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. Subglottic Stenosis in the Adult There are many causes of subglottic stenosis: intubation and blunt external trauma remain the principal etiologic culprits. In 1975 McDonald and colleagues presented a series of patients with non-traumatic non-neoplastic subglottic stenosis and noted the primary causes to be rhinoscleroma, Wegener's granulomatosis, relapsing polychondritis, and amyloidosis. These entities, while rare, are important to consider when evaluating a subglottic lesion of unclear etiology. Rhinoscleroma is a granulomatous disease that affects multiple sites in the upper aerodigestive tract and is caused by the aerobic gram negative rod, Klebsiella rhinoscleromatis. It was first described in 1870 by von Hebra. In the following year Mikulicz recognized the characteristic foamy histiocytes noted in the biopsy specimens of rhinoscleroma patients. Later in 1882 the actual pathogenic bacillus was noted by von Frisch. This characteristic biopsy appearance was subsequently noted in multiple sites in the head and neck, and in 1932 the International Congress on Rhinology decided that a more appropriate and less confusing designation would be simply, scleroma. While this nomenclature is used in endemic regions such as Egypt, it has not been uniformly adopted. Rhinoscleroma is endemic in Egypt, Poland, Hungary, Ukraine, Georgia, Indonesia, and our nearby neighbors in Central America. It is recognized to occur most often in people of lower socioeconomic levels living in unhygienic conditions. Malnutrition is an important predisposing factor for contracting this illness, which is neither highly contagious nor genetically inherited. Males and females are affected equally. A study by Dogheim was unable to note any changed in humoral immunity in patients with rhinoscleroma and he suggested that a T-cell abnormality may play a role. Gamea and his Egyptian colleagues looked at the breakdown of anatomic sites affected by scleroma and found the following. One-hundred percent of patients presented with nasal crusting, granulomatous lesions, or cicatrix. The second most prevalent site was the eustachain tube, which showed lesions in 27.5%. A high prevalence was also noted in the maxillary sinus antrum and the tracheobronchial tree. The third most common site of predilection was the larynx, which was affected 26% of the time. Eighteen of these 21 cases occurred in the subglottis. The staging of scleroma is broken down into three phases. Initially, in the exudative phase, the individual experiences active inflammation, edema, congestion, and suppurative necrosis of the affected site, which is most often the nose. Histologic specimens taken from lesions in this phase rarely demonstrate the pathogenic organism. The proliferative or granulomatous stage is next, and is characterized by multiple reddish nodules in the nose, pharynx, larynx, and bronchi. Biopsies of these lesions show the highest concentrations of the Klebsiella organism and the most recognizable histologic pattern. The disease progresses inexorably from this point toward the final fibrotic stage. Here the previously reddish lesions have become whitish and are recognizable as cicatricial tissue. Biopsy at this point will reveal a nondiagnostic pattern in most instances. Clinical suspicion is important in order to make a successful diagnosis, especially in a patient form an endemic region. A thorough examination is needed to identify all sites of involvement. Radiographic studies are not diagnostic, but a CT scan typically shows concentric irregularities and narrowing in the subglottic space. Laboratory studies are significant for a positive complement fixation test in approximately 90% of cases. A biopsy is needed for the definitive diagnosis. A low power photomicrograph in the proliferative phase classically demonstrated acute and chronic inflammation with clusters of vacuolated histiocytes called Mikulicz cells. Warthins-Starry silver stain can be used to demonstrate the Klebsiella organisms. There is no definitive cure for this disease. Treatment should be directed according to the clinical stage. In the proliferative or granulomatous stage of the disease prolonged antimicrobial therapy is the treatment of choice. In a study by Perkins, Hammill, and Musher from our institution in 1992, 11 antimicrobial agents were tested for in vitro activity against Klebsiella rhinoscleromatis. Several antibiotics have been noted to be effective with Ciprofloxicin showing the greatest in vitro activity. Regimens should be continued from 6 months to 1 year at minimum. For symptomatic disease that has progressed to the fibrotic stage, only surgery is effective. If the width of subglottic involvement is less than 1 cm, then CO2 