Allergic fungal rhinosinusitis.

Allergic fungal rhinosinusitis (AFRS) is a subset of chronic rhinosinusitis with nasal polyps (CRSwNP) characterized by antifungal IgE sensitivity, eosinophil-rich mucus (ie, allergic mucin), and characteristic computed tomographic and magnetic resonance imaging findings in paranasal sinuses. AFRS develops in immunocompetent patients, with occurrence influenced by climate, geography, and several identified host factors. Molecular pathways and immune responses driving AFRS are still being delineated, but prominent adaptive and more recently recognized innate type 2 immune responses are important, many similar to those established in patients with other forms of CRSwNP. It is unclear whether AFRS represents merely a more extreme expression of pathways important in patients with CRSwNP or whether there are other disordered immune responses that would define a distinct endotype or endotypes. Although AFRS and allergic bronchopulmonary aspergillosis share some analogous immune mechanisms, the 2 conditions do not occur commonly in the same patient. Treatment of AFRS almost always requires surgical debridement of the involved sinuses. Oral corticosteroids decrease recurrence after surgery, but other adjunctive pharmacologic agents, including topical and oral antifungal agents, do not have a firm evidence basis for use. There is good rationale for use of biologic agents that target eosinophilic inflammation or other type 2 responses, but studies in patients with AFRS are required.

The spectrum of allergic fungal diseases of the upper and lower airways.

Fungi cause a wide spectrum of fungal diseases of the upper and lower airways. There are three main phyla involved in allergic fungal disease: (1) Ascomycota (2) Basidiomycota (3) Zygomycota. Allergic fungal rhinosinusitis (AFRS) causes chronic rhinosinusitis symptoms and is caused predominantly by Aspergillus fumigatus in India and Bipolaris in the United States. The recommended treatment approach for AFRS is surgical intervention and systemic steroids. Allergic bronchopulmonary aspergillosis (APBA) is most commonly diagnosed in patients with asthma or cystic fibrosis. Long term systemic steroids are the mainstay treatment option for ABPA with the addition of an antifungal medication. Fungal sensitization or exposure increases a patient's risk of developing severe asthma and has been termed severe asthma associated with fungal sensitivity (SAFS). Investigating for triggers and causes of a patient's asthma should be sought to decrease worsening progression of the disease.

Allergic bronchopulmonary aspergillosis.

There remains a lack of agreement on diagnostic criteria and approaches to treatment of patients with allergic bronchopulmonary aspergillosis (ABPA). The results of a survey of American Academy of Allergy, Asthma, & Immunology members regarding these 2 issues are presented and compared for concordance with published recommendations. The literature was reviewed for pertinent reports, and an electronic survey was conducted of American Academy of Allergy, Asthma, & Immunology members and fellows regarding diagnostic criteria, numbers of patients evaluated for ABPA, and treatment approaches. From 508 respondents to the survey sent to 5155 US physicians in the American Academy of Allergy, Asthma, & Immunology database of members and fellows, 245 health professionals (48%) had treated at least 1 patient with ABPA in the previous year. For the diagnosis of ABPA, there was a difference in the threshold concentration of total serum IgE because 44.9% used ≥417 kU/L, whereas 42.0% used ≥1000 kU/L. Analysis of these findings suggests that ABPA might be underdiagnosed. With regard to pharmacotherapy, oral steroids were recommended for 97.1% of patients and oral steroids plus inhaled corticosteroids plus antifungal agent were used with 41.2% of patients. The armamentarium for treatment of ABPA includes oral corticosteroids as the initial treatment with inhaled corticosteroids used for management of persistent asthma. Azoles remain adjunctive. Published experience with omalizumab has been limited.

Attitudes toward allergy: what do the pediatricians think?

