Impact of type 2 targeting biologics on acute exacerbations of chronic rhinosinusitis.

Background: Acute exacerbations of chronic rhinosinusitis (AECRS) are associated with significant morbidity and decreased quality of life. There are sparse data assessing the real-world impact of biologics on AECRS. Objectives: We sought to determine the impact of type 2-targeting biologics on the frequency of medication use for AECRS episodes. Methods: Antibiotic and/or systemic corticosteroid courses for AECRS were identified in a retrospective study from November 2015 to February 2020, at a single academic health system. The estimated yearly rates for antibiotic and corticosteroid courses were evaluated before and after initiation of type 2 biologics. Results: One-hundred and sixty-five patients with chronic rhinosinusitis (CRS) had received either omalizumab (n = 12), mepolizumab (n = 42), benralizumab (n = 44), dupilumab (n = 61), or reslizumab (n = 6). Seventy percent had CRS with nasal polyps, and 30% had CRS without nasal polyps. All the patients had asthma. When all the biologics were combined, the estimated yearly rate for antibiotics for AECRS decreased from 1.34 (95% confidence interval [CI], 1.12-1.59) to 0.68 (95% CI, 0.52-0.88) with biologic use (49% reduction, p < 0.001). Those with frequent AECRS (three or more courses of antibiotics in the 1 year before biologic use) had a larger degree of reduction, with an estimated yearly rate of 4.15 (95% CI, 3.79-4.55) to 1.58 (95% CI, 1.06-2.35) with biologic use (n = 27; 62% reduction; p < 0.001). Within the total cohort, the estimated yearly rate for systemic corticosteroids for AECRS decreased from 1.69 (95% CI, 1.42-2.02) to 0.68 (95% CI, 0.53-0.88) with biologic use (60% reduction; p < 0.001). Conclusion: Type 2-targeting biologics reduced medication use for AECRS. This suggested that biologics may be a therapeutic option for patients with frequent AECRS.

Allergic and nonallergic rhinitis.

Rhinitis is characterized by nasal congestion, rhinorrhea, sneezing, and/or posterior nasal drainage. It affects a significant portion of the population and presents a large burden economically and on quality of life. Rhinitis is broadly characterized as allergic and nonallergic, of which nonallergic rhinitis may be divided into inflammatory and noninflammatory etiologies. The inflammatory causes include nonallergic rhinitis with eosinophilia, postinfectious, and rhinitis associated with nasal polyps. The noninflammatory causes include idiopathic nonallergic (vasomotor) rhinitis, medication-induced rhinitis, hormone related (e.g., pregnancy), and systemic disease related. Allergic rhinitis is classified as intermittent or persistent and mild versus moderate-severe. The nasal mucosa is extremely vascular; parasympathetic stimulation promotes an increase in nasal cavity resistance and nasal gland secretion, whereas sympathetic stimulation leads to vasoconstriction. The diagnosis of rhinitis begins with a directed history, particularly noting pattern, chronicity, and triggers of symptoms. Examination of the nasal cavity with attention to appearance of the septum and inferior turbinates is recommended. Skin testing for aeroallergens is helpful in demonstrating the presence or absence of immunoglobulin E antibodies and to differentiate nonallergic from allergic rhinitis. Treatment includes patient education, irritant or allergen avoidance, and pharmacotherapy. Medications used for the treatment of rhinitis include intranasal corticosteroids, oral and intranasal antihistamines, intranasal anticholinergic agents, oral decongestants, and leukotriene receptor antagonists. When used in combination, an intranasal antihistamine spray and nasal steroid provide greater symptomatic relief than monotherapy. Allergen immunotherapy is the only disease-modifying intervention available for allergic rhinitis.

Chapter 6: Nonallergic rhinitis.