laser excision is optimal. For extensive local disease, more complicated techniques such as cricoid split with an interposition of hyoid bone, laryngofissure with split-thickness skin graft, and even laryngotracheal resection have been attempted. From the few articles discussing the management of more extensive lesions, there does not appear to be a consensus on the most appropriate therapy. Wegener's granulomatosis was first described in 1931 by Klinger as "atypical polyarteritis nodosa." Dr. Wegener would later describe this entity which bears his name in 1936. This is a disease manifested by necrotizing granulomas of the upper respiratory tract, pulmonary tree, and kidneys. Its etiology is unknown. Both males and females are effected equally, and most patients present in their 30s and 40s. Nasal findings are present in the greatest percentage of Wegener's patients with head and neck manifestations. Sixty to eighty percent complain of chronic sinusitis, nasal crusting, serosanguinous rhinorrhea, or septal perforation. Ocular findings are the next most prevalent with inflammation noted in approximately 40% of cases. Twenty to twenty-five percent experience serous otitis media and conductive hearing loss, and 16% have complaints of stridor as a result of subglottic stenosis. A saddle nose deformity may result from the necrotizing nasal lesions. McDonald and colleagues in 1983 looked at 108 patients with Wegener's granulomatosis to determine the frequency of subglottic involvement. In their series, 13 of 108 were noted to have subglottic stenosis. Curiously, 12 of these 13 were women. The significance of this finding is not fully appreciated. Examination typically revealed a relatively wide bank of red friable tissue circumferentially narrowing the subglottis. A thorough history and physical is critical to elucidate the multisystemic symptoms and signs of Wegener's granulomatosis. The head and neck findings have been previously discussed, and in the face of chronic rhinorrhea, sinusitis, recurrent otitis, and recurrent pulmonary infections, the diagnosis should be entertained. Laboratory studies that are helpful include a CBC (which may demonstrate a mild anemia) and inflammatory indices such as an ESR, RF, and ANA. A serum creatinine may demonstrate renal insufficiency and a urinalysis will show signs of nephritis with casts and red blood cells. Chest radiographs have been noted to show multiple cavitary lesions. An intranasal biopsy is extremely helpful, although only diagnostic around 5-0% of the time. To optimize the biopsy all crusts overlying the lesions should be removed. Special stains for AFB and fungus should be performed. And frozen section should be avoided as this technique distorts the vasculitic architecture and makes the interpretation less reliable. Histologically Wegener's biopsy specimens show inflammatory infiltrates with multinucleated giant cells and granuloma formation. Vasculitis of the small and medium vessels often results in their obliteration. The etiology of subglottic stenosis when one notes a non-specific symmetrical pink friable narrowing is often unclear. Biopsy specimens from the larynx and trachea often do not exhibit the classic giant cell granulomas and vasculitis that is characteristic of Wegener's granulomatosis. In fact, up to 50% of biopsies will be non-diagnostic. In such a case the antineutrophil cytoplasmic autoantibodies (or ANCA) test may confirm Wegener's to be the inciting disease process. The test should be interpreted cautiously though, because Wegener's granulomatosis may be present even in the face of a negative ANCA test. There appears to be greater sensitivity to this test in the presence of subglottic stenosis. Medical therapy for Wegener's begins with the institution of prednisone at a dose of 60-80 mg/d. Serum creatinine and ESR are followed to monitor response. After acute control has been achieved, cytoxan therapy is begun at 2 mg/kg is a single daily dose. It takes approximately 2 to 3 weeks for the salutary effects to be seen. At this time the steroids are tapered and the patient is maintained on cytoxan for 1 year. Surgical management of subglottic lesions becomes important in those who remain symptomatic despite appropriate medical management. Surgical approaches have been most successful in patients who are not in the active phase of disease. Treatments of subglottic lesions have included intralesional steroids, manual dilatations, and CO2 laser excision. Most respond to some degree to these measures. However, if unsuccessful, open laryngotracheoplasty has been suggested. Amyloidosis is another cause of non-traumatic, non-neoplastic subglottic stenosis. The term "amyloidosis" is a general descriptor that represents the clinical manifestations of the