Itzhak Varsano

Growth and pituitary-adrenal function in children with severe asthma treated with inhaled budesonide

BACKGROUND The increased use of inhaled corticosteroids in the management of asthma raises concern about the safety of these drugs in children. We sought to determine the safety of long-term administration of inhaled budesonide in young children with asthma. METHODS We studied 15 children 2 to 7 years old who had severe perennial asthma. They inhaled 100 micrograms of budesonide twice daily for three to five years. Efficacy was assessed by serial evaluation of respiratory symptoms and the need for other medications, and safety by serial evaluation of height, height velocity, weight, bone age, and pituitary-adrenal function. RESULTS The severity of asthma decreased within the first month after the initiation of therapy, as demonstrated by a 58 percent reduction in the number of days with symptoms of asthma and a 75 percent decrease in the use of bronchodilators. This improvement was maintained thereafter. The growth pattern of all patients, including their height, weight, and bone age, was normal (as compared with standard normal values) throughout the treatment period. Pituitary-adrenal function was not adversely affected by the treatment, as demonstrated by normal serum cortisol concentrations in the morning and 60 minutes after stimulation with corticotropin, normal 24-hour serum cortisol concentrations (mean [+/- SD] of samples collected at 30-minute intervals for 24 hours, 8.4 +/- 4.2 micrograms per deciliter [232 +/- 116 nmol per liter]), and normal urinary cortisol excretion (34 +/- 9 micrograms [95 +/- 25 nmol] per day). CONCLUSIONS Prolonged administration of 200 micrograms of inhaled budesonide daily to young children with severe asthma does not impair growth or pituitary-adrenal function.

Effectiveness and safety of inhaled corticosteroids in controlling acute asthma attacks in children who were treated in the emergency department: A controlled comparative study with oral prednisolone

BACKGROUND Inhaled corticosteroids have a greater antiinflammatory potency and fewer systemic effects than intravenous, intramuscular, or oral corticosteroids. However, their role in acute asthma has not been established. We prospectively investigated the efficacy and safety of inhaled corticosteroids in controlling moderately severe acute asthma attacks in children who were treated in the emergency department. METHODS Children who were treated in the emergency department with moderately severe asthma attacks after receiving treatment with inhaled terbutaline were allocated by double-blind design to receive 1 dose of either 1600 micro(g) budesonide turbohaler or 2 mg/kg prednisolone. The pulmonary index score and peak expiratory flow rate were measured hourly for the first 4 hours. After discharge the children were treated with the same initial doses given 4 times daily, followed by a 25% reduction in dose every second day for 1 week. Parents recorded asthma symptoms and use of beta-2 agonists on a daily diary card. Serum cortisol concentration was measured at the end of weeks 1 and 3. RESULTS Twenty-two children (11 in each group) with similar baseline parameters completed the study. There was a similar improvement in pulmonary index score and peak expiratory flow rate in the 2 groups. Children treated with budesonide showed an earlier clinical response than those given prednisolone, who also showed a decrease in serum cortisol concentration. CONCLUSION In children with moderately severe asthma attacks who were treated in the emergency department, a short-term dose schedule of inhaled budesonide turbohaler, starting with a high dose and followed by a decrease over 1 week, is at least as effective as oral prednisolone, without suppressing serum cortisol concentration.

Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study

Abstract Objectives: To examine the efficacy of aciclovir suspension for treating herpetic gingivostomatitis in young children. Design: Randomised double blind placebo controlled study. Setting: Day care unit of a tertiary paediatric hospital. Subjects: 72 children aged 1-6 years with clinical manifestations of gingivostomatitis lasting less than 72 hours; 61 children with cultures positive for herpes simplex virus finished the study. Main outcome measures: Duration of oral lesions, fever, eating and drinking difficulties, and viral shedding. Intervention: Aciclovir suspension 15 mg/kg five times a day for seven days, or placebo. Results: Children receiving aciclovir had oral lesions for a shorter period than children receiving placebo (median 4v 10 days (difference 6 days, 95% confidence interval 4.0 to 8.0)) and earlier disappearance of the following signs and symptoms: fever (1 v 3 days (2 days, 0.8 to 3.2)); extraoral lesions (lesions around the mouth but outside the oral cavity) (0 v 5.5 days (5.5 days, 1.3 to 4.7)); eating difficulties (4 v 7 days (3 days, 1.31 to 4.69)); and drinking difficulties (3 v 6 days (3 days, 1.1 to 4.9)). Viral shedding was significantly shorter in the group treated with aciclovir (1 v 5 days (4 days, 2.9 to 5.1)). Conclusions: Oral aciclovir treatment for herpetic gingivostomatitis, started within the first three days of onset, shortens the duration of all clinical manifestations and the infectivity of affected children. Further studies are needed to evaluate the ideal dose and length of treatment. Key messages Herpetic gingivostomatitis is the most common clinical manifestation of primary herpes simplex virus infection in young children The efficacy of oral aciclovir suspension was studied in a double blind placebo controlled study All clinical symptoms and viral shedding were shorter in children receiving aciclovir than in those receiving placebo Aciclovir was highly effective in treating children with herpetic gingivostomatitis

Montelukast, a leukotriene receptor antagonist, reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma.