BACKGROUND: In 1971, we published a survey regarding pediatricians' attitudes toward the field of allergy/immunology (A/I). Results indicated general attitudes and practices fell short of what most allergist-immunologists would hope. We revisited this in 1998 to determine how pediatricians' attitudes toward A/I had changed nearly 3 decades later. Despite some advances, results from 1998 revealed that A/I remained a misunderstood specialty. With the increasing incidence of atopic disorders and improving awareness of primary immunodeficiency, it is more important today than ever before that pediatricians and general practitioners have a strong appreciation for the scope of disorders the subspecialty of A/I encompasses. OBJECTIVE: To reevaluate attitudes and practices of pediatricians toward A/I 40 years after the initial study and 13 years after this topic was last addressed. METHODS: A 25-question survey was mailed to 293 pediatricians in the St Louis area. Surveys were completed confidentially. Pearson correlation and χ(2) analyses were performed. RESULTS: Of 293 pediatricians polled, 135 (46%) responded. Referrals to allergist-immunologists for urticaria have increased. Fewer pediatricians are referring asthma and atopic dermatitis patients to allergist-immunologists. Personal experience referring to an allergist-immunologist remains the greatest influence on current attitudes toward A/I. Prior exposure to A/I during medical education continues to have the least influence on pediatricians' attitudes toward A/I. CONCLUSION: Increased appropriate referrals and improved patient outcomes could result from efforts to enhance A/I education during medical school and residency, maintain effective communication with referring physicians, and break down referral barriers to improve physicians' attitudes toward A/I.

Chronic bilateral pruritic arm dermatitis in a 61-year-old woman.

A 61-year-old woman presented to our Allergy/Immunology clinic for pruritic dermatitis of both arms since 2006. Initial symptoms included pruritus and burning dysesthesias of the upper extremities without a rash. Months later an excoriated, papular rash developed along the upper extremities. Cold compresses provided some relief, whereas sun exposure worsened symptoms. Over the years consultations with multiple dermatologists did not elicit a diagnosis, and symptoms did not improve after numerous trials of topical corticosteroids and systemic antihistamines. The differential diagnosis of pruritic rash is extensive; however, in the case of chronic pruritus without a primary rash other diagnoses should come to mind. Although pruritus is a hallmark of many atopic conditions, as allergists-immunologists it is important to remember that not all pruritus is atopic in nature. Prompt recognition and treatment of an occult process presenting primarily with pruritus will likely result in improved outcomes for the patient.

Fungi and allergic lower respiratory tract diseases.

Asthma is a common disorder that in 2009 afflicted 8.2% of adults and children, 24.6 million persons, in the United States. In patients with moderate and severe persistent asthma, there is significantly increased morbidity, use of health care support, and health care costs. Epidemiologic studies in the United States and Europe have associated mold sensitivity, particularly to Alternaria alternata and Cladosporium herbarum, with the development, persistence, and severity of asthma. In addition, sensitivity to Aspergillus fumigatus has been associated with severe persistent asthma in adults. Allergic bronchopulmonary aspergillosis (ABPA) is caused by A fumigatus and is characterized by exacerbations of asthma, recurrent transient chest radiographic infiltrates, coughing up thick mucus plugs, peripheral and pulmonary eosinophilia, and increased total serum IgE and fungus-specific IgE levels, especially during exacerbation. The airways appear to be chronically or intermittently colonized by A fumigatus in patients with ABPA. ABPA is the most common form of allergic bronchopulmonary mycosis (ABPM); other fungi, including Candida, Penicillium, and Curvularia species, are implicated. The characteristics of ABPM include severe asthma, eosinophilia, markedly increased total IgE and specific IgE levels, bronchiectasis, and mold colonization of the airways. The term severe asthma associated with fungal sensitization (SAFS) has been coined to illustrate the high rate of fungal sensitivity in patients with persistent severe asthma and improvement with antifungal treatment. The immunopathology of ABPA, ABPM, and SAFS is incompletely understood. Genetic risks identified in patients with ABPA include HLA association and certain T(H)2-prominent and cystic fibrosis variants, but these have not been studied in patients with ABPM and SAFS. Oral corticosteroid and antifungal therapies appear to be partially successful in patients with ABPA. However, the role of antifungal and immunomodulating therapies in patients with ABPA, ABPM, and SAFS requires additional larger studies.