deposition of extracellular amyloid protein. Historically, Rokitansky was the first to recognize systemic amyloid deposits in 1842. Later, Virchow, in 1853, actually coined the term amyloid after noting its reaction with iodine. In 1875, Burrow and Neuman presented the first case of laryngeal stenosis caused by amyloidosis. The classification system for amyloidosis is basically divided into systemic and organ-limited groups. Each is further described by its own unique amyloid fibril protein. The fibril protein in laryngeal disease is felt to be an A-light chin. Recent further studies have implicated beta-2 microglobulin as the amyloid protein in laryngeal disease. Systemic amyloidosis has a markedly shortened life expectancy when compared to organ-limited disease. Fortunately in the presence of laryngeal amyloidosis however, systemic disease is rare. Males are more frequently affected by amyloidosis with a male to female ratio of 2 to 1. Most patients present between the 5th and 7th decades. Involvement can be in virtually any organ system. In the head and neck, macroglossia is the most prevalent finding, and is seen in 15 to 20% of cases. Subglottic stenosis caused by amyloid constitutes 1% of all benign laryngeal lesions. Sites in the larynx that show predilection for nodular or polypoid amyloidosis include the ventricles, false cords, aryepiglottic folds, and the subglottis. Virtually all other anatomic locations in the head and neck may be involved. Given the frequently vague presentation of amyloidosis the diagnosis is often delayed. Biopsy of the lesion noted should be performed if clinical suspicion suggests amyloidosis. The gold standard for diagnosis in the past was the rectal biopsy. Recently, fine needle aspiration of abdominal fat has found to have equal sensitivity, and fewer complications. In the head and neck, biopsy of the lesion itself should be sufficient to demonstrate the characteristic submuclosal extracellular deposits of amyloid protein. Hematoxylin-eosin staining demonstrates the pink homogeneous extracellular amyloid deposits. a typical "apple-green" birefringence pattern seen with the Congo red stain is helpful. There is no effective medical treatment for amyloidosis, and excision remains the treatment of choice. The CO2 laser is touted as the best method of dealing with subglottic obstructing lesions as it achieves excellent hemostasis. Microlaryngeal instrument resection of amyloid lesions has been noted to stimulate brisk bleeding, and caution is stressed when using this approach. Fortunately when subglottic lesions are completely excised recurrence is rare, and a cure can be expected. In 1923 Jaksch-Wartenhorst described a clinically destructive form of "polychondropathy." Thirty-seven years later Pearson definitively classified relapsing polychondritis as a clinical entity. Patients with this condition typically present between 40 to 60 years of age and the clinical course is highly variable. It primarily presents in an indolent manner, but may present in a fulminant manner leading to death from infectious causes. An autoimmune etiology has been clearly described. Autoantibodies to Type II collagen, which is present only in cartilage, have been noted in a significant percentage in patients with active disease. And, unsurprisingly, 25% of patients with this condition have an antecedent autoimmune disease. Diagnostic criteria have been established for relapsing polychondritis. Commonly noted findings include: 1) recurrent chondritis of both auricles; 2) nonerosive inflammatory polyarthritis; 3) chondritis of the nasal cartilages, 4) ocular inflammation; 5) chondritis of the laryngeal or tracheal cartilages, often resulting in subglottic stenosis; and 6) cochlear or vestibular damage manifesting as sensorineural hearing loss or vertigo. To make the diagnosis of relapsing polychondritis, three of the above findings must be present or one of the above along with a confirmatory biopsy showing inflammatory changes in the cartilage. McAdam and colleagues looked at a large series of patients with relapsing polychondritis and found that most of the presenting complaints involved the head and neck. The most common site of active inflammation was the auricle. In the active stage this is manifested as a red, warm, painful swelling of the pinna. After the inflammatory episode resolves significant destruction of the ear can be noted. General joint complaints, ocular inflammation, cochleo-vestibular damage, nasal cartilage destruction, and laryngotracheal chondromalacia and stenosis were also commonly seen. Management of relapsing polychondritis focuses primarily on suppressing the acute inflammatory process. NSAIDS have generally been unsuccessful. Corticosteroids have been successfully used for