção secundária, sendo necessárias hospitalização e terapia com antibiótico e corticoide oral, com melhora progressiva. Biópsias das lesões foram compatíveis com farmacodermia. O paciente teve resposta virológica sustentada, apesar dos efeitos adversos. Tinha história de farmacodermia há um ano, atribuída ao uso de topiramato, responsiva a corticoterapia oral. Conclusão Os tratamentos livres de interferon raramente causam eventos adversos graves, como lesões cutâneas. Pacientes em uso de ribavirina e com história de farmacodermia ou doença cutânea prévia podem ser mais susceptíveis. Não existe consenso sobre como prevenir reações cutâneas nesses pacientes.

Retrospective analysis of hepatitis B virus chronic infection in 247 patients: clinical stages, response to treatment and poor prognostic factors

Abstract Background: Chronic hepatitis B is a major cause of cirrhosis, and the natural history of the disease has several clinical stages that should be thoroughly understood for the implementation of proper treatment. Nonetheless, curing the disease with antiviral treatment remains a challenge. Aims: To describe the clinical course, response to treatment, and poor prognostic factors in 247 hepatitis B virus chronic infection patients treated in a tertiary hospital in Brazil. Methods: This was a retrospective and observational study, by analyzing the medical records of HBV infected patients between January 2000 and January 2015. Results: Most patients were male (67.2%) and 74.1% were HBeAg negative. Approximately 41% had cirrhosis and 8.5% were hepatitis C virus coinfected. The viral load was negative after two years on lamivudine, entecavir and tenofovir in 86%, 90.6%, and 92.9% of the patients, respectively. The five-year resistance rates for lamivudine, adefovir, entecavir, and tenofovir were 57.5%, 51.8%, 1.9%, and 0%, respectively. The overall seroconversion rates were 31.2% for HBeAg and 9.4% for HBsAg. Hepatocellular carcinoma was diagnosed in 9.7% of patients, liver transplantation was performed in 9.7%, and overall mortality was 10.5%. Elevations of serum alanine aminotransferase (p = 0.0059) and viral load (p < 0.0001) were associated with progression to liver cirrhosis. High viral load was associated with progression to hepatocellular carcinoma (p < 0.0001). Significant risk factors associated with death were elevated alanine aminotransferase (p = 0.0039), liver cirrhosis (p < 0.0001), high viral load (p = 0.007), and hepatocellular carcinoma (p = 0.0008). HBeAg positive status was not associated with worse outcomes, and treatment may have been largely responsible. Conclusions: Elevations of viral load and serum alanine aminotransferase may select patients with worse prognosis, especially progression to cirrhosis and hepatocellular carcinoma, which were strongly association with death.

In search of a tolerance-induction strategy for cow's milk allergies: significant reduction of beta-lactoglobulin allergenicity via transglutaminase/cysteine polymerization

OBJECTIVE: To explore the use of β-lactoglobulin polymerized using microbial transglutaminase and heating to identify whether protein polymerization could reduce in vivo allergenicity and maintain in vitro and ex vivo immunoreactivity for use in tolerance-induction protocols. METHODS: Based on previous protocols applied in mice and children, we performed in vivo challenges (using a skin prick test) with native and polymerized β-lactoglobulin in adult patients with an IgE-mediated allergy to plactoglobulin. In vitro humoral immunoreactivity was analyzed using immunoblotting. Cell-mediated immunoreactivity was analyzed using ex vivo challenges with native and polymerized β-lactoglobulin and monitored by leukocyte adherence inhibition tests. RESULTS: The skin tests demonstrated that there was a significant reduction in immediate cutaneous reactivity after polymerization. Polymerization did not decrease the immunoblotting detection of s-IgE specific to β-lactoglobulin. Cell-mediated immunoreactivity, as assessed by ex vivo challenges and leukocyte adherence inhibition tests, did not exhibit significant differences between leukocytes challenged with native versus polymerized β-lactoglobulin. CONCLUSIONS: The polymerization of β-lactoglobulin decreased in vivo allergenicity and did not decrease in vitro humoral or ex vivo cell-mediated immunoreactivity. Therefore, we conclude that inducing polymerization using transglutaminase represents a promising technique to produce suitable molecules for the purpose of designing oral/ sublingual tolerance induction protocols for the treatment of allergies.

Ulcera péptica / peptic ulcer

A úlcera péptica é uma doença muito freqüente em nos- so meio. É causada na maioria das vezes pela bactéria Helícobacter pylorí ou pelo uso de antiinfiamatórios não, esteroídais. Não há quadro clínico característico e muitos doentes podem ter sintomatología pobre. A dor epigástrica é o sintoma mais comum e pode ter relação com a alimentação. O diagnóstico das úlceras gastroduodenais é feito através de endoscopia digestiva alta, que permite ainda verificar a exístêncía ou não da infecção pelo H.pylori. A erradicação da bactéria é o tratamento de escolha nos portadores do microrganismo. A utilização de medicamentos redutores de se- creção ácida gástrica é capaz de cicatrizaras úlceras da grande maioria dos pacientes, independente da etiologia. Os mais eficazes são os inibidores da bomba de prótons. Eles podem ser usados profílaticamente nos usuários crônicos de antiin- flamatórios que tenham risco aumentado de lesões, como nos idosos, nos que utilizam corticosteróides ou anticoagulantes e nos pacientes com doenças sistêmicas graves.

Estudo do esvaziamento gástrico e da distribuiçäo intragástrica de uma dieta sólida através da cintilografia: diferenças entre os sexos / Scintigraphic study of gastric emptying and intragastric distribution of a solid meal: gender differences

Gender-related differences in gastric emptying are still controversial. The aims of this study were: to confirm the sex-related difference in gastric emptying of a solid meal and to investigate its association with different patterns of meal distribution between the proximal and distal gastric compartments. Eighteen healthy volunteers (nine males, mean age 35 +/- 9 years; nine females, mean age: 41 +/- 11 years) were studied in the morning, after ingestion of the solid test-meal (an omelette labeled with 185MBq of 99mTc-sulfur colloid). Simultaneous anterior and posterior images of the stomach were acquired immediately after ingestion of the meal and every 10 minutes for 120 minutes. Time versus activity curves were obtained for the whole, proximal and distal stomach. Gastric T1/2 was longer in women (96.1 +/- 17.2 min) than in men (79.9 +/- 17.8 min; P = 0.02). The analysis of the meal distribution inside the stomach showed no differences between males and females in proximal gastric emptying, but the meal retention in the distal compartment was significantly increased among women (P = 0.04). In conclusion, gastric emptying of a solid meal is slower in pre-menopausal women than in age-matched men, probably due to an increased retention of the meal in the distal compartment. This should be taken into consideration to avoid misleading diagnosis of gastroparesis for female patients