Monitoring of omalizumab therapy in children and adolescents.

BACKGROUND: Omalizumab is a successfully implemented supplementary therapy for improving asthma control in children aged 6 years and older with severe persistent allergic asthma. The dosage of omalizumab depends on body weight and IgE level, yet no parameter has been established to guide dosage changes during therapy. Clinical studies in patients with allergic asthma or allergic rhinitis revealed a clinically relevant improvement by using omalizumab leading to concentrations of free serum IgE reported to be lower than 50 ng/ml. Therefore, only the question concerning the concentrations of free IgE used in a therapy with omalizumab is regarded of clinical importance, while total IgE (free and omalizumab-bound IgE) increases during treatment. PATIENTS AND METHODS: Ten patients, 8 to 17 years of age, received therapy with omalizumab due to severe allergic asthma. In addition, the patients had pronounced rhinoconjunctivitis, food allergy, insect sting allergy, and/or neurodermitis. The total IgE in the serum was measured in the patients 3 - 6 months before each omalizumab injection as a potential progress parameter (Sandwich-Immunoassay ADVIA Centaur). RESULTS: Six months after beginning of the therapy with omalizumab, a significant decrease of the total IgE concentration was found, in comparison to the baseline values (p < 0.003). In all patients the tolerability of omalizumab was very good: there was a reduction in the frequency of the asthma exacerbations and rescue medications. All patients reported a clearly improved quality of life. CONCLUSIONS: A general increase in IgE was not observed in any of the children we treated with omalizumab. Apart from the development of routine assays to determine free serum IgE levels, the significance of the total serum IgE as a suitable control of an omalizumab therapy should be further investigated in controlled studies with regard to sensitivity and specificity. In order to only administer the lowest necessary dose of omalizumab especially in children and adolescents, the establishment of laboratory parameters (free IgE and/or total IgE) to adequately monitor the therapy is urgently needed. Patients undergoing an omalizumab therapy require medical supervision at close intervals.

[Renal carbuncle and perirenal abscess in children and adolescents]. / Nierenkarbunkel und perinephritischer Abszess im Kindes- und Jugendalter.

Renal abscesses are rare in childhood. The diagnosis is often complicated by non-specific symptoms and the typical signs of urinary tract infections are frequently absent. The currently available imaging methods are necessary and helpful for a differentiated therapeutic approach; nevertheless, cases are continuously being found in which a renal abscess is only diagnosed intraoperatively. In most patients a combined intravenous therapy including an antibiotic which is effective against staphylococci is sufficient. The therapy is supported if necessary by percutaneous abscess drainage. Open revision or even nephrectomy is rarely required.

[Effectiveness and practicality of an internet-based asthma refresher course for children and adolescents]. / Effektivität und Praktikabilität einer internetbasierten Asthma-Nachschulung im Kindes- und Jugendalter.

BACKGROUND AND METHODS: The effectiveness and practicality of the "Luftikids" (www.luftikids.de) structured, internet-based asthma refresher course was evaluated in a pilot study with 53 patients (ages 8 - 14 years). All patients had previously participated in either an inpatient or outpatient asthma education program. This prospective study examined the effect of a 4-week refresher course on parameters such as asthma symptoms (coughing, dyspnea), the number of unscheduled doctor's visits, use of on-demand medications, number of days absent from school, and asthma monitoring using the Asthma Control Questionnaire (ACQ) and lung function tests. The duration of program use and the number of logins was used to investigate acceptance of the game format. Data were collected at the beginning of the study and at 4 - 6 months after the end of the online refresher course. RESULTS: Significant changes were shown with regard to the decrease in intensity of asthma symptoms such as coughing (p = 0.001) and dyspnea (p = 0.007), reduction in the number of unscheduled doctor's visits (p = 0.005), the use of on-demand medications (4.0 ± 6.5 vs. 1.5 ± 4.9, p = < 0.002), and the number of days absent from school (1.2 ± 2.0 vs. 0.4 ± 1.2, p = 0.003). No changes in lung function parameters were observed. The "Luftikids" program was used for an average of 302.5 ± 210.9 minutes, and the number of logins was 14 ± 9. From their self-evaluations, the children and adolescents derived "much" to "very much" benefit. Only 7.5% reported no effect. CONCLUSIONS: Participation in the "Luftikids" internet-based asthma refresher course resulted in fewer asthma symptoms, a decrease in unscheduled doctor's visits, reduction in the use of on-demand medications, decrease in the number of days absent from school, and improved asthma knowledge. No effect in lung function could be demonstrated. The results support the effectiveness and good acceptance of an outpatient, internet-based asthma refresher course. Young asthma patients in particular can succeed with and be motivated by this form of refresher course.

