Letter to the Editor Regarding Eosinophilic Otitis Media.

We commend Varghese et al. for "mandating a different outlook" in their recent article on eosinophilic otitis media (EOM). Their statements are supported by medical literature dating back to 1931, reported by Proetz, Shambaugh, Zhang, Draper, Doyle, Pelikan, Ojala, McMahan, Tomonaga, Nsouli, Lasisi, Nguyen, Tian, Sobol, Smirnova, Shim, Smirnova, Luong, and ourselves. Allergy causes EOM and it responds to immunotherapy.

Clinical Relevance and Advantages of Intradermal Test Results in 371 Patients with Allergic Rhinitis, Asthma and/or Otitis Media with Effusion.

BACKGROUND: We evaluated the value of positive intradermal dilution testing (IDT) after negative skin prick tests (SPT) by retrospectively determining allergy immunotherapy (AIT) outcomes. METHODS: This private practice, cohort study compared the relative value of SPT vs. IDT in 371 adults and children with suspected manifestations of allergy: chronic allergic rhinitis (AR), asthma and/or chronic otitis media with effusion (OME). The primary outcome measure was symptom resolution following immunotherapy, as determined by symptom severity questionnaires completed by patients before and after AIT. RESULTS: Positive IDT identified 193 (52%) patients who would not otherwise have been diagnosed. IDT detected 3.7-fold more allergens per patient than SPT (8.56 vs. 2.3; p < 0.01). Patients positive only on IDT responded to AIT equally well as those identifiable by SPT, independent of allergen sensitivity (67% by SPT vs. 62% by IDT; p = 0.69, not significantly different). CONCLUSION: Intradermal titration can identify patients who will benefit from allergy immunotherapy more accurately than SPT. Outcomes analysis in 371 patients shows that IDT doubled their chance of successful treatment with no greater risk of therapeutic failure. Positive IDT, following negative SPT, is clinically relevant and offers superior sensitivity over SPT for detecting allergens clinically relevant to diagnosis of AIT-responsive atopic disease.

Intradermal Testing Doubles Identification of Allergy among 110 Immunotherapy-Responsive Patients with Eustachian Tube Dysfunction.

The purpose of this study was to determine whether the sensitivity advantage of intradermal dilutional testing (IDT) is clinically relevant in patients with obstructive Eustachian tube dysfunction (ETD) or otitis media with effusion (OME). This retrospective, private-practice cohort study compared the sensitivity of skin prick tests (SPT) vs. IDT in 110 adults and children with suspected allergy and OME. Primary outcome measure was symptom resolution from allergy immunotherapy (AIT). IDT identified 57% more patients as being allergic, and 8.6 times more reactive allergens than would have been diagnosed using only SPT. Patients diagnosed by IDT had the same degree of symptom improvement from immunotherapy, independent of allergen sensitivity (66% by SPT vs. 63% by IDT; p = 0.69, not different). Low-sensitivity allergy tests, which may fail to identify allergy in over two thirds of children aged 3 to 15 as being atopic, or among 60% of patients with ETD, may explain why many physicians do not consider allergy as a treatable etiology for their patient's OME/ETD. IDT offers superior sensitivity over SPT for detecting allergens clinically relevant to treating OME/ETD. These data strongly support increased utilization of intradermal testing and invite additional clinical outcome studies.

The Relation of Allergy to Eustachian Tube Dysfunction and the Subsequent Need for Insertion of Pressure Equalization Tubes.

INTRODUCTION: The most basic question to be answered in each case in which the choice of using a pressure equalization tube (PET) is being considered is: "what is the underlying pathophysiology of the middle ear disease being addressed?" METHODS: We will evaluate the hypothesis that the Eustachian Tube (ET) may become "dysfunctional" due to allergic mucosal edema and obstruction. We review the literature that evaluates the role of ET, the proposed affect that allergy may contribute to ET dysfunction (ETD), and the relation of allergic rhinitis to otitis. RESULTS: Proof that allergy affects the middle ear was supported by (1) over a dozen investigators using objective immunotherapy demonstrating over the past 70 years that 72% to 100% of the children with otitis media with effusion (OME) are atopic, (2) an association of allergic Th2 immune-mediated histochemical reactivity within the target organ itself, (3) establishment that inflammation within the middle ear is truly allergic in nature, and (4) direct evidence of a dose-response curve and consistency of results, which confirm that OME resolves on allergy immunotherapy. CONCLUSION: Current medical evidence should heighten the awareness of physicians of the physiology that underlies ETD. The evidence supports the link between allergy and OME. The middle ear behaves like the rest of the respiratory tract, and what has been learned about the atopic response in the sinuses and lungs may be applied to the study of the immunologic mechanisms within the middle ear that lead to ETD requiring the use of PET.

Safety of intradermal skin tests for inhalants and foods: a prospective study.

BACKGROUND: Intradermal skin testing is a useful allergy diagnostic tool. Although considered safe when properly performed, systemic reactions have been reported. This is the first large, prospective study to record and evaluate all systemic reactions from intradermal skin testing (IDT) to inhalant or food antigens. METHODS: A 24-month prospective study by 40 physician practices, recording all IDT tests, including reactions, symptoms, severity, time after injection, and reaction treatments. RESULTS: Eighty systemic reactions (22 major) occurred among 20,530 patients (878,583 wheals). Nine had epinephrine treatment, 4 were observed in an emergency department, and there were no hospitalizations or fatalities. The overall systemic reaction risk was 0.009%. The risk of having a major reaction was 0.003%, or 1 reaction per 933 patients. CONCLUSION: Intradermal skin tests for inhalants or foods, when performed with appropriate precautions, have a safety profile comparable to skin prick tests.

