Primary Acquired Cold Urticaria Research Articles

Cold, Red, Itching, and Miserable

A military-centric case study of a 29-year-old woman with no significant medical history presented with urticaria induced by cold. She was clinically diagnosed with primary acquired cold urticaria (ACU). This case is a catalyst for the discussion of a workup for ACU, the differential diagnosis of ACU, and treatment of ACU.

Cold Urticaria: An Underrecognized Cause of Postsurgical Periorbital Swelling

To report cold urticaria as an under-recognized cause of potential periorbital and facial edema after elective oculofacial plastic surgery. Retrospective case series of three patients with primary acquired cold urticaria with review of the clinical aspects of each of the cases. Two of the patients had significant postoperative swelling attributed to primary acquired cold urticaria after the routine use of cool compresses to their surgical sites. The third patient had known primary acquired cold urticaria and required special perioperative management. All three patients ultimately had a good surgical outcome with no long-term sequelae. Although primary acquired cold urticaria is generally not a serious condition, it can be easily overlooked and misdiagnosed as a localized adverse reaction to injected anesthetic, topical antibiotic ointments, or early preseptal cellulitis after eyelid or facial surgery. Rarely, this condition can be fatal and should be recognized by the surgeon to ensure both optimal surgical results and general medical management. Three simple screening questions should identify most patients with this disorder.

Mizolastine in primary acquired cold urticaria

Background: Treatment of primary acquired cold urticaria (CU) is quite difficult because of variable clinical effectiveness and side effects of classic antihistamines. Objective: The objective of the study was to assess the efficacy and safety of mizolastine, an antihistaminic with antiallergic properties, versus placebo in primary acquired CU. Methods: This study was a phase II, multicenter, randomized, double-blind, crossover, placebo-controlled study of mizolastine (10 mg, once daily) versus placebo in 28 patients with primary acquired CU. Efficacy was measured by the cold-stimulation time test, the wheal response, and pruritus intensity after an ice-cube test. Results: Mizolastine delayed the cold-induced wheal reaction, reduced wheal response at 3 and 10 minutes, and reduced pruritus intensity. Statistically significant differences were observed versus placebo for the cold-stimulation time test, wheal response at 3 and 10 minutes, and pruritus intensity ( P = .006, .015, .009, and .005, respectively). No clinically relevant adverse events were reported. Conclusions: Mizolastine (10 mg, once daily) was shown to be superior to placebo for both delaying and reducing the cold-induced wheal reaction without significant adverse events. Results suggest that mizolastine may be effective in the treatment of CU. (J Am Acad Dermatol 2003;48:578-83.)

Association of Platelet-Activating Factor with Primary Acquired Cold Urticaria

We investigated the possibility that the inflammatory reaction in primary acquired cold urticaria might be associated with the release of platelet-activating factor. Six patients with the disease and five normal controls were subjected to cold-water challenges during which blood samples were obtained for measurement of the release of possible mediators: i.e., histamine, neutrophilic chemotactic activity, and platelet-activating factor-like lipid (PAF-LL). Four of the patients had pronounced experimentally induced cold urticaria with angioedema and release of mediators. Levels of the three mediators were not elevated in five normal controls or in two patients in whom cold challenges induced only mild urticaria and angioedema. The effective suppression of cold-induced urticaria in three patients treated with doxepin correlated with inhibition of PAF-LL release but not inhibition of histamine or neutrophilic chemotactic activity release. These data suggest a positive correlation between PAF-LL release and cold urticaria, although the exact relation between PAF-LL and cutaneous lesions of primary acquired cold urticaria has not yet been established.

Primary Acquired Cold Urticaria

• Eight subjects with primary-acquired cold urticaria were treated with chlorpheniramine maleate, cyproheptadine hydrochloride, and placebo in a double-blind clinical trial. During three separate seven-day treatment periods, each patient took 4 mg of either active drug or lactose placebo three times a day. Objective measurements were made at the beginning and end of each treatment period by establishing the minimum time (MT) of cold stimulus application required to provoke urtication. In addition, the spontaneous appearance of cold urticaria lesions was recorded during each treatment period. The MT required for induction of urtication with a cold stimulus was significantly greater for eight patients receiving cyproheptadine as compared to chlorpheniramine or placebo (P &lt; .01). The study demonstrated that cyproheptadine had a significant suppressive action on experimental cold-induced urticaria, while placebo and chlorpheniramine proved ineffective. (<i>Arch Dermatol</i>113:1375-1377, 1977)

Primary acquired cold urticaria. Double-blind comparative study of treatment with cyproheptadine, chlorpheniramine, and placebo

