Hereditary Angioedema (HAE) patients experience recurrent episodes of angioedema attacks that can be painful, disfiguring and even life-threatening. The disorder results from a mutation in the gene that controls the synthesis of C1-inhibitor (C1INH). C1INH is a major regulator of activation of the contact system. It is often assumed that attacks results from uncontrolled, local activation of the contact system with subsequent formation of bradykinin. OBJECTIVE: To evaluate involvement of inflammatory reactions in HAE, we analyzed C-reactive protein (CRP) levels before, during, and after HAE attacks. METHODS: HAE patients included in a clinical database of recombinant human C1- inhibitor (rhC1INH) studies were evaluated. For the current study we analyzed CRP levels when patients were asymptomatic, during a clinical attack and in a follow up period, and correlated these with the clinical manifestations of the attack. RESULTS: Data from 68 HAE patients were analyzed and included CRP levels at 273 occasions. While asymptomatic, 20% of the patients analyzed had increased CRP. At the onset of the attack (p=0.049) and over the next 24 hours CRP rose significantly (p=.002) in patients with an abdominal location, and post-attack levels were significantly higher in these patients than in patients with attacks at other locations (p=.034). CONCLUSION: CRP levels are elevated in a substantial proportion of asymptomatic HAE patients. Levels of CRP significantly increase during an abdominal attack. These data suggest low-grade systemic inflammatory reactions in HAE patients as well as a triggering event for attacks that starts prior to symptom onset