Ketoprofen hypersensibility and idiosyncratic response - a case report.

Context: Ketoprofen is widely used to remove pain. A steady increase on allergic reactions and photoallergic contact dermatitis related to ketoprofen has been reported when there is topical use. However, there are few documented cases of hypersensitivity when it is administered systemically.Objective: Present a case of hypersensitivity reaction after systemic administration of ketoprofen for pain control in nephritis crisis.Case description: A 43-years-old Caucasian man diagnosed with renal colic (kidney lithiasis), who was initially treated with 100 mg of tramadol (IV), followed by 4 mg of thiocolchicoside (IM) which caused no relief. Then 100 mg of ketoprofen was administered (IV). Right after the patient began to show hypersensitivity reaction type I characterized by intense coughing, rhinitis, angioedema, periorbital edema, rash, and scleral jaundice.Discussion and conclusion: Maybe it was a case of drug-induced liver disease, however therapeutic dosages of all administered drugs only once. The mechanisms involved were not investigated, but may be the result of allergic and immunologic aspects caused by ketoprofen and facilitated by a history of hypersensitivity to other NSAIDs as reported by the patient. As for jaundice can be attributed to drug toxicity since laboratory parameters did not reveal any evidence of liver disease.

Incidence of Childhood Eosinophilic Esophagitis in Central Brazil: How Many Are We Missing?

BACKGROUND: Few studies have assessed the incidence of eosinophilic esophagitis (EoE) in childhood. Our study aimed to determine the incidence of EoE in pediatric patients undergoing upper gastrointestinal endoscopy (UGE), with analysis of epidemiological data including sex, age, symptoms, frequency of atopy, and endoscopic and histological findings. METHODS: We performed a retrospective, observational, analytical study of the medical records of patients aged 0 to 14 years who underwent UGE in a tertiary hospital from January 2004 to January 2014. RESULTS: A total of 4071 upper digestive endoscopies were performed in 2651 patients. Esophageal eosinophilia was found in 405 biopsy reports, and 127 patients had ≥15/HPF. The clinical histories of 70 patients were analyzed. Sixty-three fulfilled the diagnostic criteria for EoE, 3 fulfilled the criteria for eosinophilic gastroenteritis, and 4 cases were secondary to caustic ingestion. The mean annual incidence was 2.48/100 000 individuals/year and the cumulative incidence over 10 years was 24.8/100 000. No statistical differences were found between responders to proton pump inhibitors and nonresponders for age, gender, atopic diseases, symptoms, and endoscopy findings. CONCLUSIONS: The incidence of EoE in the present study was similar to that reported in the literature. However, these data may be underestimated owing to difficulties accessing UGE. Increased knowledge of esophageal eosinophilic diseases in childhood requires associated improvements in health infrastructure.

Effect of once-daily generic ciclesonide on exhaled nitric oxide in atopic children with persistent asthma.

BACKGROUND: Ciclesonide (CIC) is an effective inhaled corticosteroid for treating asthmatic children. However, its effect on airway inflammation assessed by the fraction of exhaled nitric oxide (FENO) in children with persistent asthma is virtually unknown. We aimed to assess the effect of once-daily generic CIC, 80 or 160 µg, on FENO, lung function, asthma control and bronchial hyperresponsiveness, in atopic children with persistent asthma. METHODS: This was a 12-week, randomised, double-blind, parallel-group study. Sixty children with mild-to-moderate persistent asthma were recruited. Changes in FENO, asthma control score, lung function (FEV1) and bronchial hyperresponsiveness to methacholine (BHR) were used to assess the effects of both CIC doses. Non-normally distributed variables were log-transformed to approximate normality, and parametric tests were used for comparisons within and between groups at baseline and after 12 weeks of treatment. RESULTS: In the CIC 80 µg group, FENO decreased from 45.0 ppb (95% CI 37.8-53.7) to 32.7 ppb (95% CI 21.0-47.3) at the end of study (P=0.021), whereas in the CIC 160 µg group, FENO decreased from 47.3 ppb (95% CI 40.4-55.3) to 30.5 ppb (95% CI 24.1-38.7) (P<0.001). The difference between groups in FENO at the end of study was not significant (P=0.693). There was a significant improvement of asthma control with both CIC doses but there was no significant change in BHR or FEV1 in either group. CONCLUSION: Once-daily generic ciclesonide (80 µg or 160 µg), for 12 weeks, is effective to improve airway inflammation and asthma control in atopic children with persistent asthma.