Allergic bronchopulmonary aspergillosis in asthma and cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a Th2 hypersensitivity lung disease in response to Aspergillus fumigatus that affects asthmatic and cystic fibrosis (CF) patients. Sensitization to A. fumigatus is common in both atopic asthmatic and CF patients, yet only 1-2% of asthmatic and 7-9% of CF patients develop ABPA. ABPA is characterized by wheezing and pulmonary infiltrates which may lead to pulmonary fibrosis and/or bronchiectasis. The inflammatory response is characterized by Th2 responses to Aspergillus allergens, increased serum IgE and eosinophilia. A number of genetic risks have recently been identified in the development of ABPA. These include HLA-DR and HLA-DQ, IL-4 receptor alpha chain (IL-4RA) polymorphisms, IL-10-1082GA promoter polymorphisms, surfactant protein A2 (SP-A2) polymorphisms, and cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations. The studies indicate that ABPA patients are genetically at risk to develop skewed and heightened Th2 responses to A. fumigatus antigens. These genetic risk studies and their consequences of elevated biologic markers may aid in identifying asthmatic and CF patients who are at risk to the development of ABPA. Furthermore, these studies suggest that immune modulation with medications such as anti-IgE, anti-IL-4 and/or IL-13 monoclonal antibodies may be helpful in the treatment of ABPA.

Distinctions between allergic fungal rhinosinusitis and chronic rhinosinusitis.

BACKGROUND: Recent reports have attempted to redefine the accepted diagnostic criteria for allergic fungal rhinosinusitis (AFRS), a form of chronic rhinosinusitis (CRS) with nasal polyps. As a result, the existence of AFRS as a distinct entity has been questioned, suggesting that allergy has no role in CRS with sinonasal eosinophilia, and the condition should be referred to as eosinophilic fungal rhinosinusitis. The purpose of the study was to differentiate between AFRS and CRS by studying antibody responses in these two clearly defined patient groups. METHODS: Ninety-nine patients were enrolled and classified as AFRS or CRS (without AFRS). Serum total IgE, IgG anti-Alternaria-specific antibodies (UniCAP 100), and IgE antifungal antibodies (immunoblotting) were compared between the groups. RESULTS: Sixty-four patients fit the traditional criteria for AFRS, with 35 as CRS. Mean serum total IgE and mean IgG anti-Alternaria-specific antibodies were statistically significantly increased in AFRS over CRS patients. There was also a statistically significant increase in the mean number of IgE antifungal bands from AFRS compared with CRS patients. CONCLUSION: We have shown a clear immunologic difference between AFRS and CRS patients. The overwhelming evidence of increased total IgE and fungal-specific IgE in AFRS supports an allergic component in AFRS. IgG anti-Alternaria-specific antibodies also point to an exaggerated fungal immune response in these patients. These results support the existence of AFRS as a separate, distinct entity of CRS. It is important to recognize AFRS to ensure proper treatment in these patients.

Special considerations in treatment of allergic rhinitis in the elderly: role of intranasal corticosteroids.

Once viewed as a "young person's disease," allergic rhinitis (AR) is becoming increasingly common in the elderly. Effective treatment is necessary not only to minimize the impact of AR in the older population, but to prevent the onset or exacerbation of asthma. This review was conducted to examine the clinical evidence regarding the efficacy and safety of therapies for AR in the elderly. MEDLINE searches of the literature were performed to identify key consensus statements, expert opinions, and clinical trials related to the management of AR in older individuals. The selection of treatment for elderly patients with AR must consider age-dependent physiologic factors (such as metabolic alterations, changes in the nasal mucosa, difficulty swallowing, and visual or motor problems) that may affect responses to therapy. Both first- and second-generation antihistamines are associated with a higher incidence of adverse events and drug:drug interactions in older than younger individuals, and oral decongestants pose risks in the presence of a variety of comorbidities known to be more common in the elderly. Leukotriene receptor antagonists are as effective as antihistamines, but are inferior to intranasal corticosteroids and have the potential for interactions with a wide range of drugs. Intranasal corticosteroids have the most favorable safety and efficacy profiles in older individuals with AR. The diagnosis and management of AR in the elderly require approaches tailored to specific age-related factors. Based on the available evidence, intranasal corticosteroids offer the best option for the treatment of older patients with AR.