BACKGROUND Leukotrienes are bronchoactive mediators secreted by inflammatory cells in the respiratory mucosa on exposure to asthma triggers. OBJECTIVE We investigated the effect of montelukast, a leukotriene receptor antagonist, on the release of leukotrienes in the respiratory mucosa of children with persistent asthma. METHOD Twenty-three children aged 6 to 11 years with moderately severe asthma were treated in a cross-over design starting, after a 2-week run in period, with either montelukast (n = 12) or cromolyn (n = 11) for 4 weeks with a 2-week washout period between treatments. Twelve of them were then treated with either montelukast or beclomethasone for 6 months. The use of beta(2)-agonists was recorded on a diary card. The concentration of leukotriene C(4) (LTC(4)) was measured by HPLC in nasal washes obtained before and at the end of each treatment period. Eosinophilic cationic protein (ECP) was measured in the nasal washes by RIA. RESULTS The LTC(4) concentration significantly decreased in the children treated for the first 4 weeks with montelukast, from 5.03 +/- 1.17 to 1.42 +/- 0.33 ng/mL (P <.005), and a nonsignificant increase was noted in children treated with cromolyn, from 3.37 +/- 1.11 to 5.88 +/- 2.17 ng/mL (P =.17). ECP concentration also decreased in the children receiving montelukast (P =.12). The concentration of LTC(4) remained low after 3 and 6 months of treatment with montelukast (0.8 +/- 0.7 and 1.0 +/- 0.3 microg/mL) and was lower than with beclomethasone. Children treated with montelukast required significantly fewer beta(2)-agonists (P <.04), CONCLUSION Montelukast reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma parallel to reduction in ECP and clinical improvement. This effect was not observed when the same children were treated with cromolyn.

Rapid induction of clinical response with a short-term high-dose starting schedule of budesonide nebulizing suspension in young children with recurrent wheezing episodes

BACKGROUND There are no data currently available on the correct schedule for the initiation of treatment with nebulized suspension of budesonide in children with recurrent wheezing episodes. We compared the efficacy and safety of starting with a high dose followed by a stepwise decrease to a continuous low dose. METHODS In a double-blind design, 42 children aged 6 months to 3 years were randomly allocated to receive either a high starting dose of 1 mg budesonide twice daily followed by a stepwise decrease of 25% every second day for 1 week (group A) or a low dose of 0.25 mg twice daily for 1 week (group B). Efficacy was assessed with daily symptom scores and the systemic effect of the corticosteroids with the adrenocorticotropic hormone test. RESULTS The two groups were comparable for all parameters evaluated. During the first week of treatment, there was a significant decrease in asthmatic symptomatology only in group A: a 59% decrease for wheezing (p = 0.0001), 39% for diurnal cough (p = 0.036), and 39% for nocturnal cough (p = 0.04). Mean time to clinical response was 3.0 days in group A and 5.7 days in group B (p = 0.02). This early improvement was sustained for the rest of the follow-up period. The high dose starting schedule was not associated with any change in serum cortisol level. CONCLUSIONS The administration of nebulized suspension of budesonide at a high starting dose schedule followed by a rapid (1 week) stepwise decrease yields a significant early improvement in asthma symptoms and causes no change in serum cortisol levels.

Effectiveness of Inhaled Corticosteroids in Controlling Acute Asthma Exacerbations in Children at Home

