History

• 40 yo F presents to the ED with lower lip swelling
• PMH of recurrent lip/tongue/pharyngeal swelling suspicious for acquired vs hereditary angioedema
• Has required intubation twice before.
• Today presents with swelling of her lower lip that started about 2 hours ago while she was at work.
• She took 50mg PO benadryl at work but symptoms worsened
• Denies no nausea, vomiting, diarrhea, shortness of breath, wheezing, or rashes.
• No ACEi in medication list.
• No known exposures to allergens or new foods/substances.

Physical Exam

BP 126/70  | Pulse 77  | Temp 98 °F (36.7 °C) (Oral)  | Resp 20  | SpO2 100% on room air

• Awake, alert, oriented, no distress.
• Swelling in R side of lower face. R sided tongue deviation on tongue protrusion. R sided neck fullness. Uvula and posterior pharynx not swollen. Uvula hanging midline with space on either side. No tracheal deviation present. No difficulty managing secretions. 
• Effort normal and breath sounds normal. No stridor. No respiratory distress. She has no wheezes. She has no rales. 
• Normal cardiac exam
• Normal abdominal exam
• Normal skin exam

Differential Diagnosis

• Angioedema - hereditary vs acquired; vs allergic reaction (no 2 system involvement to suggest anaphylaxis), though no known exposures to allergens.

Management

• Given methylprednisolone, benadryl, famotidine, and C1 esterase inhibitor (human derived Berinert) to treat possible etiologies of symptoms. 
• On presentation, airway was not compromised, so ED team decided to closely monitor over the next one hour rather than immediately intubate patient.
• One hour later, called to bedside fter patient had alerted RN that symptoms were progressing.
• On repeat physical exam, there was now swelling in uvula and surrounding tissue bilaterally. The rest of the exam was unchanged.
• Discussed findings with patient and decided to proceed with intubation before critical airway compromise in the setting of worsening symptoms and exam despite maximal medical management.
• Because of potential for significant swelling causing difficult intubation, the ED team decided to proceed with awake intubation with flexible intubating video scope.
• Patient was pre-treated with nebulized lidocaine, viscous lidocaine, glycopyrrolate, and zofran.
• The flexible intubating scope was inserted into patient’s mouth, and once the vocal cords were in clear view, the patient was given a dose of propofol. Once somewhat sedated, the ETT was passed through the vocal cords. 

Hospital Course

• Admitted to the ICU
• Slowly had improvement of her swelling, and was eventually extubated and discharged home.
• She is still being evaluated for the etiology of her symptoms by rheumatology and immunology

Learning Points

• Hereditary angioedema (HAE) is caused by a deficiency in C1 esterase inhibitor. 
• Patients can have low levels of the enzyme (Type 1), or can have dysfunctional form of the enzyme (Type 2).
• Hereditary angioedema is an autosomal dominant disorder, but up to 25% of cases arise from a spontaneous new mutation
• HAE differs from an allergic reaction (mediated by histamine) in that attacks are caused by effects of bradykinin. 
• C1 esterase inhibitor usually acts on complement and contact plasma cascades to reduce bradykinin release. When there is decreased or dysfunctional C1E-inhibitor, there is increased amount of bradykinin.
• Bradykinin functions to increased vascular permeability and extravasation, which causes edema. 
• Patients can present with submucosal edema in the upper airway and in the bowels (can present with abdominal pain, nausea, vomiting, diarrhea!) and/or with subcutaneous edema under the skin (can be present in face or extremities).
• Treatment options include airway management if necessary and pharmacologic treatments:

• C1 esterase inhibitor can be administered directly. Human and recombinant forms exist.

• Icatibant is a bradykinin B2 receptor antagonist and acts to reverse effects of bradykinin

• Ecallantide is a human plasma kallikrein inhibitor, which inhibits conversion of kiningen to bradykinin.

• FFP can also be used, but it contains additional kinins and complement factors beyond what is needed, which creates potential risk of worsening symptoms.

References

Gower RG, Busse PJ, Aygören-Pürsün E, et al. Hereditary angioedema caused by c1-esterase inhibitor deficiency: a literature-based analysis and clinical commentary on prophylaxis treatment strategies. World Allergy Organ J. 2011;4(2 Suppl):S9-S21. doi:10.1097/WOX.0b013e31821359a2

Rowe, BH., Gaeta, TJ. Anaphylaxis, Allergies, and Angioedema. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide 8th edition. 74-79.