Allergic fungal sinusitis: the role of immunotherapy.

The role of surgery and anti-inflammatory therapy (such as corticosteroids) in the management of allergic fungal sinusitis is accepted fairly universally. Although once thought to be contraindicated in the treatment of allergic fungal sinusitis, specific immunotherapy with fungal antigens has been shown to be extremely beneficial to these patients, when combined with surgery and adjunctive medical management. Recurrences have been prevented and systemic corticosteroid requirements virtually eliminated in an experience that now spans over 4 years.

Outcomes after discontinuing immunotherapy for allergic fungal sinusitis.

Although the treatment of allergic fungal sinusitis with specific immunotherapy after surgical intervention has proved successful, the question of what happens when such injections are discontinued remains unanswered. In this initial, admittedly small series, no recurrence has been noted in follow-up of 7 to 17 months.

Mold testing by RAST and skin test methods in patients with allergic fungal sinusitis.

RAST tests have traditionally been considered less sensitive than skin tests during investigation of atopy involving molds. This has been attributed to technical problems such as difficulty in binding the mold antigen to the carrier substrate. Ten patients with proven allergic fungal sinusitis were evaluated for sensitivity to 11 important molds by both RAST and dilutional intradermal testing. A predictable correlation between RAST and skin test scores was observed in many, but not all, cases. Most often this disparity was in the form of greater sensitivity indicated by skin testing than by RAST, sometimes differing by as many as 3 classes. The lack of concordance was not confined to testing for the fungi cultured from the sinuses, nor was it more or less pronounced in the case of dematiaceous fungi. The most likely causes for the disparity noted in this series are subtle differences in antigens used in skin test material and for RAST standards. Skin tests allow for evaluation of delayed and late-phase reactions, a measurement not possible by specific IgE testing with RAST. Delayed skin test reactions were not noted in this series of patients. An additional important finding was the sensitivity of patients with allergic fungal sinusitis to virtually every fungal antigen to which they were tested.

Electrocochleographic changes after intranasal allergen challenge: A possible diagnostic tool in patients with Meniere's disease.

Numerous observers have suggested a relationship between allergy and Meniere's disease, but objective proof has heretofore been limited. Using standard criteria, we studied a group of 7 patients with previously diagnosed Meniere's disease in whom significant allergy to 1 or more inhalants had also been diagnosed. Patients underwent a baseline electrocochleographic study followed by intranasal challenge with a carefully quantified amount of the allergen to which they were most sensitive. This was followed by a second electrocochleogram. Four of the 7 patients demonstrated at least a 15% increase in the summating potential/action potential ratio in 1 ear, associated with the production of subjective inner ear symptoms. We present this protocol as a potentially useful tool to further study whether inhalant allergy may be a causative factor in patients with Meniere's disease.

Immunotherapy for allergic fungal sinusitis: three years' experience.

Since August 1994, we have treated patients with histologically proven allergic fungal sinusitis with surgery followed by immunotherapy, employing fungal and nonfungal antigens to which hypersensitivity has been demonstrated. Our results continue to be encouraging. Not only have we encountered no indication that fungal immunotherapy has worsened these patients' condition or caused a recurrence of disease, we have confirmed dramatic improvement in these patients compared with the generally accepted course of this disease. Of 11 patients who have received immunotherapy for 1 to 3 years (mean 28 months), none has required regular or frequent treatment with a single brief course of systemic steroids, and only three are receiving topical nasal steroids. No repeat surgeries for recurrent allergic fungal sinusitis have been required in the treatment group. This combination of surgery and immunotherapy has continued to prove beneficial, and we urge others to consider this approach to therapy.

Treatment of allergic fungal sinusitis: a comparison trial of postoperative immunotherapy with specific fungal antigens.

