Desensibilización a levotiroxina: caso clínico / Successful oral desensitization to levothyroxine: report of one case

We report a 39-year-old female who underwent a total thyroidectomy as treatment for a thyroid papillary cancer. She suffered several episodes of mild angioedema in lips and tongue, after using different commercial Levothyroxine formulations, with and without excipients. Given the need to use this drug, the patient was admitted in our hospital and we proceeded to desensitize her with oral Levothyroxine. The patient fasted throughout the whole procedure, was properly monitored and had an adequate peripheral venous access. On the first day of the procedure, a 15-step protocol was performed, first administering placebo and then, compounded formulations of Levothyroxine starting from 0.01 ug, followed by doubling doses every 15 minutes until the cumulative dose of 111.95 ug was completed, corresponding to the daily dose of Levothyroxine her endocrinologist prescribed (112 ug). The patient was monitored at baseline, between each dose and up to 3 hours after the procedure was completed. There were no incidents such as urticaria, angioedema, or others. On the second day, the patient received a single-full dose of 112 ug on an empty stomach. The medication was successfully tolerated and she was discharged. Thereafter, she tolerates daily Levothyroxine.

Does Maintaining a Bottle of Adhesive Without the Lid Significantly Reduce the Solvent Content?

This study aimed to evaluate the effect of maintaining a bottle of adhesive without its lid on the solvent loss of the etch-and-rinse adhesive systems. Three 2-step etch-and-rinse adhesives with different solvents (acetone, ethanol or butanol) were used in this study. Drops of each adhesive were placed on an analytical balance and the adhesive mass was recorded until equilibrium was achieved (no significant mass alteration within time). The solvent content of each adhesive and evaporation rate of solvents were measured (n=3). Two bottles of each adhesive were weighted. The bottles were maintained without their lids for 8 h in a stove at 37 ºC, after which the mass loss was measured. Based on mass alteration of drops, acetone-based adhesive showed the highest solvent content (46.5%, CI 95%: 35.8-54.7) and evaporation rate (1.11 %/s, CI95%: 0.63-1.60), whereas ethanol-based adhesive had the lowest values (10.1%, CI95%: 4.3-16.0; 0.03 %/s CI95%: 0.01-0.05). However, none of the adhesives bottles exhibited significant mass loss after sitting for 8 h without their lids (% from initial content; acetone - 96.5, CI 95%: 91.8-101.5; ethanol - 99.4, CI 95%: 98.4-100.4; and butanol - 99.3, CI 95%: 98.1-100.5). In conclusion, maintaining the adhesive bottle without lid did not induce significant solvent loss, irrespective the concentration and evaporation rate of solvent.

Este estudo avaliou o efeito da manutenção do frasco do adesivo sem sua tampa na perda de solvente de sistemas adesivos convencionais. Três adesivos convencionais de 2 passos com diferentes solventes (acetona, etanol ou butanol) foram usados neste estudo. Gotas de cada adesivo foram colocadas em uma balança analítica e a massa dos adesivos foi registrada até a obtenção do equilíbrio (nenhuma alteração significativa com o tempo). O conteúdo de solvente de cada adesivo e a taxa de evaporação dos solventes foram mensurados (n=3). Dois frascos de cada adesivo foram pesados. Os frascos foram mantidos sem suas tampas por 8 h em uma estufa a 37 ºC, seguido pela mensuração da pera de massa. Baseado na alteração de massa das gotas, o adesivo a base de acetona demonstrou o maior conteúdo de solvente (46,5%, IC 95%: 35,8-54,7) e de taxa de evaporação (1,11 %/s, IC95%: 0,63-1,60), enquanto que o adesivo à base de etanol teve os menores valores (10,1%, IC95%: 4,3-16,0; 0,03 %/s IC95%: 0,01-0,05). Entretanto, nenhum dos frascos dos adesivos exibiu perda significante de massa após ficar por 8 h sem suas tampas (% do conteúdo inicial; acetona - 96,5, IC95%: 91,8-101,5; etanol - 99,4, IC95%: 98,4-100,4; e butanol - 99,3, IC95%: 98,1-100,5). Em conclusão, a manutenção do frasco do adesivo sem tampa não induziu perda significante de solvente independente da concentração e da taxa de evaporação do solvente.

