A Tall Cool Glass of Water

A 51-y-old woman with no prior medical history presented to the emergency department complaining of itching in her throat with a sensation of throat swelling after quickly drinking a cold glass of ice water in the middle of the night. The patient stated that she had developed hives when exposed to cold weather in the past, but that she had never had a problem with her throat. On physical examination, her lower lip and uvula appeared edematous and her voice was slightly muffled, so ENT was consulted for endoscopy. Endoscopy revealed moderate edema of the right arytenoid, obscuring the view of the cords (Figures 1 and 2). A brief glimpse of the cords demonstrated a patent airway (Figure 3).

Figure 1

View of the soft palate, hypopharynx, and supraglottic region demonstrating watery edema at the inferior aspect of the right lateral pharyngeal wall (A) and the right arytenoid mucosa (B). There was no edema of the base of the tongue (C) or epiglottis (D).

Figure 2

A close view of the posterior aspect of the epiglottis (D) and the rest of the hypopharynx illustrates watery edema of the right pharyngeal wall (A) and right arytenoid cartilage (B). The rest of the mucosa appears normal.

Figure 3

The supraglottic area has clear watery edema of the right arytenoid (B). However, there is space between the swelling and the abducted vocal cords (E) showing that the airway is patent.

What is the diagnosis? How should this case be managed?

Diagnosis

Cold-induced angioedema

Discussion

The patient’s airway symptoms were managed with administration of epinephrine (0.3 mg IM), diphenhydramine (50 mg IV), dexamethasone (10 mg IV), and famotidine (40 mg IV) in the emergency department. The ENT team did not think that intubation was necessary. The patient was admitted for airway monitoring. Treatment was continued with intravenous diphenhydramine, dexamethasone, and famotidine. Her symptoms improved. She continued to breathe comfortably with a room air oxygen saturation of 100%. She was discharged after 32 h.

Isolated cold-induced angioedema is rarely seen or reported and remains a poorly understood condition. It usually occurs in patients who have a history of cold urticaria. ¹ Our patient did relate a history of cold urticaria symptoms without a formal diagnosis. The prevalence of cold urticaria in the general population is thought to be 0.05%. ² One study showed that angioedema was present in 23% of these cases. ¹ In addition to airway symptoms, angioedema can be associated with systemic reactions, including anaphylactic shock. It is critical to monitor closely for airway and hemodynamic compromise. Future exposure to cold water should be discouraged. ²

Cold-induced urticaria is thought to be due to mast cell degranulation and release of proinflammatory mediators after cold exposure of the skin or mucous membranes. ² We treated our patient with epinephrine, dexamethasone, diphenhydramine, and famotidine with good control of her symptoms. This is consistent with a histaminergic etiology. The formal diagnosis of cold urticaria can be made with a cold stimulation test, in which an ice cube is placed on the patient’s skin and the skin is allowed to rewarm. A wheal and flare reaction is considered a positive test. In addition to cold avoidance, the primary prophylactic treatment option described for cold urticaria is taking high-dose H1 antihistamines before cold exposure; a 2012 study demonstrated complete efficacy in 30%, partial benefit in 50% and no preventive benefit in 20% of patients. ³

Our patient was discharged the following day with a prescription for an epinephrine auto-injector as recommended for cold urticaria patients at risk for systemic reactions. ⁴ Six months later she continued to do well. She had no recurrent episodes of airway angioedema and only rare issues with cold-induced urticaria due to thoughtful efforts at cold avoidance. Comprehensive allergen panel testing with an allergy specialist was negative.

Note: The images presented in this article were obtained using a disposable, flexible laryngoscope and monitor.