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Evaluation and management of acute uvular edema
CASE REPORT
angioedema uvula, edema
Evaluation and Management of Acute Uvular Edema From the Departments of Emergency Medicine* and Otolaryngology,~ Los Angeles County-University of Southern California, Los Angeles; and the Department of Emergency Medicine, Northwestern University, Chicago, Illinois.'* Receivedfor publication October 9, 1991. Revision received February 17, 1992. Accepted for pub]icationjune 1, 1992.
Richard Goldberg, MD* Ronald Lawton, MD ¢ Edward Newton, MD* Warren S Line Jr, MD t
Acute uvular edema is a potentially life-threatening condition with a variety of causes. Other upper airway structures, most notably the epiglottis, may also become involved, and complete or partial airway obstruction may ensue rapidly. An accurate diagnosis may be essential in establishing effective treatment. [Goldberg R, Lawton R, Newton E, Line WS Jr: Evaluation and management of acute uvular edema. Ann EmergMed February 1993;22:251-255.] INTRODUCTION Acute uvular edema is a relatively rare but potentially fatal cause of pharyngeal symptomatology. A variety of etiologies, including injection, 1-3 trauma,,-7 neoplasm,S and angioedema 9 are recognized. Treatment depends to a large degree on the ability to differentiate from among these causes. Because of uvular edema's life-threatening potential, the emergency physician should be familiar with the differential diagnosis and management of this entity.
CASE REPORT A 38-year-old man presented to the emergency department with a chief complaint of sore throat and difficulty breathing progressively over a two-hour period. There was no history of trauma fever, chills, or recent upper respiratory symptoms. The patient was generally in good health, although he had experienced an episode of complete airway obstruction six years earlier. At that time, he was diagnosed as having hereditary angioneurotic edema. He was started on danazol, an attenuated androgen, which he took for one year. His medical history was otherwise unremarkable. Physical examination revealed an alert patient who appeared to be anxious. Vital signs were blood pressure, 140/80 mm Hg; pulse, 100; oral temperature, 37 C; and respirations, 20. Examination of the head and neck revealed no drooling or stridor initially, although the patient's voice was muffled and had a "hot potato" quality
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The uvula and soft palate were pale and markedly edematous. The remainder of the physical examination was entirely normal. Laboratory investigations included CBC, urinalysis, culture and sensitivity of the throat and blood, serum electrolytes, and arterial blood gas. All tests including cultures were normal except for a leukocyte count of 12,400/mm. Arterial blood gases on 40% humidified 0 2 revealed a pH of 7.53, Po 2 of 237 mm Hg, and Pco 2 of 26 mm Hg. A lateral soft tissue radiograph of the neck revealed diffuse swelling of the supraglottic tissues, including the arytenoids and epiglottis. The patient rather suddenly developed increasing respiratory distress with obvious stridor. He was intubated nasotracheally with a 7F endotracheal tube. Chest radiograph confirmed proper tube position and demonstrated clear lung fields. The patient was treated with IV ampicillin 2 g and IV dexamethasone 12 mg and was admitted to the ICU. The hospital course was benign. The patient was maintained on IV ampicillin 500 mg every six hours and IV dexamethasone 8 mg every 12 hours for 48 hours. On the day after admission, flexible fiberoptic endoscopy of the pharynx and laryngeal area was performed and demonstrated substantial resolution of the swelling noted previously. The patient was extubated without difficulty approximately 24 hours after admission. He was discharged home on ampicillin 500 mg four times daily, a tapering course of prednisone, and danazol 200 mg three times daily. DISCUSSION
Whatever the initiating event,, acute uvular edema is ultimately the result of increased vascular permeability, lo Angioedema, also known as angioneurotic edema and Quincke's disease, is a particularly common etiologic factor and is defined as a well-localized edematous condition that may variably involve the deeper skin layers and subcutaneous tissues as well as the mucosal surfaces of the upper respiratory and gastrointestinal tracts. ~>13 Immediate hypersensitivity type 1 reactions, seen with atopic states and specific allergen sensitivities, are among the most common causes of angioedema. These reactions involve the interaction of an allergen with IgE antibodies bound to the surface of basophils or mastocytes. The resulting degranulation of these cells causes the release of a variety of vasoactive substances that promote the dilation of blood vessels and leakage of fluid and colloid into tissue, s4 Physical agents, including cold, pressure, light, and vibration, or processes that increase core