[Important aspects in pediatric care of children and adolescents with chronic disease using the example of bronchial asthma]. / Wichtige Aspekte bei der Betreuung chronisch kranker Kinder und Jugendlicher am Beispiel des Asthma bronchiale.

When treating children or adolescents with chronic disease one should take the specific age-related features of the course of disease, differential diagnosis, and the psychosocial environment, as well as the avoidance of complications and side effects of therapy into account. These may impair the patient's physical and psychosocial development and quality of life in the context of family, school and occupational life. Continued care of growing children from the start of the disease when they are infants to the point when they assume personal responsibility as adults is one of the major concerns of the pediatrician. This concept requires interdisciplinary cooperation and a large body of personnel which would include training programs, inclusion of family members and in some cases psychosomatic therapy. Given the increasing prevalence of chronic diseases in this age group and their sociopolitical significance it is important to activate preventive potentials in terms of content and structure - by quality assurance - especially to avoid long-term complications. Various care structures are used in Europe to achieve this goal. Asthma is the most common chronic disease in children and adolescents. It influences quality of life as well as the child's personal, educational and occupational development to a significant extent. The special aspects of the treatment of these patients will be addressed to illustrate the therapy of chronic disease.

[Acute urinary retention in children: initial manifestation of caudal regression syndrome]. / Akuter Harnverhalt im Kleinkindalter : Erstmanifestation eines kaudalen Regressionssyndroms.

Caudal regression syndrome is a rare and sporadic congenital developmental defect of the lower spinal segments and the neural tube. Movement disorders and sensory neurological deficits of the lower extremities in conjunction with impaired bladder and bowel control are the major symptoms. Abnormal visual aspects of the sacral region in combination with maternal gestational diabetes are further diagnostic indications. This article reports the unusual case of a toddler presenting with acute urinary retention as the initial symptom of caudal regression syndrome.

Capnovolumetry: a new tool for lung function testing in children with asthma.

In capnovolumetry, the expiratory CO2 concentration of exhaled air is plotted against the volume and thereby allows to determine functional dead space volumes. This method might offer additional information in lung function testing in children and adolescents with bronchial asthma. We aimed at determining whether a bronchospasmolysis (BSL) effect in the lower airways could also be detected by capnovolumetry as reflected by changes in the functional threshold dead space volumes (VDT). In 47 patients (aged 4-16 years) with a mild persistent bronchial asthma, VDT were determined before and after bronchodilation prior to starting therapy with inhaled steroids and after 6 months of treatment. Additionally, spirometry and body plethysmography were performed in all patients. There were significantly higher VDT values after BSL before and after 6 months of therapy (P<0.0001). VDT values before BSL were tendatively higher after 6 months of therapy compared with baseline values (P=0.07). VDT values correlated with parameters derived from conventional pulmonary function testing, i.e. vital capacity, forced expiratory volume in 1 s (FEV1), and maximum expiratory flow (MEF50). As VDT values particularly reflect the volumes of the lower bronchi this method may provide supplementary information to conventional lung function tests which are based on breathing mechanics. This seems to be especially helpful in situations where body plethysmography is not available or cooperation in forced expiration manoeuvres is insufficient.

Reduction of the total IgE level by omalizumab in children and adolescents.

BACKGROUND: Current data from clinical studies show that patients with severe allergic asthma experience a significant improvement from omalizumab. The early and late allergic reactions are inhibited by formation of complexes with free circulating immunoglobulin E (IgE), independent of which antigen activates the allergic cascade. The dosage of omalizumab depends on body weight and IgE level, yet no parameter has been established to guide dosage changes during therapy. The aim of this study was to investigate the value of the determination of total IgE by ADVIA Centaur assay to monitor the therapy progress. PATIENTS AND METHODS: Nine patients, 8 to 17 years of age, received therapy with omalizumab due to severe allergic bronchial asthma. In addition, the patients had pronounced rhinoconjunctivitis, food allergy, insect sting allergy, and/or neurodermitis. The total IgE in the serum (Sandwich-Immunoassay ADVIA Centaur) was measured in the patients once monthly before each omalizumab injection as a potential progress parameter. RESULTS: Six months after the beginning of therapy with omalizumab, a significant decrease of the total IgE concentration was found, in comparison to the baseline values (p < 0.01). In all patients, the tolerability of omalizumab was very good; there was a reduction in the frequency of the asthma exacerbations and rescue medications. The dosage of inhaled glucocorticoids could be lowered. All patients reported a clearly improved quality of life. CONCLUSIONS: The increase of the total IgE concentrations after administration of omalizumab described in the literature could not be confirmed. The value of total serum IgE as a progress parameter should be investigated in controlled studies with regard to sensitivity and specificity of the respective assays. The establishment of a test procedure for therapeutic monitoring appears urgently necessary, so that the appropriate dosage of omalizumab is applied in children and adolescents. Patients receiving omalizumab therapy should be closely monitored.

