Faculty Bibliography

OBJECTIVE: Interleukin (IL)-33 has been associated with atopic and inflammatory conditions. IL-33 may be atheroprotective inducing a Th1-to-Th2 immunologic switch. However, the role of IL-33 in cardiovascular disease remains unclear. This study examines the effect of physiological and elevated IL-33 levels in plasma from atopic patients (AP) on cholesterol metabolism in human macrophages as compared to plasma from healthy controls (HC). METHODS: Twenty-five AP and 25 HC were enrolled in this study. Plasma samples were analysed for levels of IL-33, IFN-gamma, TNF-alpha, IL-17alpha, IL-5 and soluble ST2. THP-1 differentiated macrophages were exposed to HC and AP plasma. Expression of proteins involved in reverse cholesterol transport (ABCA1, ABCG1 and 27-hydroxylase) and scavenger receptors, responsible for uptake of modified lipids (CD36, ScR-A1, CXCL16 and LOX-1), was measured using QRT-PCR and immunoblotting techniques. RESULTS: IL-33 was significantly higher in AP plasma: 106.7 +/- 95 pg/mL versus HC plasma (53.4 +/- 23 pg/mL). IL-33 concentration strongly correlated with levels of IFN-gamma (r = 0.85), TNFalpha (r = 0.9) and IL-17alpha (r = 0.94). No significant difference was found in soluble ST2 levels. An important contrast was observed for 27-hydroxylase: normal IL-33 in AP plasma amplified 27-hydroxylase while increased IL-33 suppressed it. Expression of CD36 and SR-A1 was greater in macrophages exposed to plasma with high IL-33, while CXCL16 was higher in cells grown in the presence of plasma with normal IL-33. CONCLUSIONS: Here, we demonstrate that high levels of IL-33 and a high IL-33/soluble ST2 ratio correlates with elevated levels of IFN-gamma, TNF-alpha and IL-17alpha as well as IL-5, demonstrating that IL-33 has pleiotropic effects. However, elevated IL-33 did not significantly impact lipid accumulation in macrophages overall. Given the wide variety of cellular responses regulated by IL-33, further investigation with a larger sample size will allow us to clarify the threshold concentration of IL-33 that leads to optimal cholesterol balance.

Contact dermatitis is a common disease seen by allergists, dermatologists, and primary care physicians. The gold standard for diagnosing allergic contact dermatitis (ACD) is patch testing and is indicated in any patient with a chronic, pruritic, eczematous, or lichenified dermatitis if underlying or secondary ACD is suspected. Patients with acute generalized dermatitis who have extensive eczema on the back, are on immunosuppressant medications, and have applied topical corticosteroids, topical calcineurin inhibitors, or ultraviolet radiation to the patch test (PT) site may have suppressed PT reactions. The procedure of patch testing is not a difficult one to perform, but the interpretation of the PT needs some critical components, including having an appropriate level of suspicion for the diagnosis of ACD, testing the relevant allergens in their proper vehicle and concentration, and the necessary experience to properly interpret the results. Careful history and physical examination must be correlated with the result of the PT to establish clinical relevance. Once the PT is completed, allergens are identified, and relevance has been established, educating the patient about the avoidance of exposure is critical. The Joint Task Force of the American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology has developed updated practice parameters for contact dermatitis and patch testing, and their recommendations will be discussed (Fonacier LF, Bernstein DI, Pacheco K, Holness DL. Contact dermatitis: a practice parameter update 2015. J Allergy Clin Immunol Pract 2015; 3(3S):S1-S40.).

Flexural eczema and atopic dermatitis are frequently synonymized. As respiratory atopy is rarely tested for and found in these patients, systematically equating a flexural distribution of dermatitis with atopic dermatitis may too frequently result in misclassified diagnoses and potentially missed opportunity for intervention toward improving patients' symptoms and quality of life. We present a critical review of the available evidence for the atopic dermatitis diagnosis and discuss the similarities between atopic dermatitis and allergic contact dermatitis. Because neither flexural predilection nor atopy is specific for atopic dermatitis, we conclude that the term atopic dermatitis is a misnomer and propose an etymologic reclassification of atopic dermatitis to "atopy-related" dermatitis. Allergic contact dermatitis can induce an atopic dermatitis-like phenotype, and thus, flexural dermatitis cannot be assumed as atopic without further testing. Patch testing should at least be considered in cases of chronic or recurrent eczema regardless of the working diagnosis.

This parameter was developed by the Joint Task Force on Practice Parameters, which represents the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "Contact Dermatitis: A Practice Parameter-Update 2015." This is a complete and comprehensive document at the current time. The medical environment is changing and not all recommendations will be appropriate or applicable to all patients. Because this document incorporated the efforts of many participants, no single individual, including members serving on the Joint Task Force, are authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information or interpretation of this practice parameter by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by the pharmaceutical industry in drug development or promotion. Previously published practice parameters of the Joint Task Force on Practice Parameters for Allergy & Immunology are available at http://www.JCAAI.org or http://www.allergyparameters.org.

Because both atopic dermatitis (AD) and contact dermatitis (CD) are characterized by a similar morphologic appearance and similar distribution of skin involvement, the diagnosis of CD in AD has been difficult. Historically, it was thought that patients with AD were unable or less likely to develop CD due to various studies in which patients with AD stimulated with strong allergens failed to develop sensitization at rates similar to patients without AD. However, more recent evidence from the United States and Europe has shown that patients with AD have similar if not higher rates of positive patch test results to common contact allergens, including metals and fragrance, than those patients without AD. In this review, we highlight evidence for and against the role of contact allergy in patients with AD and seek to give clinically relevant management recommendations for the evaluation of CD in the patient with AD.