Steroid-dependent Children Research Articles

Childhood Idiopathic Nephrotic Syndrome: Does the Initial Steroid Treatment Modify the Outcome? A Multicentre, Prospective Cohort Study.

Background: A great majority of children with idiopathic nephrotic syndrome will relapse after successful treatment of the initial episode. The possibility that different steroid dosing regimens at onset, adjusted for risk factors, can reduce the rate of relapse represents an interesting option to investigate.Objectives: To evaluate the effect of the initial steroid regimen, adjusted for time to remission (TTR), on the frequency of relapses and steroid dependence, and to verify the influence of prognostic factors on disease course.Methods: A multicentre, prospective, cohort study. Children with nephrotic syndrome, with TTR ≤ 10 days (Group A), were given a 20-week prednisone regimen (2,828 mg/m2) and those with a TTR >10 days, a 22-week regimen (3,668 mg/m2) (Group B). Previously published retrospective data from the same centers were also evaluated. Main outcomes were: relapse rate, number of frequent relapsers + steroid dependent children and total prednisone dose after induction.Results: 143 children were enrolled. Rate of relapsed subjects (77 vs. 79%) and frequent relapsers + steroid dependent subjects (40 vs. 53%) did not differ between Groups A and B, or between the retrospective and prospective cohorts. The cumulative prednisone dose taken after the induction treatment was similar in both groups and in the retrospective and prospective cohorts. TTR was not associated with relapse risk. Age at onset and total serum protein were significantly lower in relapsing patients. At ROC analysis, the best cut-off was 5.3 years for age at onset and 4.2 g/dL for total serum protein. According to these cut-offs, older children with higher total serum protein had a higher relapse free survival rate (58%) than younger children with lower total serum protein (17%).Conclusions: TTR was not found to be a prognostic factor of relapse; because of this, different steroid regimens, adjusted for TTR, did not modify the relapse rate in any relevant measure. Conversely, younger age and low total serum protein were independent predictors of relapse risk, however this outcome was not modified by higher prednisone regimens.Clinical Trial Registration:https://www.ClinicalTrials.gov/, identifier: NCT01386957 (www.nefrokid.it).

Nephrotic Syndrome Outcome in Children: An Epidemiological Study

Background: Nephrotic syndrome (NS) as a glomerular basal membrane disease has different outcomes. The current study aimed at evaluating epidemiologic status in NS and its correlation with the outcome in children. Methods: The current hospital based study evaluated the patients of pediatric clinic at Amir-Kabir hospital. Demographic information was obtained by interviewing both the physicians and patients. Also, to determine the sesitivityto steroid drugs, children were given prednisolone (2 mg/kg/day with maximum dose of 60 mg/day) for four weeks and syndromes were determined based on children responses to the drug. Patients were divided into four groups of 25. At the end, data were transfered to SPSS program and the correlations between epidemiological information and different types of NS were investigated Results: Results of the current study showed that steroid responded children with frequent relapse as well as steroid dependent children had better epidemiological and socioeconomic status compared with the steroid resistance ones (P < 0.05). Conclusions: Prognosis of NS or medication responses was related to epidemiological status of children.

Predictive risk factors of steroid dependent nephrotic syndrome in children

Background: Development of steroid dependency is one of the difficult problems in the management of children with idiopathic nephrotic syndrome, leading to increased morbidity, complications and cost of treatment. Thus, predicting early in the disease course will be useful in counseling parents and may improve treatment strategy. Objectives: To determine the clinical characteristics that can predict the development of steroid dependency early in the initial episodes of steroid sensitive nephrotic syndrome (SSNS). Patients and Methods: The study included 52 children with SSNS. Their ages ranged from 3 to 16 years. Patients were divided into two groups. Group A consisted of 24 patients with steroid dependency or frequent relapses nephrotic syndrome and group B consisted of 28 patients with complete remission or recurrent nephrotic syndrome. Data obtained retrospectively from patients’ files. Results: Children who require a cumulative steroid dose equal or more than 140 mg/kg to maintain remission during the first 6 months of the disease are at high risk to require steroid sparing agents (SSA) for disease control, and who did not achieve remission by day 20 of the initial prednisone course became steroid dependent with 96% specificity but with low sensitivity (50%). All steroid dependent children in this study showed relapses associated significantly with upper respiratory tract infections. Conclusions: Cumulative steroid dose in the first 6 months of treatment and the need of more than 20 days to achieve initial remission can predict steroid dependency in children with nephrotic syndrome.

