Plasma combats angioedema: A case report

Shadiya Sulthana1, Jayavignesh2, Dominic Rodriguez3

[1, 2]General medicine resident, Kauvery Hospital, Tennur, Trichy

[3]General Physician, Kauvery Hospital, Tennur, Trichy

Introduction

C1 esterase inhibitor deficiency, also known as hereditary angioedema, results in the unchecked production of the vasodilator bradykinin. This increase in bradykinin leads to an increase in smooth muscle relaxation in the walls of blood vessels and resultant edema in the hands, feet, gastrointestinal tract, and in severe cases, the larynx. In severe cases, the airway can be compromised by the increasing oedema, preventing air movement into and out of the lungs.

Case Report

A 40 -years- aged male, with a history of recurrent laryngeal edema since the age of 15 years, recently presented with similar complaints, with acute onset of breathlessness, swelling of lips and throat for one day, and difficulty in swallowing.

On examination, he was noted to have a swollen uvula. No history of pruritus or skin rashes. No history of any medications in the recent past. He revealed a significant family history of similar episodes of oedema and breathlessness in his mother, grandmother and maternal uncle; his children had mild symptoms.

Initially his C4 level was low and C3 was normal suggestive of C1 esterase deficiency.

Cervical spine lateral X-ray was taken which revealed increased prevertebral fascia shadow indicating laryngeal edema. C1 Esterase inhibitor level was estimated and was found to be extremely low (0.5). C1 esterase inhibitor deficiency was confirmed. As there may be an inadequate response to steroids and antihistamines, he was given 2 bags of FFP and Tranexamic acid.

He became symptomatically better. Edema decreased. Patient and relatives were counselled about the condition and advised to give 2 units FFP in case of similar complaints.

He was discharged with oral Danazol as a prophylaxis.

Fig (1): X-ray C- Spine Lateral View – showing increased prevertebral fascia shadows suggestive of laryngeal edema

Discussion

Hereditary angioedema (HAE) is a fully penetrant, autosomal dominant disease due to a mutation in the SERPING1 gene leading to a deficiency of C1INH (type 1) in ~85% of patients or to a dysfunctional protein (type 2) in the remainder affecting 1:30,000–80,000 in the general population. A third, less common type of HAE has been described in which C1INH function is normal, and the causal lesion is a mutant form of factor XII, which leads to generation of excessive bradykinin. It is also known as Quincke’s Disease named after internist and surgeon Heinrich Quincke.

C1INH deficiency can also develop in a sporadic acquired form as a result of excessive consumption of C1INH due either to formation of immune complexes or to the generation of an autoantibody directed to C1INH in the setting of lymphoproliferative or autoimmune disease.

C1INH blocks the catalytic function of activated factor XII (Hageman factor) and of kallikrein, as well as the C1r/C1s components of C1, with the common result of degrading bradykinin. During clinical attacks of angioedema, C1INH function or levels fall, patients develop elevated plasma levels of bradykinin leading to angioedema, and excessive activation of C1 results in a decline in C4 and C2 levels.

The use of ACE inhibitors results in impaired bradykinin degradation, which explains the idiosyncratic angioedema that can occur in ACE inhibitor–exposed patients with a normal C1INH. Bradykinin-mediated angioedema, whether caused by ACE inhibitors or by C1INH deficiency, is noteworthy for the conspicuous absence of concomitant urticaria or pruritus, the frequent involvement of the gastrointestinal tract, and the duration of symptoms >24 hr.

History

J L Milton was the first to describe HAE, in 1876, and Quincke was the first to assign the name “angioneurotic edema” to the disease, in 1882. Mental stress was observed to have an effect on exacerbations of the disease, thus the word “neurotic” was used as part of its name. Sir William Osler, in 1888, was the first to provide a detailed description of HAE over five generations, thus noting the hereditary component of this disease. The biochemical basis for hereditary angioneurotic edema – the absence of C1-INH – was discovered several decades later and first published by Donaldson and Evans in 1963. Since that study, a plethora of information regarding the genetic basis, pathophysiology, clinical manifestation, and management of HAE has been discovered and published.

Diagnosis

The diagnosis of HAE is suggested not only by family history but also by the lack of pruritus and of urticarial lesions, the prominence of recurrent gastrointestinal attacks of colic, and episodes of laryngeal edema.

Laboratory diagnosis depends on demonstrating a deficiency of C1INH antigen (type 1) or a nonfunctional protein (type 2) by a catalytic inhibition assay. C4 and C2 are chronically depleted and fall further during attacks due to the activation of additional C1.

Patients with the acquired forms of C1INH deficiency have the same clinical manifestations but differ in the lack of a familial element. Furthermore, their sera exhibit a reduction of C1 function and C1q protein as well as C1INH, C4, and C2. Lastly, type 3 HAE is associated with normal levels of complement proteins and a factor XII gene mutation.

Treatment

Infusion of plasma-derived C1INH protein and lanadelumab, a monoclonal antiplasma kallikrein antibody, is approved for prophylaxis of HAE attacks.

Administration of plasma-derived or recombinant C1INH protein, a bradykinin 2 receptor antagonist (icatibant), or a kallikrein inhibitor (ecallantide) may be used for treatment of an acute attack of HAE.

Older, less expensive preventative options include attenuated androgens, which stimulate production by the normal gene of an amount of functional C1INH.

The antifibrinolytic agent ε-aminocaproic acid may be used for preoperative prophylaxis but is contraindicated in patients with thrombotic tendencies or arterial atherosclerosis.

Fresh frozen plasma infusion can be used for acute attacks in a setting that lacks access to newer modalities. Published studies are conflicting on the efficacy of bradykinin 2 receptor antagonists and C1INH protein in the treatment of ACE inhibitor–induced angioedema.

Treatment of the underlying autoimmune disease or malignancy is indicated for acquired C1INH deficiency.

St. Helena Island and hereditary angioedema

The island of St Helena lies in the South Atlantic Ocean and is isolated by distance from any land mass and by lack of a harbour or airfield. St Helena has a largely closed population, which means that Saints mostly have children with other Saints. This restriction on genetic diversity can cause relatively unusual diseases to become widespread in the population.

The estimated prevalence of HAE in the general population is one individual per 50,000, with reported ranges from 1:10,000 to 1:150,000.

In St. Helena Island, the prevalence of HAE is found to be much higher and patients with the same have been provided plasma derived C1 inhibitor pens for use during attacks.

Conclusion

Hereditary angioedema is an acute emergency and has to be differentiated from anaphylaxis and urticaria as this condition has an inadequate response to steroids, antihistamines and epinephrine. This can be treated by FFP which contains the C1 inhibitor and bradykinin receptor antagonist and kalleikrein inhibitor. Successful identification is by complete history including family history that led to accurate treatment in our patient.

Dr. Shadia Sultana
Resident, DNB Internal Medicine

Dr. G. Dominic Rodriguez - Top General Physician in Trichy Tennur

Dr. G. Dominic Rodriguez
General Physician

Journals

Kauvery Hospital
Find Doctor
Book Appointment