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Cold Contact Urticaria Combined With Cold-Dependent Dermographism and Serum Autoreactivity

What Have We Ignored?

Chen, Qi-Quan; Zhong, Hua; Song, Zhi-Qiang; Hao, Fei*

International Journal of Dermatology and Venereology: March 2019 - Volume 2 - Issue 1 - p 43–44
doi: 10.3760/cma.j.issn.2096-5540.2019.01.010
Case Reports

Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.

Corresponding author: Dr. Fei Hao, Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. E-mail:

Conflicts of interest: The authors reported no conflicts of interest.

Received October 31, 2018

Received in revised form December 28, 2018

Accepted January 13, 2019

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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Urticaria is a common disease in dermatology. Physical urticarias are a group of urticaria that are induced by various physical stimulations, including shear force, cold, heat, pressure, and solar and vibratory stimu-lations. Cold contact urticaria (CCU), the second most common subtype among all physical urticarias in China, is characterized by itchy wheals and edema on skin following exposure to cold. The ice cube skin contact test is one of the most used methods by which to make the diagnosis of CCU.1 Dermographism, the appearance of stripe-shaped wheals within 2-3 min after shear force at the skin surface as a result of rubbing or scratching that is accompanied by a local itching and/or burning sensation, is the characterized symptom of factitia urticaria.2 The autologous serum skin test (ASST) has been mostly used to show serum autoreactivity in chronic spontaneous urticaria (CSU), whereas serum autoreactivity has rarely been reported in physical urticaria. Here, we report a case of CCU combined with cold-dependent dermographism and serum autoreactivity.

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Case report

A 32-year-old female presented to Department of Dermatology, Southwest Hospital, in October 2016 due to a four-year history of itchy wheals and edema on the neck and limbs after exposure to the cold wind after riding a motorcycle in the winter, on the hands after washing with cold water, and on the oral mucosa and lips after eating ice cream. The itchy wheals and edema usually disappeared after 1 - 2 h. Additionally, she complained that pruritic stripe-shaped wheals appeared upon scratching of skin, and it usually happened when the temperature was 2 - 6 °C. She had not response to traditional Chinese medicine or H1 antagonists prescribed by a previous medical facility. No associated systemic concomitant symptoms, like fever, myalgia, or dyspnea, were linked with these attacks. The patient told us that she had experienced anaphylactic rhinitis in childhood, but she denied a family history of atopy dermatitis.

Routine laboratory tests demonstrated that she had unremarkable changes in complete blood count, urinalysis, and serum chemical analysis results. There were no hives on her body at room temperature. We performed the ice cube test by holding the ice cube on her medial upper arm for 5 min and then observed a corresponding hive on the contacted area (Fig. 1A). To elicit dermatographism, we scratched her back skin; however, no reaction was observed in the 10 min after scratching (Fig. 1B). Based on her history, we placed a chilled water bag (stored in a refrigerator at 4 °C) on her forearm for 5 min. In response, only flushing, but no wheals appeared; however, when we scratched the area of skin that had contacted the water bag, prominent dermatographism confined to the scratched area was observed (Fig. 1C). While, scratching the skin after it returned to room tempera-ture did not produce dermatographism. Interestingly, we performed an ASST incidentally on her other forearm, and the result was strongly positive (++++) (Fig. 1D). Her signs and symptoms completely resolved after taking a double dose of ebastine. She took the medicine for six months, and the symptoms had a mild recurrence after she stopped the therapy.

Figure 1

Figure 1

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Thirty years ago, Kaplan described a case of der-matographism that was detectable only upon chilling the skin prior to scratching it, which, as far as we know, is the only previously described case of cold-dependent dermatographism.3 The difference between that patient and ours is that our patient's condition was combined with CCU but Kaplan's was not. In both cases, the wheals and pruritis did not appear when skin was exposed to the cold temperature (4 °C) unless it was simultaneously scratched, which indicates that the temperature threshold of inducing CCU is much lower than that for the cold-dependent dermatographism of our patient. To the best of our knowledge, this is the first report of a case of CCU with concomitant cold-dependent dermatographism.

Dermographism is a common physical urticaria usually concomitant with CSU and other inducible urticaria.4 Our case and the one reported by Kaplan indicate that, among patients with negative dermatographism, there is a subset of patients with cold-dependent dermatographism, and these patients have been ignored because dermatographic tests are negative without cold exposure. More cases are needed to confirm this phenomenon. Cold-dependent exercise-induced anaphy-laxis and cold-induced cholinergic urticaria have been reported,5 and our case supports that cold-dependent dermatographism may be a distinct entity that can be concomitant with CCU.

Serum autoreactivity has been well defined in CSU; about 30%-60% patients have serum autoreactivity as confirmed by ASST. Functional autoantibodies against either IgE or high affinity IgE receptor (FceRIa) were considered as the main factors con-tributing to serum autoreactivity, which plays an important role in the pathogenesis of CSU.6 However, serum autoreactivity in physical urticaria or CCU is rarely reported. Our case concomitant with cold-dependent dermatographism is rare with a positive response to ASST. Since ASST is not routinely tested in patients with CCU, this case suggests that autoreac-tivity may also be an important feature in CCU, and could be an important characteristic of CCU that has been previously ignored. Further studies are needed to reveal the prevalence of auto-reactivity and its role in CCU.

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[1]. Krause K, Zuberbier T, Maurer M. Modern approaches to the diagnosis and treatment of cold contact urticaria. Curr Allergy Asthma Rep 2010;10(4):243–249. doi:10.1007/s11882-010-0121-3.
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[6]. Chen Q, Zhai Z, Xu J, et al Basophil CD63 expression in chronic spontaneous urticaria: correlation with allergic sensitization, serum autoreactivity and basophil reactivity. J Eur Acad Dermatol Venereol 2017;31(3):463–468. doi:10.1111/jdv.13912.
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