Cold Agglutinins and Cryoglobulins Associate With Clinical and Laboratory Parameters of Cold Urticaria

Abstract

Mast cell-activating signals in cold urticaria are not yet well defined and are likely to be heterogeneous. Cold agglutinins and cryoglobulins have been described as factors possibly associated with cold urticaria, but their relevance has not been explained. We performed a single-center prospective cohort study of 35 cold urticaria patients. Cold agglutinin and cryoglobulin test results, demographics, detailed history data, cold stimulation test results, complete blood count values, C-reactive protein, total immunoglobulin E levels, and basal serum tryptase levels were analyzed. Forty six percent (n = 16) of 35 tested patients had a positive cold agglutinin test and 27% (n = 9) of 33 tested patients had a positive cryoglobulin test. Cold agglutinin positive patients, when compared to cold agglutinin negative ones, were mainly female (P = 0.030). No gender-association was found for cryoglobulins. A positive cold agglutinin test, but not a positive cryoglobulin test, was associated with a higher rate of reactions triggered by cold ambient air (P = 0.009) or immersion in cold water (P = 0.041), and aggravated by increased summer humidity (P = 0.007). Additionally, patients with a positive cold agglutinin test had a higher frequency of angioedema triggered by ingestion of cold foods or drinks (P = 0.043), and lower disease control based on Urticaria Control Test (P = 0.023). Cold agglutinin levels correlated with erythrocyte counts (r = −0.372, P = 0.028) and monocyte counts (r = −0.425, P = 0.011). Cryoglobulin concentrations correlated with basal serum tryptase levels (r = 0.733, P = 0.025) and cold urticaria duration (r = 0.683, P = 0.042). Results of our study suggest that cold agglutinins and cryoglobulins, in a subpopulation of cold urticaria patients, are linked to the course and possibly the pathogenesis of their disease.

Risk factors for systemic reactions in typical cold urticaria: Results from the COLD‐CE study

“…Cold urticaria (ColdU) is a subtype of chronic inducible urticaria (CIndU) where wheals, angioedema or both, with or without systemic signs or symptoms occur in response to cooling of the skin and/or mucosal tissue and/or the whole body. [1][2][3] Patients react to a wide range of triggers including cold air, contact with cold liquids, contact with cold solid surfaces, and the ingestion of cold food or drinks. 2,3 ColdU is classified into typical and atypical forms.…”

Investigating the impact of cold agglutinins on red blood cell parameters in a trauma patient: A case Report

“…In a report by Nikousefat et al, a female patient with a low RBC count, incompatible Hct and Hb, and increasing RBC indices assessed on an automated Sysmex analyzer was diagnosed with coronary artery disease (CAD), and warming the sample to 37 oC led to accurate results . Using the ABX Pentra 80 hematology analyzer, Ercan S. et al discovered comparable results in their study [9] . They examined the level of CAs antibodies and After proper sample transit in a heated container and immediate analysis on a hematology analyzer, valid laboratory results were obtained.…”

“…Aside from standard laboratory analysis issues, CAs makes blood type detection challenging. Lodi et al described the case of a 48-year-old patient whose blood group could not be established due to analytical difficulties caused by the presence of CAs in the patient's sample and who died after receiving an emergency transfusion of universal RBCs [8,9]. According to a Norwegian study, the prevalence of cold agglutinins and CAD is 16 cases per million inhabitants, and the incidence rate is one per million per year.…”

Cold-induced urticaria associated with type I cryoglobulinemia, successfully treated with rituximab

“… 8 Lastly, in a cohort of 35 patients with ColdU, 46% had detectable cold agglutinins, and 27% had cryoglobulins. 9 None of these studies explored the potential of rituximab as treatment for cryoglobulin-associated ColdU.…”