LIMITED CUTANEOUS SYSTEMIC SCLEROSIS MIMICKING HEREDITARY ANGIOEDEMA WITH NORMAL C1 INHIBITOR

Abstract

<h3>Introduction</h3> Hereditary angioedema with normal C1 inhibitor (HAE-nl-C1INH) is often diagnosed when patients with antihistamine-resistant angioedema respond to bradykinin-targeted therapies. We present a patient with limited cutaneous scleroderma initially diagnosed as HAE-nl-C1INH, with variable response to HAE therapy. <h3>Case Description</h3> 56-year-old woman with hypertension presented with recurrent periorbital swelling while on ACE inhibitor therapy. After discontinuation, she continued to have episodes of angioedema for two months, responsive to recombinant C1 inhibitor therapy. Initial workup included normal C1 esterase inhibitor antigen and function, C4, C1q, SPEP, tryptase, and thyroid studies. After a six-month symptom-free period, angioedema recurred in the setting of stressful life events, viral infection, and antihypertensive medication changes. When on-demand therapy with recombinant C1 esterase inhibitor was observed to provide insufficient control, she started lanadelumab prophylaxis which stabilized her symptoms. She then developed episodic fluid retention with daily joint and subcutaneous swelling involving the hands, abdomen, and lower extremities coincident with additional changes to her antihypertensive regimen. Discontinuation of suspected culprit medications did not resolve the progression of her symptoms. Evaluation by rheumatology for joint symptoms and persistent hand swelling led to the diagnosis of limited cutaneous systemic sclerosis (scleroderma). Angioedema symptoms resolved after starting mycophenolate mofetil and she no longer required HAE therapy. <h3>Discussion</h3> Our case highlights the complicated and nuanced nature of diagnosing HAE-nl-C1INH, particularly in patients with partial response to HAE therapy. Limited cutaneous scleroderma either mimicked or triggered angioedema in our patient. Her partial response to C1 inhibitor infusions and lanadelumab may have represented off-target effects of HAE therapy.