Tongue oedema etiologies treatments in patient poly medicated statin, beta blockers, concor, ezetemib, crestor, atacand, aspirine,etc...


Thank you for your inquiry.

First of all, let me call your attention to a previous entry on our website regarding tongue swelling. I have copied below this previous inquiry and our response. Part of the reason I am sending it along with my answer is that there are some references listed within the answer that you might find helpful.

Having said this, I think the most important question to ask is whether or not the tongue swelling is evanescent (lasting 24 to, at the maximum, 48 hours) or whether it is persistent (lasting days at a time). I am assuming that you are describing an intermittent, recurrent, evanescent swelling of the tongue which would be consistent with angioedema. However, since you did not describe the symptoms in more detail, I did want to mention that the differential diagnosis varies considerably according to whether or not the swelling is evanescent or persistent.

Persistent angioedema has a large differential diagnosis including acromegaly, hypothyroidism, tumors, and amyloidosis. I am not aware of any chronic swelling of the tongue that would be due to medications, but certainly such cases may have been reported that I have not been able to find.

In the case of chronic swelling, you would of course need to consider a biopsy to be able to determine the cause.

I assume, however, that you are referring to an evanescent swelling which would be due to angioedema. Unfortunately, if this is the case, I know of no way to identify the culprit amongst the drugs that you mentioned other than withdrawal followed by resolution of symptoms, and then to confirm the the cause by a challenge. There is no in vivo or in vitro test of which I am aware that would allow you to discern the responsible drug, if any was the cause of the angioedema.

However, in many instances, angioedema is idiopathic in nature and is not in any way related to the drugs that the patient is taking. There are of course clear-cut exceptions to this, especially in regards to angiotensin enzyme inhibitors, but in the majority of cases, angioedema of the tongue is idiopathic in nature.

I would obtain, if you have not already, a complement 4 level looking for C1 inhibitor deficiency syndrome.

In summary, it is important to distinguish whether the edema is chronic (days at a time) versus acute, recurrent (lasting no more than 24 to 48 hours). If it is chronic, then you need to consider a biopsy of the tongue. If it is acute, evanescent and recurrent, I am afraid there is no test for you to determine if anyof the drugs your patient is taking is responsible other than withdrawal of the drug followed by, if necessary, a challenge to confirm the etiology.

The only other test I would consider ordering would be a complement 4 level in search of a C1 esterase inhibitor deficiency.

Thank you again for your inquiry and we hope this response is helpful to you.

Previously Posted Question and Response :
I am puzzled with a case of painless episodic anterior unilateral tongue swelling in a middle-aged (54-year old) male. Over the past 6 months, he had 5 episodes of unilateral anterior tongue swelling without any airway

obstruction. No angioedema or urticaria elsewhere was noticed. The swelling did subsided with epi, Benadryl and systemic steroids. I did ruled out HAE, food/drug allergy and ACE inhibitor meds. He has no dental disease. He has had no other systemic symptoms such as abdominal pain associated with the tongue swelling. I am not sure whether I need to look into any dental paste or do any other work up. I am lost in trying to find the etiology. I need your expert opinion sir.

Please respond before he gets into more serious episodes. He does carry an EpiPen at home.

I would really like more information regarding your patient to be able to answer this question. Specifically important is how long the swelling persists. However, based on your description, the most likely diagnosis is angioedema. Unilateral anterior tongue swelling is a very common manifestation of recurrent idiopathic angioedema episodes. Angioedema is almost always asymmetrical and the tongue itself is a very frequently involved target organ. If the episodes come and go within a matter of 24 hours, then angioedema of the tongue is certainly the most likely diagnosis. If the swelling persists days to weeks at a time, then the differential becomes more complex, and a biopsy is needed.

