In a few isolated cases, usually those caused by hereditary angioneurotic edema, the swelling of the uvula and adjacent structures may be so severe that the airway is compromised, but this is a rare occurrence. The medical literature is quite deficient and confusing in its discussion of acute uvular edema, and most emergency medicine textbooks don't even reference it in the index.
This is certainly a process with a number of diverse etiologies. Scattered case reports shed some clinical light on the process, but these tend to characterize this condition as more serious than is commonly encountered. The literature tends to lump hereditary angioneurotic edema (HANE), allergic reactions, and idiopathic isolated swelling of the uvula into the same category, but these are very different conditions that require different clinical approaches.
Evaluation and Management of Acute Uvular Edema, Goldberg R, et al Ann Emerg Med 1993;22:251
Simultaneous Uvulitis and Epiglottis Without Fever or Leukocytosis, Jarrad D, et al Am J Emerg Med 1996;14:551
The authors of this case report and review of the literature characterize acute uvular edema as a potentially life-threatening condition stemming from a variety of causes. A number of etiologies have been suggested, including trauma, neoplasm, and angioedema. In the case report in this article, a 38-year-old man presented to the ED with a chief complaint of a sore throat and difficulty breathing that progressed over a two-hour period. There was no history of trauma, fever, or recent upper respiratory symptoms.
The patient had been in good health, but had had a similar episode that resulted in complete airway obstruction six years earlier. At that time he was diagnosed as having hereditary angioneurotic edema (HANE). On this occasion, the patient had normal vital signs with no drooling or stridor. Initially he had a muffled voice. The uvula and soft palate were pale and markedly edematous. The rest of the examination was unrevealing. Except for a slightly elevated WBC count, all laboratory tests were normal.
A lateral neck x-ray demonstrated diffuse swelling of the supraglottic tissues, including arytenoids and the epiglottis. The patient suddenly developed increasing stridor and respiratory distress, necessitating tracheal intubation. The nasal tracheal route was chosen, and a 7 F tracheal tube was used. The airway was secured and the patient was administered ampicillin and dexamethasone. Within 24 hours, the swelling markedly decreased, and he was discharged without complications. He was treated with a tapering dose of prednisone and prophylactic danazol (an androgen) as an outpatient for HANE.
The authors note that angioedema of the uvula is often known as angioneurotic edema or Quincke's disease. This is confusing because Quincke's disease is uvular edema from any cause (of which there are many), and HANE is a specific disorder that can cause Quincke's disease. Strictly speaking, HANE is edema of the mucosal surfaces of the skin and upper respiratory tract and occasionally the GI tract. These authors state that uvular angioedema can occasionally be considered as an acute hypersensitivity reaction, essentially an allergic phenomenon that is IgE mediated. HANE is a genetic disorder of the complement system. It's characterized by a deficiency or absence of C1 esterase inhibitor. The lack of this inhibitor generates a vasoactive kinin-like molecule that produces vasogenic edema. A variety of other causes of angioedema are listed, including mast cell degranulation secondary to medications and diagnostic agents, and an idiopathic condition. Occasionally there are infectious causes, although this is best termed uvulitis, not angioedema.
Regardless of the cause of uvular edema, the clinical condition is manifested as a foreign body sensation in the throat, dysphagia, muffled voice, gagging, and occasionally signs of upper airway obstruction. With associated fever and pain, there is usually an infection. When the cause is noninfectious angioedema, the uvula resembles a large white grape (termed uvular hydrops). Usually the laboratory is of no value, although a CBC might suggest an allergic reaction if eosinophilia is present, and a C-4 level is a screening test for HANE or an acquired complement deficiency.
As an overview, the authors outline a suggested management. This includes a variety of interventions, including standard medications used to treat generic allergic reactions. They would include epinephrine, antihistamines (both H1 and H2 blockers) and corticosteroids. In the case of C-1 esterase inhibitor deficiency, fresh frozen plasma or epsilonaminocaproic acid (a plasminogen inhibitor) may be of value. Of course, the most worrisome issue for the emergency physician is upper airway swelling that is severe enough to cause airway compromise.
A number of surgical interventions, including attempts to drain the angioedema by making slices in the uvular with a needle or actually excising the distal tip of the uvula to allow fluid egress have been recommended in unusual cases.
