Netherton syndrome-A therapeutic challenge in childhood.

Key Clinical Message: High-dose intravenous immunoglobulin exhibits great potential in the treatment of Netherton syndrome. Abstract: Netherton syndrome (NS) is a rare autosomal recessive genodermatosis (OMIM #256500) characterized by superficial scaling, atopic manifestations, and multisystemic complications. It is caused by loss-of-function mutations in the SPINK5 gene, which encode a key kallikrein protease inhibitor. There are two subtypes of the syndrome that differ in clinical presentation and immune profile: ichthyosiform erythroderma and ichthyosis linearis circumflexa. NS is a multisystemic disease with numerous extracutaneous manifestations. Current therapy for patients with NS is mainly supportive, as there is no curative or specific treatment, especially for children with NS, but targeted therapies are being developed. We describe an 8-year-old boy with genetically proven NS treated with intravenous immunoglobulin for recurrent skin and systemic infections from infancy, growth retardation, and associated erythroderma. Under this therapy, his skin status, infectious exacerbations, and quality of life all improved. Knowledge of the cytokine-mediated pathogenesis of NS and the development of new biologic drugs open new possibilities for NS patients. However, the different therapeutic options have been applied in a limited number of cases, and variable responses have been shown. Randomized controlled trials with a sufficient number of patients stratified and treated according to their specific immune profile and clinical phenotype are needed to evaluate the safety and efficacy of treatment options for patients with NS.

Elevated IgE Levels-An Allergy or an Underlying Inborn Error of Immunity in Children with Recurrent Infections?

Elevated immunoglobulin E (IgE) is a hallmark of allergic diseases. However, high IgE levels also occur in a number of other infectious and noninfectious diseases. In most cases, elevated IgE levels indicate allergy, eczema, or chronic skin infection. Very high IgE levels are not uncommon in patients with active eczema but more often indicate monogenic atopic disorder or inborn errors of immunity with an atopic phenotype. We conducted a retrospective study of 385 children with suspected immune deficiency referred to the clinic over a 9-year period. Measurement of IgE, IgG, IgA, IgM, and IgG subclasses in blood samples revealed that nearly one-third of the patients had elevated serum IgE levels. Most of the cases with elevated IgE were children with underlying atopy-mainly atopic dermatitis and, to a lesser extent, bronchial asthma-whereas 40.12% (37 children) had no atopy at all. In the most severe cases (with extremely elevated IgE or severe dermatitis), we confirmed genetic mutations for underlying immunodeficiency. Our results indicate that allergic phenotype should not be underestimated and that children with more severe allergic disease should be evaluated for an underlying inborn error of immunity. If inborn error of immunity (IEI) is suspected, a comprehensive immunologic evaluation is required. Genetic testing helps identify the specific genetic abnormality, which provides important insight into the immunopathogenesis of the disease and accurate determination of optimal therapy.

Antimicrobial susceptibility of Pseudomonas aeruginosa before and after initiation of inhaled tobramycin in Bulgaria.

INTRODUCTION: In aim to achieve better infection control and possible eradication of the pathogens involved in chronic infections of patients with cystic fibrosis (CF) scientists have developed a new way to administer antimicrobials - inhalation. The first and so far the only available inhalable antimicrobial in Bulgaria is inhaled tobramycin (TOBI), introduced in 2009. We aimed to evaluate the antimicrobial susceptibility of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients before and after initiation of TOBI in the regular treatment regimen. METHODOLOGY: We have determined the minimal inhibitory concentration (MIC) of 17 antimicrobials by the E-test (LIOFILCHEM) in sputa samples of 118 CF patients for the period of 2005-2014. The results were interpreted according to the annual Clinical and Laboratory Standards Institute guidelines. RESULTS: In the sputa of 70 patients a total of 102 P. aeruginosa isolates were found. Sixty-eight out of 102 (66.7%) were susceptible to all studied antimicrobials. We divided the isolates in two chronological groups: those collected before the introduction of TOBI as a regular treatment in 2009 and those collected after 2009. A significant reduction (p < 0,001-0,02) in susceptibility for the strains after 2009 was noted towards piperacillin (100% vs 50%), ceftazidime (100% / 77.3%), cefepime (97.9% / 68.2%), amikacin (100% / 63.6%), gentamicin (95.7% / 40.9%), tobramycin (93.6% / 59.1%) and ciprofloxacin (93.6% / 45.5%). CONCLUSION: The introduction of inhaled tobramycin as a regular therapy for CF patients in Bulgaria lead to a significant change in antimicrobial susceptibility of CF P. aeruginosa.

Pulmonary exacerbation due to colistin-resistant Stenotrophomonas maltophilia in a Bulgarian cystic fibrosis patient.

In patients with cystic fibrosis (CF) lung damage secondary to chronic infection is the main cause of death. Treatment of lung disease to reduce the impact of infection, inflammation and subsequent lung injury is therefore of major importance. As Pseudomonas aeruginosa is the dominant pathogen in CF patients it has been the major target of all treatment strategies, possible antibiotic regimens and recommendations for years. More sophisticated antibiotic therapies introduced over the last decades have helped to improve the prognosis in cystic fibrosis, but then new multidrug-resistant pathogens emerged. We present a case of cystic fibrosis in a 16-year-old boy with pulmonary exacerbation due to colistin-resistant Stenotrophomonas maltophilia. This case raises some interesting questions regarding the antibiotic policy and treatment options in our country for patients with CF and multidrug-resistant strains. Colistin is used at present in Bulgaria as a strategic last option for the CF patients but with the advent of new more drug-resistant strains therapeutic approach should change - for instance, there should be restrictions imposed on the use of levofloxacin and trimethoprim/sulfamethoxazole which are regarded as "cheap and not so potent" antibiotics suitable for any infection and use them only in strict dependence on the respective culture results.