[A new breath actuated dry powder inhaler (Auto-Jethaler)]. / Ein neuer atemzuggesteuerter Pulverinhalator (Auto-Jethaler).

BACKGROUND: The aim was to examine the handling of the recently developed breath actuated dry powder inhaler Auto-Jethaler (PulmoTec GmbH/Höchstädt, launch by Ratiopharm and CT Berlin). METHOD: 75 patients suffering from asthma, cystic fibrosis or primary ciliary dysfunction (age: 3 to 34 years; 29 female, 46 male) with mild or moderate bronchial obstruction took part in the study. Lung function testing including body plethysmography was performed to measure bronchial obstruction independent of effort. Peak Inspiratory Flow (PIF) was measured using a Fleisch pneumotachograph equipped with or without a Auto-Jethaler. Instead of the commercially available drug tablet a stainless steal ring device of equivalent resistance, easy to disinfect, was used. Actuation of the rotation mechanism which was triggered by inspiration at an inspiratory flow of about 40 L/min was accompanied by a rattling noise. Aims of the study were to examine, whether the subjects were able to handle the new device, and to measure PIF without and via Auto-Jethaler. RESULTS: Handling of the Auto-Jethaler was found to be easy. All patients managed to reach or surpass the critical value of 40 L/min, even those with mild to moderate bronchial obstruction. PIF without Jethaler was 85 to 599 L/min, via Auto-Jethaler 40 to 215 L/min. PIF was significantly age dependent (p<0.001). CONCLUSIONS: These findings suggest that the Auto-Jethaler will be an appropriate device for drug administration in children older than 3 years provided that they understand the inspiratory breathing manoeuvre.

[Wegener's granulomatosis as a rare cause of hemoptysis in childhood]. / Wegener-Granulomatose als seltene Ursache der Hämoptyse im Kindesalter.

Wegener's granulomatosis is together with Churg-Strauss syndrome and microscopic polyangiitis a very rare cause of hemoptysis in childhood. We report on a 14 years old girl who developed arthralgia, purpura, glomerulonephritis and a diffuse alveolar haemorrhage with hemoptysis after a short time period of unspecific symptoms.

Late-onset nephrotic syndrome and severe cerebellar atrophy in Galloway-Mowat syndrome.

Galloway-Mowat syndrome (GMS) is a rare autosomal-recessive disorder characterised by nephrotic syndrome, microcephaly, and variable brain anomalies. The prognosis is poor with death almost inevitably supervening before the age of 6 years, but atypical cases with later onset of proteinuria and a more protracted course are on record. We report a female offspring from consanguineous parents suffering from microcephaly, profound psychomotor retardation, epilepsy, hiatal hernia, and striking cerebellar atrophy in whom a nephrotic syndrome became apparent at age 16 years. Renal biopsy revealed focal segmental glomerulosclerosis and glomerular basement membrane abnormalities. We postulate that this patient had a milder form of GMS with severe and diffuse cerebellar atrophy as the leading central nervous system abnormality.

[A modified ultra-rush-protocol of allergen immunotherapy in children and adolescents with insect venom allergy]. / Ein modifiziertes Ultra-Rush-Verfahren der spezifischen Immuntherapie bei Kindern und Jugendlichen mit einer Insektengiftallergie.

BACKGROUND: In Germany the prevalence of insect venom allergy in the population is about 5 %, 10-40 deaths are reported every year. With a success rate of 95 % venom immunotherapy (SIT) has a convincing protective effect. The purpose of this study was to investigate the safety of the original ultra-rush-protocol in children and reduce from 9 to 8 doses by avoiding a second application of 100 micro g insect venom. METHODS: Nineteen children and adolescents with insect venom allergy were treated according to the modified ultra-rush-protocol. The first 5 children were hyposensitized according to the original protocol suggested by Brehler et al., the remaining 14 children (age 6-18 years) received only 8 injections (0.01/0.1/1/10/20/40/80/100 micro g). 5 patients were discharged on the second day four hours after the final application of 100 micro g insect venom. RESULTS: Extensive reddening due to inflammation was found in injection spot in 5 patients. Four patients had an amplified wheal formation. No systemic reactions were observed. The maintenance therapy was well tolerated. CONCLUSION: The modified ultra-rush-protocol increases compliance by short inpatient stay. In addition the modified hyposensitization was sure and well tolerated.

[Acute Renal Failure in Twin-to-Twin Transfusion Syndrome: Differential Diagnosis]. / Akutes Nierenversagen beim feto-fetalen Transfusionssyndrom: Differenzialdiagnose.

In the differential diagnosis of acute renal failure in Newborns prerenal, renal and postrenal causes must be considered. Additionally, in twin-to-twin transfusion syndrome especially the donor can suffer from acute renal failure caused by longterm intrauterine hypoperfusion of the kidneys resulting in severe retardation of renal development.