Comment: This article is one of the few that appear in the emergency medicine literature on this topic, and it is somewhat confusing. It essentially attempts to discuss the evaluation and management of acute uvular edema from any cause by presenting a classic case of HANE. In addition, all other causes of acute uvular swelling are briefly discussed. The condition that faces most emergency physicians is not similar to the case in this report. I have never knowingly seen a case of HANE, but I have seen dozens of cases of edematous uvalae.
The acute uvular swelling that usually presents to the ED involves a previously healthy individual who wakes up with a sensation of swelling or a lump in the throat, looks in the mirror, and sees a strange pendulous object in the pharynx (an elongated uvula), and comes to the emergency department in an anxious state. This is usually a benign but annoying condition that has no significant potential for airway compromise. When the pharynx is examined, the physician will see a pale, boggy, edematous, gelatinous, enlarged, bullous-appearing uvula that looks like it was injected with water. It is not painful and is neither red nor cyanotic, and the surrounding structures are normal. The larynx, soft palate, and tonsils are notably uninvolved. Usually the patient has no idea why this happened, and the physician is left scratching his head trying to figure out the cause and clinical course of action.
In the absence of pain, fever, or other signs and symptoms of pharyngitis, it is difficult to implicate an infection. In the absence of pruritus or urticaria, laryngeal edema, or flushing, an allergic reaction seems quite unlikely. I have seen such patients on numerous occasions, probably six to eight times a year, and I have been unable to find an etiology in any case. In my experience, this is not a recurrent problem, and if it were, I would consider it HANE or perhaps a legitimate allergy. If you try to look up acute uvulitis or angioedema of the uvula in the index of most emergency medicine textbooks, you won't find it.
The clinician is now faced with a stable patient with an annoying, enlarged uvula, often of a rather impressive size. Once airway problems have been ruled out, most clinicians feel that they should do something. I am unaware of any literature that suggests an actual benefit of any of the common interventions, but it's difficult not to give antihistamines and corticosteroids and occasionally subcutaneous epinephrine. Some of my colleagues have tried inhaled nebulized racemic epinephrine (you can also use regular asthma-like epinephrine), essentially treating it like epiglottitis. Others have suggested coating the swollen uvula with a cotton Q-tip saturated with the asthma concentration of epinephrine (1:1000) to produce topical vasoconstriction. I'm very skeptical about the therapeutic value of any intervention.
Most of my colleagues will treat this condition as an acute allergic reaction with standard medications, watch the patient for a few hours, and observe slow resolution of the process. The response is certainly not dramatic. In the absence of progressive swelling, airway compromise, or other coexistent conditions, patients can be discharged. They will quickly return if the uvular edema increases, but in my experience this does not occur. Somewhere in the back of my mind, I remember reading that acute uvular edema has been associated with smoking crack cocaine, probably related to thermal injury, but I was unable to find reference to this in the literature. Trauma from intubation, sticking a finger down the throat to induce vomiting, and overly aggressive suctioning are other causes. I do not believe that antibiotics are indicated under the scenario that I have discussed, and I do not think that any laboratory investigation or cultures are helpful.
I have on occasion tried scratching the uvula with an 18 gauge needle in an attempt to decompress the swelling. This anecdotal procedure has been described previously, and I found it mentioned in an older edition of Tintinalli's study guide. In my experience, this technique is not dangerous, but it has not been particularly successful. Some patients have trouble tolerating the procedure, although it appears to be a relatively benign intervention. The intent is to drain serous fluid, similar to draining a blister. Longitudinal slashes are made in the uvula to theoretically drain intestinal fluid. After the first few times that it was unsuccessful, I gave it up. Occasionally you can produce some bleeding which tends to make the patient more anxious.
Another unique treatment has been described, but its value is unproven. Peltz (J Allergy Clin Immunol 1996;97:717) sprayed topical concentrated epinephrine (0.3 ml of 1:1000) on an enlarged uvula with a 27 gauge needle, and noted a rapid but temporary diminution of the uvular edema. This is similar to painting the uvula with a topical epinephrine solution. Others have actually injected the uvula with a small amount of epinephrine, but this has the potential to necrose the uvula from prolonged vasoconstriction, and I recommend against it. In my case series of two patients where I did actually inject the uvula, one had a remarkable recovery and the other had no change in size but did develop a deeply cyanotic uvula for one hour until I reinjected the uvula with phentolamine to reverse the epinephrine. It pinked up in a few minutes, but I wonder what would have happened if I had waited a bit longer. I have decided to abandon this approach.
