**6. Vibratory urticaria (VU)**

**5. Cold contact urticaria (CCU)**

40 A Comprehensive Review of Urticaria and Angioedema

responds dramatically to interleukin‐1 antagonists [31].

test (ASST) [34].

with subthreshold temperatures.

Cold contact urticaria (CCU) is characterized by the appearance of wheals and angioedema after exposure to cold. Lesions occur a few minutes following the cold contact. Lesions usually do not spread beyond the contact area [28]. This form of PU can be fatal in some cases. After extensive cold contact, severe angioedema or shock can be seen, mostly following swimming in cold water [29]. CCU is mostly seen in young adults and can continue for 5–8 years [2].

There are some rare variants of CCU. In some cases, CCU lesions develop 24–48 h after cold exposure. In this case, it is called *delayed CCU*. In *cold‐ dependent dermatographism,* the lesions are seen in cold‐exposed and mechanically stimulated areas. *Cold‐ induced cholinergic urticaria* is the case that happens after physical exercise in cold air [30]. Familial cold auto‐inflamma‐ tory syndrome (FCAS) is a rare autosomal dominant condition in which wheals appear within 2 h of systemic cold exposure. The lesions in this syndrome cannot be brought out by localized cold exposure. In FCAS, CIAS1/NLRP3 mutation leads to the activation of NLRP3 inflamma‐ some complex, and finally, interleukin‐1β is released from the mast cells. That is why FCAS

CCU lesions and symptoms arise as a result of the release of some mediators such as hista‐ mine, prostaglandin D2, platelet‐activating factor, and leukotrienes. Yet, it is not known why cold exposure causes the release of these mediators [32]. Half of the CCU patients are positive for antibodies against immunoglobulin E (IgE). IgE binding of some possible, unproven cold‐ depended skin antigens can be the reason of mast cell degradation [33]. It is also shown that CCU patients have circulating histamine‐releasing factors and positive autologous serum skin

Suspecting CCU or angioedema, one should perform cold stimulation test since fatality has been reported in several cases. In this test, the volar aspect of the forearm is exposed to ice cube in a thin plastic bag for 5 min. Ten minutes after the removal of the bag, the response should be assessed. If a well‐demarcated, palpable wheal with a pruritic and burning sensation is present, the test is considered as positive. Ice cube should be in a thin bag in order to avoid any confusion with aquagenic urticaria [35]. Further critical temperature threshold tests with sophisticated devices can enable the patients to avoid situations that cause whealing [28]. More accurate testing is possible with computer‐aided thermoelectric Peltier device. This device can also be used for the evaluation of the success of the treatments. In most of the studies, the criti‐ cal temperature threshold is about 15–20°C [36]. The avoidance of below threshold tempera‐ tures is hard to manage in daily life. Even so, the patients should be warned to avoid contact

The essential of the treatment of CCU is to avoid cold exposure. Non‐sedating H1 antihista‐ mines are accepted as the first‐line therapy by the current European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Network (GA2

European Dermatology Forum (EDF)/World Allergy Organization (WAO) guidelines [5]. Usually high doses of H1 antihistamines are necessary to control CCU. Siebenhaar et al. claimed that high dose of desloratadine is better in controlling CCU when compared with

LEN)/

Vibratory urticaria (VU) is a rare form of PU in which whealing and pruritus of the skin is observed after vibration at the contact area [43]. For proper diagnosis, provocation testing can be done by using a laboratory vortex mixer at a frequency of 1000 r.p.m. Test is considered positive with swelling 10 min after provocation [4]. Nonsedating H1 antihistamines are the first‐line therapy [9].