Immunoelectron microscopy study of superficial skin nerves in drug-induced acute urticaria / Estudo de microscopia imunoeletrônica dos nervos superficiais da pele na urticária aguda induzida por medicamentos

BACKGROUND: Few studies have evaluated the ultrastructure of the superficial skin nerves in urticaria. OBJECTIVE: The objective of this study was to describe findings in superficial skin nerves in cases of drug-induced acute urticaria. METHODS: Seven patients with drug-induced acute urticaria were included in the study. Skin biopsies were obtained from the urticarial lesion and from the apparently normal skin. The 14 fragments collected were processed for immunogold electron microscopy using single stains for antitryptase and anti-FXIIIa antibodies, as well as double immunogold labeling for both. RESULTS: Some sections showed mast cells in the process of degranulation. Following double immunogold staining, 10 nm (FXIIIa) and 15 nm (Tryptase) gold particles were found together throughout the granules in mast cells, indicating that tryptase and FXIIIa are located inside each one of the granules of these cells. Interestingly, we found strong evidence of the presence of tryptase and factor XIIIa in the superficial skin nerves of these patients, both in cases of urticarial lesions (wheals) and in the apparently normal skin. CONCLUSIONS: Tryptase and FXIIIa are present in the superficial nerves of the skin in drug-induced acute urticaria. This is the first report of tryptase and FXIIIa expression in the superficial skin nerves of patients with urticaria. Tryptase may be participating in neural activation in these patients, while FXIIIa may be present in the nerves to guarantee the functional integrity of structures.

FUNDAMENTOS: Poucos autores têm estudado a ultraestrutura dos nervos superficiais na urticária. OBJETIVO: Descrever os achados nos nervos cutâneos superficiais em casos de urticária aguda induzida por medicamentos. MÉTODOS: Sete pacientes com urticária aguda induzida por medicamentos foram incluídos no estudo. Foram obtidas biopsias da pele da lesão urticariforme e da pele aparentemente normal. Os 14 fragmentos coletados foram processados usando imunomarcação com ouro para anticorpos anti-triptase e anti-FXIIIa separadamente, além da dupla imunomarcação com ambos anticorpos. A seguir as amostras foram submetidas à análise por microscopia imunoeletrônica. RESULTADOS: Alguns cortes demonstraram mastócitos em processo de degranulação. Após a imunomarcação dupla, partículas de ouro de 10 nm (FXIIIa) e partículas de ouro de 15 nm (Triptase) apresentavam-se juntas em grânulos de mastócitos indicando que a triptase e o FXIIIa se localizam dentro de cada um dos grânulos dessas células. Curiosamente, foi encontrada uma forte evidência da presença da triptase e do fator XIIIa nos nervos superficiais dos pacientes avaliados, tanto em lesões urticadas, como na pele aparentemente normal. CONCLUSÕES: A triptase e o FXIIIa estão presentes nos nervos superficiais da pele na urticária aguda medicamentosa. Este é o primeiro relato da expressão de triptase e de FXIIIa nos nervos superficiais na urticária. A triptase poderia estar participando da ativação neural nos pacientes estudados. O FXIIIa poderia estar presente nos nervos, com a finalidade de manter a integridade funcional dessas estruturas.

Is the skin sensitivity test required for administering equine rabies immunoglobulin.

Background. Rabies immunoglobulins are life-saving in patients with severe exposure to rabies. Despite the high degree of purification of equine rabies immunoglobulin (ERIG), the product inserts still recommend a skin sensitivity test before administration of this heterologous serum. A recent WHO recommendation states that there are no scientific grounds for performing a skin test before administering ERIG because testing does not predict reactions and it should be given irrespective of the result of the test. In this conflicting situation, we assessed the use of the skin sensitivity test in predicting adverse events to ERIG. Methods. The data analysed were from the Antirabies Clinic of the Kempegowda Institute of Medical Sciences Hospital, Bengaluru, India. The period of study was 26 months (June 2008–July 2010). The skin sensitivity test was validated by evaluating its sensitivity, specificity, predictability, falsepositive and false-negative results. Results. A total of 51 (2.6%) adverse events were reported in 31 (1.5%) subjects. Most of these were mild to moderate in nature and subsided without medication. There was no serious adverse event. The sensitivity and specificity of the skin sensitivity test to predict an adverse event was 41.9% and 73.9%, respectively. Conclusion. Our experience with the skin sensitivity test suggests that it may not be required before administering ERIGs, as recommended by WHO.