Many clinicians advise their patients to increase the dose of inhaled corticosteroids during acute asthma exacerbations, without strong clinical evidence supporting this treatment. This study investigates the effectiveness of inhaled corticosteroids in controlling acute asthma exacerbations in children at home. The study population consisted of children with mild intermittent, mild and moderate persistent asthma aged 1 to 14 years who were treated in our outpatient clinic with inhaled budesonide for 1 year. After participating in an asthma education session, the parents were instructed to initiate treatment with inhaled budesonide at the first signs of asthma exacerbation, starting with 200 to 400 pg budesonide, in combination with beta-2 agonists 4 times a day and followed by a decrease in the dose in 4 to 8 days. Asthma status and peak expiratory flow rates were measured in the 3 monthly follow-up visits. Only children who complied with the treatment regimen and came for follow-up visits regularly were included in the final analysis. One hundred fifty children used our treatment protocol with inhaled budesonide to control their asthma attacks. Clinical improvement of asthma symptoms was achieved after a mean of 1.8 +0.7 days from the beginning of treatment. The parents were able to control 94% of the 1,061 episodes of asthma exacerbation occurring during a cumulative follow-up period of 239 years. In the 3-month period before enrollment, 101 children (67%) had used oral corticosteroids to control their asthma attacks and 50 (33%) were hospitalized. During the entire follow-up period, only 11 children (7%) used oral corticosteroids, and none of the children were hospitalized. The present study demonstrates that children with asthma can control their exacerbations at home using inhaled corticosteroids (budesonide). Treatment, starting with relatively high doses followed by a rapid reduction in dose over 4-8 days, resulted in a decrease in the use of oral steroids and in hospitalization. To achieve good results, patient compliance is essential.

Lidocaine as a diluent for administration of benzathine penicillin G

OBJECTIVE Benzathine penicillin G is recommended for secondary prophylaxis of rheumatic fever. Its main disadvantage is local pain and discomfort associated with the injection. Lidocaine as a diluent may reduce this discomfort. We compared the administration of benzathine penicillin G with two diluents; sterile water and lidocaine hydrochloride 1% for penicillin concentrations and pain of injection. DESIGN In a randomized double blind, crossover trial, 18 children ages 11 to 19 years who required prophylactic treatment for rheumatic fever were randomly divided into two groups. One received an injection of benzathine penicillin G diluted with 3.2 ml of sterile water, followed 1 month later by an injection of benzathine penicillin G diluted in lidocaine hydrochloride 1%; the second group received the same regimen in the reverse order. Serum penicillin concentrations and subjective pain sensation were determined after each injection. RESULTS Peak serum penicillin concentrations at 24 h after injection were similar for both preparations (0.100 microg/ml for water, 0.102 microg/ml for lidocaine), as were the other serum values measured throughout the month. After 28 days detectable concentrations (> or =0.020 microg/ml) were found in 44 and 291% of the subjects, respectively (P = 0.4). Urine penicillin concentrations on Day 28 were 1.81 +/- 0.25 and 2.31 +/- 0.25 microg/ml, respectively. The pain score immediately after the injection was significantly lower with the lidocaine than with the sterile water dilution. CONCLUSION Use of lidocaine hydrochloride as a diluent for benzathine penicillin G does not change the penicillin concentration in body fluids and significantly reduces the pain of injection. We suggest the use of lidocaine hydrochloride 1% as a diluent for benzathine penicillin G.

Serum-Sickness-Like Reaction Associated with Minocycline Therapy in Adolescents

OBJECTIVE: TO describe a serum-sickness-like reaction in five adolescents treated with minocycline. CASE SUMMARY: Five adolescents developed a rash and arthralgias/arthritis after taking minocycline for 10-30 days. Symptoms resolved gradually after the medication was stopped. DISCUSSION: Serum sickness is not described in the pharmacology literature as an adverse effect of minocycline, and in the English literature there are only two case reports. The migration inhibitory factor assay and mast cell degranulation test were positive in four of the five patients. The results of these assays were consistent with a role for minocycline in causing these reactions. CONCLUSIONS: Clinicians should be aware of the possibility of serum-sickness-like reaction as an adverse effect of minocycline.

Cutaneous Manifestations of Henoch-Schönlein Purpura in Young Children

Abstract: We evaluated the anatomic distribution and pattern of skin involvement in 155 pediatric patients with Henoch‐Schönlein purpura treated in our center over the last 20 years. Of these, 120 (77.4%) presented with cutaneous signs; only 10% of them had no leg involvement. Seven patients (4.5%) had edema of the hands, feet, or face. The mean age of this subgroup was 9.2 ± 2.2 months, compared to 6.8 ± 2.3 years for the entire group (p < 0.05). Skin biopsies were performed in 18 of these patients, including the 7 with edema, to confirm the clinical diagnosis. All biopsy specimens showed leukocytoclastic vasculitis, with IgA deposits in two and C3 deposits in one. It is important that clinicians keep in mind that an atypical presentation of Henoch‐Schönlein purpura is not unusual.

Scrotal involvement in Henoch-Schönlein purpura in children

Different rates of scrotal involvement in Henoch-Schonlein purpura (HSP) have been reported. We assessed scrotal involvement in 86 children over a 20-year period: 10 patients suffered from scrotal involvement and 9 of them also had arthritis. The possible association between scrotal involvement and arthritis may help the physician in the differential diagnosis of atypical presentations.