The role of allergy in otitis media with effusion.

The role of allergy in chronic otitis media with effusion (OME) is controversial. New evidence from cellular biology and immunology explain the basics of allergic reactions and allow more accurate diagnosis of allergies and inflammatory disease throughout the unified airway. This article examines the epidemiologic, methodological, and immunologic studies of allergic causes of OME, including (1) evidence for and against OME as an allergic disease, (2) allergy as a cause for eustachian tube obstruction, (3) examination of the most sensitive diagnostic tests for allergy, and (4) the effect of treatment of underlying allergies in improving and resolving middle ear disease.

Efficacy of allergy immunotherapy as a treatment for patients with chronic otitis media with effusion.

OBJECTIVE: Controversy persists over the significance of allergy as it might relate to chronic middle-ear disease as no controlled study of the efficacy of allergy immunotherapy has been published. The aim of this study was (1) to evaluate the atopic status of patients with intractable chronic otitis media with effusion or drainage from their middle ear and (2) to determine in this select population the efficacy of specific allergy immunotherapy in preventing or limiting the duration of their chronic middle-ear disease. METHODS: This was a prospective, cohort study of patients cared for in a private community practice. History, examination, audiogram, tympanometry and recurrence of effusion/infection were recorded on 89 patients (52 children <15 years old, 37 adults) referred with (1) effusion found to warrant myringotomy and ventilation tubes, or (2) chronic drainage from a perforation or tube. All were evaluated for allergy by intradermal skin testing according to criteria of the American Academy of Otolaryngic Allergy. A control cohort of 21 patients who refused therapy was included. Intervention consisted of immunotherapy for dust, pollen, and molds. Recurrence or persistence of fluid or drainage following 2-8 years of therapy was compared to the patient's pretreatment status. RESULTS: All 89 OME patients proved to be atopic. Most were allergic to dust (94%), animals (44%) and molds (88%) while 9% were allergic only to seasonal pollens. Associated allergic diseases included asthma (21%) and allergic rhinitis/sinusitis (63%). Otitis was the sole symptom among 37%. Immunotherapy provided complete resolution of effusion or drainage in 85% of 127 ears. CONCLUSION: Intradermal testing proved all 89 patients with intractable middle-ear disease in this study who presented with chronic effusion or chronic draining perforations or tubes to be atopic. Specific allergy immunotherapy significantly improved 5.5% and completely resolved 85% of chronic otitis media with effusion in these ears. None of the controls resolved spontaneously (p<0.001). This supports the hypothesis that in many, otitis media with effusion is an immune mediated allergic disease and suggests that these patients deserve consideration for aggressive evaluation and allergy treatment, as most respond to immunotherapy.

The importance of glycerin-containing negative control tests in allergy research studies that use intradermal skin tests.

OBJECTIVE: We sought to assess skin whealing with glycerin-containing control injections for intradermal skin tests. DESIGN: Observational. METHODS: Wheal sizes were measured at 0, 10, and 15 minutes after intradermal injection of 0.01 and 0.02 mL of phenolated normal saline and 0.5% and 5% concentrations of glycerin in the same quantity of phenolated saline. RESULTS: Intradermal injection of 0.01 mL of phenolated saline produced an average 4.9-mm wheal, which expanded to 5.2 mm at 10 minutes and to 6.0 mm at 15 minutes. Intradermal injection of 0.02 mL of phenolated saline produced a 6.4-mm wheal, which expanded to 7.0 mm at 10 minutes and 8.0 mm at 15 minutes. The addition of glycerin produced proportionally larger wheals. CONCLUSIONS: Because glycerin increases whealing beyond that with phenolated saline, skin tests containing glycerin must be compared with glycerin-containing negative controls. Intradermal skin tests that fail to compare findings in this manner contain an inherent methodologic flaw and are uninterpretable.

The impact of atopy on neutrophil activity in middle ear effusion from children and adults with chronic otitis media.

OBJECTIVE: To identify the relationship of neutrophil activity to allergy as reflected by the level of myeloperoxidase (MPO) in ears of atopic patients with chronic otitis media with effusion (OME) by objective testing. DESIGN: Evidence of neutrophils was measured in the effusion of atopic patients with chronic OME. Atopy was determined by intradermal and/or in vitro testing of allergic reaction to 10 inhalants, 2 molds, and 5 foods. SUBJECTS: Effusion MPO was measured prospectively in 138 ears from 106 consecutive patients with chronic OME. RESULTS: A total of 86 (81%) of 106 patients with OME tested atopic by in vitro or in vivo testing. Excluding 36 ears with purulence, the mean MPO level was 3132 microg/L in 84 atopic vs 142 microg/L in 18 nonatopic ears (P<.001). A total of 78 (90%) of 87 patients with OME were atopic. CONCLUSIONS: The surprising finding of marked elevation of effusion MPO in atopic patients but very low levels in nonatopic patients (P < .001) suggests that atopy may contribute to elevated levels of neutrophil activity in OME. An atopic patient may respond differently from a nonatopic one to the microbial or viral products of acute inflammation owing to the presence of primed inflammatory cells. This study provides confirmation on a cellular level that neutrophils are an integral part of the inflammatory process in OME to a disproportionate degree among atopic patients.