Curine inhibits mast cell-dependent responses in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Curine is a bisbenzylisoquinoline alkaloid and the major constituent isolated from Chondrodendron platyphyllum, a plant that is used to treat inflammatory diseases in Brazilian folk medicine. This study investigates the effectiveness of curine on mast cell-dependent responses in mice. MATERIALS AND METHODS: To induce mast cell-dependent responses, Swiss mice were subcutaneously sensitized with ovalbumin (OVA-12 µg/mouse) and Al(OH)3 in a 0.9% NaCl solution. Fifteen days later, the animals were challenged with OVA through different pathways. Alternatively, the animals were injected with compound 48/80 or histamine, and several parameters, including anaphylaxis, itching, edema and inflammatory mediator production, were analyzed. Promethazine, cromoglycate, and verapamil were used as control drugs, and all of the treatments were performed 1h before the challenges. RESULTS: Curine pre-treatment significantly inhibited the scratching behavior and the paw edema induced by either compound 48/80 or OVA, and this protective effect was comparable in magnitude with those associated with treatment with either cromoglycate or verapamil. In contrast, curine was a weak inhibitor of histamine-induced paw edema, which was completely inhibited by promethazine. Curine and verapamil significantly inhibited pleural protein extravasations and prostaglandin D2 (PGD2) and cysteinyl leukotrienes (CysLTs) production following allergen-induced pleurisy. Furthermore, like verapamil, curine inhibited the anaphylactic shock caused by either compound 48/80 or an allergen. In in vitro settings, these treatments also inhibited degranulation as well as PGD2 and CysLT production through IgE-dependent activation of the mast cell lineage RBL-2H3. CONCLUSION: Curine significantly inhibited immediate allergic reactions through mechanisms more related to mast cell stabilization and activation inhibition than interference with the pro-inflammatory effects of mast cell products. These findings are in line with the hypothesis that the alkaloid curine may be beneficial for the treatment of allergic disorders.

Monoterpenes isolated from Minthostachys verticillata (Griseb.) Epling essential oil modulates immediate-type hypersensitivity responses in vitro and in vivo.

In a previous work, we have demonstrated that Minthostachys verticillata essential oil has immunomodulatory effects in vitro on cells from allergic patients. Here we characterized main components of M. verticillata essential oil and also tested if these compounds modulate In vitro and in vivo the immediate-type allergic reaction. Gas chromatography was used to identify main components of the essential oil. Pulegone (63.4 %), menthone (15.9 %), and limonene (2.1 %) were found as main classes. IL-13 levels were evaluated from lymphocytes cultures stimulated with allergen alone or combined with monoterpenes. All compounds stimulated cell proliferation but, interestingly, promoted a reduction of IL-13 values, limonene and the mixture of the three compounds being the most active. ß-Hexosaminidase release was determined from basophils to which essential oil or monoterpenes were added. We observed that, whichever combination of monoterpenes was used, ß-hexosaminidase release was diminished in all cases. Obtained values were even lower than those of antiallergic drug desloratadine. Essential oil and limonene inhibited mast cell activation and degranulation in the skin when testing passive cutaneous anaphylaxis, limonene being the most active. In conclusion, limonene was the compound that showed the most potent immunomodulatory activity. This fact suggests that it constitutes a promising natural alternative for a novel treatment of allergic diseases.

Response to budesonide among atopic and non-atopic infants/preschoolers with recurrent wheezing.

BACKGROUND: The treatment in non-atopic young children with recurrent wheezing remains controversial. OBJECTIVE: The aim of the study was to compare the response of inhaled budesonide in atopic versus non-atopic infants/preschoolers with recurrent wheezing (more than three episodes in the last year or one episode per month in the last three months). METHODS: One hundred and seventy three infants/preschoolers (mean age 1.58+/-0.9 yrs) with recurrent wheezing without previous use of inhaled corticosteroids were enrolled and divided into two categories: atopics (eosinophils in peripheral blood > or =4%) and non-atopics (<4%). Both groups were treated with budesonide (200 mcg bid delivered by MDI and spacer) for three months. The primary outcome was the prevalence of wheezing exacerbation episodes at the end of the treatment. RESULTS: Thirty-seven out of 173 (21.4%) were atopics and they were significantly younger, more frequently with a father with asthma, maternal grandparents with asthma and rhinitis, paternal and maternal grandparents with eczema, and higher number of wheezing episodes in the last year than non-atopics. At the end of the study, among those with good compliance (>70% of the weekly doses), the proportion of wheezing episodes were similar among atopics and non-atopics (57.7% vs. 44.1%, p=0.25, respectively); the number of exacerbations requiring emergency department (ED) visits and hospital admission were also similar. CONCLUSION: Regular budesonide therapy may decrease the episodes of wheezing in infants/preschoolers with recurrent wheezing, independently of atopy.

