Erik Eriksen is a remarkable individual. He has no college degrees yet is Professor of Human Development at Harvard University. He came to psychology via art, which explains why the reader will find him painting contexts and backgrounds rather than stating dull facts and concepts. He has been a training psychoanalyst for many years as well as a perceptive observer of cultural and social settings and their effect on growing up. This is not just a book on childhood. It is a panorama of our society. Anxiety in young children, apathy in American Indians, confusion in veterans of war, and arrogance in young Nazis are scrutinized under the psychoanalytic magnifying glass. The material is well written and devoid of technical jargon. The theme of the volume is that it is human to have a long childhood which will leave a lifelong residue of emotional immaturity in man. Primitive groups and

Childhood and Society.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

/pdf/european-position-paper-on-rhinosinusitis-and-nasal-polyps-mj734vsl7p.pdf

European Position Paper on Rhinosinusitis and Nasal Polyps 2020

This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Sectionof the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/all.13397

The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria.

Atopic dermatitis (AD) is a complex skin disease frequently associated with other diseases of the atopic diathesis. Recent evidence supports the concept that AD can also recognize other comorbidities, such as chronic inflammatory bowel or cardiovascular diseases. These comorbidities might result from chronic cutaneous inflammation or from a common, yet-to-be-defined immunologic background leading to immune deviations. The activation of immune cells and their migration to the skin play an essential role in the pathogenesis of AD. In patients with AD, an underlying immune deviation might result in higher susceptibility of the skin to environmental factors. There is a high unmet medical need to define immunologic endotypes of AD because it has significant implications on upcoming stratification of the phenotype of AD and the resulting targeted therapies in the development of precision medicine. This review article emphasizes studies on environmental factors affecting AD development and novel biological agents used in the treatment of AD. Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti-IL-4 receptor α-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players. These targeted molecules can be expressed on or drive the cellular players infiltrating the skin (eg, T lymphocytes, dendritic cells, or eosinophils). Such approaches can have immunomodulatory and thereby beneficial clinical effects on the overall skin condition, as well as on the underlying immune deviation that might play a role in comorbidities. An effect of these immunologic treatments on pruritus and the disturbed microbiome in patients with AD has other potential consequences for treatment.

Cellular and molecular immunologic mechanisms in patients with atopic dermatitis

BackgroundInterleukin-31 may play a role in the pathobiologic mechanism of atopic dermatitis and pruritus. We wanted to assess the efficacy and safety of nemolizumab (CIM331), a humanized antibody against interleukin-31 receptor A, in the treatment of atopic dermatitis. MethodsIn this phase 2, randomized, double-blind, placebo-controlled, 12-week trial, we assigned adults with moderate-to-severe atopic dermatitis that was inadequately controlled by topical treatments to receive subcutaneous nemolizumab (at a dose of 0.1 mg, 0.5 mg, or 2.0 mg per kilogram of body weight) or placebo every 4 weeks or an exploratory dose of 2.0 mg of nemolizumab per kilogram every 8 weeks. The primary end point was the percentage improvement from baseline in the score on the pruritus visual-analogue scale (on which a negative change indicates improvement) at week 12. Secondary end points included changes in the score on the Eczema Area and Severity Index (EASI, on which a negative change indicates improvement), and body-surfa...

Anti-interleukin-31 receptor a antibody for atopic dermatitis

Background Chronic urticaria is a frequent and debilitating skin disease. Its symptoms commonly fluctuate considerably from day to day. As of yet, the only reliable tool to assess disease activity is the Urticaria Activity Score, which prospectively documents the signs and symptoms of urticaria for several days. Objective We sought to develop and validate a novel patient-reported outcome instrument to retrospectively assess urticaria control, the Urticaria Control Test (UCT). Methods Potential UCT items were developed by using established methods (literature research and expert and patient involvement). Subsequently, item reduction was performed by using a combined approach, applying impact and regression analysis. The resulting UCT instrument was then tested for its validity, reliability, and screening accuracy. Results A 4-item UCT with a recall period of 4 weeks was developed based on 25 potential UCT items tested in 508 patients with chronic urticaria. A subsequent validation study with the 4-item UCT in 120 patients with chronic urticaria demonstrated that this new tool exhibits good convergent and known-groups validity, as well as excellent test-retest reliability. In addition, the screening accuracy to identify patients with urticaria with insufficiently controlled disease was found to be high. Conclusions The UCT is the first valid and reliable tool to assess disease control in patients with chronic urticaria (spontaneous and inducible). Its retrospective approach and simple scoring system make it an ideal instrument for the management of patients with chronic urticaria in clinical practice.

https://www.jacionline.org/article/S0091-6749(14)00004-9/pdf

Development and validation of the Urticaria Control Test: a patient-reported outcome instrument for assessing urticaria control.