Use of levamisole in children with nephrotic syndrome: A retrospective study to examine its adverse effects in children with nephrotic syndrome

Introduction: Levamisole, a synthetic imidazothiazole derivative has been used as a steroid sparing agent in children with Frequently Relapsing Nephrotic Syndrome (FRNS) and Steroid Dependent Idiopathic Nephrotic Syndrome (SDNS). Levamisole has been essentially considered a safe drug with minimal toxicity. We conducted this study to re-examine the safety of Levamisole in children with nephrotic syndrome and to describe the clinical profile of these children. Materials and Methods: Records of children with idiopathic nephrotic syndrome between June 2014 and December 2016 were reviewed. We identified frequently relapsing or steroid dependent children between 1-18 years of age who had received Levamisole for at least six months or in whom Levamisole was started but had to be withdrawn due to some adverse events in the first 6 months. Results: 21 children were started on Levamisole in the study period. 13 (61.90%) were FRNS and remaining had a steroid dependent course. Levamisole had to be withdrawn in one child at 1 month 13 days after initiation when the child developed severe headache. Levamisole also had to be discontinued in a 9 years old girl at 13 months after initiation of therapy due to polyarticular arthralgia involving both the small and large joints. Conclusions: The use of Levamisole warrants caution in children with Nephrotic Syndrome and its efficacy needs to be balanced against its potential side effects.

Adalimumab Treatment in Children with Refractory Crohn’s Disease

Information on safety and efficacy of adalimumab in children with Crohn's disease (CD) is limited. We present a case-series of 14 children with severe CD treated with adalimumab during a 3.5-year period. Fourteen children (nine boys, five girls), aged 13.9 years (range 1.9-19.1) were treated with adalimumab during 12.5 months (range 7-42). All had steroid or immunosuppression-drugs refractory disease. Ten patients (71%) had been previously treated with infliximab, 13/14 were treated with different immunosuppressive drugs and all were steroid-dependent or resistant. Seven children (50%) showed full clinical response and 5/14 (35%) improved partially. Two children (15%) had loss of response after a period of transient improvement. Adalimumab treatment enabled complete steroids withdrawal in 8/14 (57%) of steroid-dependent children. Currently, five children are in complete remission with adalimumab monotherapy for a median 14 months (range 9-24). Adalimumab may induce and maintain remission in children with severe, refractory CD. Prospective safety and efficacy confirmation of this data in children is necessary.

Does cyclosporine achieve a real advantage for treatment of idiopathic nephrotic syndrome in children? A long-term efficacy and safety study

Cyclosporine (CsA) was found to be efficient in decreasing proteinuria in both steroid-dependent and steroid-resistant nephrotic patients. We aimed to explore the potential long-term benefits and hazards of CsA and their predictors among a large group of nephrotic patients. In this retrospective analysis, we included 197 pediatric patients with idiopathic nephrotic syndrome (INS) of whom 103 were steroid dependent and 94 steroid resistant. CsA induced complete remission in 132 (67%) and partial response in 13 (6.6%). Cyclosporine was received for a period of 22.16 +/- 12.21 months. Univariate analysis showed that the response to CsA was significantly better in steroid-dependent children, in minimal change disease (MCD), diffuse mesangial proliferative glomerulonephritis (DMP) and focal segmental glomerulosclerosis (FSGS) than in other pathological lesions and in those who had lower quantities of pretreatment proteinuria. Only the prior response to steroids and concomitant use of ketoconazole with CsA were valid predictors for better response to CsA with multivariate analysis. Discontinuation of the drug in 40 patients resulted in relapse in 26 patients while the remaining 14 patients maintained remission. Renal dysfunction developed in 18 patients of whom 12 recovered completely on drug discontinuation. Thirty-seven patients developed hypertension. Multivariate analysis showed that all side-effects were significantly more prevalent in CsA-resistant patients. CsA is effective and well tolerated in the long-term treatment of INS in children, however two thirds of cases showed relapse after CsA discontinuation.