Update on occupational rhinitis and asthma.

The workplace is emerging as an increasingly important venue for the development of rhinitis and asthma. There is no question that allergic diseases of the respiratory tract caused by occupational exposure are on the increase. The clinician's diagnostic index of suspicion must be high so that a diagnosis of occupational rhinitis and/or asthma can be made in a timely fashion. Altering the environment of the workplace or removing the patient from that workplace may spare the patient permanent damage.

Treating rhinitis in the older population: special considerations.

Rhinitis in the elderly is a common but often neglected condition. Structural changes in the nose associated with aging, predisposes the elderly to rhinitis. There are a number of specific factors that affect medical treatment of the elderly including polypharmacy, cognitive dysfunction, changes in body composition, impairment of liver and renal function and the cost of medications in the face of limited resources. Rhinitis in the elderly can be placed in several categories and treatment should be appropriate for each condition. The most important aim is to moisten the nasal mucosa since the nose of the elderly is so dry. Great caution should be used in treatment with first generation antihistamines and decongestants. Medications generally well tolerated by the elderly are second generation antihistamines, intra-nasal anti-inflammatory agents, leukotriene modifiers and iprapropium nasal spray.

Criteria to screen for chronic sinonasal disease.

BACKGROUND: Sinusitis and rhinitis are associated with uncontrolled asthma. There are no simple, validated tools to screen for these diseases. The objective of this study was to assess instruments to assist in the diagnosis of chronic sinonasal disease. METHODS: Participants without acute sinonasal symptoms underwent an extensive evaluation. The results were submitted to an expert panel that used the Delphi method to achieve consensus. Using the consensus diagnosis of the panel, we determined the sensitivity and specificity of test procedures to diagnose chronic sinonasal disease. We determined the reproducibility of the most sensitive and specific instrument in a separate cohort. RESULTS: Fifty-nine participants were evaluated, and the expert panel reached consensus for all (42 participants with chronic sinonasal disease, 17 participants without chronic sinonasal disease). A six-item questionnaire based on the frequency of nasal symptoms was the most sensitive tool used to diagnose sinonasal disease (minimum specificity, 0.90). Reproducibility testing in a separate cohort of 63 participants (41 chronic sinonasal disease with asthma, 22 chronic sinonasal disease without asthma) showed a concordance correlation coefficient of 0.91 (95% CI, 0.85 to 0.94) when this questionnaire was limited to five items (ie, excluding a question on smell). This five-item questionnaire had a sensitivity of 0.90 (95% CI, 0.77 to 0.97), a specificity of 0.94 (95% CI, 0.71 to 1.00), and an area under the receiver operating characteristic curve of 0.97 (95% CI, 0.93 to 1.0). Sinus CT scans and nasal endoscopy lacked sensitivity for use in the diagnosis of chronic sinonasal disease. CONCLUSIONS: We have developed a sensitive, specific, and reproducible instrument to screen for chronic sinonasal disease. Validation studies of this five-item questionnaire are needed, including in patients with asthma.

Asthma symptom re-emergence after omalizumab withdrawal correlates well with increasing IgE and decreasing pharmacokinetic concentrations.

