IMMUNOTHERAPY AND ALLERGIC FUNGAL SINUSITIS

Correspondence IMMUNOTHERAPY AND ALLERGIC FUNGAL SINUSITIS To the Editor: We read with great interest the review article titled “Medical treatment of allergic fungal sinusitis” by Mark S. Schubert, MD, PhD which was published in the August 2000 issue of the Annals of Allergy, Asthma and Immunology.1 In this review article, the author advocates allergen immunotherapy as a treatment option for allergic fungal sinusitis. He states that a recent study had suggested that allergen immunotherapy to relevant aeroallergens including molds provided significant clinical benefit even though the specific mold causing the allergic fungal sinusitis was generally not available for treatment.2 When we read the cited reference, we were surprised to find that the “immunotherapy” that was used in this study was done by means of skin endpoint titration in a manner that would be considered unproven and controversial by board-certified allergy and immunology specialists.3 Also, the doses of immunotherapy with which the patients were treated is approximately 100 times less concentrated than those we generally use. We feel that until conventional standard high-dose immunotherapy studies are done, the use of immunotherapy for allergic fungal sinusitis should still be considered controversial or, at best, experimental. BRYAN D. STONE, MD JOHNNY J. CHOI, MD Department of Allergy & Immunology Lahey Clinic Medical Center Burlington, Massachusetts REFERENCES 1. Schubert MS. Medical treatment of allergic fungal sinusitis. Ann Allergy Asthma Immunol 2000;85:90 –101. 2. Mabry RL, Marple BF, Folker RJ,

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Mabry CS. Immunotherapy for allergic fungal sinusitis: three years’ experience. Otolaryngol Head Neck Surg 1998;119:648 – 651. 3. American Academy of Allergy, Asthma and Immunology. Position statement on skin titration (Rinkel Method). J Allergy Clin Immunol 1981;67:333–338.

Response: I thank Drs. Stone and Choi for their interest and comments regarding the review article “Medical treatment of allergic fungal sinusitis.”1 The article by Mabry et al2 on allergen-specific immunotherapy (SIT) for allergic fungal sinusitis (AFS) had a number of potential limitations in design. First, like all published studies examining any form of treatment for AFS, their study was neither blinded nor placebo-controlled. Their allergy testing used both the “otolaryngic allergy” technique of “dilutional intradermal testing” for specific molds, and allergen-specific immunoglobulin E radioallergosorbent testing (RAST) for non-mold aeroallergens that included pollens, dust mite, and animal danders. They found that reliance on dilutional intradermal skin testing for molds gave more positives than RAST,3 which suggests that selection of specific molds for inclusion in their SIT mix could be more sensitive to overtreatment as opposed to undertreatment. Although the use of RAST testing is accepted as a diagnostic test in allergy, it too is known to be subject to sensitivity and specificity issues, as well as lab-to-lab variability.4 Lastly, the specific mold(s) involved in each of the patients’ AFS was generally not available for SIT treatment. Using their protocols, they concluded that SIT containing all possible relevant aeroallergens to which the patient was allergic gave significant clinical benefit in AFS. They stated that the maintenance SIT dosage used was the maximal tolerated dose. This was determined by SIT administration and advancement

which for many of their AFS patients, occurred at approximately 0.05 mL of a 1:100 wt/vol concentration of allergens. A review by Ferguson5 stated that the Mabry group advanced their SIT dosages “to the highest tolerated concentration that did not promote a systemic reaction or a local reaction larger than 3 cm in diameter.” I believe a concentration of maintenance SIT that fits this definition should be considered to be within acceptable guidelines for SIT treatment. This appears not to be the Rinkel method for endpoint skin test titration to determine the therapeutic (often subtherapeutic) maintenance SIT dose that Drs. Stone and Choi are concerned about, where maintenance SIT is usually 0.5 mL of the endpoint dilution obtained by a dilutional skin testing technique.6 We also find that the highest tolerated SIT dosages in AFS patients often occur between 0.05 and 0.5 mL of an equivalent 1:100 wt/vol concentration of allergen-specific SIT mixes (unpublished observation). It may be that regional variations in specific pollen and mold sensitizations (including the etiologic AFS mold itself) contribute to any differences found in the maximal maintenance dosage capability. Although the paper by Mabry et al has limitations which should be understood, no adverse consequences from SIT in their AFS patients were reported. This is in line with our experience.7 We reported a retrospective analysis of 67 consecutive AFS patients over 8 years, comparing differences in AFS clinical outcomes between those treated with or without postoperative oral corticosteroids (OCS). As stated in the review article,1 both groups were similar in the use of SIT that included all relevant aeroallergen positives by traditional allergy skin prick and intradermal testing, including molds.7 We found both significant clinical improvements with the use of OCS and no evidence for adverse consequences from SIT. Gold-

ANNALS OF ALLERGY, ASTHMA, & IMMUNOLOGY