[Rhinitis, sinusitis and allergy]. / Rinitis, sinusitis y alergia.

The allergic and infectious diseases of the nasal mucous represent two of the most frequent and chronic upper airways diseases in children and young adults. They are a public health problem of great magnitude due to the high prevalence that causes a great welfare pressure in terms of ambulatory consultations, significant deterioration of the quality of life so much for the patient who suffers them, like for the relatives and affect the community for the high socioeconomic costs that these generate. It is indispensable to know the physiopathology to be able to realize in time a suitable diagnosis and with it to offer a treatment adapted to diminish it recurrence.

Warifteine, a bisbenzylisoquinoline alkaloid, decreases immediate allergic and thermal hyperalgesic reactions in sensitized animals.

Warifteine is a bisbenzylisoquinoline alkaloid isolated from the Cissampelos sympodialis Eichl (Menispermaceae). This plant is used in the folk medicine for the treatment of airway respiratory diseases. A murine model of immediate allergic reaction was used to evaluate warifteine treatment in the IgE production, leukocyte activation, thermal hyperalgesia, mast cell degranulation and scratching behavior. BALB/c mice treated with warifteine (0.4-10 mg/Kg) 1 h before OVA sensitization reduced OVA induced paw edema as well as the OVA-specific IgE serum titers as compared with non-treated and OVA-sensitized animals. Warifteine also reduced the mice death evoked by IgE-dependent anaphylactic shock reaction at 30 min after intravenous OVA challenge. To assess the effect of warifteine treatment on T cell proliferative response, spleen cells from warifteine treated or non-treated and OVA-sensitized animals were evaluated. Spleen cells from warifteine treated animals (2.0 mg/kg) did not proliferate following OVA stimulation as compared with spleen cell cultures from non-treated animals. This response may be related with the increase of NO production as observed in peritoneal macrophage cultures treated with warifteine. Thermal hyperalgesia evoked by IgE or histamine/5-hydroxytryptamine challenge was inhibited on rats at dose of 4.0 mg/kg. Warifteine treatment (0.6 or 6.0 microg/ml) also decreased the IgEalphaDNP-BSA sensitized mast degranulation after DNP-BSA challenge measured by histamine release. In addition, compound 48/80-induced scratching behavior was also sensitive to warifteine treatment. These results demonstrate for the first time that warifteine treatment reduced the allergy-associated responses.

Nonsteroidal anti-inflammatory drugs: cyclooxygenase 2 inhibitors.

OBJECTIVES: To analyze selective COX 2 inhibitor nonsteroidal anti-inflammatory drugs (NSAID) in terms of their mechanism of action, principal indications, posology and most common adverse effects. SOURCES: MEDLINE and LILACS databases and Food and Drug Administration (FDA) and National Agency for Sanitary Vigilance (ANVISA - Agência Nacional de Vigilância Sanitária) websites. The most important articles were selected and preference was given to articles published within the last 5 years. SUMMARY OF THE FINDINGS: The principal indications for NSAID are for control of pain and acute and chronic inflammation. There is no overwhelming evidence that demonstrates the superiority of one NSAID over another in terms of effectiveness. To date none of the COX 2 inhibitors has been liberated for use in the pediatric age group. Only meloxicam and etoricoxib can be prescribed for adolescents (13 and 16 years, respectively). Selective COX 2 inhibitors are indicated for patients with adverse effects that have proven to be associated with nonselective NSAID use. Selective COX 2 inhibitors can be prescribed in some cases of allergy to aspirin, but they must be used with care. Principal adverse effects include cardiovascular events and thrombotic phenomena. CONCLUSIONS: Selective COX 2 inhibitors are medicines that have been used in certain well-defined clinical situations and which may offer certain advantages over nonselective NSAID. Nevertheless, taking into consideration the higher cost involved and the potential for adverse cardiovascular effects, they should be employed only in accordance with strict criteria.