Eight subjects with primary-acquired cold urticaria were treated with chlorpheniramine maleate, cyproheptadine hydrochloride, and placebo in a double-blind clinical trial. During three separate seven-day treatment periods, each patient took 4 mg of either active drug or lactose placebo three times a day. Objective measurements were made at the beginning and end of each treatment period by establishing the minimum time (MT) of cold stimulus application required to provoke urtication. In addition, the spontaneous appearance of cold urticaria lesions was recorded during each treatment period. The MT required for induction of urtication with a cold stimulus was significantly greater for eight patients receiving cyproheptadine as compared to chlorpheniramine or placebo (P less than .01). The study demonstrated that cyproheptadine had a significant suppressive action on experimental cold-induced urticaria, while placebo and chlorpheniramine proved ineffective.

Treatment of cold urticaria with cyproheptadine

We have been able to effectively treat cold-induced urticaria with cyproheptadine. In 8 of 9 patients with primary acquired cold urticaria treated with this drug, there was a striking prolongation of the minimum time required for the induction of a wheal with a cold stimulus. Concomitant with this change there was a significant reduction or elimination of cold sensitivity following natural exposure. The one treatment failure occurred in a patient with an atypical familial form of cold urticaria. The apparent effectiveness of cyproheptadine may be related to its broad antimediator activities.

Immunologic characterization of serum factors responsible for cold urticaria

Serum factors from 2 patients with primary acquired cold urticaria have been characterised. These serum factors, which can passively transfer cold urticaria to normal recipients, are low in titer, have short skin-fixation times, and are relatively thermostable. Reduction with dithiothreitol or mercaptoethanol followed by alkylation with iodoacetamide destroyed the cold urticaria transfer activity. The passive transfer factor in both cases was recovered in Sephadex G-200 gel filtration fractions that primarily contained IgM immunoglobulins. Cold urticaria transfer activity was obtained in euglobulin fractions produced by dialysis of whole serum against lowionic strength low-pH buffers. While the fractions contained low concentrations of all classes of immunoglobulins, only IgM was present in significant amounts (20 to 40 per cent of whole serum IgM). Cold urticaria passive transfer activity persisted after specific adsorption of IgA, IgG, or IgE from various fractions or whole sera. It was, however, removed after complete adsorption of IgM. These data suggest that the serum factors responsible for cold urticaria in these patients belong to the IgM class. Possible mechanisms for the urtication phenomenon are discussed.

Cold urticaria: Immunologic studies

Four cases of primary acquired cold urticaria are described. In all four cases a serum factor was present which, when injected intradermally into normal human subjects, would cause localized urticaria at the sensitized sites after exposure to cold. In order to gain some insight into the pathogenesis of the cold urticarial reaction, attempts were made to characterize the factor in the serum of these four patients. The factor in the different serum specimens remained fixed to the skin of a recipient for periods of 7 to 28 days. The skin-sensitizing activity of the factor was destroyed by heating the serum at 56°C for varying periods. Reduction with 2-mercaptoethanol, followed by alkylation with iodoacetate also destroyed the activity. The cold urticaria factor was further analyzed by Sephadex® G-200 gel filtration and DEAE-cellulose chromatography. It was not found in fractions containing only IgG and IgM but was eluted with the 0.025M and 0.035M phosphate buffers (where most IgE skin-sensitizing antibodies are found). Absorption studies showed that the passive transfer activity could be removed from the four serum specimens by monospecific antiserum to IgE but not by antiserum to any of the other immunoglobulins. All of these characteristics are quite similar to those of IgE skin-sensitizing antibodies. Four cases of primary acquired cold urticaria are described. In all four cases a serum factor was present which, when injected intradermally into normal human subjects, would cause localized urticaria at the sensitized sites after exposure to cold. In order to gain some insight into the pathogenesis of the cold urticarial reaction, attempts were made to characterize the factor in the serum of these four patients. The factor in the different serum specimens remained fixed to the skin of a recipient for periods of 7 to 28 days. The skin-sensitizing activity of the factor was destroyed by heating the serum at 56°C for varying periods. Reduction with 2-mercaptoethanol, followed by alkylation with iodoacetate also destroyed the activity. The cold urticaria factor was further analyzed by Sephadex® G-200 gel filtration and DEAE-cellulose chromatography. It was not found in fractions containing only IgG and IgM but was eluted with the 0.025M and 0.035M phosphate buffers (where most IgE skin-sensitizing antibodies are found). Absorption studies showed that the passive transfer activity could be removed from the four serum specimens by monospecific antiserum to IgE but not by antiserum to any of the other immunoglobulins. All of these characteristics are quite similar to those of IgE skin-sensitizing antibodies.