C1 Esterase Inhibitor Deficiency

When suspecting C1 esterase deficiency, key historical findings such as a family history for the disease or upper airway swelling may be noted. Additionally, a history of unexplained recurrent episodes of self-limited colicky abdominal pain may be present. A history of angioedema without urticaria, pruritus, ACE inhibitor, NSAID, or allergic exposure is highly suggestive as well. Common sites that are affected include the hands and feet as well.[1]

When suspecting C1 esterase inhibitor deficiency, it is generally may present with airway compromise from laryngeal edema or a more benign presentation of unexplained hands and feet swelling. First, care should be taken to ensure the airway is secured; this can be via traditional airway methods but will be made difficult due to airway swelling. Further evaluation should take place by a trial basis of classic allergic airway swelling management (epinephrine, steroids, antihistamines). In the case of C1 inhibitor deficiency, these methods will not work. At this point, a presumptive diagnosis can be made, but for definitive diagnosis, clinicians can obtain C4 levels. In the case of C1 inhibitor deficiency, C4 levels will be low. Further testing can include C1NH protein levels and function studies for definitive diagnosis.[4]

Management of C1 esterase inhibitor deficiency is mostly in response to airway compromise. If only mild symptoms present and patient has a known diagnosis, it is reasonable to manage conservatively with observation. If more severe symptoms and impending airway compromise are present, a definitive airway is necessary. Presumptive treatment with epinephrine, steroids, and antihistamines is recommended of the undifferentiated patient with airway compromise secondary to laryngeal edema. However, in the setting of C1 esterase inhibitor deficiency, this is ineffective but should be attempted as allergic airway compromise is more common, and these methods have a high reward with relatively little downside.[5]

Specific therapy for C1 esterase inhibitor deficiency with laryngeal edema involves replacing the deficient enzyme. The easiest way is to give human plasma which contains C1 esterase inhibitor. An initial dose of human plasma is 2 units. C1INH concentrate derived from human plasma may be a therapeutic option. The initial dose is 1500 units.[6]

More specific, less widely used medications include Icatibant and ecallantide. Icatibant is a synthetic bradykinin B2-receptor antagonist while ecallantide is a recombinant plasma kallikrein inhibitor.[5][6]

Differential diagnosis in the setting of airway edema includes:

• Anaphylaxis/allergic
• ACE inhibitor-induced edema
• Idiopathic
• Autoimmune disorders
• Superior vena cava syndrome
• Thyroid disorders
• Cheilitis granulomatosa
• Trichinosis 

The possible differentials can broaden when symptoms relate solely to extremity swelling: 

• Lymphedema
• Deep vein thrombosis
• Cellulitis

Depending on the response to therapy, the patient should return to normal health. Occasionally patients are very resistant to therapy and will require intubation. After the acute event and extubation, the patient should have a full recovery. The chance of recurrence, however, is always present.[7]

The most severe complication is airway compromise requiring intubation or surgical airway; standard airway procedures and protocols should manage this situation.[6]

If attempts at airway are unsuccessful, a surgical airway may be necessary. Consultation with the anesthesia team may be of some benefit if there is the possibility a difficult airway.

• Avoid physical and psychological stressors
• Medications to avoid include: estrogen, tamoxifen, and ACE inhibitors
• Patients who are to undergo oral surgery should receive prophylaxis which includes attenuated androgens, regular C1INH infusions, and tranexamic acid infusion

When caring for a patient with hereditary angioedema, the ABC's of resuscitation should be first and foremost. Assigning team roles and frequently assessing the patient for airway compromise is paramount. Having the appropriate tools for intubation such as visual laryngoscopes and back up airway devices are part of the key to success. Patients with even concern for airway compromise should be monitored closely in the intensive care setting.[6]