OBJECTIVE: To determine the effect of immunotherapy (IT) with fungal antigens on clinical outcome in patients with allergic fungal sinusitis (AFS). STUDY DESIGN: Prospective case control. METHODS: In this comparison study, 22 patients meeting the diagnostic criteria of allergic fungal sinusitis (AFS) were evaluated after a mean of 33 months' therapy. All received similar treatment consisting of endoscopic sinus surgery, corticosteroids, and antibiotics as needed for complicating purulent sinusitis. Eleven patients received postoperative immunotherapy (IT) with fungal and nonfungal antigens to which sensitivity had been demonstrated, while the remaining 11 received no immunotherapy. RESULTS: The effect of IT was to significantly improve patient outcome as assessed objectively by an AFS endoscopic mucosal staging system (P < .001) and a sinusitis-specific quality-of-life scale, the Chronic Sinusitis Survey (P = .002). In addition, IT was shown to reduce reliance on systemic (P < .001) and topical nasal (P = .043) corticosteroid therapy to control disease. Follow-up was similar in the two groups and was not a determinant of differences in outcome (P = .7). CONCLUSIONS: Results from this study indicate that specific IT with fungal antigens improves patient outcome in AFS.

Comparison of Multi-Test device skin testing and modified RAST results.

The initial purpose of this study was to determine the potential correlation between allergy test results obtained with the Multi-Test skin testing method and the radioallergosorbent test (RAST) blood test (used as a "standard"). Twenty patients with a history and physical examination findings suggestive of inhalant allergy underwent both a Multi-Test system screen (14 antigens plus histamine and glycerine controls) and RAST testing. The relationship between wheal size and Multi-Test system grade for each antigen and the corresponding RAST class was studied. The correlation between positive Multi-Test system and RAST results was poor, with an average agreement by antigen of 56.26% and overall agreement of 67.86%. However, the overall agreement between negative Multi-Test system results (< or =1+) and negative RAST results (< or =class 1) was 95.15%, with an average agreement by antigen of 83.99%. On the basis of results of this preliminary study, it appears that a negative Multi-Test system result indicates that significant inhalant allergy is unlikely, whereas a positive Multi-Test system result necessitates follow-up with more definitive testing by additional skin testing or RAST.

Immunotherapy for allergic fungal sinusitis: the second year.

Since August 1994 we have followed a protocol of treating patients with histologically proven allergic fungal sinusitis with surgical extirpation of the involved sinuses, followed by immunotherapy using both fungal and nonfungal antigens to which hypersensitivity is demonstrated by in vitro and skin testing methods. Despite predictions to the contrary, we have encountered no evidence that these injections have worsened the condition of any patients. Rather, we have noted a marked decrease in nasal crusting in all patients, with a minimum amount of recurrent polypoid mucosa and a lessened or absent requirement for corticosteroids (systemic or topical). Two patients treated with immunotherapy required systemic corticosteroids and subsequent revision surgery for residual disease that was present before the start of immunotherapy, and they have done well since. Our experience indicates that the triad of adequate surgery, frequent follow-up and medical management, and immunotherapy with relevant fungal and nonfungal antigens represents an effective means of treating patients with allergic fungal sinusitis. Nevertheless, an even longer period of study will be necessary to provide the final answer regarding the role of immunotherapy in the treatment of allergic fungal sinusitis.

Quality of life analysis of patients undergoing immunotherapy for allergic rhinitis.

Allergic rhinitis has been conservatively estimated to affect 35 million Americans, with an annual US expenditure of more than $2 billion for treatment. Immunotherapy is generally administered to patients with allergic rhinitis when avoidance is impossible or impractical, when pharmacotherapy provides insufficient relief, and/or symptoms span more than one season. Immunotherapy based on quantified testing (e.g., dilutional intradermal testing [SET] or in vitro methods [RAST, ELISA]) allows administration of antigens in a manner that achieves therapeutic antigen doses more rapidly, yet more safely than immunotherapy administered through a schedule that mixes all antigens at the same concentration and advances on an empirical basis. Sixty patients who received at least one year of quantified testing-based immunotherapy were evaluated using a quality of life questionnaire and individual interviews. Changes in physical, social and emotional well-being were determined. Also investigated were changes in productivity and medication usage. The majority of patients noted significant improvement in all areas within four to six months of initiating immunotherapy, and an overwhelming majority felt that such treatment represented a worthwhile investment of their time and money.

The screening RAST: is it a valid concept?

Dr. William King in 1982 advocated the use of a "miniscreen" panel of six antigens to cost-effectively initiate allergy testing. In a study of 100 consecutive patients, we found that a "midiscreen" of nine antigens was more sensitive and efficient and more accurately identified negative responders. However, the miniscreen was also effective if adjusted for regional antigen differences.

Immunotherapy in the treatment of allergic fungal sinusitis.

