C1 Esterase Inhibitor (C1-Inh)

Elevated C1 esterase inhibitor usually reflects an acute‑phase response or hormonal states (pregnancy, estrogen therapy), liver disease, infection, or recent C1‑INH replacement therapy. It is not typical for hereditary angioedema, which shows low or dysfunctional C1‑INH. Interpretation depends on clinical context; your clinician may order C4 and C1‑INH functional assays and review medications and conditions to determine significance.

C1‑esterase inhibitor deficiency (bradykinin‑mediated) angioedema is treated acutely with C1‑INH concentrate, icatibant (bradykinin B2 blocker) or ecallantide; fresh frozen plasma can be used if specific agents are unavailable. Airway protection and emergency care are essential. For prevention, regular C1‑INH replacement, lanadelumab or oral berotralstat are options; attenuated androgens or tranexamic acid are alternatives. Antihistamines, steroids and epinephrine are generally ineffective.

C1 inhibitor drugs are replacement (plasma‑derived or recombinant) proteins that restore C1 esterase inhibitor activity. They block complement and contact‑system enzymes (kallikrein, FXII), preventing bradykinin‑mediated angioedema. Used to treat acute hereditary angioedema attacks and for short‑ or long‑term prophylaxis, they are given IV or subcutaneously depending on the product. Adverse effects can include infusion reactions and, rarely, thrombotic events.

C1 inhibitor (C1-INH) deficiency is usually a genetic disorder (hereditary angioedema) caused by SERPING1 mutations, not an autoimmune disease. However, an acquired form exists where autoantibodies against C1-INH cause low C1 levels; this acquired deficiency is often associated with autoimmune or lymphoproliferative conditions. Diagnosis and treatment differ between hereditary and acquired forms.

Normal C1 esterase inhibitor levels are reported two ways. Antigenic (protein) concentration is typically about 21–39 mg/dL (0.21–0.39 g/L). Functional activity is usually expressed as a percentage, with normal roughly 70–130% (lab-dependent); activity below about 50–60% generally indicates deficiency and may merit further evaluation for hereditary or acquired angioedema.

Acquired angioedema causes sudden, painless swelling of the face, lips, tongue, throat, eyes, hands and feet. Swelling often occurs without itching or hives. Laryngeal involvement can cause hoarseness, stridor or breathing difficulty and may be life‑threatening. Abdominal attacks cause severe cramping, nausea, vomiting and diarrhea from intestinal wall swelling. Episodes develop over hours and may recur.