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temperature, may also cause edema through the IgE pathway. 15 Component parts of the complement system also have been implicated as a cause of angioedema, presumably by promoting the release of kinin-like substances, which may cause increased capillary permeability and edema, s< 1r Hereditary angioedema, a genetic disorder of the complement system, is characterized by either an absence or functional deficiency of C'I esterase inhibitor (C1E1).ll,12,18J 9 A deficiency of C1E1 allows unopposed activation of the first component of complement, with subsequent breakdown of its two substrates, the second (C'2) and fourth (C'4) components of the complement cascade. This process, in the presence of plasmin, generates a vasoactive kinin-like molecule that causes angioedema. 16 Acquired C1E1 deficiency and other complement consumption states have been described in patients with malignancies 2o-22 and immune complex disorders, including serum sickness and the vasculidities. 12,23 Other causes of angioedema include a direct degranulation effect on mast cells and basophils by certain medications and diagnostic agents (opiates, d-tubocurarine, curare, and radiocontrast materials)24-26; substances such as aspirin, nonsteroidal anti-inflammatory drugs, azo dyes, and benzoates that alter the metabolism of arachidonic acid by blocking its conversion to prostaglandins, 2r thus increasing smooth muscle permeability28; angiotensin-converting enzyme inhibitors, implicated presumably by promoting the production of bradykinin29; and mechanisms not yet elucidated called idiopathic. The inflammatory edema seen with infection, trauma, and occasionally neoplasm and cyst formation is mediated through byproducts of the complement system, either by triggering the release of histamine from mast ceils or by causing activation of the kinin system by activation of tissue kaflikrein. 16 The known infectious causes of uvulitis include group A streptococci, Haemophilis in~uenzae, and Streptococcus pneumoniae. 1,3,30An associated cellulitis may contiguously involve the uvula with the tonsils, posterior pharynx, or epiglottis.3, 8 The clinical manifestations of uvular edema may include foreign body sensation, dysphagia, muffled voice, gagging, and signs of upper airway obstruction such as drooling or stridor. 31 The latter symptoms may arise either from a swollen uvula or concomitant laryngeal edema.30, 32 Pain, odynophagia, and fever usually are associated with infectious etiologies. An infected uvula will have a typical inflammatory appearance and, as noted above, may be associated with pharyngitis, tonsillitis, or epiglottiditis.3, 8
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An angioedematous uvula is usually nonerythematous, pale, and swollen and resembles a large, white grape (uvular hydrops).r, 8 There may be associated allergic manifestations such as cutaneous flush, urticaria, or wheezing.l< 34 In addition, there may be a history of exposure to physical stimuli, specific allergens, or recurrent seasonal incidence. 1 With hereditary angioedema, the edema often involves the uvula and soft palate together, s Historical features of hereditary angioedema include recurrent episodes of edema with a family history of the same, absence of urticaria and pruritis, the occurrence of attacks of severe peripheral edema and abdominal colic, and the occasional occurrence of an erythematous, macular rash.go 2 Attacks may be precipitated by dental, pharyngeal, or upper respiratory manipulation. Signs of obstruction may begin slowly or develop quite rapidly. 12,~<~s In a review of 89 patients with hereditary angioedema, 76 had occurrence of head or neck edema, and 45 had symptoms of airway obstruction. 11 The laboratory workup of uvular swelling will depend primarily on whether the physician suspects an infectious or angioedematous condition to be present. The two are usually distinguishable on clinical grounds. The ED evaluation of angioedema is limited. A CBC may suggest an allergic reaction if eosinophilia is present. If hereditary angioedema or an acquired complement deficiency disorder is suspected, a C-4 level is an excellent screening test. More comprehensive tests include immunochemical and functional assays for C1E1 as well as levels of the natural substrates of the complement Figure 1.
Management o/ uvular edema Acute Attacks Institute definitiveairwaymeasures(intubatioo,cricothyrotomy)as indicated Epinephrine,1:1,000,0.3 to 0.5 mL subcutaneousevery20 minutesx 3 Diphenhydramine,50 mg IM/IV everythreeto four hours Cimetidine,300 mg iV slowly (overthree minutes) Epinephrinebitartrate Methylprednisolone,125 mg IV four times daily Epsilonaminocaproicacid, 8 to 10 gm IV drip, first four hours, up to 16 to 20 g/day Fresh-frozenplasma(?) PurifiedCl E1 concentrates(notyet availablein the UnitedStates) Uvulardecompressionas indicated Antibiotics as indicated ProphylacticManagement Attenuatedandrogens(danazol,stanozolol) Antifibrinolyticagents(aminocaproicacid) PurifiedC1E1concentrates
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cascade.tt,12,~< 21 In addition, appropriate cultures and serology should be obtained when warranted. A therapeutic approach to the management of acute uvular edema is outlined (Figure 1). Because of the known association of uvular with hypopharyngeal swelling, either laryngoscopy or a soft tissue lateral radiograph of the neck should be considered. 3 The most immediate concern in managing patients with acute uvular edema is the degree to which the airway is compromised, either from uvular swelling itself or from associated hypopharyngeal involvement, 2,3,11-13 Those patients with substantial symptoms should have an IV line established and intubation equipment set up at the bedside. If an infection is clinically apparent, an antibiotic with a spectrum that includes Haemophiris *n/luenzae should be started. Hospitalization of patients with infectious uvulitis may not always be necessary but is warranted if any doubts exist as to airway competency, ls-~3 Typical allergic reactions, as opposed to episodes of hereditary angioedema, will respond well to incremental doses of epinephrine and parenteral antihistamine (H1 and I-I2) agents. The use of nebulized racemic epinephrine has also proved useful, especially when administered against a closed glottis. 1l, 12,21,33 Steroids are typically part of the therapeutic regimen, although their efficacy is unproven. 16,25 Patients with noninfectious uvulitis who do not respond to the above measures should be suspected of having a complement deficiency disorder and should also receive the plasmmogen inhibitor epsilonamino-caprolic acid., 1,12 Figure 2.
