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.

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.

A real - life observational pilot study to evaluate the effects of two-week treatment with montelukast in patients with chronic cough.

BACKGROUND: Different conditions make the proximal airways susceptible to tussigenic stimuli in the chronic cough (CC) syndrome. Leukotrienes can be implicated in the inflammatory mechanism at play in it. Montelukast is a selective cysteinyl-leukotriene receptor antagonist with proven effectiveness in patients with asthma. The aim of our real-life pilot study was to use montelukast to relieve cough symptoms in patients with CC allegedly due to the two frequent causes other than asthma - upper airway cough syndrome and gastroesophageal reflux (GER). METHODS: 14 consecutive patients with CC were evaluated before and after 2 weeks of treatment with montelukast 10 mg daily. Cough was assessed by validated cough questionnaire. Questionnaires regarding the presence of gastroesophageal reflux were also completed. Cough reflex sensitivity to incremental doubling concentrations of citric acid and capsaicin was measured. Lung function, airway hyperresponsiveness and exhaled breath temperature (EBT), a non-invasive marker of lower airway inflammation, were evaluated to exclude asthma as an underlying cause. Thorough upper-airway examination was also conducted. Cell counts, eosinophil cationic protein (ECP), lactoferrin, myeloperoxidase (MPO) were determined in blood to assess systemic inflammation. RESULTS: Discomfort due to cough was significantly reduced after treatment (P < 0.001). Cough threshold for capsaicin increased significantly (P = 0.001) but not for citric acid. The values of lactoferrin and ECP were significantly reduced, but those of MPO rose. EBT and pulmonary function were not significantly affected by the treatment. CONCLUSION: Patients with CC due to upper airway cough syndrome or gastroesophageal reflux (GER) but not asthma reported significant relief of their symptoms after two weeks of treatment with montelukast. ECP, lactoferrin, MPO altered significantly, highlighting their role in the pathological mechanisms in CC. Clinical trial ID at Clinicaltrials.gov is NCT01754220.