Nonsteroidal anti-inflammatory drugs: cyclooxygenase 2 inhibitors

OBJETIVO: Analisar os antiinflamatórios não-hormonais (AINH) inibidores seletivos da Cox 2 quanto ao mecanismo de ação, principais indicações, posologia e efeitos adversos mais comuns. FONTES DOS DADOS: MEDLINE e LILACS, sites da Food and Drug Administration (FDA) e da Agência Nacional de Vigilância Sanitária (ANVISA). Foram selecionados os artigos mais importantes, com destaque para as publicações dos últimos 5 anos. SíNTESE DOS DADOS: As principais indicações dos AINH são o controle da dor e da inflamação aguda e crônica. Não existem evidências que demonstrem maior efetividade de um AINH sobre outro. Até a presente data, nenhum inibidor da Cox2 foi liberado para uso na faixa etária pediátrica. Apenas o meloxicam e o etoricoxibe podem ser prescritos para adolescentes (13 e 16 anos, respectivamente). Os inibidores seletivos da Cox 2 são indicados em pacientes com efeitos adversos comprovadamente relacionados aos AINH não seletivos. Em alguns casos de alergia à aspirina, os Cox 2 seletivos podem ser prescritos, mas seu uso deve ser cuidadoso. Os principais efeitos adversos incluem os cardiovasculares e os fenômenos trombóticos. CONCLUSÕES: Os inibidores seletivos da Cox 2 são medicamentos que vêm sendo utilizados em algumas situações clínicas bem determinadas e podem oferecer algumas vantagens com relação aos AINH não seletivos. No entanto, devido ao custo mais elevado e aos potenciais efeitos adversos cardiovasculares, seu emprego deve ser criterioso.

OBJECTIVE: To analyze selective COX 2 inhibitor nonsteroidal anti-inflammatory drugs (NSAID) in terms of their mechanism of action, principal indications, posology and most common adverse effects. SOURCES: MEDLINE and LILACS databases and Food and Drug Administration (FDA) and National Agency for Sanitary Vigilance (ANVISA - Agência Nacional de Vigilância Sanitária) websites. The most important articles were selected and preference was given to articles published within the last 5 years. SUMMARY OF THE FINDINGS: The principal indications for NSAID are for control of pain and acute and chronic inflammation. There is no overwhelming evidence that demonstrates the superiority of one NSAID over another in terms of effectiveness. To date none of the COX 2 inhibitors has been liberated for use in the pediatric age group. Only meloxicam and etoricoxib can be prescribed for adolescents (13 and 16 years, respectively). Selective COX 2 inhibitors are indicated for patients with adverse effects that have proven to be associated with nonselective NSAID use. Selective COX 2 inhibitors can be prescribed in some cases of allergy to aspirin, but they must be used with care. Principal adverse effects include cardiovascular events and thrombotic phenomena. CONCLUSIONS: Selective COX 2 inhibitors are medicines that have been used in certain well-defined clinical situations and which may offer certain advantages over nonselective NSAID. Nevertheless, taking into consideration the higher cost involved and the potential for adverse cardiovascular effects, they should be employed only in accordance with strict criteria.

How pediatricians in Spain manage the first acute wheezing episode in an atopic infant. Results from the TRAP study.

BACKGROUND: Although the treatment of asthma has been addressed in several guidelines, the management of the first acute wheezing episode in infants has not often been evaluated. We surveyed practicing pediatricians in Spain about the treatment they would provide in a simulated case. MATERIAL AND METHODS: A random sample of 3000 pediatricians and physicians who normally treated children was surveyed. The questionnaire inquired about how they would treat a first mild-to-moderate wheezing attack in a 5-month-old boy with a personal and family history of allergy. Pediatricians were asked about their professional background. RESULTS: A total of 2347 questionnaires were returned with useful data (78.2%). Most (90.4%) of the pediatricians would use a short-acting beta2 agonist (SABA) via a metered-dose inhaler with a spacer and a face mask or nebulizer. However, only 34.5% chose a SABA alone: 31.3% added an oral steroid and 27.6% added an inhaled corticosteroid (ICS). The factors associated with the use of ICS in the acute attack were: (1) lack of specific training in pediatrics (OR 1.45; 1.12-1.85) and (2) primary care health center setting (OR 1.31; 1.01-1.69) or rural setting (OR 1.28; 1.01-1.66). Forty-four percent did not recommend any follow-up treatment while 20.7% prescribed ICS as maintenance therapy. The factors related to this decision were the same as those described above. CONCLUSIONS: The management of a first wheezing episode seems to meet published guidelines among Spanish pediatricians with formal training in pediatrics and in those who work in a hospital setting or in urban areas.

