History
A 42-year-old black male presented to the hospital with facial swelling. The intensive care unit requested an ocular consult, because the patient reported “swollen eyes” that had persisted for three days.

While the patient explained that he had difficulty seeing because he was unable to open his eyes, he did not complain of pain or vision loss. When the lids were held open, his vision was intact. His ocular history was noncontributory.

His systemic history was significant for medically controlled hypertension and previous bouts of facial swelling. (However, in the past, the swelling didn’t affect his eyes this dramatically.) He reported no known allergies of any kind.

Diagnostic Data
His best-corrected entering visual acuity was 20/20 OU at distance and near. This measurement was achieved when his lids were held open with the assistance of a Desmarres retraction blade.

External examination uncovered palpable, soft edema of the face and orbital adnexa without warmth, pain or tenderness. There was no evidence of afferent pupillary defect, and confrontational visual fields were normal.

Aside from the adnexal edema, the anterior segment findings were normal. Intraocular pressure measured 14mm Hg OU. Dilated funduscopy was within normal limits in both eyes.

Your Diagnosis
How would you approach this case? Does the patient require any additional tests? What is your diagnosis? How would you manage this patient?

What is the likely prognosis?

Thanks to Todd Dimmick, OD, of Philadelphia, for contributing to this case.

Discussion

	Gross inspection of our 42-year-old patient reveals marked swelling around both eyes. What is your diagnosis?

Additional testing included a full motility study to confirm his ocular range of motion. The facial areas were palpated to rule out cellulitis. Corneal sensitivity testing also was performed to rule out the possibility of damaged sensory nerves.

The diagnosis in this case is angioneurotic edema of the face and orbital adnexae. Angioneurotic edema, sometimes referred to as angioedema, is swelling that occurs deep within the mucocutaneous tissues that surround the eyes, lips, hands, feet and throat.^1,2 Often, this condition manifests as an acute allergic reaction to medications and foods.^1-3

There are three forms of this rare disorder.^1-3

• The most frequently identified cause in general practice is allergic/pseudoallergic and idiopathic reactions.2 The condition may occur secondary to serum sickness, immune system disorders and eosinophilia.¹

• A hereditary form of angioedema seems to be related to unchecked tissue bradykinin formation, with biochemically low plasma C4 and low quantitative or functional C1 inhibitor levels.1,3 Congenital C1 inhibitor deficiency also is associated with B-cell lymphoproliferative disease.¹

Acquired variants mediated by a histaminic element often are triggered by use of certain drugs, including angiotensin-converting enzyme inhibitors.^1-3 Ancillary environmental elements, such as dust exposure, pressure on the skin and exercise, also can catalyze angioneurotic edema.

However, in some instances, the trigger is ambiguous or undetermined.²

• Recently, a third type of angioedema was defined. It occurs exclusively in women, and has no association with detectable abnormalities of the complement system.³ This form of the response seems to be caused by C1 esterase inhibitor deficiency. However, the response also can be acquired following complications from lymphoma and autoimmune connective tissue disease.³

The majority of angioedema patients have accompanying urticaria. Pathophysiologically, the allergic angioedemas can be categorized as histaminergic (histamine) and non-histaminergic (kinin formation).² Angiotensin-converting enzyme inhibitor-induced angioedema (non-histaminic) is caused by the inhibition of enzymatic degradation of tissue bradykinin.³ In any case, an autoimmune process leads to dermal mast cell degranulation––which yields symptoms that may or may not include urticaria (hives).³

Angioedema of any kind is a potentially life-threatening condition that requires prompt systematic management. Because angioedema may be either histaminergic or non-histaminergic, the treatment varies accordingly.² Generally, management is governed by removal of the offending trigger and suppression of the responding systems via immunomodulation.^1-4

Most patients are treated with a combination of oral, topical and intravenous corticosteroids (87%); H1-antagonists (89%); and H2-antagonists (74%).4 Occasionally, patients require epinephrine (1%).⁴ Inhaled H2-agonists also can be used. Additional symptom relief is achieved with narcotics, hydration and fresh frozen plasma (FFP).⁴ Androgens and FFP frequently are used despite multiple, significant side effects. Newer therapies include C1-inhibitors and human plasma, as well as recombinant and contact system modulators (e.g., ecallantide and icatibant).⁴

Following treatment, most patients experience symptom remission.^1-4

1. Matsumura Y, Miyachi Y. Angioedema. Nihon Rinsho. 2005;63(1):117-20.
2. Rye Rasmussen EH, Bindslev-Jensen C, Bygum A. Angioedema--assessment and treatment. Tidsskr Nor Laegeforen. 2012;132(21):2391-5.
3. Kaplan AP, Greaves MW. Angioedema. J Am Acad Dermatol. 2005;53(3):373-88.
4. Buyantseva LV, Sardana N, Craig TJ. Update on treatment of hereditary angioedema. Asian Pac J Allergy Immunol. 2012;30(2):89-98.