Proposed mechanism by which Cj esterase inhibitor deficiency promotes angioedema
Precursor C 1
I Plasmin C~
C4 + C 2
C1 esterase
L
[
J C,42
C2kinin
Hagernanfactor C~esterase
High molecularweight kinogen / Bradykinin
Angioederna
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Use of this agent is based on the observation that plasmin activates C1 from its precursor state, setting the stage for complement cascade activation (Figure 2). Although aminocaproic acid has been shown to be effective in the prophylactic management of hereditary angioedema, its value in the management of acute symptoms has not been well established.11, ~2 Similarly, the attenuated androgens danazol and stanoz0101 have been highly successful prophylactic agents, but their use in an acute setting has not been conclusively demonstrated. ~2,18 Specific replacement therapy with purified C1E1 has been used successfully in Europe, both in the management of acute episodes and as a prophylactic agent. C1E1 has not yet been approved for use in the United States. 12,33 Likewise, the use of fresh-frozen plasma has been advocated by some as a means of increasing C1 levels. 34 Others have pointed out that fresh-frozen plasma, by supplying substrate for the complement cascade, may actually serve to increase the severity of attacks. ~~,s2a8 No specific recommendations regarding fresh-frozen plasma can be made at this time. Uvular decompression is another treatment modality that may be useful, espedally in those patients who are resistant to other treatment or whose symptoms are rapidly progressive. The procedure involves grasping the uvula with forceps and either making several lacerations with a sterile needler or snipping the distal centimeter as a partial uvulectomy. 35 If there is any indication that the uvular edema is progressing despite any or all the above measures, definitive airway management should be instituted immediately. Once stabilized and admitted to the hospital, the patient should be evaluated by an immunologist/allergist if a noninfectious etiology is suspected. 7,8,13 Patients with recurrent, disabling attacks of hereditary angioedema are candidates for long-term prophylactic treatment, either with antifibrinolytic agents such as aminocaproic acid or with purified C1E1.
REFERENCES 1. Kotkoff KL, Weld ER: Uvulitis in children. PediatrlnfectDis 1983;2:392-393. 2. Winder SG, Lampe RM, ShoemakerME: Uvulitis and HemophilusinfluenzaeB. PediatrEmerg Care1986;2:23-25. 3. RapkinRH: Simultaneous uvulitis and apigfottitis. JAMA 1980;243:1843. 4. Ravindrin R, Priddy S: Uvular edema, a rare complication of endotracheal intubation. Anesthesiology1978;48:374-375. 5. FishA, LigumskyM, Wolnerman JS: Necrosis of the uvula after endoscopy. Gastreintest Endosc1984;3:317. 6. Schulman MS: Uvular edema without endotracheal intubation. Anesthesiology1981;55:82-83. 7. Marlowe FL, AghamohamadiA: Otolaryngologicemergencies, in Tintinalli JE, Rothstein RJ, Krome RL (ads): EmergencyMedicine:A ComprehensiveStudyGuide. New York, McGraw-Hill, 1985, p 730-738. 8. ReddyCR, Margolin SJ: Acute uvular edema. Am J Dis Child1983;137:1205-1206. 9. Simons HM: Dermatologic emergencies, in Schwartz GR, Safer P, Stone JH, et al (ads): Principlesand Practiceof EmergencyMedicine. Philadelphia,WB Saunders, 1978, p 1280. 10. Jarvis 8L, CoreyJP: Acute uvular edema. EarNosa ThroatJ 1988;669:665-666. 11. Pruet CW, Kornblut AD, Bdckman C, et al: Management of the airway in patients with angioedema. Laryngoscope1983;93:749-755. 12. Sire TC, Grant JA: Hereditary angioedema: Its diagnostic and managementperspectives.Am J Mad 1990;88:656-664. 13. EvansTC, Roberge RJ: Quincke'sdisease of the uvula. Am J EmergMed1987;5:2f1-221. 14. Kantor FS: Angioneurotic edema, in Veeson PB, McDermott W, Wyngarden JE {eds): Cecil Textbookof Medicine. Philadelphia,WB Saunders, 1979, p 162. 