Chronic inducible urticaria can require some detective work

Chronic inducible urticaria (CindU) is less common than spontaneous urticaria but can also have a dramatic negative impact on quality of life. Novel treatment options aim at depleting or silencing mast cells [1].

“About 1 in 4 patients suffers from CindU, the most common being symptomatic dermographism, cold urticaria, and cholinergic urticaria,” Prof. Marcus Maurer (Charité Universitätsmedizin Berlin, Germany) explained [1]. COLD-CE is an international, multicentre, prospective, cross-sectional academic study aiming to better understand cold-induced urticaria. In this study, real-world data is collected on still ill-defined characteristics, such as subforms of cold-induced urticaria. The researchers found subforms like food-dependent CindU. One patient only suffered from cold-induced urticaria after a specific meal: steak. “There are rare subforms that require our detective work and these projects are in the process of identifying and characterising them,” Prof. Maurer said.

Regarding therapy, omalizumab seems to be effective in cold urticaria, although it is not an approved indication. At the moment, many different biologics are developed for CindU and other forms of urticaria. An interesting novel approach is CDX-0159, an anti-KIT monoclonal antibody that aims to starve mast cells by inhibiting differentiation, migration, and maturation of mast cells (see Figure).

Figure: CDX-0159, an anti-KIT monoclonal antibody, aims to treat CindU by mast cell depletion [2]

CindU, chronic inducible urticaria; IgE, Immunoglobulin E; MC, mast cell; SCF, stem cell factor

Cholinergic urticaria is brought on by raised body temperature or sweating and entails a significant burden for affected patients. “We put patients on a treadmill and challenge them because then we can determine thresholds before wheals start to come,” Prof. Maurer explained. This can greatly help patients to cope with the situation. Antihistamine treatment is often ineffective in cholinergic urticaria. Sometimes, a response can be gained by updosing but a little more than 60% of patients with cholinergic urticaria do not respond sufficiently to elevating antihistamines. “So, clearly, we have to develop better treatment options,” stated Prof. Maurer. A complete response to omalizumab standard dose was shown by 13% of patients, and 47% had at least a major response. “If you change the dose and interval of omalizumab, you get up to two-thirds of patients to respond,” Prof. Maurer recommended. However, even with optimised dosing, there are non-responders, particularly in the male population. Furthermore, the standard dose is often not sufficient in patients with cholinergic urticaria.

Another novel approach is the silencing of mast cells with Siglec-8, an inhibitory mast cell silencing receptor antibody. In a phase 1b study, 7 patients that were treated with this agent showed a very good response. In addition, there is an ongoing study with dupilumab, the CHED study (NCT NCT03749148), in patients with cholinergic urticaria.

There are also new tools to assess disease activity and disease control in CindU, the most important being the urticaria control test. “Let’s use these tools in clinical practice to better treat patients,” Prof. Maurer concluded.

1. 
   
   1. Maurer M. News in inducible urticarias. D2T05.1C, EADV 2020 Virtual Congress, 29-31 Oct.
   
   
   2. Maurer M, et al. CDX-0159, an anti-KIT monoclonal antibody, demonstrates dose-dependent reductions in serum tryptase and a favorable safety profile in a phase 1a healthy volunteer study. Abstract 1829, EAACI Digital Congress 2020, 6-8 June.