ABSTRACT
BACKGROUND: Approximately 10% of European children are classified as allergic to drugs. In the majority of these children, no allergy to ß-lactam antibiotics (BLA) can be found. In most cases, the exanthema is caused by the infection. MATERIALS AND METHODS: The objective of this paper is to describe the causes and consequences of a misdiagnosis of drug allergy. We propose a method for establishing a correct diagnosis in the case of a history of a delayed reaction during treatment with a BLA. For this purpose, a proposal was discussed via e-mail communication, and consensus was reached among the members of the drug allergy working groups of the participating medical societies. RESULTS: The suspicion of a BLA allergy based on the medical history alone can have a negative impact on future antibiotic treatment. Exanthema associated with febrile infections not related to drug administration is a frequent finding in children. This makes it all the more important to be able to recommend a standardized procedure for clarification in children and adolescents with suspected hypersensitivity reactions. The medical history should be the basis on which to diagnose either a drug allergy or another possible differential diagnosis. A mild maculopapular exanthema (MPE) can be an expression of a drug allergy or a nonspecific viral exanthema. Uncomplicated MPE is not associated with significant systemic involvement, and there is no involvement of the mucous membranes or cutaneous blistering. Only a small number of children with uncomplicated MPE show positive skin tests and only ~ 7 - 16% of suspected BLA diagnoses can be confirmed by provocation tests. Thus, in children with uncomplicated MPE, drug provocation can be performed in an outpatient setting even without prior skin testing. This paper presents a 3-day outpatient direct provocation scheme for BLA delabeling in children with uncomplicated MPE. CONCLUSION: Many children and adolescents are unnecessarily denied treatment with BLA after an uncomplicated MPE while being treated with a BLA.
ABSTRACT
Background: In 2016, nationwide cystic fibrosis newborn screening (CFNS) was newly implemented in Germany, using an immunoreactive trypsin/pancreatitis-associated protein/DNA screening algorithm that differs from most other nationwide screening programmes. Methods: We analysed real-life feasibility of the confirmation process with respect to our pre-specified procedural objectives. These included overall accuracy through false-negative and false-positive results, effectiveness of the Bavarian tracking system, and accuracy of Macroduct and Nanoduct sweat conductivity compared with quantitative chloride determination. All consecutive CFNS-positive newborns assigned to our CF centre and born between 1 September 2016 and 31 August 2021 (n=162) were included. Results: The German CFNS was feasible at our CF centre as all procedural objectives were met. The positive predictive value (PPV) of positive CFNS was low (0.23) and two initially negatively screened children were later diagnosed with CF. The tracking system was highly efficient with a 100% tracking rate. The Macroduct and Nanoduct systems had comparable success rates (93.2% versus 95.9%). Importantly, conductivity via Macroduct was more accurate than via Nanoduct (zero and four false-positive newborns, respectively). Conclusions: CF confirmation diagnostics of neonates in a certified regional CF centre was well managed in daily routine. The PPV of the German CFNS needs to be improved, e.g. by extending the DNA analysis within the screening algorithm and by increasing the number of variants tested. The Bavarian tracking system can serve as a successful model for other tracking systems. We preferred the Macroduct system because of its more accurate sweat conductivity readings.
ABSTRACT
BACKGROUND: The majority of patients with childhood interstitial lung disease (chILD) caused by pathogenic variants in ATP binding cassette subfamily A member 3 (ABCA3) develop severe respiratory insufficiency within their first year of life and succumb to disease if not lung transplanted. This register-based cohort study reviews patients with ABCA3 lung disease who survived beyond the age of 1 year. METHOD: Over a 21-year period, patients diagnosed as chILD due to ABCA3 deficiency were identified from the Kids Lung Register database. 44 patients survived beyond the first year of life and their long-term clinical course, oxygen supplementation and pulmonary function were reviewed. Chest CT and histopathology were scored blindly. RESULTS: At the end of the observation period, median age was 6.3 years (IQR: 2.8-11.7) and 36/44 (82%) were still alive without transplantation. Patients who had never received supplemental oxygen therapy survived longer than those persistently required oxygen supplementation (9.7 (95% CI 6.7 to 27.7) vs 3.0 years (95% CI 1.5 to 5.0), p=0.0126). Interstitial lung disease was clearly progressive over time based on lung function (forced vital capacity % predicted absolute loss -1.1% /year) and on chest CT (increasing cystic lesions in those with repetitive imaging). Lung histology pattern were variable (chronic pneumonitis of infancy, non-specific interstitial pneumonia, and desquamative interstitial pneumonia). In 37/44 subjects, the ABCA3 sequence variants were missense variants, small insertions or deletions with in-silico tools predicting some residual ABCA3 transporter function. CONCLUSION: The natural history of ABCA3-related interstitial lung disease progresses during childhood and adolescence. Disease-modifying treatments are desirable to delay such disease course.
