C1INH is also known as C1 esterase inhibitor that normally prevents activation of a cascade of proteins. It is a plasma protein an enzyme. C1INH is a member of the serpin family of proteases like alpha-antitrypsin, antithrombin III, and angiotensinogen. This serpin protease inhibitor inhibits the association of C1r and C1s with C1q to prevent the formation of the C1-complex which leads to activation of other proteins of the complement system.

In short it inhibits various proteins of coagulation cascade but the side effects like thrombosis and hemorrhage are rare due to the deficiency of this enzyme.

Symptoms

Patients can present with any combination of cutaneous angioedema, severe abdominal pain, or acute airway obstruction. The deficiency of enzyme also leads to a condition called as Hereditary Angioedema. Patients can develop recurrent attacks of swollen tissues, pain in the abdomen, and swelling of the larynx which can compromise breathing.

What exactly happens in C1 Esterase Inhibitor deficiency

C1INH is synthesized primarily by hepatocytes and also synthesized by monocytes. C1INH inhibits also components of the fibrinolytic, clotting, and kinin pathways. C1INH inactivates plasmin activated Hageman factor or factor XII, activated factor XI, PTA, and kallikrein. 

The diagnosis is suspected if a history of recurrent angioedema is there. Patients will have recurring attacks of transient edema suddenly appearing in areas of the skin or mucous membranes and occasionally of the viscera, often associated with dermatographism, urticaria, erythema, and purpura. The deficiency can also lead to Hereditary angioedema. Various forms of deficiencies that exist are

• Type I – in this type levels of C1INH are decreased, 85% cases have this type of hereditary angioedema.
• Type II - C1INH levels are normal but function is decreased, only 15% of the cases diagnosed have this type of disorder
• Type III – There is no abnormality in C1INH and the disorder occurs in an X-linked dominant fashion and mainly affects women. Risk factors for this type are pregnancy and use of hormonal contraception. It has relation with mutations in the factor XII gene.
• Angioedema can be autoimmune disorder, due to antibody formation against C1INH and is associated with the development of lymphoma.

Consumption of some foods which are vasodilators such as alcohol or cinnamon can increase the probability of an angioedema episode in susceptible patients. The onset of episode may be delayed overnight or by some hours, making the correlation with their consumption difficult. Bromelain in combination with turmeric may be beneficial in reducing symptoms. Ibuprofen or aspirin may increase the probability of an episode in some patients.

Diagnosis and Investigations

• Complete blood count
• Blood electrolytes
• Renal function test
• Mast cell tryptase levels are elevated
• Liver Function Tests

Treatment and Drugs

Treatment will differ as per the triggering factor or the type of angioedema the patient is having. It will also vary case to case basis as many other complications may be associated with some of the patients. Apart from treatment various precautionary measures like avoidance of particular allergens and avoidance of particular drugs is advised to the patients.