15. Sotor NA, Wasserman SI: IgE dependent urticaria, angioederna,and anaphylaxis, in Fitzpatrick TB, EisenAZ, Wolff K, et al (ads): Dermatologyin GeneralMedicine. New York, McGraw-Hill, 1979, p 532-541. 16. Synkowski DR: Urticaria. EmergMed Clin NorthAm 1985;3:737-745. 17. KlernpererMR, Donaldson8H, RosenFS: Effect of C1 esterase on vascular permeability and man: Studies in normal and complement deficient individuals and in patients with hereditary angioneurotic edema. J Clin Invest1968;47:604-611. 18. FrankMM, Galfand JA, Atkinson JP: Hereditary angioedema:The clinical syndromeand its management. Ann InternMad 1976;84:580-593. 19. Osier W: Hereditary angioneurotic oedema.Am J Mad Sci1888;95:362-367. 20. Gottleib M, Campbell K, PalzmannK, et ah Long-standingangioedema with Cl-esterase inhibitor deficiency associated with occult lymphoma. WestJMed1983;138:258-260. 21. RosenfeldSI, Staples PJ, LeddyJP: Angioedema and hypecomplementemia:Unusual features of lymphoma (abstract). J AIlergy Clin Immuno11975:55:104.
SUMMARY
Acute uvular edema is a potentially life-threatening condition with a variety of causes, the most common of which are allergic, infectious, or related to the complement cascade system. An accurate history may be critical in establishing the diagnosis and determining management. Treatment may include antibiotics, antihistamines, sympathomimedc agents, steroids, and plasminogen-inhibiting agents. Because of the frequently noted association of uvular with hypopharyngeal edema, the primary concern
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in the management of this entity is adequacy of the airway. As was demonstrated in the case report, the emergency physician must be prepared to quickly institute intubation or other definitive airway measures should more conservative measures prove ineffective.
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22. CohenSH, Clothe SS, Kozin F, et al: Acquired angioedema associated with rectal carcinoma--Its responseto danazol therapy. JAflergy Clin Immortal1978;62:217-221. 23. Gelfand JA, Sheerins RJ, Alflng DW, et al: Treatment of hereditary angioedemawith danazok N EnglJ Mad 1976;295:1444-1448. 24. Scheenfeld MR: Acute allergic reactions to morphine, codeine, meperidine, hydrochloride and opium alkaloids. N EnglJ Mad 1960;60:2591-2593. 25. ComroeJE, Dripps RD: Histamine-like action ef curare and tubocurarina injected intracutaheouslyand intra-arterially in man. Anaesthesiology1947;7:260-262. 26. Arroyave CM, Bhat KN, Crown R: Activation of the alternative pathway of complement system by radiographic contrast media. Jlmmuno11976;117:1866-1869.
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27.8odey J, there M, Malet A, et al: Aspirin-induced recurrent urticaria and recurrent angioedernain nen-atopic children. Ann Allerg 1984;53:265-267. 28. Yechies LD, KaplanAP: Urticaria, in ParkerC (ed): Clinical Immunology.Philadelphia,WB Saunders, 1980, p 1286-1288. 29. GornezHJ, Cirille VJ, Irvin JD: EnalaprihA review of human pharmacology. Drugs 1985;30(suppl 1):13-24. 30. Li KI, Kiernan S, Wald ER, et al: Isolated uvulitis due to ftaemophilus influenzaetype B. Pediatrics 1984;74:I054-1057. 31. DeWeese DB, SaundersWH: Textbookof Otolaryngolegy.St Louis, CV Mosby, 1982, p 53.
The authors thank Janet Goldberg for her help in preparing the manuscript.
Address for reprints: Richard Goldberg, MD LAC-USC Medical Center 1200 North State Street, Room 1011 Los Angeles, California 90033
32. Hasalby KA, McNeice WL: Respiratoryobstruction from uvular edema in a pediatric patient. Anesth Analg 1983;62:1127-1128. 33. Bark K, Whitzke G: Long-term prophylaxis with 01 inhibiter concentrate in patients with recurrent angioedernacaused by hereditary and acquired C1 inhibitor deficiency. J Allergy Clin Immunol 1989;83:677-682. 34. Coheng, PetersonA: Treatment of hereditary angioedernawith frozen plasma. Ann Allergy 1972;30:690-692. 35. Waekerle JF, Smith HA, McNabney WK: Hereditary angioneurotic edema treated with partial uvulectomy. JACEP1976;5:446-448.