Nonallergic rhinitis represents a non-IgE-mediated group of disorders that share the symptoms of nasal congestion, rhinorrhea, sneezing, and/or postnasal discharge but not pruritus that characterizes allergic rhinitis. Nonallergic rhinitis may be divided into two broad categories, inflammatory and noninflammatory etiologies. The inflammatory causes include postinfectious (viral and bacterial), rhinitis associated with nasal polyps, and nonallergic rhinitis with eosinophilia, where eosinophils are present in nasal smears but skin testing for aeroallergens is negative. The noninflammatory causes include idiopathic nonallergic rhinitis (formerly referred to as vasomotor rhinitis or colloquially as an "overreactive nose"); rhinitis medicamentosa, which is medication-induced rhinitis; hormone related (pregnancy); systemic disease related (severe hypothyroidism); and structural defect related (deviated septum, head trauma causing cerebrospinal fluid rhinorrhea). The classic symptoms of idiopathic nonallergic rhinitis are nasal congestion, postnasal drip, and sneezing triggered by irritant odors, perfumes, wine, and weather changes. The diagnosis of rhinitis begins with a directed history and physical exam. Examination of the nasal cavity with attention to appearance of the septum and inferior turbinates is recommended. Skin testing for seasonal and perennial aeroallergens is helpful in establishing the presence or absence of IgE antibodies and to help differentiate nonallergic from allergic rhinitis. Topical H(1)-receptor antagonist (antihistamine) nasal sprays, intranasal steroids, intranasal anticholinergics, and oral decongestants are options for pharmacotherapy. It is important to inquire about hypertension, arrhythmias, insomnia, prostate hypertrophy, or glaucoma to prevent undesirable side effects associated with the oral decongestant pseudoephedrine.

Apocrine sweat gland obstruction by antiperspirants allowing transdermal absorption of cutaneous generated hormones and pheromones as a link to the observed incidence rates of breast and prostate cancer in the 20th century.

Breast and prostate cancer share similarities and likely represent homologous cancers in females and males, respectively. The role of hormones such as testosterone and estrogen in carcinogenesis is well established. Despite worldwide research efforts, the pathogenesis of these diseases is largely not well understood. Personal care products containing estrogens or xenoestrogens have raised concern as a breast cancer risk, especially in young African-American women. In the United States (US) there is a parallel rise in the incidence in breast and prostate cancer compared to selected non-hormone dependent tumors. Observed US and global breast and prostate cancer incidence increases were occurring before exogenous hormone replacement and xenoestrogen exposure were commonplace. An unintentional, inadvertent, and long term hormone exposure may occur from transdermal absorption of sex hormones and pheromones (androgens) from axillary apocrine sweat gland obstruction by aluminum-based antiperspirants. The global rise in antiperspirant use parallels rises in breast and prostate cancer incidence and mortality rates. A multi-disciplinary literature based set of evidence is presented on how such a link is possible, to prompt confirmatory investigations in the pursuit of unmet needs in breast and prostate cancer etiology and prevention.

Hypersensitivity to aldesleukin (interleukin-2 and proleukin) presenting as facial angioedema and erythema.

Aldesleukin is a human recombinant interleukin-2 product. It also is known as interlukin-2 and Proleukin in the United States. It is indicated for the treatment of adults with metastatic renal cell carcinoma as well as for adults with metastatic melanoma. However, its use has been limited because of severe systemic toxicity. There have been no reports of aldesleukin producing a hypersensitivity reaction. This is the first reported case of an immediate systemic hypersensitivity reaction occurring after aldesleukin administration confirmed by enzyme-linked immunosorbent assay for specific immunoglobulin E against aldesleukin.

Immediate systemic hypersensitivity reaction associated with topical application of Australian tea tree oil.

Australian tea tree oil has been used as a veterinary antiseptic for many years and, more recently, has been extended into human use. There have been many reports of allergic contact dermatitis and toxicity reactions, but it has never been implicated in immediate systemic hypersensitivity reactions. A 38-year-old man experienced immediate flushing, pruritus, throat constriction, and lightheadedness after topical application of tea tree oil. Our purpose was to determine whether this represented an immunoglobulin E (IgE)--mediated reaction. Skin-prick and intradermal testing was performed, as well as enzyme-linked immunosorbent assays for specific IgG and IgE against tea tree oil. The patient had a positive wheal and flare reaction on intradermal testing with tea tree oil. All five patient controls were negative on skin testing. No specific IgG or IgE was detected. We present the first reported case of an immediate systemic hypersensitivity reaction occurring after topical application of Australian tea tree oil, confirmed by positive wheal and flare reaction on skin testing.