Hormônio de crescimento e hipersensibilidade por imunocomplexo (Tipo III): uma contraindicação para a dessensibilização / Growth hormone therapy and hypersensitivity type III reaction: a contraindication for desensitization

As reações alérgicas ao GH são raras e usualmente representadas por reações de hipersensibilidade tipo I (IgE mediadas), passíveis de tratamento por dessensibilização. Neste relato de caso, descrevemos a presença de reação alérgica ao GH mediada por imunocomplexo (hipersensibilidade tipo III). Nesta situação, a tentativa de dessensibilização pode perpetuar a formação de imunocomplexo, cujo depósito pode determinar insuficiência renal e respiratória.

Allergic reactions against GH are rare, and usually represented by the hypersensitivity type I (IgE-mediated). This type of reaction can be treated by desensitization. In this case report, we present a patient showing an allergic reaction soon after starting GH therapy mediated by immune complex (hypersensitivity type III reaction). In this condition, the attempt to perform the desensitization procedure can perpetuate immune complex deposition determining a life threatening renal and respiratory insufficiency.

Functional changes of dendritic cells in hypersensivity reactions to amoxicillin

A better understanding of dendritic cell (DC) involvement in responses to haptenic drugs is needed, because it represents a possible approach to the development of an in vitro test, which could identify patients prone to drug allergies. There are two main DC subsets: plasmacytoid DC (pDC) and myeloid DC (mDC). β-lactams form hapten-carrier conjugates and may provide a suitable model to study DC behavior in drug allergy reactions. It has been demonstrated that drugs interact differently with DC in drug allergic and non-allergic patients, but there are no studies regarding these subsets. Our aim was to assess the functional changes of mDC and pDC harvested from an amoxicillin-hypersensitive 32-year-old woman who experienced a severe maculopapular exanthema as reflected in interleukin-6 (IL-6) production after stimulation with this drug and penicillin. We also aim to demonstrate, for the first time, the feasibility of this method for dendritic cell isolation followed by in vitro stimulation for studies of drug allergy physiopathology. DC were harvested using a double Percoll density gradient, which generates a basophil-depleted cell (BDC) suspension. Further, pDC were isolated by blood DC antigen 4-positive magnetic selection and gravity filtration through magnetized columns. After stimulation with amoxicillin, penicillin and positive and negative controls, IL-6 production was measured by ELISA. A positive dose-response curve for IL-6 after stimulation with amoxicillin and penicillin was observed for pDC, but not for mDC or BDC suspension. These preliminary results demonstrate the feasibility of this methodology to expand the knowledge of the effect of dendritic cell activation by drug allergens.

Improvement in Erythropoieis-stimulating Agent-induced Pure Red-cell Aplasia by Introduction of Darbepoetin-alpha When the Anti-erythropoietin Antibody Titer Declines Spontaneously

Anti-erythropoietin antibodies usually cross-react with all kinds of recombinant erythropoietins; therefore, erythropoiesis-stimulating agent (ESA)-induced pure red-cell aplasia (PRCA) is not rescued by different ESAs. Here, we present a case of ESA-induced PRCA in a 36-yr-old woman with chronic kidney disease, whose anemic condition improved following reintroduction of darbepoetin-alpha. The patient developed progressive, severe anemia after the use of erythropoietin-alpha. As the anemia did not improve after the administration of either other erythropoietin-alpha products or erythropoietin-beta, all ESAs were discontinued. Oxymetholone therapy failed to improve the transfusion-dependent anemia and a rechallenge with ESAs continuously failed to obtain a sustained response. However, her anemia improved following reintroduction of darbepoetin-alpha at 3 yr after the initial diagnosis. Interestingly, anti-erythropoietin antibodies were still detectable, although their concentration was too low for titration. In conclusion, darbepoetin-alpha can improve ESA-induced PRCA when the anti-erythropoietin antibody titer declines and its neutralizing capacity is lost.