BACKGROUND: Physicians have questioned whether omalizumab can be discontinued or the dose reduced after clinical improvement is seen in patients with severe asthma. OBJECTIVES: To examine the relationships among omalizumab, free IgE, and clinical outcomes in a randomized, placebo-controlled trial in patients with severe persistent allergic asthma following a posology based on pretreatment total IgE and body weight. METHODS: A pharmacokinetic-pharmacodynamic binding model was used to calculate free IgE, omalizumab, and total IgE concentrations during the 28-week treatment and 16-week follow-up of the INvestigation of Omalizumab in seVere Asthma TrEatment (INNOVATE) study. These were plotted against the mean changes in the total asthma symptom score, morning peak expiratory flow, and rescue medication use for physician-defined treatment responders and nonresponders. RESULTS: The model accurately fitted omalizumab and free and total IgE, allowing reconstruction of the entire time course for each patient. Free IgE was rapidly suppressed below the 50 ng/mL (20.8 IU/mL) target, although there was a notable period before clinical measures stabilized. After treatment cessation, free IgE and omalizumab returned toward baseline and, after a delay, asthma symptoms re-emerged. Model-derived omalizumab and free IgE concentrations correlated well with changes in clinical outcomes, particularly in omalizumab-treated responders. Asthma symptoms exhibited different correlations during response onset compared with response offset (hysteresis), indicative of physiological time delays between changes in IgE levels and pulmonary function. CONCLUSION: Omalizumab and free IgE correlated well with clinical symptoms. Reducing omalizumab doses below those in the dosing table cannot be recommended; the resulting increase in free IgE would cause a deterioration in asthma control.

Are fish oil supplements safe in finned fish-allergic patients?

Fish oil supplements are popular alternative medicines. Many manufacturers label their products with the warning "avoid this product if you are allergic to fish." The objective of this study was to determine if finned fish (FF)-allergic patients could safely tolerate fish oil supplements. Six FF-sensitive subjects as determined by history and skin testing were selected. They were skin tested with two different fish oil supplements and given an oral challenge of each supplement 1 hour apart. Vital signs were measured at baseline and at 20-minute intervals after each challenge. Spirometry was measured at baseline and 1 hour after each challenge. Six of six patients with positive skin tests to at least one FF had negative skin tests to both fish oil supplements. All six subjects then had negative oral challenges to both supplements. In this pilot study, FF-sensitive patients tolerated fish oil supplements.

The tale of the allergist's life: a series of interesting case reports.

The practicing allergist has the unique opportunity to see an extraordinary variety of fascinating patients. Identifying the precise cause of the patient's complaints makes for a satisfying intellectual endeavor. This is exemplified by the description of nine cases seen in a university allergy clinic. The cases include uncommon pets such as monkey, hedgehog, and iguana; occupational allergens such as slime mold and nematodes; household exposure to spider and lady bugs; and recreational exposure to earthworms and algae. Instituting environmental control measures results in a gratifying response in the patient.

Seafood allergy and radiocontrast media: are physicians propagating a myth?

BACKGROUND: Recent surveys have indicated that the misconception that seafood allergy confers a disproportionately increased risk of adverse reactions to radiocontrast media remains pervasive among physicians and patients. One possible explanation for the persistence of this notion is that physicians responsible for radiocontrast administration are inadvertently contributing to its propagation. METHODS: An anonymous survey was sent to 231 faculty radiologist and interventional cardiologists at 6 Midwest academic medical centers. Two questions dealt directly with seafood allergy related to radiocontrast media administration, and 6 questions served as distracters. RESULTS: Sixty-nine percent of responders indicated that they inquire about a history of seafood allergy before radiocontrast media administration. Some 37.2% of responders replied that they would withhold radiocontrast media or recommend premedication on the basis of a history of seafood allergy. CONCLUSION: Even among faculty physicians at university medical centers, the notion of seafood allergy as a significant risk factor for adverse radiocontrast media reactions remains pervasive. Even if no action is taken on the basis of the answer, it seems probable that the act of inquiring about seafood allergy before radiocontrast media administration could lead patients and trainees to presume an inherent risk in patients who are seafood allergic, thus propagating the notion. Physician education with respect to seafood allergy and radiocontrast media administration is vital to halting the persistence of this misconception.