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Immunology of atopic eczema: overcoming the Th1/Th2 paradigm

Atopic eczema (AE) is a challenge for modern medicine, because it is prevalent, severely affects quality of life of patients and their families, and causes high socioeconomic costs. The pathogenesis of AE is complex. While initial studies suggested a Th2 deviation as primary reason for the disease, numerous studies addressed a genetically predetermined impaired epidermal barrier as leading cause in a subgroup of patients. Recently, immune changes beyond the initial Th2 concept were defined in AE, with a role for specialized dendritic cells as well as newly identified T helper cell subsets such as Th17 and Th22 cells. Furthermore, trigger factors are expanded beyond classical Th2 allergens such as pollen or house dust mites to microbial products as well as self-antigens. This review pieces together our current understanding of immune as well as barrier abnormalities into the pathogenesis mosaic of AE.

Diagnosis of penicillin allergy revisited: the value of case history, skin testing, specific IgE and prolonged challenge

Background Skin testing in duplicate, correlation between case history of immediate and nonimmediate reactions and challenge outcome and prolonged oral treatment with penicillin in the diagnostic evaluation of allergic reactions to β-lactam antibiotics, mimicking real-life situations, have only been addressed in few studies. Methods A total of 342 patients suspected of having β-lactam allergy were investigated according to the European Network for Drug Allergy (ENDA) guidelines and patients found to be negative in the ENDA program were supplemented with a 7-day oral treatment with penicillin. Skin testing with penicillins was performed in duplicate. Patients with case histories of reactions to other β-lactams were also subsequently challenged with the culprit drug. Results Nineteen patients were IgE-sensitized to penicillin. Then, intracutaneous tests (ICTs) were performed, in which 35 patients tested positive for allergy, 21 with delayed and 14 with immediate reactions. Only three patients tested positive for the major (PPL) and/or minor (MDM) penicillin determinants, all being positive for penicillin G in ICT. The remaining 291 patients were challenged with penicillin: 10 tested positive in single-dose challenge and 23 tested positive in the 7-day challenge. A total of 17 of 78 patients with a negative penicillin challenge tested positive during challenges with other β-lactams. We found no correlation between case histories of immediate and nonimmediate reactions and reaction time during challenge. Conclusion The data suggest that case history is often insufficient to discriminate between immediate reactors and nonimmediate reactors. A 7-day challenge with the culprit β-lactam may yield more positive reactions than the accepted one- or 2-day challenge. Interpretation of skin testing should be made with caution.

Probiotics in primary prevention of allergic disease – follow-up at 8–9 years of age

Background Long-term effects of probiotics in primary prevention of allergic disease need further evaluation. We previously reported a reduced cumulative incidence of infant eczema by feeding Lactobacillus paracasei ssp paracasei F19 (LF19) during weaning. Therefore, we assessed effects of LF19 on the prevalence of allergic disease at school age. Methods In a double-blind placebo-controlled trial infants were randomized to daily intake of cereals with (n = 89) or without LF19 108 CFU (n = 90) from 4–13 months of age. At age 8–9, we evaluated the prevalence of allergic disease (eczema, allergic rhinitis, asthma, and food allergy) by clinical examination and validated questionnaires. IgE sensitization was assessed by skin prick test (inhalant allergens) and specific IgE levels (food allergens). Lung function was evaluated by a spirometry reversibility test. Fractional exhaled nitric oxide (FENO) was measured. Results Of 171 children that completed the intervention, 121 were assessed at age 8–9. In the probiotic group, 15/59 (25%) were diagnosed with any allergic disease vs 22/62 (35%) in the placebo group [OR (95% CI) 0.62 (0.28–1.36)]. Corresponding numbers for IgE-associated allergic disease were 9/53 (17%) vs 12/59 (20%) [0.80 (0.31–2.09)]. Median (25th-75th percentile) FENO was 9 (8–12) in the probiotic vs 8 (7–12) ppb in the placebo group (P > 0.05). There was no effect of LF19 on lung function measures (P > 0.05). Conclusions There was no long-term effect of LF19 on any diagnosed allergic disease, airway inflammation or IgE sensitization. This suggests delayed eczema onset but to fully examine long-term benefits a larger study population had been needed.

Macrolides for the long-term management of asthma – a meta-analysis of randomized clinical trials

Background Macrolide antibiotics, which have anti-inflammatory and immune modulatory effects, have been studied as adjuncts for the management of asthma. However, results have been contradictory and trials underpowered. We therefore sought to conduct a meta-analysis of randomized controlled trials (RCT). Methods All RCT of prolonged macrolides (3+ weeks) for asthma treatment, published up to January 2013 in MEDLINE, Scopus, CINAHL, Highwire, and The Cochrane Collaboration Library, were included. Fixed- or random-effects models were used to calculate pooled weighted or standard mean differences (WMD or SMD, respectively). Results A total of 12 studies were included for analysis. The pooled effect of macrolides on FEV1 (eight trials, 381 subjects) was not significant (SMD 0.05, 95% CI −0.14–0.25), but there was a significant increase in peak expiratory flow (four trials, 419 subjects; WMD 6.7, 95% CI 1.35–12.06). Pooled analysis also showed significant improvements in symptom scores (eight studies, 478 subjects; WMD −0.46, 95% CI −0.60 to −0.32), quality of life (five trials, 346 subjects; WMD 0.18, 95% CI 0.001–0.37), and airway hyper-reactivity (two trials, 131 subjects; SMD 1.99, 95% CI 0.46–3.52). Post hoc evaluation showed limited statistical power to detect significant differences in FEV1. Conclusions Macrolide administration for asthma for three or more weeks was not associated with improvement in FEV1, but produced significant improvements in peak expiratory flow, symptoms, quality of life, and airway hyper-reactivity. Macrolides may therefore be beneficial as adjunct asthma therapy. Future trials, focusing on long-term safety and effectiveness, should use standardized outcomes and procedures.

Causes of SLIT discontinuation and strategies to improve the adherence: a pragmatic approach

Sublingual immunotherapy (SLIT) is often discontinued, and many patients do not renew the prescription. We evaluated the reasons for discontinuation and set up an educational/follow-up plan to improve the adherence. In a first phase, the adherence at 4 months was directly assessed. Based on those results, an action plan (education, frequent contacts, and strictly scheduled visits) was developed and tested in other patients. A group of matched patients did not undergo the follow-up plan (controls). In the first phase, involving 252 subjects, at 4 months, there were 30% dropouts, mainly due to side-effects. In the second phase, 149 patients underwent education/follow-up and 90 received no intervention. In the first group, discontinuations at 4 months were 5%, vs 18% in the controls (P = 0.01). After one year, 12% of patients were lost in the first group and 35% in the control group (P < 0.001). An adequate education and a strict follow-up can significantly reduce SLIT's discontinuations.

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