Drug Hypersensitivity to Previously Tolerated Phenytoin by Carbamazepine-induced DRESS Syndrome

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome associated with anticonvulsant drugs is a rare but potentially life-threatening disease that occurs in response to arene oxide producing anticonvulsant such as phenytoin and carbamazepine. There have been many reports of cross reactivity among the anticonvulsants upon first exposure to the offending drugs. However, there has been few data describing the development of DRESS syndrome after switching medication from previously well-tolerated phenytoin to carbamazepine, and the induction of hypersensitivity to phenytoin by DRESS to carbamazepine. We experienced a case of a 40-yr-old man who had uncontrolled seizure that led to the change of medication from the long-term used phenytoin to carbamazepine. He developed DRESS syndrome after changing the drugs. We stopped carbamazepine and restored phenytoin for seizure control, but his clinical manifestations progressively worsened and he recovered only when both drugs were discontinued. Patch tests with several anticonvulsants showed positive reactions to both carbamazepine and phenytoin. Our case suggests that hypersensitivity to a previously tolerated anticonvulsant can be induced by DRESS to another anticonvulsant, and that the patch test may be a useful method for detecting cross-reactive drugs in anticonvulsant-associated DRESS syndrome.

Reações alérgicas a medicamentos / Allergic drug reactions

OBJETIVO: Rever as publicações recentes mais relevantes sobre alergia medicamentosa e oferecer ao clínico subsídios para uma maior compreensão dessa problemática de grande relevância para a saúde pública. FONTES DOS DADOS: Busca de artigos originais e revisões indexados nas bases MEDLINE, Pubmed e Lilacs, publicados na última década, relacionando o tema de alergia a medicamentos com mecanismos imunológicos, epidemiologia, diagnóstico laboratorial, lesões cutâneas, manejo clínico e reexposição ao fármaco. SíNTESE DOS DADOS: As reações alérgicas representam um terço das reações adversas a medicamentos. São consideradas eventos raros, mas com elevada morbimortalidade. Apesar da descrição de Gell & Coombs, útil para classificar reações alérgicas a fármacos, algumas permanecem sem classificação devido ao desconhecimento dos mecanismos imunológicos envolvidos. A existência de subpopulações de células T com características diversas daquelas comumente descritas revela a complexidade do tema e, ao mesmo tempo, elucida inúmeras questões inerentes ao mesmo. Recentemente, um novo conceito de apresentação de fármaco a linfócitos T surgiu, diante de evidências crescentes do seu envolvimento nas lesões cutâneas decorrentes de reações alérgicas a medicamentos. Na prática clínica, é muito difícil a correlação de sinais e sintomas das reações alérgicas a medicamentos com o mecanismo imunológico envolvido sem o auxílio de testes laboratoriais. Testes cutâneos in vivo e testes in vitro têm sido empregados nas suspeitas de reações alérgicas a medicamentos. No entanto, há poucos produtos comerciais adequados para sua execução. CONCLUSÕES: As reações alérgicas a fármacos constituem uma fração importante dos eventos adversos a medicamentos. É importante enfatizar a necessidade de notificação dessas reações pelos profissionais envolvidos no tratamento do paciente de forma sistematizada, por meio de ações de farmacovigilância, bem como a identificação dos possíveis mecanismos imunológicos envolvidos através de testes laboratoriais, história e avaliação clínica detalhadas.

Endocarditis por Abiotrophia defectiva en paciente adulto / Endocarditis caused by Abiotrophia defectiva in an adult patient

Abiotrophia defectiva, formerly designated as a member of nutritionally variant streptococci, is part of normal oral flora and may be a cause of culture-negative endocarditis. We report a case of infective endocarditis caused by A. defectiva in a 37-year-old man, allergic to penicillin. We also review the literature for antibiotic treatment alternatives and the microbiological diagnostic possibilities at present.

Abiotrophia defectiva es una cocácea grampositiva considerada anteriormente como parte del grupo de los estreptococos nutricionalmente variables. Es parte de la microbiota oral y puede ser causante de endocarditis bacteriana con cultivo negativo. Se reporta el caso de un paciente varón de 37 años de edad, alérgico a penicilina, con endocarditis infecciosa causada por A. defectiva y se realiza revisión de la literatura sobre las alternativas terapéuticas y el estado actual del diagnóstico microbiológico de este agente.