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angioedema uvula, edema
Evaluation and Management of Acute Uvular Edema From the Departments of Emergency Medicine* and Otolaryngology,~ Los Angeles County-University of Southern California, Los Angeles; and the Department of Emergency Medicine, Northwestern University, Chicago, Illinois.'* Receivedfor publication October 9, 1991. Revision received February 17, 1992. Accepted for pub]icationjune 1, 1992.
Richard Goldberg, MD* Ronald Lawton, MD ¢ Edward Newton, MD* Warren S Line Jr, MD t
Acute uvular edema is a potentially life-threatening condition with a variety of causes. Other upper airway structures, most notably the epiglottis, may also become involved, and complete or partial airway obstruction may ensue rapidly. An accurate diagnosis may be essential in establishing effective treatment. [Goldberg R, Lawton R, Newton E, Line WS Jr: Evaluation and management of acute uvular edema. Ann EmergMed February 1993;22:251-255.] INTRODUCTION Acute uvular edema is a relatively rare but potentially fatal cause of pharyngeal symptomatology. A variety of etiologies, including injection, 1-3 trauma,,-7 neoplasm,S and angioedema 9 are recognized. Treatment depends to a large degree on the ability to differentiate from among these causes. Because of uvular edema's life-threatening potential, the emergency physician should be familiar with the differential diagnosis and management of this entity.
CASE REPORT A 38-year-old man presented to the emergency department with a chief complaint of sore throat and difficulty breathing progressively over a two-hour period. There was no history of trauma fever, chills, or recent upper respiratory symptoms. The patient was generally in good health, although he had experienced an episode of complete airway obstruction six years earlier. At that time, he was diagnosed as having hereditary angioneurotic edema. He was started on danazol, an attenuated androgen, which he took for one year. His medical history was otherwise unremarkable. Physical examination revealed an alert patient who appeared to be anxious. Vital signs were blood pressure, 140/80 mm Hg; pulse, 100; oral temperature, 37 C; and respirations, 20. Examination of the head and neck revealed no drooling or stridor initially, although the patient's voice was muffled and had a "hot potato" quality
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The uvula and soft palate were pale and markedly edematous. The remainder of the physical examination was entirely normal. Laboratory investigations included CBC, urinalysis, culture and sensitivity of the throat and blood, serum electrolytes, and arterial blood gas. All tests including cultures were normal except for a leukocyte count of 12,400/mm. Arterial blood gases on 40% humidified 0 2 revealed a pH of 7.53, Po 2 of 237 mm Hg, and Pco 2 of 26 mm Hg. A lateral soft tissue radiograph of the neck revealed diffuse swelling of the supraglottic tissues, including the arytenoids and epiglottis. The patient rather suddenly developed increasing respiratory distress with obvious stridor. He was intubated nasotracheally with a 7F endotracheal tube. Chest radiograph confirmed proper tube position and demonstrated clear lung fields. The patient was treated with IV ampicillin 2 g and IV dexamethasone 12 mg and was admitted to the ICU. The hospital course was benign. The patient was maintained on IV ampicillin 500 mg every six hours and IV dexamethasone 8 mg every 12 hours for 48 hours. On the day after admission, flexible fiberoptic endoscopy of the pharynx and laryngeal area was performed and demonstrated substantial resolution of the swelling noted previously. The patient was extubated without difficulty approximately 24 hours after admission. He was discharged home on ampicillin 500 mg four times daily, a tapering course of prednisone, and danazol 200 mg three times daily. DISCUSSION
Whatever the initiating event,, acute uvular edema is ultimately the result of increased vascular permeability, lo Angioedema, also known as angioneurotic edema and Quincke's disease, is a particularly common etiologic factor and is defined as a well-localized edematous condition that may variably involve the deeper skin layers and subcutaneous tissues as well as the mucosal surfaces of the upper respiratory and gastrointestinal tracts. ~>13 Immediate hypersensitivity type 1 reactions, seen with atopic states and specific allergen sensitivities, are among the most common causes of angioedema. These reactions involve the interaction of an allergen with IgE antibodies bound to the surface of basophils or mastocytes. The resulting degranulation of these cells causes the release of a variety of vasoactive substances that promote the dilation of blood vessels and leakage of fluid and colloid into tissue, s4 Physical agents, including cold, pressure, light, and vibration, or processes that increase core
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temperature, may also cause edema through the IgE pathway. 15 Component parts of the complement system also have been implicated as a cause of angioedema, presumably by promoting the release of kinin-like substances, which may cause increased capillary permeability and edema, s< 1r Hereditary angioedema, a genetic disorder of the complement system, is characterized by either an absence or functional deficiency of C'I esterase inhibitor (C1E1).ll,12,18J 9 A deficiency of C1E1 allows unopposed activation of the first component of complement, with subsequent breakdown of its two substrates, the second (C'2) and fourth (C'4) components of the complement cascade. This process, in the presence of plasmin, generates a vasoactive kinin-like molecule that causes angioedema. 