Recommendations to withhold immunotherapy with fungal antigens from patients with allergic fungal sinusitis (AFS) have been based primarily on retrospectively reviewed, anecdotal case reports and theoretical considerations. A study that was approved by the investigational review board of our institution is ongoing in our department to administer immunotherapy with relevant fungal antigens to patients with histologically proven AFS. After 1 year, no instances of worsening of symptoms as a result of this therapy have been observed. Objective measurement of improvement has been difficult, but our initial clinical impression is that this treatment regimen has resulted in significant reduction in the reaccumulation of crusts and allergic mucin within the sinuses, has led to a reduction in the use of topical nasal steroids, and has made systemic steroid therapy unnecessary, thereby improving the quality of life of the patient. A further study of immunotherapy for patients with AFS is recommended, and suggestions for modification of the current protocol are presented.

Use of a screening RAST in a large neuro-otologic practice.

Evidence in the literature emphasizes the role of the immune system in disorders of the inner ear and eustachian tube. We initially investigated the presence of inhalant allergy in selected patients seen for otologic problems by means of a screening radioallergosorbent test (RAST), using either a microscreen or a limited antigen panel. This study analyzed the results of tests performed over a 2-year period on 186 patients seen by one of us (WLM) for treatment of vertigo (66%), tinnitus (63%), hearing loss (49%), aural fullness (48%), Meniere's quadrad (27%), balance disturbance other than true vertigo (21%), and eustachian tube dysfunction (4%). We found an incidence of immunoglobulin E-mediated hypersensitivity of nearly 40% in a patient population selected solely for neuro-otologic symptoms and not for sinonasal symptoms. This figure is more than double that quoted for the general population. We also found a surprisingly high incidence of mold antigen atopy in this selected population. Allergy can contribute to a number of otologic symptoms, including eustachian tube dysfunction, vertigo, tinnitus, hearing loss, aural fullness, and nonspecific balance disturbance. Allergy also has been emphasized as an etiologic factor in a portion of patients diagnosed with Meniere's syndrome. A screening RAST, combined with clinical evaluation, appears to be an excellent tool for evaluating these patients for inhalant allergy as part of a comprehensive workup.

Correlation of modified radioallergosorbent test scores and skin test results.

In addition to a significantly increased sensitivity as compared with the initial Phadebas radioallergosorbent test, a major advantage of the Fadal-Nalebuff modified RAST is its correlation with skin testing using skin end point titration. This correlation allows physicians to use both these modalities in the diagnosis and treatment of allergic disorders. However, it has been anecdotally believed that the correlation of radioallergosorbent test classes and skin test end points varied somewhat with different antigens. Fifty-three patients were tested by radioallergosorbent test for 12 inhalant antigens common to the North Texas region. These patients subsequently underwent confirmation of their radioallergosorbent test results by application of intradermal tests at a concentration of one fivefold step weaker than the corresponding radioallergosorbent test level (a "RAST minus one" dilution). The relationship between radioallergosorbent test and skin test results will be critically analyzed.

Making the diagnosis of allergy.

A thorough and continuing history is the primary means for establishing the diagnosis of inhalant allergy. Confirmation of offending allergens may be accomplished by either skin tests or in vitro methods. Clinical judgment is necessary to draw appropriate inferences from the allergy history, confirmatory physical examination, adjunctive tests and specific allergen skin tests or in vitro assays.

Significance of borderline levels of specific IgE obtained by FAST-Plus assay.

The significance of "borderline" levels of allergen-specific IgE as measured by in vitro assays has been questioned. Patients whose specific IgE tests Patients were tested for twelve antigens using the FAST-Plus methodology. All 0/1 results were checked using skin tests at a 1:500 concentration. Positive (histamine) and negative (diluent) controls were used. The antigen-induced wheals were compared with those produced by a control wheal of 2% glycerine (the glycerine concentration in a 1:500 dilution). Positive wheals were arbitrarily considered to be those whose diameter after 10 minutes exceeded that of the glycerine control wheal by 2 mm or more. Using the limits of calibrator fluorescence for the FAST-Plus test in effect before 1990, a significant discordance between skin test results and the class 0/1 in vitro readings was evident. Using the standards in effect since 1990, marked concordance between class 0/1 results and positive skin tests was noted. This was most marked for pollens, less so for molds. Using current standards, FAST-Plus class 0/1 results are best considered positive (pending clinical confirmation), rather than negative.