Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature. Pathology and Pathogenesis of Otits Media Pathology Understanding the pathology and pathogenesis of otitis media (OM) is important in predicting the prognosis and sequelae of the disease. In this way treatment can be tailored to individual needs. There have been several attempts to gain a consensus definition of OM. In 1980, the Ad Hoc Committee on the Classification of Otitis Media defined OM based on the temporal sequence: Acute < 3 weeks; Subacute 4-8 weeks; Chronic >9 weeks. In 1989, the Task Force of the 4th International Symposium on Otitis Media published a working classification. Acute Suppurative OM refers to an identifiable infection of the middle ear of short duration and sudden onset. Secretory OM refers to the presence of a middle ear effusion without acute signs or symptoms. Chronic Suppurative OM refers to a chronic middle ear discharge through a perforated tympanic membrane. Much of our understanding of the pathology of OM comes from experimental animal models and from temporal bone preparations. After Eustachian tube obstruction in the cat and chinchilla, edema hyperemia, subepithelial hemorrhage with PMN infiltration are noted, modeling acute Suppurative OM. In addition mucoperiosteal thickening and osteitis can be seen. Mild metaplasia from squamous to cuboidal epithelium is noted. Continued Eustachian tube obstruction models secretory OM. Early transudation of serum into the subepithelial space is seen within 18-24 hours. More metaplasia is seen with increased numbers of pseudostratified, ciliated columnar epithelial cells, and goblet cells. Resorption of water is thought to promote thickening of the effusion converting thin serous fluid into a thick mucoid effusion. In temporal bone preparations, thickening and fibrosis of the tensor tympanic is seen. This is felt to be important in the development of spasm and contracture of the muscle resulting in retraction and fixation of the tympanic membrane. In chronic OM models, columnar metaplasia is greatest. fibroblastic density is increased. A lymphoid infiltrate is noted with polypoid changes present in the mucosa. Osteitis and osteoneogenesis are also commonly noted. Friable immature granulation tissue with neovascularization and fibroblastic proliferation is seen. Mature granulation with subepithelial fibrosis and decreased vascularity are found in long standing disease. The sequelae of COM including tympanosclerosis, cholesterol granuloma, and cholesteatoma can also be encountered. Paparella's group has proposed that OM exists as a continuum of mucoperiosteal disease. Epidemiologic evidence comes from studies showing the overlap and progression of disease from acute suppurative OM to secretory OM or chronic OM. One out of 5 cases of Acute OM is superimposed on a chronic mucoid OM. Temporal bone histology also demonstrates the continuum of mucosal disease. Lastly, experimental animal models of Eustachian tube obstruction followed longitudinally have demonstrated the gradual change from suppurative, to secretary, to chronic histopathology. Pathogenesis Since the time of Politzer, the Eustachian tube has been identified as central to the pathogenesis of OM. For OM to occur, three conditions must be met. Bacteria must adhere to the nasopharyngeal mucosa. The bacteria must the enter the Eustachian tube and finally, the bacteria must be able to multiply in the middle ear environment. Pathogenic bacteria bind to cell surface receptors in a highly specific fashion. The adhesin receptor binding mechanism prevents colonizing bacteria from being swept away by the mechanical cleansing action in the nasopharynx. Adhesion through a receptor mechanism is suggested by the fact that adherence can be saturated by an increase in bacterial concentration. In general, the more adherent an organism is to the nasopharyngeal mucosa, the more likely it will be a successful pathogen. In children, the adenoid bed is an important source of pathogenic bacteria. In addition, Influenza A can cause destruction of the normal tubal mucosa promoting bacterial entry. One study showed a 5-fold increase in the rate of pneumococcal OM in chinchillas infected with the virus. The Eustachian tube itself is cartilaginous in its lower 2/3 portion. It is normally in the closed position. The main dialator of the tube is the tensor veli palatini innervated by the mandibular division of the trigeminal nerve. Comparing the infant to the adult tube, the