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Medical Journal Review

November 2017

WAO Reviews – Editors' Choice

The Editors select articles for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases, and whenever possible they seek articles that everyone can access freely. The Editors’ Choice comes to you from Juan Carlos Ivancevich, MD, WAO Web Managing Editor, and summary author, John J. Oppenheimer, MD, FACAAI, FAAAAI, WAO Reviews Editor.

World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management
Gottlib J
American Journal of Hematology 2017; 92(11): 1243-1259. DOI:10.1002/ajh.24880

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In this World Health Organization (WHO) update on hypereosinophilia, the author reviews the diagnosis, risk stratification and management of this illness. The diagnosis is made when the peripheral blood eosinophil count is greater than 1500/mm3 and may be associated with tissue damage. Furthermore, the diagnosis of primary eosinophilia relies upon a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ-hybridization, flow immunocytometry, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder. Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2016 World Health Organization endorses a semimolecular scheme of disease subtypes which includes the major category “myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2,” and the “MPN subtype, chronic eosinophilic leukemia, not otherwise specified” (CEL, NOS). Lymphocyte-variant hypereosinophilia is an aberrant T-cell clone-driven reactive eosinophilia, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion.

The author stresses that the goal of therapy is to mitigate organ damage secondary to eosinophil upregulation. For patients with milder forms of eosinophilia (e.g.,<1500/mm3) without symptoms or signs of organ involvement, the author recommends a “watch and wait” approach with close-follow-up. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these disease subyptes to imatinib. Corticosteroids are first-line therapy for patients with lymphocyte-variant hypereosinophilia and hypereosinophil syndrome (HES). Hydroxyurea and interferon-alpha have demonstrated efficacy as initial treatment and steroid-refractory cases of HES. In addition to hydroxyurea, second line cytotoxic chemotherapy agents and hematopoietic cell transplant have been used for aggressive forms of HES and CEL with outcomes reported in limited numbers of patients only. The author closes by noting that antibodies against interleukin-5 (IL-5) (mepolizumab), the IL-5 receptor (benralizumab), and CD52 (alemtuzumab), as well as other targets on eosinophils are hopeful interventions for the future.

Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness
Edwards MR, Strong K, Cameron A, Walton RP, Jackson DJ et al.
Journal of Allergy and Clinical Immunology 2017; 140(4): 909-920  DOI:10/1016/j.jaci.2017.07.025

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In this excellent review, Edwards and colleagues explore the literature regarding how the allergic diathesis impacts viral infections. It is well known that viral respiratory tract infections are associated with asthma inception in early life and asthma exacerbations in older children and adults. What is not well known is the mechanism(s) of how this occurs. Much of this review focuses on the innate interferon-mediated host response to respiratory viruses and discusses and reinforces that this response is impaired or suboptimal. The authors elegantly make the argument that there is a reciprocal negative regulation between innate interferons and TH2 mediators. They further suggest that this may be the reason for why anti-TH2 biologics are particularly successful in controlling asthma exacerbations and suggest ways in which future clinical studies could be used to confirm this hypothesis.

A systematic review of safety and efficacy of systemic corticosteroids in atopic dermatitis
Yu S, Drucker AM, Lebwohl M, Silverberg J
Journal of American Dermatology 2017; Article in press, published online 13 October. DOI:10.1016/j.jaad.2017.09.074


Surprisingly, despite the fact that systemic corticosteroids are often used to treat atopic dermatitis (AD), few studies assessed the safety and efficacy of systemic corticosteroids in AD. Thus, the purpose of this study by Yu et al., was to systematically review the literature regarding the efficacy and safety of systemic corticosteroid use (oral, intramuscular, intravenous) patients of all ages with AD. Although there was incomplete reporting and heterogeneity across studies, the general consensus in the literature (52 reviews and 12 studies) is to limit the use of systemic steroids to short courses as a bridge to steroid-sparing therapies, in attempt to prevent the potential for significant side effects which can occur. 

Fatal anaphylaxis: Mortality rate and risk factors
Turner PJ, Jerschow E, Umasunthar T, Lin R, Campbell DE, Boyle RJ
Journal of Allergy and Clinical Immunology: In Practice 2017; 5(5): 1169-1178  DOI:10/1016/j/jaip.2017.06.031

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This is an excellent review of fatal anaphylaxis. As noted by the authors, despite the fact that up to 5% of the U.S. population has suffered from anaphylaxis, fatal anaphylaxis constitutes less than 1% of total mortality risk. Furthermore, the incidence of fatal anaphylaxis has not increased in line with hospital admissions for anaphylaxis. The authors explore risk factors for fatal anaphylaxis, which have been shown to vary according to cause. Lastly, they highlight that although fatal anaphylaxis is a rare event, it has a significant negative impact on quality of life, suggesting that quality of life impairment should be a key consideration when making treatment decisions in patients at risk for anaphylaxis.

Asthma control and sputum eosinophils: A longitudinal study in daily practice
Demarche SF, Schleich FN, Paulus VA, Henket MA, Van Hees TJ, Renaud EL
Journal of Allergy and Clinical Immunology: In Practice 2017; 5(5): 1335-1343.e5   DOI:10/1016/j.jaip.2017.01.026

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There has been some controversy in the literature regarding the impact of change in sputum eosinophils and asthma control. Thus, this study by Demarche and colleagues is of importance. They performed a retrospective longitudinal study of 187 patients with asthma who had undergone at least 2 sputum inductions in a Belgian asthma clinic. They relied upon a linear mixed model to assess the relationship between asthma control and individual changes in sputum eosinophils. They also determined minimal import differences (MID) in sputum eosinophils that were associated with a change of at least 0.5 Asthma Control Questionnaire (ACQ) score MID. Via this analysis, they found that asthma control was independently associated with individual fluctuations in sputum eosinophil count (P<0.01). Furthermore, in those patients with eosinophilic asthma, they found a minimal important decrease of 4.3% in percentage of sputum eosinophils (P<0.01), for a significant improvement in asthma control and a minimal important increase of 3.5% for a significant worsening in asthma control. Thus, demonstrating at the individual level, asthma control was associated with changes in the sputum eosinophil count over time.