If this is indeed angioedema, and it certainly sounds like it is, it is very unlikely that you will find a cause, and symptomatic therapy is all that is available. However, it would be extremely unlikely for anterior tongue swelling, in the absence of C1 esterase inhibitor deficiency syndrome, to result in airway compromise. It does not sound as if he has this syndrome but you can easily screen for it by ordering a complement 4 level (C4). This would be the only workup I would suggest at this time. Usually preventive therapy is ineffective for episodes of idiopathic angioedema.

In summary, if the swelling occurs spontaneously and resolves within 24 hours, clearly the most likely diagnosis is angioedema. If it persists for days at a time, then there is a more complex differential, and to make a diagnosis, you would require a biopsy. If indeed this is angioedema (transient swelling, usually lasting less than 24 hours), I do not feel you will find a cause because most such episodes are idiopathic.

If you would like further reading in this regard, I would recommend Dr. Allen Kaplan's chapter entitled “Urticaria and Angioedema,” which is in the most recent edition of Middleton's Allergy: Principles and Practice (7th edition), Volume 2, page 1063, 2009.

I have also copied below the abstracts of two other reviews of this issue. You should find them helpful.

Abstract 1:
Allergy Asthma Proc. 2009 Jan-Feb;30(1):11-6. Links
The spectrum of chronic angioedema.
Banerji A, Sheffer AL.
Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
This article focuses specifically on angioedema. Chronic angioedema represents a wide range of diseases and can be categorized into several forms including hereditary, acquired, drug induced, and idiopathic. Hereditary and acquired angioedema are known to be a result of abnormalities in C1 inhibitor protein while the mechanism of drug-induced and idiopathic angioedema is less clear. Significant advances have been made in recent years with regard to diagnosis and management of these patients leading to a significant reduction in morbidity and mortality. Several novel therapies are in clinical trials and should be available in the United States within the next year. There is still a lot to learn about the pathophysiology, diagnosis, and treatment of patients with chronic angioedema. This review will hopefully provide more information to the readers who care for patients with these disorders and also stimulate further interest and research into the pathophysiology of these conditions.

Abstract 2:
J Am Acad Dermatol. 2005 Sep;53(3):373-88; quiz 389-92. Links
Kaplan AP, Greaves MW.
Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
Although first described more than 130 years ago, the pathophysiology, origin, and management of the several types of angioedema are poorly understood by most dermatologists. Although clinically similar, angioedema can be caused by either mast cell degranulation or activation of kinin formation. In the former category, allergic and nonsteroidal anti-inflammatory drug-induced angioedema are frequently accompanied by urticaria. Idiopathic chronic angioedema is also usually accompanied by urticaria, but can occur without hives. In either case, an autoimmune process leading to dermal mast cell degranulation occurs in some patients. In these patients, histamine-releasing IgG anti-FcepsilonR1 autoantibodies are believed to be the cause of the disease, removal or suppression by immunomodulation being followed by remission. Angiotensin-converting enzyme inhibitor-induced angioedema is unaccompanied by hives, and is caused by the inhibition of enzymatic degradation of tissue bradykinin. Hereditary angioedema, caused by unchecked tissue bradykinin formation, is recognized biochemically by a low plasma C'4 and low quantitative or functional C'1 inhibitor. Progress has now been made in understanding the molecular genetic basis of the two isoforms of this dominantly inherited disease. Recently, a third type of hereditary angioedema has been defined by several groups. Occurring exclusively in women, it is not associated with detectable abnormalities of the complement system. Angioedema caused by a C'1 esterase inhibitor deficiency can also be acquired in several clinical settings, including lymphoma and autoimmune connective tissue disease. It can also occur as a consequence of specific anti-C'1 esterase autoantibodies in some patients. We have reviewed the clinical features, diagnosis, and management of these different subtypes of angioedema.
Learning Objective: After completing this learning activity, participants should be aware of the classification, causes, and differential diagnosis of angioedema, the molecular basis of hereditary and non-hereditary forms of angioedema, and be able to formulate a pathophysiology-based treatment strategy for each of the subtypes of angioedema.

Phil Lieberman, M.D.

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