short-term control, but have well-known long-term consequences. Dapsone, which functions ostensibly be decreasing lysosomal release of enzymes responsible for cartilage resorption, shows some promise in the treatment of this rare disease. And cytoxan and cyclosporin A have been reserved for severe disease where more benign treatments have failed. Surgical intervention should be withheld if possible until the acute inflammatory process resolves. It is at this time that CO2 laser and microsurgical excision as well as laryngotracheal reconstruction are most likely to succeed. Tracheostomy and possibly laryngeal stenting may be required. In conclusion, these clinical entities are four of the more rare causes of subglottic stenosis. A thorough history and physical usually allows one to diagnose routine causes of subglottic stenosis. However, when the etiology is unclear, these four entities should be considered. Special laboratory studies and biopsy specimens will often assist in making the diagnosis. Medical management is attempted in all cases except in amyloidosis where the initial treatment is surgical. Often medical therapy in these diseases fails to relieve symptoms and surgical intervention is required by the otolaryngologist. Case Presentation A 48-year-old, non-smoking Hispanic man presented to the emergency room with a complaint of progressively increasing respiratory difficulty of 2 to 3 months duration. Past medical history was significant for mild dyspnea beginning 15 years earlier. There was no prior intubation or airway trauma. However, the patient had throat problems for which an oropharyngeal biopsy was performed in Mexico 12 years previously. He could not recall the pathologic diagnosis, but did note that subsequent steroid therapy was not helpful. Pulmonary function tests ordered by the pulmonary service revealed a pattern consistent with a fixed airway obstruction, and the otolaryngology service was consulted. Flexible laryngoscopy showed a whitish, fibrotic-appearing anterior subglottic lesion which obstructed over two-thirds of the lumen. Granular nodules were noted in both nasal cavities with nasal synechiae obstructing both choanae. A similar granular lesion was seen in the oropharynx. The pharyngeal lesion was biopsied and revealed a histologic pattern consistent with rhinoscleroma. Surgical management of airway obstruction included an awake tracheostomy followed by laryngoscopy and excision of the obstructing lesion. At the time of the tracheostomy, an inferiorly-based trapdoor flap was elevated with difficulty as a result of extension of the fibrotic obstruction to 3cm below the glottis. Following this, a microsuspension laryngoscopy was performed and the anterior subglottic mass was excised. The patient tolerated the procedure well and is currently continuing on a 6-month regimen of ciprofloxacin with improvement of his airway obstruction and breathing difficulty. Bibliography Abou-Seif SG, Baky FA, El-Ebrashy F, Gaafar HA. Scleroma of the upper respiratory passages: a CT study. J Laryngol Otol 1991;105:198-202. Batsakis JG, El-Naggar AK. Rhinoscleroma and rhinosporidiosis. Ann Otol Rhinol Laryngol 1992;101:879-882. Batsakis JG, Manning JT. Relapsing polychondritis. Ann Otol Rhinol Laryngol 1989;98:83-84. Berg AM, Troxler RF, Grillone G, Kasznica J, Kane K, Cohen AS, et al. Localized amyloidosis of the larynx: evidence for light chain composition. Ann Otol Rhinol Laryngol 1993;102:884-889. Breathnach SM. Amyloid and amyloidosis. J Am Acad Dermatol 1988;18:1-16. Clark LJ, Wakeel RA, Ormerod AD. Relapsing polychondritis - two cases with tracheal stenosis and inner ear involvement. J Laryngol Otol 1992;106:841-844. Cobb WB, Sudderth JF. Intralesional steroids in laryngeal stenosis. Arch Otolaryngol 1972;96:52-56. Conley JJ. Reconstruction of the subglottic air passage. Ann Otol Rhinol Laryngol 1953;62:477-495. Cotton RT, Gray SD, Miller RP. Update of the Cincinnati experience in pediatric laryngotracheal reconstruction. Laryngoscope 1989;99:1111-1116. Daly JF. Relapsing polychondritis of the larynx and trachea. Arch Otolaryngol 1966;84:570-573. Damiani JM, Levine HL. Relapsing polychondritis - report of ten cases. Laryngoscope 1979;89:929-946. de Vries N, Gans RO, Donker AJ, Goldschmeding R, Hoorntje SJ, Snow GB. Autoantibodies against constituents of neutrophils in the diagnosis and treatment of (isolated) subglottic stenosis. Arch Otolaryngol Head Neck Surg 1992;118:1120-1123. Djalilian M, McDonald TJ, Devine KD, Weiland LH. Nontraumatic, nonneoplastic subglottic stenosis. Ann Otol Rhinol Laryngol 1975;84:757-763. Dolan DL. Relapsing polychondritis: analytical literature review and studies on pathogenesis. Am J Med 1966;41:285-299. Eliachar I, Lichtig C. Local amyloid deposits of the larynx: electron microscopic studies of three cases. Arch Otolaryngol 1970;92:163-166. Finn DG, Farmer JC. Management of amyloidosis of the larynx and trachea. Arch Otolaryngol 1982;108:54-56. Foidart J, Shigeto A, Martin GR, et al. Autoantibodies to type II collagen in relapsing polychondritis. N Engl J Med 1978;229:1203-1207. Fukuda K, Yuasa K, Uchizono A, Matsuyama H, Shimada K, Ohyama M. Three cases of Wegener's granulomatosis treated with an antimicrobial agent. Arch Otolaryngol Head Neck Surg 1989;115:515-518. Gamea AM. Role of endoscopy in diagnosing scleroma in its uncommon sites. J Laryngol Otol 1990;104:619-621. Heiner ER. Primary amyloidosis of the larynx. Arch Otolaryngol 1968;87:413-415. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener's granulomatosis: an analysis of 158 patients. Ann Intern Med 1992;116:488-498. Hurbis CG, Holinger LD. Laryngeal amyloidosis in a child. Ann Otol Rhinol Laryngol 1990;99:105-107. Irani BS, Martin-Hirsch DP, Clark D, Hand DW, Vize CE, Black J. Relapsing polychondritis - a study of four cases. J Laryngol Otol 1992;106:911-914. Kornblut AD, Wolff SM, deFries HO, Fauci AS. Wegener's granulomatosis. Otolaryngol Clin North Am 1982;15:673-683. Lebovics RS, Hoffman GS, Leavitt RY, Kerr SG, Travis WD, Kammerer W, et al. The management of subglottic stenosis in patients with Wegener's granulomatosis. Laryngoscope 1992;102:1341-1345. Maher AI, El-Kashlan HK, Soliman Y, Galal R. Rhinoscleroma: management by carbon dioxide surgical laser. Laryngoscope 1990;100:783-788. McAlpine JC. Fuller AP. Localized laryngeal amyloidosis, a report of a case with a review of the literature. J Laryngol Otol 1964;78:296-314. McCaffrey TV. Classification of laryngotracheal stenosis. Laryngoscope 1992;102:1335-1340. McCaffrey TV. Management of subglottic stenosis in the adult. Ann Otol Rhinol Laryngol 1991;100:90-94. McDonald TJ, DeRemee RA. Wegener's granulomatosis. Laryngoscope 1983;93:220-231. McDonald RJ, DeRemee RA, Weiland LH. Wegener's granulomatosis and polymorphic reticulosis - two diseases or one? Experience with 90 patients. Arch Otolaryngol 1981;107:141-144. McDonald TJ, Neel HB 3rd, DeRemee RA. Wegener's granulomatosis of the subglottis and the upper portion of the trachea. Ann Otol Rhinol Laryngol 1982;91:588-592. Michet JM. Relapsing polychondritis: survival and predictive role of early disease manifestations. Ann Intern Med 1986;104:74-78. Miller RH, Weatherly RA. Experience with anterior cricoid split for difficult neonatal extubation. Arch Otolaryngol Head Neck Surg 1986;112:972-975. Mitrani M, Biller HF. Laryngeal amyloidosis. Laryngoscope 1985;95:1346-1347. Parrish KL, Miller RH. Subglottic stenosis. J La Med Soc 1991;143:7-10. Perkins BA, Hamill JR, Musher DM, O'Hara C. In vitro activities of streptomycin and 11 oral antimicrobial agents against clinical isolates of Klebsiella rhinoscleromatis. Antimicrob Agents Chemother 1992;36:1785-1787. Prasad S, Grundfast KE, Lipnick R. Airway obstruction in an adolescent with relapsing polychondritis. Otolaryngol Head Neck Surg 1990;103:113-116. Raymond AK, Sneige N, Batsakis JG. Amyloidosis in the upper aerodigestive tracts. Ann Otol Rhinol Laryngol 1992:101:794-796. Rifai M. Laryngotracheal resection for post scleromatous laryngeal stenosis. J Laryngol Otol 1989;103:935-938. Samuelson TE, Bailey BJ. Degenerative and idiopathic diseases. In: Bailey BJ, ed. Head and Neck Surgery - Otolaryngology. Philadelphia: Lippincott, 1993:149-162. Schwartz RS, Cohen JR, Schrier SL. Therapy of primary amyloidosis with melphalan and prednisone. Arch Intern Med 1979;139:1144-1146. Simpson GT 2nd, Strong MS, Skinner M, Cohen AS. Localized amyloidosis of the head and neck and upper aerodigestive and lower respiratory tracts. Ann Otol Rhinol Laryngol 1984;93:374-379. Stome M. Subglottic stenosis: therapeutic considerations. Otolaryngol Clin North Am 1984;17:63-68. Symmers W. Primary amyloidosis: a review. J Clin Pathol 1956;9:127-211. Talbot A. Laryngeal amyloidosis. J Laryngol Otol 1990;104:147-149. Watson J, Donald PJ, Gourley IM, et al. Composite vascularized free-rib and pleural transfer for laryngotracheal reconstruction. Otolaryngol Head Neck Surg 1983;91:384-395. Waxman J, Bose WJ. Laryngeal manifestations of Wegener's granulomatosis: case reports and review of the literature. J Rheumatol 1986;13:408-411. Wegener F. Über eine eigenurtige rhinogene Granulomatose mit besonderer Beteilung des Arteriensystems und der Nieren. Beitr Pathol 1939;102:36-68. Wegener F. Über generalisierte, septische Getasser kranukungen. Vest Dtsch Path Ges 1936;29:202-210. Grand Rounds Archive | Department Home page BCM Public | BCM Intranet | Privacy Notices | Contact BCM | BCM Site Map | ©2001-2006 Baylor College of Medicine
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