Thalidomide therapy for recalcitrant systemic onset juvenile rheumatoid arthritis

Systemic onset juvenile rheumatoid arthritis unresponsive to nonsteroidal anti-inflammatory drugs may be controlled with corticosteroids, but these drugs have significant side effects. We report 2 steroid-dependent children with systemic onset juvenile rheumatoid arthritis who did not respond to multiple nonsteroidal anti-inflammatory drugs, methotrexate, azathioprine, cyclosporine, and etanercept. Both children had significant improvement with thalidomide therapy. (J Pediatr 2002;140:125-7)

Humoral immunity in steroid-dependent children with asthma and hypogammaglobulinemia

OBJECTIVE: To determine primary and secondary antibody responses in children with hypogammaglobulinemia attributed to corticosteroid use. RESULTS: In seven patients with steroid-dependent asthma and significant hypogammaglobulinemia (IgG concentration, 275 to 443 mg/dl), antibody responses to protein and polysaccharide antigens were shown to be normal, as were primary and secondary responses to a neoantigen, bacteriophage ΦXC174. CONCLUSIONS: Patients with asthma, and with hypogammaglobulinemia resulting from steroid therapy, have normal humoral immunity, and immunoglobulin replacement therapy is not indicated. (J Pediatr 1996;129:898-903)

Milk of calcium fluid collection in dermatomyositis: Ultrasound findings

Extensive subcutaneous and intermuscular calcium laden fluid collections (milk of calcium) were found in two young girls with severe dermatomyositis. Sonographic examination clearly showed the nature and extent of the collections. Knowledge of this new feature of dermatomyositis should help avoid confusing these fluid collections with soft tissue infection and deep abscess in these often steroid dependent children.

Evaluation of chlorambucil therapy in steroid-dependent and cyclophosphamide-resistant children with nephrosis

A prospective study was performed to evaluate the efficacy of chlorambucil in inducing long-term remission in children with steroid-dependent or cyclophosphamide-resistant primary nephrotic syndrome (NS). The 16 steroid-dependent children had a relapse rate of 5.3/patient per year (range 4-8) and a mean age of 8.4 years (range 2-13). The chlorambucil dosage was 0.2 mg/kg per day for a total of 8 weeks. Nine patients (56%) remained in complete remission for an average of 39.2 months (range 16-70). The interval to the first relapse in the remaining 7 ranged from 4 to 41 months and the relapse rate decreased significantly to 0.6 relapses/patient per year (P less than 0.05). Five children had steroid- and cyclophosphamide-resistant NS, 4 with focal segmental glomerulosclerosis and 1 with mesangiol proliferative glomerulonephritis. Chlorambucil was given in a dose of 0.2 mg/kg per day for 8-16 weeks. Complete remission was obtained in 4 patients; 2 patients relapsed. No serious long-term complications were observed in our patients.

Methylprednisolone and troleandomycin in treatment of steroid-dependent asthmatic children.

Oral methylprednisolone combined with troleandomycin has been reported to be successful in treating poorly controlled, severe asthma in adults. We found this drug combination to be effective in treating 11 steroid-dependent children with poorly controlled asthma who were aged 7 to 13 years, for 12 to 28 months. Improvement of clinical and pulmonary functions was achieved within seven days, with the forced expiratory volume in 1 s increasing by 38% and the maximal midexpiratory flow rate increasing by 55% over the baseline value. By one year, the former improved to 98% of predicted value and the latter, to 79% of predicted value. Compared with the prior 12 months, patients at this time required fewer emergency visits, missed fewer days of school, and had fewer hospitalizations. Side effects included transient-increased cushingoid features, abdominal pain, and liver enzyme level elevation. Patients showed less evidence of adrenal suppression.

Short-term Double-blind Evaluation of Flunisolide Aerosol for Steroid-dependent Asthmatic Children and Adolescents

The purpose of this study was to compare the effectiveness of flunisolide aerosol prescribed as .5 mg (two inhalations) twice daily and placebo in terms of oral steroid sparing ability in a population of 32 known steroid-dependent children and adolescents. Patients were stabilized on the lowest tolerated dose of daily AM or alternate AM oral corticosteroid for at least one month before entering the study. They were randomly assigned to either flunisolide or placebo treatment for the 12-week, double-blind trial. Patients were seen every two weeks for symptom assessment, physical examination, and pulmonary function testing. Tests of adrenal function were done initially and at the study's conclusion. The flunisolide group had improved asthma control compared with the placebo group. The daily oral steroid requirement decreased in 100 percent of the flunisolide group compared with 53 percent of the placebo group (P less than .01). Pulmonary function and endocrine function remained stable for both groups. There were no adverse effects. Flunisolide aerosol in doses of .5 mg twice daily appears to be topically active and to have oral steroid potential without apparent adverse effects.