Eustachian tube is shorter (13mm vs 31-38mm), shallower (10 deg. vs 45 deg from horizontal), and has abundant goblet cells. These anatomic features make the pediatric Eustachian tube much more likely to become dysfunctional. Eustachian tube function can be divided into ventilation, drainage, and protection from nasopharyngeal secretions. Bluestone has described 4 functional abnormalities radiographically by instilling contrast material into the nasopharynx. The abnormalities include retrograde obstruction, abnormal distensibility, middle ear reflux, and retrograde obstruction with abnormal distensibility. The patulous Eustachian tube predisposes to middle ear reflux. The abnormally compliant Eustachian tube could result in middle ear reflux with slight increases in nasopharyngeal pressure. On the other hand, rapid changes in pressure could cause locking of the tube and functional obstruction. The ventilatory function of the Eustachian tube is also affected by the gaseous equilibrium of the middle ear space. Large rapid changes can occur because the middle ear space is a relatively small pocket of gas surrounded by vascular mucosa. Gas is exchanged between the middle ear cavity and the mucosa. Recent evidence suggests that the diffusion gradient is due to the nitrogen partial pressure gradient. Anatomically, neoplasms, cleft palate, and large adenoids can cause obstruction of the Eustachian tube. In children, it appears that adenoid size does not correlate with the incidence of OM. Adenoids act as a source of pathogenic bacteria rather than anatomic obstruction in the pathogenesis of OM. The final stage in the development of OM is bacterial replication in the middle ear space. Therefore, the immunology of OM has generated great interest. In human studies, IgG is the predominant immunoglobulin involved. Several clinical series have shown lower levels of IgG2 in otitis prone children. These children have greater susceptibility to non-typeable H.Flu. Higher levels of interleukin-1 have been found in both younger children and those with cleft palate with Eustachian tube dysfunction and OM. Increased levels of specific hydrolase activity and higher levels of lipoxygenase products have also been found in otitis media effusions. Case Presentation An 11-month-old full term white male child presented with a history of otitis media for the past 5 months. He completed six courses of several different antibiotics without resolution. Physical exam showed dull, slightly retracted tympanic membranes and no other abnormalities. Visual reinforcement audiometry showed normal sensitivity for age. Acoustic immittance measurements showed type C tympanograms. In view of the persistence of the effusion, the patient underwent bilateral myringotomy and placement of pressure equalization tubes. Thin viscous fluid was aspirated from both middle ear cavities. One month postoperative assessment revealed that the child was doing fine with well-placed, patent PE tubes. Bibliography Beachey EH, Courtney SH. Bacterial adherence: attachment of group A streptococci to mucosal surfaces. In: Lim DJ, ed. Proceedings of the Fourth International Symposium Recent Advances in Otitis Media, June 1-4, 1987, Bal Harbour, Florida. Toronto: B.C. Decker, 1988:291-296. Bernstein JM. Immunologic reactivity in the middle ear in otitis media with effusion. Otolaryngol Clin North Am 1991;24:845-858. Biegink GS, Ripley-Petzoldt ML, Juhn SK, Aeppli D, Tomasz A, Tuomanen E. Contribution of pneumococcal cell wall to experimental otitis media pathogenesis. Ann Otol Rhinol Laryngol 1988;97:28-30. Bluestone CD, Paradise JL, Beery QC. Physiology of the eustachian tube in the pathogenesis and management of middle ear effusion. Laryngoscope 1972;82:1654-1670. Bluestone CD, Rood SR, Swarts JD. Anatomy and physiology of the eustachian tube. In: Cummings, DW, Harker LA, eds. Otolaryngology -Head and Neck Surgery, Volume 4, 2nd ed. St. Louis: Mosby, 1993:2548-2565. Cantekin EI, Casselbrant ML, Doyle WJ, Brostoff LM. Eustachian tube function: prospective study of eustachian tube function and otitis media. In: Lim DJ, ed. Proceedings of the Fourth International Symposium Recent Advances in Otitis Media, June 1-4, 1987, Bal Harbour, Florida. Toronto: B.C. Decker, 1988:58-60. Collins ME, Coker NJ, Igarashi M. Inflammatory disease of the anterior epitympanum. Am J Otol 1991;12:11-15. Diven WF, Doyle WJ, Vietmeier B. Hydrolytic enzymes in otitis media pathogenesis. Ann Otol Rhinol Laryngol 1988;97:6-9. Diven WF, Doyle