16 Acquired C1E1 deficiency and other complement consumption states have been described in patients with malignancies 2o-22 and immune complex disorders, including serum sickness and the vasculidities. 12,23 Other causes of angioedema include a direct degranulation effect on mast cells and basophils by certain medications and diagnostic agents (opiates, d-tubocurarine, curare, and radiocontrast materials)24-26; substances such as aspirin, nonsteroidal anti-inflammatory drugs, azo dyes, and benzoates that alter the metabolism of arachidonic acid by blocking its conversion to prostaglandins, 2r thus increasing smooth muscle permeability28; angiotensin-converting enzyme inhibitors, implicated presumably by promoting the production of bradykinin29; and mechanisms not yet elucidated called idiopathic. The inflammatory edema seen with infection, trauma, and occasionally neoplasm and cyst formation is mediated through byproducts of the complement system, either by triggering the release of histamine from mast ceils or by causing activation of the kinin system by activation of tissue kaflikrein. 16 The known infectious causes of uvulitis include group A streptococci, Haemophilis in~uenzae, and Streptococcus pneumoniae. 1,3,30An associated cellulitis may contiguously involve the uvula with the tonsils, posterior pharynx, or epiglottis.3, 8 The clinical manifestations of uvular edema may include foreign body sensation, dysphagia, muffled voice, gagging, and signs of upper airway obstruction such as drooling or stridor. 31 The latter symptoms may arise either from a swollen uvula or concomitant laryngeal edema.30, 32 Pain, odynophagia, and fever usually are associated with infectious etiologies. An infected uvula will have a typical inflammatory appearance and, as noted above, may be associated with pharyngitis, tonsillitis, or epiglottiditis.3, 8
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An angioedematous uvula is usually nonerythematous, pale, and swollen and resembles a large, white grape (uvular hydrops).r, 8 There may be associated allergic manifestations such as cutaneous flush, urticaria, or wheezing.l< 34 In addition, there may be a history of exposure to physical stimuli, specific allergens, or recurrent seasonal incidence. 1 With hereditary angioedema, the edema often involves the uvula and soft palate together, s Historical features of hereditary angioedema include recurrent episodes of edema with a family history of the same, absence of urticaria and pruritis, the occurrence of attacks of severe peripheral edema and abdominal colic, and the occasional occurrence of an erythematous, macular rash.go 2 Attacks may be precipitated by dental, pharyngeal, or upper respiratory manipulation. Signs of obstruction may begin slowly or develop quite rapidly. 12,~<~s In a review of 89 patients with hereditary angioedema, 76 had occurrence of head or neck edema, and 45 had symptoms of airway obstruction. 11 The laboratory workup of uvular swelling will depend primarily on whether the physician suspects an infectious or angioedematous condition to be present. The two are usually distinguishable on clinical grounds. The ED evaluation of angioedema is limited. A CBC may suggest an allergic reaction if eosinophilia is present. If hereditary angioedema or an acquired complement deficiency disorder is suspected, a C-4 level is an excellent screening test. More comprehensive tests include immunochemical and functional assays for C1E1 as well as levels of the natural substrates of the complement Figure 1.
Management o/ uvular edema Acute Attacks Institute definitiveairwaymeasures(intubatioo,cricothyrotomy)as indicated Epinephrine,1:1,000,0.3 to 0.5 mL subcutaneousevery20 minutesx 3 Diphenhydramine,50 mg IM/IV everythreeto four hours Cimetidine,300 mg iV slowly (overthree minutes) Epinephrinebitartrate Methylprednisolone,125 mg IV four times daily Epsilonaminocaproicacid, 8 to 10 gm IV drip, first four hours, up to 16 to 20 g/day Fresh-frozenplasma(?) PurifiedCl E1 concentrates(notyet availablein the UnitedStates) Uvulardecompressionas indicated Antibiotics as indicated ProphylacticManagement Attenuatedandrogens(danazol,stanozolol) Antifibrinolyticagents(aminocaproicacid) PurifiedC1E1concentrates
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cascade.tt,12,~< 21 In addition, appropriate cultures and serology should be obtained when warranted. A therapeutic approach to the management of acute uvular edema is outlined (Figure 1). Because of the known association of uvular with hypopharyngeal swelling, either laryngoscopy or a soft tissue lateral radiograph of the neck should be considered. 3 The most immediate concern in managing patients with acute uvular edema is the degree to which the airway is compromised, either from uvular swelling itself or from associated hypopharyngeal involvement, 2,3,11-13 Those patients with substantial symptoms should have an IV line established and intubation equipment set up at the bedside. If an infection is clinically apparent, an antibiotic with a spectrum that includes Haemophiris *n/luenzae should be started. Hospitalization of patients with infectious uvulitis may not always be necessary but is warranted if any doubts exist as to airway competency, ls-~3 Typical allergic reactions, as opposed to episodes of hereditary angioedema, will respond well to incremental doses of epinephrine and parenteral antihistamine (H1 and I-I2) agents. The use of nebulized racemic epinephrine has also proved useful, especially when administered against a closed glottis. 1l, 12,21,33 Steroids are typically part of the therapeutic regimen, although their efficacy is unproven. 16,25 Patients with noninfectious uvulitis who do not respond to the above measures should be suspected of having a complement deficiency disorder and should also receive the plasmmogen inhibitor epsilonamino-caprolic acid., 1,12 Figure 2.
