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.

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.

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.

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.

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.

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.

Allergic contact dermatitis.

The pathophysiology of ACD follows an intricate design and results in the characteristic, delayed inflammatory response. Although the astute physician may correctly diagnose ACD from its initial, classic history and presentation, alternative diagnoses should be considered and excluded. Patch testing performed with a relevant panel of contact allergens is the ultimate confirmatory test of ACD. Correctly identifying the inciting allergen permits appropriate personal avoidance. Corticosteroids remain the principal treatment options.

Rhinosinusitis: Developing guidance for clinical trials.

The Rhinosinusitis Initiative was developed by 5 national societies. The current guidance document is an expansion of the 2004 publication, "Rhinosinusitis: Establishing definitions for clinical research and patient care" and provides templates for clinical trials in antimicrobial, anti-inflammatory, and symptom-relieving therapies for the following: (1) acute presumed bacterial rhinosinusitis, (2) chronic rhinosinusitis (CRS) without nasal polyps, (3) CRS with nasal polyps, and (4) classic allergic fungal rhinosinusitis. In addition to the templates for clinical trials and proposed study designs, the Rhinosinusitis Initiative has developed 6 appendices, which address (1) health outcomes, (2) nasal endoscopy and staging of CRS, (3) radiologic imaging, (4) microbiology, (5) laboratory measures, and (6) biostatistical methods.

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.

Rhinosinusitis and pediatric asthma.

Rhinosinusitis is a common disease in patients of all age groups. Rhinosinusitis arises from a variety of infectious and inflammatory mechanisms. There is ample evidence that rhinosinusitis can directly influence asthma. There is also growing evidence that rhinosinusitis may be associated with asthma as different manifestations of the same disorder. A great deal of future research is required to fully elucidate the different mechanisms whereby rhinosinusitis influences or associates with asthma, but it is clear that rhinosinusitis needs to be considered in patients with severe or refractory asthma.

MHC restriction in allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a rare complication in patients with asthma but more common in patients with cystic fibrosis. In the presence of the fungus Aspergillus fumigatus (Af) in the lower respiratory tract, patients mount a heightened IgG and IgE humoral response specific for Af antigens. Studies on ABPA have suggested a pathogenic role for antigen specific CD4+ Th2 like T lymphocytes producing increased levels of IL-4 and IL-5. MHC class II genes coding for highly polymorphic HLA molecules have been shown to be the likely candidates for controlling immune responses to common allergens. However there has been a lack of information on the pathophysiological role of HLA genes in the development of ABPA. This review describes an association between HLA- class II alleles and the specific responses to Af antigen (Asp f 1) in ABPA. These studies focused on MHC restriction and distribution of HLA- class II alleles in two groups of unrelated North American Caucasian patients with cystic fibrosis and/or asthma. One group consisted of patients with a confirmed diagnosis of ABPA and a second group of patients with Af sensitivity but no ABPA. HLA association studies revealed that the predisposition to develop ABPA is associated with HLA-DR2 and DR5, and possibly DR4 or DR7. A strong association of HLA-DR antigens with ABPA reflects that HLA-DR molecules may present disease-causing peptides. On the other hand a significant association of HLA-DQ2 with Af sensitive nonABPA indicates the involvement of HLA-DQ molecules in protection. A combination of these genetic factors determines the outcome of ABPA in patients with cystic fibrosis and asthma.

T-cell receptor bias in patients with allergic bronchopulmonary aspergillosis.

CD4(+) Th2 helper cell mediated immune responses have been shown to play a crucial role in the pathogenesis of ABPA. HLA and TCR are the candidate genes, which can influence the specificity of these responses. We have previously established a strong association of HLA DR2/5 in ABPA susceptibility. The study was designed to determine whether allergen specific T cell express a limited usage of T cell receptor (TCR) Vbeta gene repertoire in ABPA and to find an association of susceptible HLA-DR determinants with the identified TCR gene segments. TCR Vbeta typing was performed on antigen specific T cell lines from 14 ABPA and 12 nonABPA patients. The majority of ABPA patients (86%) expressed allergen specific T cells with Vbeta13 genes indicating its role in susceptibility, whereas in nonABPA controls, Vbeta1 genes T cell repertoires were predominantly expressed. The unrestricted pattern of Vbeta gene amplification seen before antigen stimulation suggests an oligoclonal expansion of a specific T cell population in response to the allergen Asp f 1 in ABPA and nonABPA patients. The increased usage of Vbeta13 in ABPA and Vbeta1 in nonABPA indicates their importance in susceptibility and resistance, respectively.

Occupational rhinitis.

This article aims to define occupational rhinitis, classify its various causes, review the steps in its diagnosis, and describe its nonpharmacologic and pharmacologic principles of management. Occupational rhinitis frequently coexists with asthma but also occurs alone. Although it does not have the same impact as occupational asthma, occupational rhinitis causes distress, discomfort, and work inefficiency. By concentrating on the patient's workplace, the clinician has an opportunity to practice preventive medicine: to recognize substances in the patient's micro- and macroenvironment that are causing the problems and then to intervene by altering the environment or removing the patient from the environment.

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.