[Hereditary deficiency of C1-esterase inhibitor presenting with recurrent abdominal pain]. / Hereditäres Angioödem Typ I durch C1-Inhibitor-Mangel als Ursache von rezidivierenden Bauchschmerzen.

Hereditary deficiency of C1-esterase inhibitor (C1-INH) which clinically manifests as hereditary angioedema is a rare disorder. In previously not diagnosed cases, a fatality rate of up to 30 % has been reported. The diagnosis of C1-esterase inhibitor deficiency should not be missed in patients presenting with angioedema in the face, stem or extremities. We report the case of a 17-year-old girl with recurrent abdominal pain and swelling of the hands.

[Familial Mediterranean fever]. / Familiäres Mittelmeerfieber.

BACKGROUND: Familial Mediterranean fever (FMF) is characterized by febrile attacks, acute abdominal pain, pleuritis or arthritis and predominantly observed in ethnic groups of the Mediterranean area (Sephardic Jews, Turks, Armenians). Its most ominous manifestation is amyloidosis potentially leading to chronic renal failure. FMF is an inherited disorder caused by mutations of the FMF-gene, which first was described in 1997. CASE REPORT: We report a 10-year old turkish boy and his family presenting with an increased blood sedimentation rate (WBC) and recurrent attacks of acute abdominal pain. A molecular analysis was carried out, confirming a typical mutation of the FMF-gene. The patient remained free of symptoms after starting therapy with colchicine. CONCLUSION: Investigation of the FMF gene enables an early diagnosis in case of clinical suspect findings, subsequent colchicine administration may prevent amyloidosis.

[Treatment of hepatitis B virus-associated membranous glomerulonephritis with interferon alfa in a 7 year old boy]. / Therapie der membranösen Glomerulonephritis mit alpha-Interferon bei einem 7-jährigen Jungen mit chronisch persistierender Hepatitis B.

BACKGROUND: The association between Hepatitis B virus infection and membranous nephropathy has been confirmed by sources in several countries. Most commonly, the illness is seen as a nephrotic syndrome. Optimal treatment remains undefined. Antiviral therapies observed with recombinant human interferon alpha may be the best treatment option. CASE REPORT: We present a 7-year old boy with membranous glomerulonephritis and nephrotic syndrome. Twelve months after the initial hospitalization therapy was started with recombinant alpha-interferon s.c. three times weekly for six months. After the therapy the patient is stable, without proteinuria, edema or renal failure. He was seronegative for HBsAg, HBV-DNA and antibody to HBeAg. CONCLUSIONS: This case report suggests that alpha interferon is effective in the complete resolution of proteinuria in HBV membranous nephropathy.

The value of renal scintigraphy during controlled diuresis in children with hydronephrosis.

Dynamic renal scintigraphy (DRS) during controlled diuresis is the method of choice to diagnose the functional relevance of urinary tract obstruction in children with sonographically demonstrated hydronephrosis. However, there are no commonly accepted scintigraphic criteria for surgical intervention. On the basis of our findings, we propose four stages of washout (WO) of tracer following diuresis: in stage I, WO>50%, neither further diagnosis nor intervention is necessary; in stage II, 50%>/=WO>/=12%, repetition of DRS is advised within 3-4 months; and in stage III, 12%>WO>/=5%, DRS should be repeated within 1-2 months. Only in stage IV, WO<5%, should surgery be done immediately. This procedure reduces surgical interventions by 50% without increasing the risk of residual renal damage.

Increased urinary adrenomedullin excretion in children with urinary-tract infection.

BACKGROUND: Adrenomedullin (AM), a smooth-muscle relaxant peptide, is stimulated by cytokines and bacterial endotoxins. We hypothesized that urinary-tract infections may be associated with elevated urinary AM excretion. METHODS: AM in urine was quantified in eleven children with urinary-tract infection and 11 age- and sex-matched controls by radioimmunoassay. RT-PCR was used to demonstrate local AM mRNA expression in the urinary tract. RESULTS: In healthy controls but not in diseased children there was a significant correlation between AM and creatinine in urine (r = 0.91, P < 0.001). AM levels in children with urinary-tract infection were significantly higher than in controls (0.6 +/- 0.41 vs 0.15 +/- 0.14 ng/micromol creatinine; P < 0.001; (means +/- SD)). There was a significant correlation between white cell count and AM in urine (r = 0.78, P < 0.001). AM mRNA was expressed in renal tissue, renal pelvis, ureter, bladder, and urethra. CONCLUSION: The smooth-muscle relaxant peptide adrenomedullin that is synthesized in tissue of the human urinary tract is elevated in urine of patients with urinary-tract infections. A possible consequence might be the interference with the ureteral anti-reflux mechanisms.