Proposed mechanism by which Cj esterase inhibitor deficiency promotes angioedema
Precursor C 1
I Plasmin C~
C4 + C 2
C1 esterase
L
[
J C,42
C2kinin
Hagernanfactor C~esterase
High molecularweight kinogen / Bradykinin
Angioederna
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Use of this agent is based on the observation that plasmin activates C1 from its precursor state, setting the stage for complement cascade activation (Figure 2). Although aminocaproic acid has been shown to be effective in the prophylactic management of hereditary angioedema, its value in the management of acute symptoms has not been well established.11, ~2 Similarly, the attenuated androgens danazol and stanoz0101 have been highly successful prophylactic agents, but their use in an acute setting has not been conclusively demonstrated. ~2,18 Specific replacement therapy with purified C1E1 has been used successfully in Europe, both in the management of acute episodes and as a prophylactic agent. C1E1 has not yet been approved for use in the United States. 12,33 Likewise, the use of fresh-frozen plasma has been advocated by some as a means of increasing C1 levels. 34 Others have pointed out that fresh-frozen plasma, by supplying substrate for the complement cascade, may actually serve to increase the severity of attacks. ~~,s2a8 No specific recommendations regarding fresh-frozen plasma can be made at this time. Uvular decompression is another treatment modality that may be useful, espedally in those patients who are resistant to other treatment or whose symptoms are rapidly progressive. The procedure involves grasping the uvula with forceps and either making several lacerations with a sterile needler or snipping the distal centimeter as a partial uvulectomy. 35 If there is any indication that the uvular edema is progressing despite any or all the above measures, definitive airway management should be instituted immediately. Once stabilized and admitted to the hospital, the patient should be evaluated by an immunologist/allergist if a noninfectious etiology is suspected. 7,8,13 Patients with recurrent, disabling attacks of hereditary angioedema are candidates for long-term prophylactic treatment, either with antifibrinolytic agents such as aminocaproic acid or with purified C1E1.
REFERENCES 1. Kotkoff KL, Weld ER: Uvulitis in children. PediatrlnfectDis 1983;2:392-393. 2. Winder SG, Lampe RM, ShoemakerME: Uvulitis and HemophilusinfluenzaeB. PediatrEmerg Care1986;2:23-25. 3. RapkinRH: Simultaneous uvulitis and apigfottitis. JAMA 1980;243:1843. 4. Ravindrin R, Priddy S: Uvular edema, a rare complication of endotracheal intubation. Anesthesiology1978;48:374-375. 5. FishA, LigumskyM, Wolnerman JS: Necrosis of the uvula after endoscopy. Gastreintest Endosc1984;3:317. 6. Schulman MS: Uvular edema without endotracheal intubation. Anesthesiology1981;55:82-83. 7. Marlowe FL, AghamohamadiA: Otolaryngologicemergencies, in Tintinalli JE, Rothstein RJ, Krome RL (ads): EmergencyMedicine:A ComprehensiveStudyGuide. New York, McGraw-Hill, 1985, p 730-738. 8. ReddyCR, Margolin SJ: Acute uvular edema. Am J Dis Child1983;137:1205-1206. 9. Simons HM: Dermatologic emergencies, in Schwartz GR, Safer P, Stone JH, et al (ads): Principlesand Practiceof EmergencyMedicine. Philadelphia,WB Saunders, 1978, p 1280. 10. Jarvis 8L, CoreyJP: Acute uvular edema. EarNosa ThroatJ 1988;669:665-666. 11. Pruet CW, Kornblut AD, Bdckman C, et al: Management of the airway in patients with angioedema. Laryngoscope1983;93:749-755. 12. Sire TC, Grant JA: Hereditary angioedema: Its diagnostic and managementperspectives.Am J Mad 1990;88:656-664. 13. EvansTC, Roberge RJ: Quincke'sdisease of the uvula. Am J EmergMed1987;5:2f1-221. 14. Kantor FS: Angioneurotic edema, in Veeson PB, McDermott W, Wyngarden JE {eds): Cecil Textbookof Medicine. Philadelphia,WB Saunders, 1979, p 162. 15. Sotor NA, Wasserman SI: IgE dependent urticaria, angioederna,and anaphylaxis, in Fitzpatrick TB, EisenAZ, Wolff K, et al (ads): Dermatologyin GeneralMedicine. New York, McGraw-Hill, 1979, p 532-541. 