Effect of LACK and KMP11 on IFN-gamma production by peripheral blood mononuclear cells from cutaneous and mucosal leishmaniasis patients.

The immune modulatory properties of recombinant antigens Kinetoplasmid membrane protein-11 (KMP11) and Leishmania homologue of receptors for activated C kinase (LACK) in cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) patients were evaluated. The mean levels of interferon-gamma (IFN-gamma) in soluble leishmania antigen (SLA) stimulated peripheral blood mononuclear cells (PBMC) of ML and CL patients were 5625 +/- 2333 pg/ml and 4422 +/- 3665 pg/ml, respectively. IFN-gamma was not detected in cultures stimulated with KMP11 or LACK. Interleukin-10 (IL-10) concentration in SLA, KMP11 and LACK-stimulated PBMC of ML patients was 13 +/- 12 pg/ml, 285 +/- 388 pg/ml and 802 +/- 483 pg/ml, respectively. Addition of KMP11 or LACK to SLA-stimulated PBMC of CL and ML patients enhanced IL-10 production (P < 0.05). Addition of KMP11 decreased IFN-gamma levels by 52% in CL patients and by 19% in ML patients. Addition of LACK to SLA-stimulated cultures decreased IFN-gamma levels by 58% in CL patients and by 30% in ML patients. Neutralization of IL-10 abrogated the downregulatory effect of LACK and KMP11. The modulatory properties of LACK and KMP11 are due to induction of IL-10 production and may be helpful for attenuating chronic inflammatory diseases. However, in some clinical conditions, as demonstrated for ML, these molecules are not able to suppress the IFN-gamma response, even inducing IL-10 production.

Evaluation of quality of life in children and teenagers with allergic rhinitis: adaptation and validation of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ).

BACKGROUND: in the last decades, the study on life quality has stimulated an increasing interest among health researchers. Instruments to evaluate the chronic disease impact on patients day-by-day, have been developed and published by researchers in many countries. The objective of this study was to adapt to the Portuguese Language (Brazilian culture), the RQLQ questionnaire (Rhinoconjunctivitis Quality of Life Questionnaire), destined for life quality evaluation in teenagers with allergic rhinitis. METHODS: in the beginning of the study, a list with 75 items, translated from the original article, was applied to 57 teenagers with perennial allergic rhinitis. The most frequent and troublesome items were selected to compose the modified questionnaire. The validation, reproducibility and responsiveness of the new instrument were evaluated through an interview with 52 patients before the beginning of the treatment, and of 2 and 4 weeks after the treatment. The obtained scores in these interviews were statistically analyzed to verify the questionnaire capacity to detect clinical improvement after the treatment. RESULTS: a significant difference was observed between the total score and those regarding domains, obtained at the first evaluation, compared to later evaluations. A positive correlation was also observed during the treatment, between the questionnaire score and the patient grades related to nasal symptom severity. CONCLUSIONS: the adapted questionnaire is reproducible, valid to be used in longitudinal studies and useful as an instrument of evaluation, but it should be submitted to other investigations to consolidate its properties.

Comparación de la eficacia y seguridad de loratadina en pacientes de 3 a 12 años con alergias crónicas de la piel / Effectiveness and security comparation of loratadine in patients from 3 to 12 years old with chronic allergies of the skin

Se realizó un estudio local, randomizado triple ciego, por grupos paralelos, de 14 días de duración comparativo entre Loratadina (5-10 mg), administrada una vez al día y Terfenadina (15-30 mg), administrada dos veces al día, en pacientes pediátricos entre 3 y 12 años de edad, con enfermedades alérgicas crónicas de la piel. Después de una semana de tratamiento, se observó una importante mejoría de los síntomas, siendo la Loratadina más efectiva que la Terfenadina. La mejoría fue más evidente durante la segunda semana de tratamiento. Los datos obtenidos mostraron que ambos medicamentos fueron seguros y bien tolerantes