Coexistence of Hereditary Angioedema and Homozygous Factor V Leiden Mutation in a 31-Year-Old Patient: A Rare Clinical Overlap.

Abstract

Background:
Hereditary angioedema (HAE) is a rare autosomal dominant disorder which is caused by deficiency or dysfunction of C1-esterase inhibitor (C1-INH). This leads to dysregulation of the kallikrein–bradykinin pathway which is responsible for recurrent episodes of non-pruritic angioedema seen in these cases. The condition typically manifests as episodic swelling of the skin, gastrointestinal tract or involvement of airway. It is frequently misdiagnosed as allergic angioedema due to overlapping clinical features. Factor V Leiden mutation the most common inherited thrombophilia is caused by a point mutation in the F5 gene that produces resistance to activated protein C and increases the risk of venous thromboembolism. Although both disorders involve dysregulationof plasma protease cascades reports describing their coexistence are exceedingly rare. This case highlights the diagnostic and therapeutic challenges associated with the simultaneous presence of HAE and homozygous Factor V Leiden mutation.
Case Report:
A 31-year-old woman presented with recurrent episodes of facial and right upper limb edema. This was accompanied by burning sensation, body aches and abdominal cramps. Episodes occurred one to two times per week and resolved spontaneously within two to six hours. The patient, diagnosed case of homozygous Factor V Leiden mutation, had a prior history of recurrent venous thromboembolism including deep venous thrombosis and pulmonary embolism. Physical examination during attacks revealed non-pitting and non-pruritic edema. There was minimal response to antihistamines and bronchodilators. Serum tryptase was normal and autoimmune markers were negative. In addition C1- INH levels were reduced with normal C1q.Complement C4 levels were decreased. These changesconfirmed the diagnosis of hereditary angioedema secondary to C1-INH deficiency. Initial treatment with fresh frozen plasma was started which was subsequently discontinued due to worsening pulmonary arterial hypertension. Therapeutic plasmapheresis was performed which caused marked symptomatic improvement.
Conclusion:
This is a rare case in whom there was coexistence of hereditary angioedema due to C1-INH deficiency and homozygous Factor V Leiden mutation. This represents a rare clinical overlap involving dysregulation of complement, kallikrein–kinin and coagulation pathways. Recognition of bradykininmediated angioedema in patients with recurrent swelling unresponsive to antihistamines is essential for appropriate management as these patients are less likely to respond to antihistamines, corticosteroids, or epinephrine