16. Synkowski DR: Urticaria. EmergMed Clin NorthAm 1985;3:737-745. 17. KlernpererMR, Donaldson8H, RosenFS: Effect of C1 esterase on vascular permeability and man: Studies in normal and complement deficient individuals and in patients with hereditary angioneurotic edema. J Clin Invest1968;47:604-611. 18. FrankMM, Galfand JA, Atkinson JP: Hereditary angioedema:The clinical syndromeand its management. Ann InternMad 1976;84:580-593. 19. Osier W: Hereditary angioneurotic oedema.Am J Mad Sci1888;95:362-367. 20. Gottleib M, Campbell K, PalzmannK, et ah Long-standingangioedema with Cl-esterase inhibitor deficiency associated with occult lymphoma. WestJMed1983;138:258-260. 21. RosenfeldSI, Staples PJ, LeddyJP: Angioedema and hypecomplementemia:Unusual features of lymphoma (abstract). J AIlergy Clin Immuno11975:55:104.
SUMMARY
Acute uvular edema is a potentially life-threatening condition with a variety of causes, the most common of which are allergic, infectious, or related to the complement cascade system. An accurate history may be critical in establishing the diagnosis and determining management. Treatment may include antibiotics, antihistamines, sympathomimedc agents, steroids, and plasminogen-inhibiting agents. Because of the frequently noted association of uvular with hypopharyngeal edema, the primary concern
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in the management of this entity is adequacy of the airway. As was demonstrated in the case report, the emergency physician must be prepared to quickly institute intubation or other definitive airway measures should more conservative measures prove ineffective.
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22. CohenSH, Clothe SS, Kozin F, et al: Acquired angioedema associated with rectal carcinoma--Its responseto danazol therapy. JAflergy Clin Immortal1978;62:217-221. 23. Gelfand JA, Sheerins RJ, Alflng DW, et al: Treatment of hereditary angioedemawith danazok N EnglJ Mad 1976;295:1444-1448. 24. Scheenfeld MR: Acute allergic reactions to morphine, codeine, meperidine, hydrochloride and opium alkaloids. N EnglJ Mad 1960;60:2591-2593. 25. ComroeJE, Dripps RD: Histamine-like action ef curare and tubocurarina injected intracutaheouslyand intra-arterially in man. Anaesthesiology1947;7:260-262. 26. Arroyave CM, Bhat KN, Crown R: Activation of the alternative pathway of complement system by radiographic contrast media. Jlmmuno11976;117:1866-1869.
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27.8odey J, there M, Malet A, et al: Aspirin-induced recurrent urticaria and recurrent angioedernain nen-atopic children. Ann Allerg 1984;53:265-267. 28. Yechies LD, KaplanAP: Urticaria, in ParkerC (ed): Clinical Immunology.Philadelphia,WB Saunders, 1980, p 1286-1288. 29. GornezHJ, Cirille VJ, Irvin JD: EnalaprihA review of human pharmacology. Drugs 1985;30(suppl 1):13-24. 30. Li KI, Kiernan S, Wald ER, et al: Isolated uvulitis due to ftaemophilus influenzaetype B. Pediatrics 1984;74:I054-1057. 31. DeWeese DB, SaundersWH: Textbookof Otolaryngolegy.St Louis, CV Mosby, 1982, p 53.
The authors thank Janet Goldberg for her help in preparing the manuscript.
Address for reprints: Richard Goldberg, MD LAC-USC Medical Center 1200 North State Street, Room 1011 Los Angeles, California 90033
32. Hasalby KA, McNeice WL: Respiratoryobstruction from uvular edema in a pediatric patient. Anesth Analg 1983;62:1127-1128. 33. Bark K, Whitzke G: Long-term prophylaxis with 01 inhibiter concentrate in patients with recurrent angioedernacaused by hereditary and acquired C1 inhibitor deficiency. J Allergy Clin Immunol 1989;83:677-682. 34. Coheng, PetersonA: Treatment of hereditary angioedernawith frozen plasma. Ann Allergy 1972;30:690-692. 35. Waekerle JF, Smith HA, McNabney WK: Hereditary angioneurotic edema treated with partial uvulectomy. JACEP1976;5:446-448.
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