EXPERT OPINION
Meet the Expert Sorena Kiani MBPhD FRCP FRCPath
Hospital Pharmacy Europe had the pleasure of speaking with Sorena Kiani , Consultant Immunologist at Barts Health NHS Trust , about the burden of the rare disease , hereditary angioedema , and recent clinical and real-world data presented at EAACI 2022
Q Please tell us a little about yourself , your organisation , and your career path
A I am consultant immunologist at Barts Health NHS Trust , where we have the largest cohort of patients with angioedema in the UK . We have been performing all the UK clinical trials on hereditary angioedema ( HAE ) so far . I did a combined medical and immunology research degree qualifying with MBPhD from University College London . I did my postgraduate training in general medicine rotating in London hospitals , followed by specialisation in clinical immunology at King ’ s College Hospital .
Q What is the pathophysiology of HAE ?
A HAE is a chronic , rare genetic disorder characterised by unpredictable severe , painful swelling attacks affecting skin or mucosa which can be life-threatening .
These swelling attacks occur because HAE affects how the immune system controls vascular permeability . HAE is caused by a deficiency or dysfunction in the gene encoding the protein C1-esterase inhibitor ( C1-INH ), which plays a central role in regulation of parts of the immune system . People living with HAE therefore have abnormal levels of functional C1-INH in their bloodstream , intermittently causing increased levels of the mediator bradykinin . Bradykinin promotes swelling by increasing the leakage of fluid through blood vessel walls to body tissues .
Q What are the hallmarks of the condition ? How important is patient screening , prompt / differential diagnosis ?
A The hallmark of HAE is frequent and unpredictable swelling attacks , which can occur in the face , extremities , genitals , abdomen and airways . 1 The median age of onset of HAE is 12-years old 2 and as a rare , genetic disease ( affecting an estimated 1 in 50,000 individuals worldwide 3 ), only children of people living with HAE are routinely tested for HAE .
It is estimated that about 20 % of patients with HAE do not have any family members
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Specialist centres , such as Barts Health NHS Trust , have been able to generate valuable real-world evidence , and allow patients with significant unmet needs to gain early access to innovative treatments
who have HAE . These patients are thought to be the first people in their line of inheritance to have the genetic abnormality . This is called a de novo mutation . For these patients , HAE is not always diagnosed from the start and can be mistaken for acute allergic reactions and / or anaphylaxis . 4 As this is a rare disease , the abdominal attacks of swelling and excruciating pain can be mistaken by emergency services for appendicitis and result in unnecessary emergency surgery . To avoid misdiagnosis at emergency services , patients often bring a letter explaining their HAE diagnosis , allowing them to receive appropriate care .
If HAE attacks are untreated , the swelling can be potentially life-threatening , particularly if it takes place in the airways . Therefore , a prompt diagnosis of HAE is vital ; it allows for the swift and efficient treatment of a painful and potentially deadly attacks .
Q Could you tell us about the burden of HAE on the patient and some of the interventions that are used to address these ?
A The frequency of HAE attacks is varied in different patients . As attacks can last anywhere between several hours to days and can be extremely painful , patients might be unable to attend work , school , or continue with normal social activities . 5 As a result of this , patients have to make significant lifestyle changes with regards to their career choices and relationships . Due to the impact of HAE on their own lives some patients carry significant guilt about the potential of passing the disease on to their children or might even reconsider having biological children . 6 , 7 Individuals with HAE can be traumatised by the experiences of their family members with HAE , as some might have passed away following asphyxiation because of a pharyngeal or laryngeal HAE attack . Up to 49.9 % of HAE patients experience mild to severe anxiety and 24 % experience depression . 7
A few decades ago , there were limited options for safe prophylaxis and poor access to medications used for acute treatment .