Reacciones alérgicas a drogas: enfoque clínico según mecanismo inmunopatogénico / Allergic reactions to drugs: clinical approach according to immunopathogenic mechanism

Las reacciones alérgicas a drogas (RAD) constituyen un desafío para el médico que las enfrenta. Requiere de un alto índice de sospecha y gran dedicación dilucidar la droga causal. En esta revisión se ofrece un esquema simplificado para enfrentar el estudio de pacientes con RAD, según el mecanismo inmunopatogénico implicado en cada uno de ellos. Es posible que en un futuro cercano se cuente con métodos diagnósticos específicos, sensibles y seguros, lo que será posible en la medida que se avance en el conocimiento de la inmunopatogenia de las RAD.

A randomized, pilot trial comparing full versus escalating dose regimens for the desensitization of AIDS patients allergic to sulfonamides

Sulfonamides are drugs extensively used in the management of AIDS patients. However, the use of sulfonamides is often associated with the development of allergic reactions, provoking the substitution of the drug (by another that may be less effective); alternatively attempts are made to desensitize the patient. OBJECTIVE: Compare two drug regimens (full vs. escalating doses) for the oral desensitization of AIDS patients allergic to sulfonamides. MATERIAL AND METHODS: AIDS patients with previous allergic reactions to sulfonamides and requiring prophylaxis against Pneumocistis carinii, central nervous system toxoplasmosis and diarrhea caused by Isospora belli were randomly assigned to a group receiving a routine dose of cothrimoxazole, or another that received escalating doses of an oral suspension of the same drug, initiating with 75mg/day of sulfamethoxazole that was doubled every 48 hours till the full dose was reached, if no allergic reaction occurred. Patients were monitored for at least 6 months after enrollment in the trial. The major end-point was the ability to maintain prophylactic treatment after that period of time. Plasma viral load (PVL) and CD4/CD8 counts were measured at baseline. Liver enzymes and hematological parameters were measured at baseline and after 1, 3 and 6 months. RESULTS: Eighteen patients were enrolled in the study (15 men and 3 women), with ages ranging from 30 to 57 years (mean 39.9). The mean CD4 counts were slightly higher for patients receiving a full dose; there was also a trend towards higher baseline CD8 counts among patients developing new reactions. The mean PVL was similar among the patients in both desensitization groups. The incidence of new allergic reactions was identical (40 percent) in the two groups. All adverse reactions were mild and no significant increase in liver enzymes were observed. CONCLUSON: Dose regimen is not a predictor of the development of new allergic reactions amongst patients challenged with sulfonamides after an initial allergic reaction.

Importancia del núcleo bencilpenicilina y las cadenas laterales de los beta-lactámicos: demostración por pruebas cutáneas y RAST en pacientes alérgicos a penicilina / Importance of the benzylpenicillin nucleus and the side chain of the beta-lactams: demonstration by skin tests and RAST in penicillin allergic patients

Se estudiaron 30 pacientes con reacciones alérgicas a Beta - Lactámicos claramente demostrados por las manifestaciones clínicas. El objetivo de este trabajo fue determinar la importancia del núcleo Beta - Lactámico y las cadenas laterales en la inducción de IgE específica para BPO, Ax y AMP por medio de las pruebas cutáneas y el RAST para estos determinantes. Este grupo se dividió previamente por historia clínica en: 1 - Acelerados (n:19); 2-Inmediatos (n:11). Las pruebas del Prick se realizaron con BPO-PL, Ax-PL, Amp-PL, MDM de BP, MDM de Ax y MDM de Amp. Presentando en el grupo acelerado: 2 (+) a BPO, 4(+) Ax/AMP, 13(+) a todos los reactivos (BPO-Ax - Amp - MDM BP/Ax/Amp). Los pacientes con reacción inmediata: 10 casos (+) a MDM-BP y 1 (+) MDM-Amp. Estos pacientes fueron estudiados con la técnica del RAST para BPO - PL, Ax-PL, Amp PL y PL. Se consideró como línea de corte positiva al nivel = a 1524 cpm, tomado de la curva estandar de Pharmacia. Los pacientes con reacción acelerada presentaron en 13/19 casos RAST (+) a BPO-PL, 1/19 (+) BPO- Ax/PL, 3/19(+) Ax-PL, 1/19(+) Am/PL y 1 negativo para todos los reactivos estudiados. Los pacientes con reación inmediata (n:11) en todos los casos fueron negativos para todos los reactivos estudiados. El grupo control (n:20) presentó en 1/20 casos positividad por Prick a Ax-PL y 19 casos negatividad total a todos los reactivos. Los RAST a todos los reactivos fueron negativos en todos los individuos estudiados. Estos resultados indican que la bensilpenicilina (BPO) es el más importante determinante y las cadenas laterales (Ax y Amp) son otros determinantes antigénicos en los Beta-Lactámicos, siendo cada uno de ellos inductores de un tipo de IgE específica y que raramente aparece una respuesta IgE a dos determinantes diferentes en un mismo sujeto. Las pruebas cutáneas son el método de elección para el estudio de alergia a penicilina ya que con el método in vitro se cubre un espectro menor de reactivos que los que producen reacción acelerada (MDM).

