Symposium on Pediatric Allergy

Allergy and Secretory Otitis Media Clinical and Immunologic Studies

Robert E. Reisman, M.D.,* and Joel Bernstein, M.D. t

The relationship of allergy to the etiology of secretory otitis media is very controversial. Most studies examining this problem have been clinical in nature and conclusions are in wide disagreement. For example, the reported incidence of allergy in children with secretory otitis media has ranged from almost zero to over 80 per cent. 2 • 6 Furthermore, when allergy has been suspected, disagreement exists over the specific etiology, i.e., inhalants or foods. More basic studies utilizing immunologic, pathologic, or pharmacologic investigations have been limited in scope and quality. The purpose of our investigations was to re-examine the relationship between allergy and secretory otitis media utilizing (1) clinical studies (2) immunologic analysis of middle ear secretions, and (3) immunohistologic examination of middle ear mucosa. Most critical to this presentation is the precise reference for the term allergy. It will be confined to classical IgE mediated immediate type hypersensitivity, type I reactions in the classification of Gell and Coombs. 3 The basic questions examined by these studies were: Is secretory otitis media per se an allergic disease or is secretory otitis media a complication of allergic disease? Clinical Studies During the period 1971-1972 the clinical course of secretory otitis media was evaluated in 200 unselected children who were seen consecutively by an otologist (J.B.). Thus there was no preselection of those children to be studied. One hundred and twelve of the 200 children had on~ myringotomy performed with insertion of a tube and 88 had multiple tubings for secretory disease of the middle ear. From the Allergy Research Laboratory of the Buffalo General Hospital and the Departments of Medicine and Otolaryngology of the State University of New York at Buffalo ''Associate Clinical Professor of Medicine and Assistant Clinical Professor of Pediatrics tClinical Associate in Surgery, Department of Otolaryngology

Pediatric Clinics of North America- Vol. 22, No. 1, February 1975






The allergy evaluation consisted of the following: (1) complete history of allergic signs or symptoms, (2) history of similar problems within the family, (3) careful physical examination of the upper airway, chest, and skin (4) intradermal skin testing with common selected allergens done in about two-thirds of the individuals studied, (5) examinations of the blood and nasal secretions for eosinophils in approximately one-third of the patients. In this group of children there were 88 males and 112 females with an age range from 3 to 15. Forty-six (23 per cent) had a family history of typical atopic disease. When all of the above criteria were considered carefully, a documented diagnosis of atopic disease could be made in only 46 of the 200 children (23 per cent). This incidence of allergy is perhaps slightly higher than one might expect from random examination of unselected children. The incidence of allergy in those children who required multiple tubings because of recurrent secretory disease of the ear was somewhat higher (35 per cent). In passing, of note were six children with severe recurrent secretory disease who were atopic. These individuals were treated with appropriate immunotherapy and environmental avoidance. Although their nasal symptoms improved markedly, there was no change in their recurrent ear problems. Within this particular group inhalant allergens such as dust, mold, and pollen were most prevalent and allergy to food was not a major factor. Thus, clinical studies alone using unselected children with secretory otitis media suggested that the incidence of allergy is at best slightly greater than what might be expected in the normal population.

Middle Ear Tissue HISTOLOGIC STUDIES. Middle ear mucosa and mastoid mucosa were obtained at the time of surgery from three atopic children with secretory otitis media. Histologic examination of these middle ear tissues revealed

Figure 1. Photomicrograph of middle ear mucosa from a patient with secretory otitis media. Multiple plasma cells and lymphocytes are present.



Figure 2. Immunofluorescent study showing plasma cells in middle ear mucosa stained specifically for lgA. lgG- and lgM-containing cells were also found.

numerous plasma cells and small lymphocytes. A relatively small number of eosinophils was observed (Fig. 1). IMMUNOLOGIC STUDIES. Immunofluorescent studies were carried out with these tissue sections. Plasma cells were examined with monospecific antisera to each of the immunoglobulins. No lgE-forming plasma cells could be found. Immunofluorescent studies did reveal many plasma cells containing IgA and IgG. lgM was also found in a few cells (Fig. 2). Secretory piece could also be detected in the middle ear tissue as it is in other external secretory systems by immunofluorescent staining (Fig. 3).

MIDDLE EAR SECRETIONS. Immunoglobulin Content. Middle ear secretions and corresponding serum from 31 clinically atopic patients were analyzed for immunoglobulin content. Middle· ear fluid was collected in a Senturia apparatus. The mucoid fluid in all instances necessitated dilution with normal saline. The fluid was centrifuged at 3000 rpm and concentrated by negative pressure dialysis. lgE was measured by the single radio radial diffusion method. 1 Other immunoglobulins were measured by the usual Mancini technique. 5 The immunoglobulin content of these secretions is shown in Table 1. IgG was found in all secretions, and lgA and IgM in almost all. Secretory piece could be identified in 19 of 31. lgE was found in only two of the secretions.





Figure 3. Immunofluorescent study of middle ear mucosa stained with specific antisera for secretory component. Specific fluorescence seen in epithelium only.

Further studies were carried out to determine the nature of this secretory piece. Figure 4 shows the reaction of antisecretory piece rabbit serum with middle ear secretions, colostrum, nasal secretions, and plasma. A precipitin band found with middle ear secretions was one of identity with the other external secretions. There was no reaction with plasma. These and other studies4 indicate that the secretory piece is identical to that found in other external secretions. lgG/lgA Ratios in Serum and Secretions. Further studies were carried out to determine the nature of the effusion in serous otitis media, in order to determine whether it is at least in part due to some locally active secretory process. IgG/IgA ratios of paired serum and secretions were compared. Table 2 shows the comparison of ratios in 14 matched pairs. Considerable variation was found in the ratios in serum and secretions. In five of the patients, the IgG/IgA ratio in secretions was markedly lower than that Table 1. Presence of Immunoglobulins and Secretory Piece in 31 Middle Ear Secretions IMMUNOGLOBULIN CONTENT













Figure 4 . Gel precipitation reaction of antisecretory piece rabbit serum (aS) with middle ear secretions (M), colostrum (C), nasal secretions (N), a nd plasma (P).

of the serum. This strongly suggests that there is a relative increase of lgA concentration of secretory fluid as compared to serum and also suggests that immunoglobulins in secretions were not the result of a simple transudation from serum. IgE Levels. Quantitative lgE measurements were made in 14 matched pairs of serum and secretions taken from clinically atopic patients. These included one additional matched pair not mentioned in the initial 200 children studied. The serum lgE ranged from 20 to over 1000 units per ml. The lgE in secretions ranged from less than 20 units per ml, the lower level of sensitivity by our technique, to 230 units per ml. lgE could be detected in only three secretions and in all cases the corresponding serum level was high (Table 3). IgE Antibody. Specific lgE antibody activity was assayed by passive

Table 2.

Comparison of IgG/IgA Ratios in Paired S erum and Secretions SERUM

4.5 8.7 34.8 14.3 20.0 13.5 7.4 8.3 10.6 19.6 15.5 21.0 30.0 14.0


3.9 3.2 5.5 10.9 10.5 15.0 7.0 6.0 11.4 9.3 15.0 9.0 > 54.0 14.0





Table 3. lgE Levels* in Paired Sera and Middle Ear Secretions of 14 Atopic Patients SERUM



230 90

340 340 90 90 20


39 75 .39 39 110

Allergy and secretory otitis media: clinical and immunologic studies.

Symposium on Pediatric Allergy Allergy and Secretory Otitis Media Clinical and Immunologic Studies Robert E. Reisman, M.D.,* and Joel Bernstein, M.D...
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