**4. Heat contact urticaria (HCU)**

to UF [3]. UF is commonly seen in young adults and the mean duration of the disease was reported 3–9 years in different studies. The etiology of UF is still unknown [4]. Infections (hepatitis, upper respiratory tract infections), medications (progesterone, statins), and diabe‐ tes mellitus have been accused, but still, there is less evidence [5]. The pathogenic mechanism is believed to be the release of histamine following a mechano‐immunological trigger [6].

In UF, itchy, white/pink/red wheals are observed after friction, scratching, rubbing, or tight clothing. Wheals appear in a few minutes following the trigger and may last a few hours. UF should come to mind in such cases, and the diagnosis should be made after positive skin

The provocation in UF can be done by scratching or rubbing the skin with a blunt object (e.g., closed ballpoint pen tip or wooden tongue depressor). The flexor aspect of the forearm is the most suitable site for the provocation. Five to ten minutes of waiting time is mostly enough to conclude [8]. Recent guidelines suggest threshold testing with more advanced devices called the dermographometer. With this device, predefined and reproducible pressures can be applied to the testing area. The minimal force which is necessary to induce whealing can be determined with dermographometer and the disease activity in time (i.e., the patient's response to therapy) can be easily monitored. A positive response is noted when the patient

Treatment of UF is mostly symptomatic. Avoidance is the best strategy. It is possible to prevent or minimize whealing by some precautions. Decreasing mechanical irritation in daily life is the essential of the therapy [10]. For symptomatic cases, new generation, nonsedating antihis‐ tamines are suggested as first‐line treatment. In case of failure, the dose can be increased to fourfold. Type of the antihistamine can be changed, leukotriene antagonists and/or H2 anti‐ histamines can be added [11]. Next two drugs in the treatment course are cyclosporine A and

Delayed pressure urticaria (DPU) manifests with pink/red whealing or angioedema of the skin at sites of sustained pressure, such as tight clothing, walking, or sitting down. It is called delayed because hours (6–8 h) are necessary for it to manifest [9, 13]. The patients suffer from severe pain and burning sensation in contrast to other PUs. Fatigue and arthralgia can accom‐ pany. The quality of life is much more affected in DPU patients when compared with other

The diversity of symptoms suggests that other mediators such as cytokines and interleukins play a role in addition to histamine in the pathogenesis of DPU. There is evidence that IL‐1, IL‐3, IL‐6, and tumor necrosis factor alpha (TNF‐α) play a role in the etiopathogenesis [12]. More recently, neuropeptides, such as substance P and calcitonin gene‐related peptide, have

provocation test [7].

38 A Comprehensive Review of Urticaria and Angioedema

omalizumab [10, 12].

shows a wheal response and complain pruritus [9].

**3. Delayed pressure urticaria (DPU)**

forms of PU. Sometimes, the lesions can last up to 72 h [14].

also shown to be taking a part in the formation of DPU [15].

Heat contact urticaria (HCU) is a rare type of PU in which wheals appear after contact to objects with temperature higher than the skin temperature itself [20]. The lesions emerge within a few minutes after the trigger and last for a few hours. Most of the patients are 20–45‐year‐old females. Most of the patients with HU have additional systemic symptoms such as weakness, headache, flushing, diarrhea, shortness of breath, and, even sometimes, syncope [21–23]. Some familial cases with autosomal dominant inheritance have been shown [2]. Most of the time, the trigger is a warm bath. Hot air, heating pads, open fire, heated stove, hair dryers, and indirect sunlight can also cause HU [24].

In case of a suspicion, container filled with hot water should be applied for about 5 min to the skin, or the patient should be asked to shower with hot water at a temperature of 45°C. If the testing area shows a palpable and clearly visible wheal and flare, it is accepted as a positive test. In most of the cases, a burning sensation can accompany the itching. In patients with a positive test result, stimulation time and temperature threshold levels should be measured [25].

Generalized HU must be differentiated from cholinergic urticaria. In HU, the whealing and flares are limited to the contact areas. The lesions are mostly in similar size and morphology. On the contrary, cholinergic urticaria is caused by an increase in the body core temperature and the lesions are small pinpoint hives with flushing [26].

In HCU, the principal of the treatment is to avoid heat if possible. Sometimes, heat desensiti‐ zation can be effective. For symptomatic cases, H1 antihistamines are the first‐line treatment, and in case of failure, the dose can be increased up to fourfold [26]. Omalizumab, montelu‐ kast, and cyclosporine are the third‐line treatments [27]. Systemic steroids, colchicine, and disodium cromoglycate can be used in resistant cases [8].