Background Chronic spontaneous urticaria (CSU) is defined by itchy hives, angioedema, or both for at least 6 weeks. Omalizumab, an anti-IgE antibody that affects mast cell and basophil function, is a promising new treatment option. As of now, however, the efficacy and safety of different doses of omalizumab used in clinical trials for CSU have not been systematically analyzed and summarized. Objective We sought to assess the efficacy and safety of different doses of omalizumab for the treatment of CSU in a meta-analysis of clinical trial results. Methods Suitable trials were identified by searching PubMed, Medline, Embase, and Web of Science databases and with the help of omalizumab's manufacturers. Only double-blind, randomized, placebo-controlled studies with omalizumab-treated versus placebo-treated patients with CSU were included in this analysis. Results We identified 7 randomized, placebo-controlled studies with 1312 patients with CSU. Patients treated with omalizumab (75-600 mg every 4 weeks) had significantly reduced weekly itch and weekly wheal scores compared with the placebo group. Omalizumab's effects were dose dependent, with the strongest reduction in weekly itch and weekly wheal scores observed with 300 mg. Rates of complete response were significantly higher in the omalizumab group (relative risk, 4.55; P Conclusion This meta-analysis provides high-quality evidence for the efficacy and safety of omalizumab in patients with CSU and for treating these patients with 300 mg of omalizumab every 4 weeks.

Omalizumab for the treatment of chronic spontaneous urticaria: A meta-analysis of randomized clinical trials

Serum autoreactivity predicts time to response to omalizumab therapy in chronic spontaneous urticaria

BACKGROUND Omalizumab is an effective and well-tolerated treatment for chronic spontaneous urticaria (CSU). Markers and predictors of response are largely unknown, but needed to optimize omalizumab treatment. Omalizumab targets IgE, and IgE levels may be linked to the effects of treatment. We evaluated whether response rates to treatment with omalizumab in patients with CSU are linked to their baseline IgE levels, their IgE levels after omalizumab treatment, and the ratio of on treatment IgE and baseline IgE levels. METHODS Chronic spontaneous urticaria (CSU) patients (n = 113) were treated with omalizumab 300 mg/4 weeks for 12 weeks, when their treatment responses, that is, no, partial, or complete response, were assessed by use of the urticaria activity score, physician and patient visual analog scale, and treatment effectiveness score. Total IgE levels were measured before treatment (bIgE) with omalizumab and 4 weeks thereafter (w4IgE). RESULTS Nonresponders to omalizumab had significantly lower bIgE levels (17.9, 17.0-55.0 IU/mL) than partial responders (82.0, 46.2-126.5 IU/mL, P = .008) and complete responders (73.7, 19.45-153.8 IU/mL, P = .032). Nonresponders also had lower w4IgE levels and lower ratios of w4IgE/bIgE levels than partial and complete responders (P < .001). Nonresponse to omalizumab was best predicted by patients' w4IgE/bIgE ratios, significantly better than by bIgE levels (P = .016). CONCLUSIONS In CSU, total IgE levels and their change predict the response to treatment with omalizumab. The assessment of pre- and post-treatment IgE levels and their ratio may help to improve the management of CSU in patients who require omalizumab treatment.

The clinical response to omalizumab in chronic spontaneous urticaria patients is linked to and predicted by IgE levels and their change

Background
The most intriguing function attributed to interleukin-31 (IL-31) is its ability to induce pruritus in pathologic conditions, such as atopic dermatitis (AD). As of today, this feature of IL-31 was tested in vivo only in animal models.

Methods
Ten patients with AD and 10 healthy controls were challenged with IL-31 and NaCl (negative control) by skin prick testing. Twenty additional healthy controls were subjected to skin prick testing with histamine. Itch and local inflammatory responses of the skin were assessed for up to 72 h.

Results
All of the histamine-challenged subjects developed immediate pruritus (i.e. within the first 5 min). In contrast, only one IL-31- and two of the NaCl-challenged subjects reported immediate itch at the provocation site (short lasting, for 2–6 min). Nine subjects (five patients with AD) reported late itch responses to IL-31 challenges with a mean delay of 143 min. No subject reported late itch responses to histamine or NaCl testing. There was no significant difference in IL-31-induced itch start time, duration and intensity between patients with AD and healthy volunteers.

Conclusion
IL-31 does not induce immediate itch responses in humans. The late onset of IL-31-induced itch supports the notion that IL-31 exerts its pruritic effect indirectly via keratinocytes and secondary mediators, rather than through its receptors on cutaneous nerves.

Tomasz Hawro

Papers

Development and validation of the Urticaria Control Test: a patient-reported outcome instrument for assessing urticaria control.

Omalizumab for the treatment of chronic spontaneous urticaria: A meta-analysis of randomized clinical trials

Serum autoreactivity predicts time to response to omalizumab therapy in chronic spontaneous urticaria

The clinical response to omalizumab in chronic spontaneous urticaria patients is linked to and predicted by IgE levels and their change

Interleukin-31 does not induce immediate itch in atopic dermatitis patients and healthy controls after skin challenge.