Cloprednol Therapy in Steroid-Dependent Asthma

Cloprednol is a new oral corticosteroid with a short half-life that is presently under investigation for use in asthma. Seventeen steroid-dependent children and adolescents were switched from daily treatment with prednisone to cloprednol for a one-year study. Patients showed a statistically significant improvement in symptoms while receiving cloprednol therapy. Two patients had extraordinarily good responses. Growth trends, bone age, and chest roentgenograms were not remarkably changed by cloprednol. Pulmonary function was stable. There was a significant improvement in fasting morning cortisol levels and ability to respond to metyrapone and adrenocorticotropic hormone (ACTH) challenge. Cloprednol appears to be a promising drug for steroid-dependent patients who require oral corticosteroid therapy.

Treatment of asthma in children with triamcinolone acetonide aerosol

Triamcinolone acetonide aerosol, 100 μg qid, was administered for 8 wk to 5 steroid-dependent asthmatic children and 10 who had not previously required continual corticosteroid treatment. Symptomatic control and pulmonary function improved in all 15 children despite discontinuation of oral corticosteroids in 3 of the steroid-dependent children. Determination of morning plasma cortisol concentrations disclosed no evidence of substantial adrenal suppression. Satisfactory symptomatic control has subsequently been maintained for 6 to 32 mo with doses of 100 μg bid to 300 μg qid without more extreme changes in plasma cortisol concentrations than were observed during the first 8 wk.

Clinical and physiological assessment of asthmatic children treated with beclomethasone dipropionate

Forty-two perennial asthmatic children were selected for a 12-wk study using beclomethasone dipropionate. The groups included 21 steroid-dependent children (Group I and 21 patients (Group II) whose disease was of sufficient severity that corticosteropd therapy was contemplated. All children received the drug in a dose of 100 μg 4 times daily. During the study, oral prednisone was withdrawn from the steroid-dependent children while other therapy was essentially unchanged. Group II children underwent a double-blind trial, receiving beclomethasone for 6 wk and placebo for 6 wk. Objective assessment of adrenal and pulmonary function was obtained at regular intervals. For the latter, total lung capacity and its subdivisions, airways resistance, maximum expiratory flow volume, and oxygen tension, were measured in both groups. In Group II static elastic recoil was measured also. For most tests the results were statistically significant. In both groups, 18 of 21 patients demonstrated an excellent clinical response, no evidence of adrenal suppression, and improvement in pulmonary function. Forty of 42 patients were followed for another 12 wk, and 19 of each group did well. After 20–24 wk of therapy, 16% of patients harbored monilia in their oropharynx, and 1 patient had clinical monilial stomatitis. Within the limits of the time of the study, beclomethasone dipropionate appeared to provide adequate clinical control in many chronic, severe, steroid-dependent and nonsteroid-dependent asthmatic children.

DISTINCTIONS BETWEEN SUBGROUPS OF ASTHMATIC CHILDREN

The present investigation was designed to explore further the hypothesis that asthma is more often employed as a learned, defensive-adaptive response by rapidly remitting than by steroid dependent asthmatic children. Specifically, it was predicted that rapidly remitting, as compared to steroid dependent children, would more often report emotional arousal with negative affect as provocative of asthma. A simple, structured interview procedure for obtaining data on children's perceptions of the precipitants of asthmatic attacks was described in some detail. The results of interviews with 38 children (20 rapidly remitting and 18 steroid dependent) offered support for the main hypothesis. In addition, extrinsic factors such as colds, allergies, and weath variations, particularly the latter, were reported as precipitants of asthma more frequently by the steroid dependent than by the rapidly remitting children. On the basis of some of the obtained data, an explanation of the relationship between crying and asthma was offered as an alternative hypothesis to the well-known concept of asthma as a symbolic, suppressed cry for the mother.

Distinctions between subgroups of asthmatic children: Some parent attitude variables related to age of onset of asthma

The central aim of this investigation was to examine the hypothesis that the asthmatic syndrome more often functions as a learned, defensive, response among rapidly remitting than among steroid dependent children. The view was expressed that asthma among steroid dependent children was linked more frequently to infectious or allergic stimuli. Two predictions were derived regarding the relationship between age of onset of asthma and certain parental attitudes. There were no significant differences between asthmatic subgroups in age of onset alone. However, findings indicated that, within the group of rapidly remitting children, relatively late age of onset was significantly associated with autocratic and restrictive attitudes on the part of the mothers of this group. These relationships were not found in either the intermediate or steroid dependent groups. In addition, significant differences were found between groups on two maternal attitude variables and one paternal attitude variable. It was emphasized that discriminations between asthmatic subgroups were extremely important in any study of the relationship between psychologically defined variables and the course of asthma. The distinctions offered in the present paper were regarded as tentative and subject to further refinement.