MUSCLE INSTABILITY ASSOCIATED WITH HEREDITARY ANGIOEDEMA

Introduction

Hereditary angioedema (HAE) is caused by C1 inhibitor deficiency or dysfunction, leading to increased prekallikrein activity and bradykinin production. HAE is associated with vasodilation and edema which could result in obstruction of the upper airway, GI symptoms, and skin swelling. Evidence of involvement of other organ systems has been sparse. Herein we demonstrate evidence of creatinine kinase (CK) elevation in HAE patients suggesting an effect of bradykinin on skeletal muscle.

Methods

During a study after IRB approval we followed CK results in patients with HAE. We assessed patients with and without exercise and with and without therapy. We included one patient with a clinical indication to check CK levels.

Results

In most studies we have not assessed CK, however, in a recent study CK was assessed and we found that some patients with HAE have persistently elevated CK. In others, even minor exercise caused CK to rise. We also noted patients on long term prophylaxis (LTP) had lower CK levels than those not on LTP. In one of these patients, muscle symptoms were profound and caused limited exercise, minimal exercise led to elevated CK, and isoenzymes were MM, confirming skeletal muscle origin.

Conclusion

Bradykinin appears to cause instability of skeletal muscle, causing CK release with even minor exercise. The effect of increases in bradykinin in HAE on muscle needs further research, but may account for some of the typical HAE symptoms. LTP may therefore have more benefits by stabilizing skeletal muscle along with decreasing skin and mucus membrane attacks.