Actividad fagocítica de polimorfonucleares en pacientes con hipersensibilidad a la aspirina, asma y pólipos nasales / Phagocytic function in patients with aspirine sensitive asthma and hypertrophy rhinosinusitis with nasal polyps

La eficiencia de la función fagocítica depende de la óptima actividad de cada estadio del proceso fagocítico. Los pacientes con hipersensibilidad a la aspirina, asma, rinosinusitis hipertrófica con pólipos nasales ®triada de la aspirina¼ (pacientes ASA) tienen indicios de defectos en la fagocitosis. Se estudiaron 34 pacientes ASA y 34 sujetos sanos. Las células polimorfonucleares, quimioluminiscencia (CL) de los pacientes ASA se estudiaron in vitro. La actividad fagocítica se midió con la técnica de quimioluminiscencia. No se encontraron diferencias estadísticas con la prueba de U de Mann Whitney (p=NS). No hubo diferencias en la capacidad fagocítica de polimorfonucleares de pacientes ASA y controles sanos. A pesar de los avances de las ciencias básicas, la causa y patogenesis de los pólipos nasales no se ha aclarado, particularmente la tinosinusitis, asma intrínseca y la intolerancia a farmacos no esteroides

Hipersensibilidade a drogas em paciente com SIDA: relato de caso / Drug hipersensibility and HIV infected patients: case report

A alergia a drogas e frequente em pacientes portadores de HIV, com incidencia maior que na populacao geral. Os autores descrevem uma crianca com SIDA e reacoes adversas a drogas utilizadas na profilaxia do Pneumocystis carinii (Sulfametoxazol-trimetoprim/Pentamidina) e outros antibioticos, entre eles a cefalexina e o cloranfenicol. Sao discutidos os provaveis mecanismos fisiopatologicos das reacoes, drogas alternativas para profilaxia do Pneumocystis carinii e dessensibilizacao para o sulfametoxazol-trimetoprim

Cambios metabólicos del ácido araquidónico en la desensibilización a la aspirina / Aspirin, metabolic change in arachidonic acid in the desensitization

La sensibilización de la aspirina se presenta en acerca del 10 por ciento de todos los pacientes asmáticos. En esta clase de asmáticos la congestión nasal y el broncoespasmo ocurren entre los 30 a 180 minutos después de la ingestión de la aspirina. Luego de la reacción respiratoria a la aspirina todos los pacientes pueden ser desensibilizados a la misma mediante la introducción repetida de pequeñas a grandes cantidades de aspirina hasta que los sujetos asmáticos pueden ingerir 650 mg del fármaco sin ningún efecto adverso. Los mecanismos de la sensibilidad a la aspirina no están totalmente esclarecidos, y las razones por las cuales la desensibilización en los pacientes asmáticos sensibles a la aspirina (ASA) ocurre de manera universal se desconocen. En este estudio, pacientes ASA y testigos asmáticos no ASA se expusieron a dosis provocadoras de aspirina. Se colectaron muestras de orina antes, durante el broncoespasmo inducido, y después de la ingestión de 650 mg de aspirina, cuando los efectos adversos habían desaparecido (fenómeno de desensibilización). Se dertminaron los niveles de los productos tipo y cicloxigenados en las muestras de orina. En este trabajo se analizan los resultados y se expone una explicación del probable mecanismo de la desensibilización