Chronic spontaneous urticaria and angioedema: similarities and differences between non-identical twins

At first glance, just like in a film, one might refer to them as ‘different twins’. This is because they are sometimes associated with one another, as happens in around four out of ten cases of what is known as urticaria-angioedema syndrome. But in other cases, they may share some similar symptoms, leading to confusion. Be careful, though. We must not confuse the two. There are very precise distinctions between chronic spontaneous urticaria and angioedema – whether acquired or hereditary – which influence the diagnostic and therapeutic approach. Above all, the two pathological processes are underpinned by different mechanisms, which must be understood even though they may sometimes overlap. Let us therefore attempt to outline the key characteristics of these two conditions, bearing in mind that early diagnosis is essential for adopting specific, case-by-case therapeutic approaches, whilst recognising that angioedema can also be hereditary, in a rare condition that requires awareness.

“Chronic spontaneous urticaria and angioedema are distinct conditions, although they often co-exist,” explains Vincenzo Patella, president of the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC). “This is why it is essential to arrive at a precise differential diagnosis, bearing in mind that this diagnosis and the associated treatments – validated by the guidelines of international scientific societies and adopted in Italia by AIFA – are divided into two pathogenic pathways.” One is the so-called histaminergic pathway, which is observed in cases of chronic spontaneous urticaria and associated angioedema: in this situation, the pathological condition is induced by the activation of mast cells. “In this instance, chronic spontaneous urticaria manifests in the superficial dermis with fleeting wheals, lasting less than 24 hours, erythema and intense pruritus,” explains Patella. ‘Histaminergic angioedema penetrates the hypodermis and the mucous membranes, with the itching persisting for a longer period.’ The other pathway that can be observed in the presence of angioedema, whether hereditary or acquired, is the so-called bradykinin pathway. In this case, there is an accumulation of bradykinin due to a deficiency of C1 inhibitor or, perhaps, the use of drugs such as ACE inhibitors, which are used to treat high blood pressure. “This condition affects deep tissues for days; it is completely free of wheals and itching, but causes severe abdominal pain and carries a risk of laryngeal asphyxia,” explains Patella. Given the complexity of the clinical presentations, treatments must, of course, be determined on a case-by-case basis: today, there are effective treatments for both forms – urticaria and angioedema. But one thing is crucial: an accurate diagnosis must be made in order to prescribe the correct treatment and save the patient’s life.”

As mentioned, angioedema can be acquired or hereditary. In this case, we are talking about a rare genetic disorder that affects around two people in every 100,000, and it is very insidious. “As we have said, the symptoms ‘mimic’ much more common conditions; diagnosis often comes years later, delaying access to appropriate treatment and exposing patients to avoidable risks and a significant impact on their quality of life,” concludes Patella. Recognising the condition early, as well as enabling targeted treatments, can also allow for the use of specific preventative measures.” The diagnosis, however, is confirmed by specific tests. But the real challenge lies in anticipating it: one must consider this condition when faced with recurrent episodes of abdominal swelling or pain without an obvious cause, taking care not to confuse it with allergies or other conditions. Underlying the disease is a genetic mutation that causes a deficiency or malfunction of the C1-inhibitor protein, affecting the inflammatory cascade and, as mentioned, leading to excessive production of bradykinin, which is responsible for the formation of oedema. However, a word of caution. Although genetics play an important role – if one parent is affected, the risk of their children developing the condition is 50 per cent – sporadic cases do exist. In around 25 per cent of cases, the condition arises even without a family history, making it even more difficult to confirm the diagnosis.