Background: The etiopathogenesis and cold stimulation mechanism are not fully understood in cold urticaria (CU). Substance P (SP) is released from skin neurons as a result of cold stimulation. It ...causes mast cell degranulation and therefore causes mast cell chymase (MCC) release. Angiotensin-converting enzyme (ACE) plays a role in removing SP from the environment. ACE also catalyses the conversion of angiotensin I (AT1) to angiotensin II (AT2), like MCC. This study aims to investigate the role of SP, ACE and MCC in the pathogenesis of CU. Methods: Patients with acquired CU were included in the study. Two punch biopsies were taken from the urticaria plaque resulting from the stimulation and the intact skin without lesions. The samples were evaluated histopathologically. All samples were stained immunohistochemically with SP, ACE and MCC antibodies. Results: The number of patients included in the study was 21. In the plaque lesion, the presence of dermal neutrophil and eosinophil, neutrophil in the vascular lumen were found to be statistically significantly higher than intact tissue (p = 0.046, P = 0.014, P = 0.014). Strong positive staining was detected in the full thickness of the epidermis, vascular endothelial cells, eccrine and sebaceous glands with ACE. MCC was statistically significantly higher in lesional skin than lesion-free skin samples (p < 0.001). Conclusions: Mast cell maintains its central role in CU pathogenesis. SP, which causes neurogenic inflammation, may not be detected due to its rapid destruction in the tissue. Strong staining of ACE, which takes part in the local renin-angiotensin-aldosterone (RAS) system in the skin, should be documented quantitatively.
Cold urticaria is a subtype of chronic inducible urticaria (CIndU) associated with significant morbidity and a risk for anaphylaxis. Few studies have assessed the prevalence, management, and ...prevalence of associated anaphylaxis of cold urticaria.
To evaluate the prevalence of cold urticaria among CIndU and chronic urticaria (CU) cases, to assess the management of cold urticaria, and to determine the prevalence of associated anaphylaxis.
We searched PubMed and EMBASE for studies pertaining to cold urticaria and/or CIndU published in the past 10 years. We conducted meta-analyses to evaluate the prevalence of cold urticaria among CIndU and CU cases, the management of cold urticaria with H1-antihistamines and omalizumab, and the prevalence of associated anaphylaxis.
Twenty-two studies were included in the systematic review and 14 in the meta-analysis. The pooled prevalence of cold urticaria among patients with CU and CIndU was 7.62% (95% confidence interval CI, 3.45% to 15.99%; I
= 98%) and 26.10% (95% CI, 14.17% to 43.05%; I
= 97%), respectively. Cold urticaria was managed by H1-antihistamines in 95.67% (95% CI, 92.47% to 97.54%; I
= 38%) of patients and omalizumab in 5.95% (95% CI , 2.55% to 13.27%; I
= 83%) of patients. The pooled prevalence of anaphylaxis among patients with cold urticaria was 21.49% (95% CI, 15.79% to 28.54%; I
= 69%).
Cold urticaria constitutes an appreciable proportion of CIndU and CU cases and is predominantly managed with H1-antihistamines; few patients receive omalizumab. Anaphylaxis is common, and an epinephrine autoinjector prescription may be considered.
Chronic urticaria (CU) is a skin disorder defined as daily or almost daily exhibition of pruritic and transient wheals that last for 6 weeks. CU is divided into two subtypes: chronic spontaneous ...urticaria (CSU) and chronic inducible urticaria (CIndU).
To evaluate the clinical features, possible causes, associated findings, and laboratory results of different subtypes of CU in children according to a new classification.
In this study, we evaluated the clinical features, laboratory investigations, and provocation tests of children with different subtypes of CU according to a new classification.
Two hundred and twenty-two children (59.9% girls) were enrolled in the study. Of the study patients, 59.9% and 40.1% were diagnosed as having CSU and CIndU, respectively. Antithyroid antibody levels were positive in 7.1% of the patients with CSU, 32.8% of the children had positive 14C-urea breath test results, and 6.5% of the patients had positive stool examination results for parasites. Autologous serum skin test results were positive in 53.5% of the patients with CSU. Of the patients with CIndU, 77.5% had symptomatic dermographism, 16.8% had cold urticaria, 2.2% had cholinergic urticaria, 2.2% had solar urticaria, and 1.1% had aquagenic urticaria.
Children with CSU represent the majority of patients with CU, and more than a half of these patients might have autoimmune urticaria. Symptomatic dermographism was the most common type of CIndU.
Acquired cold urticaria (ACU) is characterized by the development of itchy wheals after cold exposure. Generalized urticarial skin rashes triggered by cold exposure characterize certain monogenic ...autoinflammatory diseases (AIDs). The objective of this study is to investigate the presence of variants in genes causing AIDs that present with cold-induced urticarial skin rashes in patients clinically diagnosed with ACU, in order to look for susceptibility factors for the disease. Fifty patients with primary ACU were studied. Germline and post-zygotic variants on the NLRP3, NLRP12, NLRC4 and PLCG2 genes were investigated using next-generation sequencing technology. Seven patients (14%) carried 8 heterozygous germline variants in the following genes: NLRP3 (n = 1), NLRP12 (n = 3), NLRC4 (n = 1), PLCG2 (n = 3). No pathogenic or likely pathogenic variants were detected, and deep analyses of the sequences obtained did not identify any post-zygotic variant. In conclusion, ACU is not related to post-zygotic or germline pathogenic variants in the NLRP3, NLRP12, NLRC4 and PLCG2 genes.
To review the clinical features and natural courses of cold urticaria (ColdU) in a tropical country.
A retrospective chart review was performed of patients who visited Siriraj Urticaria Clinic, ...Siriraj Hospital, Bangkok, Thailand, and were diagnosed with ColdU between 2007 and 2018. Data on provocation and threshold tests, clinical courses, and laboratory work-up were analyzed and compared with data reported by studies in temperate countries.
Of 1,063 chronic urticaria patients, 27 (2.5%) were diagnosed with ColdU, with a mean age of symptom onset of 34.8 years. Half of the patients had a history of atopy, and 1 (3.7%) had a history of anaphylaxis. All patients were positive to 1 of 3 provocation tests: an ice cube test; Temp
4.0; or a tray filled with ice, salt and water. Thirteen patients underwent the ice cube test, and all had positive results. Temp
was performed on 15 patients, 8 of whom had positive results, with a mean critical temperature threshold (CTT) of 21.0°C. All of the 7 patients who had a negative Temp
result later produced positive results to the immersion of their hand and forearm in a tray filled with ice, salt, and water. All patients were treated with H₁-antihistamines, the vast majority (96.3%) being non-sedating H₁-antihistamines. Some (14.8%) needed to be administered oral corticosteroids, ciclosporin, or omalizumab. Six patients (22.2%) were in remission. A Kaplan-Meier survival curve demonstrated 5-year and 10-year remission rates of 13.8% and 42.6%, respectively.
The rate of anaphylaxis in patients with ColdU in a tropical country was lower than those reported by other studies conducted intemperate climates. On the other hand, the number of female patients, mean age at symptom onset, atopy rate, rate of concomitant chronic spontaneous urticaria and mean CTT were higher.
Aquagenic urticaria (AU) is a rare skin condition in which dermal contact with water serves as a trigger of urticaria and pruritus. To make a diagnosis, a water challenge test is useful. We herein ...report a 16‐year‐old Japanese boy diagnosed with AU by water provocation test. The induced skin lesion histologically showed prominent degranulation of mast cells and lymphocytic infiltration throughout the dermis. This is the second report documenting the histopathological features of AU.
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