Certainly if airway compromise becomes an issue, more aggressive measures would be required. Oral tracheal intubation would probably be quite difficult in the presence of a uvula that is large enough to produce airway compromise. Therefore, blind nasotracheal intubation, fiber optic-assisted nasotracheal intubation, or retrograde wire-assisted intubation would likely be the most prudent course. Because one does not need the uvula for any important life function, I see no downside of grabbing the tip of the uvular with a hemostat, and clipping it off at its mid portion in an emergency situation. In fact, uvulectomy is a common procedure for sleep apnea, and in this condition even part of the soft palate is removed. Surgical treatment should not be required for the benign idiopathic uvular edema I have described.
Hereditary angioneurotic edema (HANE) was first described by Osler. It's rare but a bad disease with a high mortality rate. This is an inherited disorder, and patients will describe family members with the same condition, and many will have experienced previous episodes. The potential for this type of uvular edema to produce respiratory compromise is quite high, and about half of affected patients will experience some airway obstruction (Laryngoscope 1983;93:749). It's a bizarre disease that involves much more than the uvula. Occasionally HANE will produce peripheral edema or GI tract edema (colic) but an absence of urticaria or pruritus. Importantly, with HANE there is involvement of the soft palate, and many upper airway structures also are edematous. Waeckerle et al (JACEP 1976;5:446) were surprisingly able to collect three cases of suspected HANE that presented with airway compromise. In these cases, the uvular edema was quite impressive, producing a uvula up to 7 cm long. The condition did not respond to standard anti-allergic medications, although, of course, it would not be expected to respond because it is not an allergic condition. In these cases, the tip of the uvula was grasped by forceps, and the distal 1 cm was excised. Bleeding was minimal, serous fluid was drained, and the edema responded quite well. Although this procedure could be used for isolated angioedema, it would be the rare case that needed it. HANE also is treated with fresh frozen plasma to replenish the deficient C-1 esterase inhibitor, and epsilonaminocaproic acid has been suggested, but these interventions are not well documented nor proven effective.
These authors describe an unusual case of uvulitis in an adult who had occult underlying epiglottitis. They note that the pediatric literature is quite clear in recommending that children with uvulitis should be regarded as having a potentially serious problem, and it is often associated with upper airway occlusion and epiglottitis. In this case a 63-year-old woman came to the ED with a complaint of trouble swallowing. She noticed pain in her throat that gradually increased. There was no fever or chills, she was taking no medications, and was afebrile. There was a history of a seafood allergy with a recent ingestion of crabmeat.
The pharynx was inflamed with a markedly enlarged uvula. She had a muffled voice. The white cell count was normal, and the treating physicians believed that the patient had an allergic reaction. She was treated with diphenhydramine and methylprednisolone. The patient appeared to have a significant initial decrease in symptoms, and a lateral soft tissue x-ray of the neck was obtained. This demonstrated a swollen epiglottis and edematous supraglottic area. Fiber optic endoscopy revealed significant edema of the areas in question. She was treated with antibiotics. Subsequent cultures of the blood and epiglottis area revealed haemophilus infuenzae, type B.
If airway compromise is an issue, more aggressive measures are required, and oral tracheal intubation would probably be quite difficult in the presence of a uvula large enough to produce airway compromise
The authors contend that this patient had epiglottitis that was masked by significant uvulitis. The uvula in this case was painful and inflamed and appeared infected. The lack of fever and elevated WBC count in the presence of a positive blood culture for H. influenza is unusual. This organism, however, used to be rather common in children with epiglottitis prior to the H. flu vaccine. Now you have to look hard and long to find a child with epiglottitis from H. flu, and currently it's an adult's disease.
The authors suggest that patients with acute uvular swelling should be evaluated for the possible coexistence of epiglottitis. They caution that initial improvement with steroids and antihistamines and mistaking this for an allergic reaction were quite misleading in this case.