WJ, Vietmeier BN. Studies in otitis media, Pittsburgh Otitis Media Research Center. Progress report 1988: Hydrolase activity in experimental middle ear effusion. Ann Otol Rhinol Laryngol Suppl 1988;133:26-27. Diven WF, LaMarco KL, Doyle WJ, Glew RH. Studies in otitis media, Pittsburgh Otitis Media Research Center. Progress report 1988: Role of bacterial hydrolases in the pathologic changes caused by otitis media. Ann Otol Rhinol Laryngol Suppl 1988;133:23-24. Diven WF, Scanlon KL, Glew RH. Studies in otitis media, Pittsburgh Otitis Media Research Center. Progress report 1988: Purification and properties of a neuraminidase from streptococcus pneumoniae culture filtrates. Ann Otol Rhinol Laryngol Suppl 1988;133:24-25. Diven WF, Vietmeier BN. Studies in otitis media, Pittsburgh Otitis Media Research Center. Progress report 1988: Isolation and characterization of chinchilla a1-antitrypsin. Ann Otol Rhinol Laryngol Suppl 1988;133:24. Gates GA, Muntz HR, Gaylis B. Adenoidectomy and otitis media. Ann Otol Rhinol Laryngol Suppl 1992;155:24-32. Giebink GS. Otitis media update: pathogenesis and treatment. Ann Otol Rhinol Laryngol 1992;101:21-23. Goycoolea MV, Buah DB, Bequer N. General surgical approach based on pathogenesis: an overall approach. Otolaryngol Clin North Am 1991;24:957-966. Goycoolea MV, Hueb MM, Ruah C. Definitions and terminology. Otolaryngol Clin North Am 1991;24:757-761. Goycoolea MV, Nuchow DC, Goycoolea HG. Otitis media: 16 years of pathogenesis approach. Otolaryngol Clin North Am 1991;24:967-980. Hellström S, Goldie P. Mechanisms of otitis medial development: involvement of neurogenic inflammation. Otolaryngol Clin North Am 1991;24:829-834. Johnson MD, Fitzgerald JE, Leonard G, Burleson JA, Dreutzer DL. Cytokines in experimental otitis media with effusion. Laryngoscope 1994:104:191-196. Juhn SK, Tolan CJ, Antonelli PJ, Giebink GS, Goycoolea MV. The significance of experimental animal studies in otitis media. Otolaryngol Clin North Am 1991;24:813-827. Jung TT. Arachidonic acid metabolites in otitis media pathogenesis. Ann Otol Rhinol Laryngol 1988;97:14-17. Jung TT, Park YM, Schlund D, Weeks D, Miller S, Wong O, et al. Effect of prostaglandin, leukotriene,m and arachidonic acid on experimental otitis media with effusion in chinchillas. Ann Otol Rhinol Laryngol 1990;99:28-32. Kenna MA. Etiology and pathogenesis of chronic suppurative otitis media. Ann Otol Rhinol Laryngol Suppl 1988;131:16-24. Klein JO, Naunton RF, Tos M, Ohyama M, Hussl B, van Cauwenberge PB. Recent advances in otitis media: definition and classification. Ann Otol Rhinol Laryngol Suppl 1989;139:10. Lim DJ, Demaria TF, Bakaletz LO. Current concepts of pathogenesis of otitis media: a review. Acta Otolaryngol Suppl 1988;458:174-180. Meyerhoff WL, Biegink GS. Pathology and microbiology of otitis media. Laryngoscope 1982;92:273-277. Meyerhoff WL, Shea DA, Giebink GS. Experimental pneumococcal otitis media: a histopathologic study. Otolaryngol Head Neck Surg 1980;88:606-612. Morizono T, Tono T. Middle ear inflammatory mediators and cochlear function. Otolaryngol Clin North Am 1991;24:824-852. Paparella MM, Schachern PA, Yoon TH, Abdelhammid MM, Sahni R, da Costa SS. Otopathologic correlates of the continuum of otitis media. Ann Otol Rhinol Laryngol 1990;99:17-22. Senturia BH, Paparella MM, Lowery HN, Klein JO, Arnold WJ, Lim DJ, et al. Report of Research Conference. Recent Advances in Otitis Media with Effusion: Modified report of the ad hoc committee on definition and classification of otitis media. Ann Otol Rhinol Laryngol Suppl 1980;69:6. Sando I, Takahashi H. Otitis media in association with various congenital diseases: preliminary study. Ann Otol Rhinol Laryngol 1990;99:13-16. Schachern P, Paparella MM, Sano S, Lamey S, Guo Y. A histopathological study of the relationship between otitis media and mastoiditis. Laryngoscope 1991;101:1050-1055. Schuknecht H. Pathology of the Ear, 2nd ed. Philadelphia: Lea and Febiger, 1993. Weir N. Otolaryngology: An Illustrated History. London: Butterworths, 1990: 14, 18, 42, 81, 206, 211-212, 218. Yoon TH, Paparella MM, Schachern PA, Lindgren BR. Morphometric studies of the continuum of otitis media. Ann Otol Rhinol Laryngol 1990;99:23-27. Yoon TH, Schachern PA, Paparella MM, Aeppli DM. Pathology and pathogenesis of tympanic membrane retraction. Am J Otol 1990;11:10-17. Grand Rounds Archive | Department Home page BCM Public | BCM Intranet | Privacy Notices | Contact BCM | BCM Site Map | ©2001-2006 Baylor College of Medicine
|