Comment: This is a single case report of a condition that has been previously described. The details are somewhat sketchy, but clearly this case is different from the more common and benign condition of idiopathic angioedema that is highlighted in this column. Specifically, the uvula in that case was red and painful. In the more common scenario of idiopathic angioedema of the uvula, pain is absent, the uvula is boggy and pale, and there is a distinct absence of involvement of the pharynx, palate, epiglottis, larynx, or supraglottic tissue. This report raises the question of the need for a routine lateral neck x-ray in the patient who presents with spontaneous, atraumatic, isolated uvular edema. The authors emphasize that the epiglottitis was subclinical or at least very unimpressive.
I would not routinely order a lateral neck x-ray or perform endoscopy in the patient who is otherwise asymptomatic, but this article is food for thought. In the case of acute spontaneous uvular edema, the lateral neck x-ray and endoscopy should be normal. This case was complicated by the fact that the patient may have had a superimposed allergic condition that caused uvular swelling, suggested by the dramatic response to the antihistamines and the presence of a seafood allergy.
Acute isolated uvular edema has been described secondary to ACE inhibitors. All emergency physicians are familiar with the potentially life-threatening tongue and laryngeal angioedema caused by ACE inhibitors, but the uvula is usually spared. ACE inhibitor angioedema is thought to be due to a build up of bradykinin. This vasoactive substance causes vasodilation, but is usually broken down by ACE, the enzyme blocked by the drugs. Kuo et al (J Emerg Med 1995;13:327) describe a single case report of isolated angioedema of the uvula thought to be secondary to lisinopril therapy. This case contains slim evidence that the ACE inhibitor was the culprit, but others have reported similar cases. This was treated with “needle decompression” (not further described), and the subsequent course was uneventful.
In summary, the etiology and treatment of the otherwise healthy adult who presents with isolated spontaneous angioedema of the uvula remains unresolved. Certainly one should consider allergic reactions. If you diagnose HANE, you should submit it for the SAEM CPC competition. Also in the differential diagnosis is upper airway infection in the presence of pain, fever, or leukocytosis and the rare case of epiglottitis. Clandestine trauma caused by the bulimic's finger is a diagnosis that will impress everyone. The physician's main concern is a compromised airway, but in the garden variety case, the patient and physician remain nonplussed by this transient albeit impressive lump in the throat that occurred for no good reason.
It would seem prudent to treat empirically with a small dose of subcutaneous epinephrine, antihistamines, and corticosteroids, and consider inhaled epinephrine mist if symptoms persist. I would not expect a dramatic reversal, however. None of these treatments has proven benefit, and their use is empiric. In the dramatic case of uvular edema that causes airway obstruction, cutting off the tip of the uvula may be warranted, but only for the very brave and aggressive clinician who cannot intubate.
Observation for a few hours to determine progression is prudent, and perhaps fiber optic endoscopy and plain lateral neck radiography may be used in selected cases, but the yield will be quite low. One would hope that the clinician would be clever enough to separate isolated uvular swelling from a condition that would involve other portions of the respiratory tract. Obtaining a drug screen for possible cocaine smoking can be supported in selected cases. The routine use of antibiotics is not warranted. The condition should slowly resolve, and in most cases the etiology will forever remain obscure. I would be interested in hearing from readers about their experience with this perplexing condition.
Suggested Management Of Uvular Angioedema by Etiology1
Assess airway for potential for obstruction
Idiopathic isolated uvular angioedema
- ▪ Epinephrine (0.3–0.5 ml (mg) of 1:1000, subcu, every 15–20 minutes for 1–3 doses)
- ▪ Diphenhydramine (usual IV doses)
- ▪ Corticosteroids (usual IV doses)
- ▪ ?H2 blocking antihistamines
- ▪ ?Inhaled nebulized epinephrine
Hereditary angioneurotic edema (HANE)
- ▪ Epsilonaminocaproic acid (8–10 gm IV drip over 4 hours, up to 20 gm/day)2
- ▪ ?Fresh frozen plasma
- ▪ Prophylactic: Androgen therapy, such as danazol
- ▪ Antibiotics (for H. influenza, type B)
- ▪ ?Corticosteroids
- ▪ ?Inhaled nebulized epinephrine
- ▪ Spraying/coating uvula with epinephrine solution
- ▪ Uvular decompression by needle scratching
- ▪ Excision of distal 1–2 cm of the uvula
- ▪ Secure airway (intubation, cricothyrotomy, retrograde wire)
No regimen has been proven effective, and interventions are empiric.
From Goldberg et al Ann Emerg Med 1993;22:251.© 2001 Lippincott Williams & Wilkins, Inc.