***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Cetirizine , a peripheral H1 antagonist , was administered to patients with delayed pressure urticaria in a double-blind , placebo-controlled , crossover study . Efficacy in reducing pressure-induced wheals and flares was evaluated . Histologic changes were also assessed with the skin window technique in weight-induced wheals . Results showed a statistically significant reduction in weight-induced wheal area ( p less than 0.01 ) after cetirizine therapy ; this improvement was accompanied by a concomitant reduction in eosinophil recruitment as demonstrated by the skin window technique ( p = 0.0029 ) . Subsequently , 14 patients with delayed pressure urticaria underwent biopsy before and after 3 weeks of cetirizine therapy to evaluate the drug 's histologic effects . A blinded observer performed the histologic studies . Weight-induced lesions showed a mixed inflammatory infiltrate , primarily polymorphonuclear ( neutrophils and eosinophils ) , whereas the unchallenged skin sites were normal . Cell counts from pressure-induced lesions showed a significant reduction in eosinophils after cetirizine treatment 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 , r and omized , 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 clinical ly 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 BACKGROUND Patients with acquired cold urticaria ( ACU ) show itchy wheals during cold exposure . This disturbing condition involves histamine and platelet-activating factor in its pathogenesis . Rupatadine is a dual antagonist of both histamine and platelet-activating factor . OBJECTIVE To assess rupatadine efficacy in preventing reactions to cold challenge in patients with ACU . METHODS A crossover , r and omized , double-blind , placebo-controlled study in which 21 patients with ACU received rupatadine , 20 mg/d , or placebo for 1 week each is presented . The main outcome was the critical stimulation time threshold ( CSTT ) determined by ice cube challenge . Secondary outcomes included CSTT and the critical temperature threshold assessed by a cold provocation device ( TempTest 3.0 ) , as well as scores for wheal reactions , pruritus , burning sensations , and subjective complaints after cold challenge . RESULTS After rupatadine treatment , 11 ( 52 % ) of 21 patients exhibited a complete response ( ie , no urticaria lesions after ice cube provocation ) . A significant improvement in CSTT compared with placebo was observed after ice cube and TempTest 3.0 challenge ( P = .03 and P = .004 , respectively ) . A significant reduction of critical temperature threshold ( P < .001 ) and reduced scores for cold provocation-induced wheal reactions ( P = .01 ) , pruritus ( P = .005 ) , burning sensation ( P = .03 ) , and subjective complaints ( P = .03 ) after rupatadine treatment were also found . Mild fatigue ( n = 4 ) , somnolence ( n = 1 ) , and moderate headache ( n = 1 ) were reported during active treatment . CONCLUSION Rupatadine , 20 mg/d , shows high efficacy and is well tolerated in the treatment of ACU symptoms The effect of nifedipine on subjective symptoms and objective dermographometer induced whealing  was assessed independently in two double-blind cross-over trials in which active drug or placebo were taken for 2 weeks . The lower dose study used nifedipine 5 mg 3 times daily and gave rise to symptomatic improvement as assessed by diary card and visual analogue scale in 5 of 11 patients . This was not statistically significant and was not accompanied by a reduction in dermographometer-induced wheal and flare responses except at highest pressures . In a separate study 7 patients were treated with nifedipine 10 mg 3 times daily .  No change in whealing occurred , 3 patients ' symptoms became worse and only 1 showed symptomatic improvement on nifedipine .  Side effects were frequent at this dose . The reasons for the unfavourable response despite in vitro evidence for inhibition of mast cell degranulation by this drug are discussed Twelve patients with symptomatic dermographism were entered into a double-blind , crossover study . Patients received 8 mg acrivastine three times daily , 60 mg terfenadine three times daily or placebo , according to a fully r and omized balanced treatment plan . Subjective clinical assessment s were performed and the response to experimentally induced dermographism was assessed . Both active treatments were well tolerated and were shown to be significantly more effective than placebo in the treatment of symptomatic dermographism and in reducing the signs and symptoms of wealing induced by a dermographometer Background Cholinergic urticaria is uncommon and accounts for 10 % of all young adults . To date , there is no effective therapy for cholinergic urticaria . Objective To determine the therapeutic efficacy of different drug combinations in the treatment of cholinergic urticaria . Patients and Methods The participants included in the study are in the age range of 16 to 29 years , with cholinergic urticaria of any duration as diagnosed by physicians . Patients were recruited from Asthma and Allergy Centers in Baghdad and Tikrit . The selected patients were divided r and omly into 3 groups according to the treatment protocol . All patients completed screening before treatment . Results The study indicated that cholinergic urticaria was completely controlled in 30.4 % of patients ( group A ) receiving 4 mg of chlorpheniramine maleate , half hour before the exercise , plus chlordiazopoxide ( 5 mg ) and clindium bromide ( 2.5 mg ) tablets , 3 times daily . However , cure rate was higher ( 83.1 % ) in patients ( group B ) receiving 4 mg of chlorpheniramine maleate ( histadine ) , 3 times daily , plus 25 mg of maprotiline HCl ( ludiomil ) , once daily at night . Furthermore , the complete cure rate was 85.4 % in patients ( group C ) receiving 4 mg of chlorpheniramine maleate (histadine)3 times daily , plus 200 mg of cimetidine ( tagadine ) , 3 times daily . The frequency of relapse was higher in group A ( 89 % ) as compared with group B ( 68.4 % ) and group C ( 23.5 % ) ( P < 0.0001 ) . Conclusions Combination of H1 and H2 antagonists was more effective based on complete control of cholinergic urticaria with lower relapsing rate . However , a future placebo-controlled clinical trial taking in consideration higher H1 antagonists than we used is warranted The efficacy of the new nonsedating antihistamines loratadine and cetirizine was compared in a r and omized , single-blind , crossover , controlled study with that of the classical antihistamines cyproheptadine and ketotifen in seven patients with primary acquired cold urticaria ( ACU ) . The patients received each of the four drugs for 14 consecutive days with a 7-day interval between drugs . We evaluated clinical symptomatology , adverse effects , minimum time of cold contact stimulation required to induce an immediate coalescent wheal ( CSTT ) , and inhibition of histamine-induced wheal response . Both loratadine and cetirizine showed suppression of symptoms with infrequent adverse effects . Important side-effects were observed in patients receiving cyproheptadine . Improvement in CSTT was statistically significant for all drugs compared with baseline values , without differences among them . The histamine-induced skin test was significantly inhibited by all antihistamines . Wheal reductions were 34.6 % for loratadine and 50.9 % for cetirizine . This study suggests that both loratadine and cetirizine may be effective in the treatment of primary ACU A double-blind , crossover trial with a new triprolidine derivative , acrivastine ( BW 825C ; 8 mg 3 times daily ) , cyproheptadine ( 4 mg 3 times daily ) and placebo was carried out in 18 patients suffering from idiopathic cold urticaria .  Acrivastine and cyproheptadine significantly ( p less than 0.01 ) reduced weal areas following ice cube challenge when compared to placebo . Acrivastine was found to be significantly more effective ( p less than 0.01 ) than cyproheptadine in reducing weal areas . Furthermore , cyproheptadine caused significantly more drowsiness than acrivastine ( p = 0.021 ) or placebo ( p = 0.013 ) , which did not differ from each other . This study shows that acrivastine is an effective agent in the treatment of cold urticaria and suggests that acrivastine in the dose used lacks adverse effects , such as drowsiness , traditionally associated with antihistamine therapy Eleven patients with primary acquired cold-induced urticaria were treated with ketotifen ( 1 mg b.i.d . ) or placebo in a double-blind , crossover design trial . After seven days of ketotifen treatment , reaction times to a cold stimulus were significantly delayed in ten of the 11 subjects . No effect was seen after placebo treatment . It is concluded that ketotifen may have a place in the treatment of primary acquired cold urticaria BACKGROUND Cholinergic urticaria does not respond well to treatment with conventional antihistamines and is difficult to study because of its highly variable clinical expression which depends on the presence of eliciting factors . OBJECTIVE We have therefore design ed a double-blind , crossover , placebo-controlled trial , with a 3-week treatment period using either 20 mg/day of cetirizine or placebo . METHODS AND RESULTS Presence of eliciting factors and symptoms were scored daily on a diary card by the patient , with a scale from 0 to 3 for erythema , wheals and pruritus . Statistical analysis was done on 11 evaluable patients during the last 2 weeks of each treatment period ( to allow for 1 week of washout ) and only for days when eliciting factors were present . Compared to placebo , cetirizine caused a statistically significant reduction of wheals ( p = 0.015 ) , erythema ( p = 0.033 ) , pruritus ( p = 0.006 ) and all symptoms ( p = 0.013 ) . No adverse events were observed . CONCLUSION These data show a high efficacy of cetirizine at twice its normally recommended dose which may be related to the specific antiallergic effects of this newer-generation antihistamine 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 In order to examine the efficacy of cetirizine in cholinergic urticaria , we studied 24 patients in a double-blind crossover design during 3-week treatment periods , with either 10 or 20 mg/d cetirizine or placebo . The placebo period was always placed in between the two verum treatments to allow for a washout of the drug . Evaluation of the patients ' daily symptom scores based on itching , erythema and whealing showed a highly significant improvement ( p < 0.01 ) . The percentage of days with mild or no symptoms was also increased significantly with the drug ( p < 0.05 ) . Except for whealing ( p < 0.05 ) , no significant differences between the two dosages of cetirizine could be determined . Since antihistamines have previously been shown to be frequently unsatisfactory in the treatment of cholinergic urticaria , the present data are encouraging 
    Output:
    
Overall , second‐generation antihistamines were more effective  than placebo , and available data indicate that updosing might be effective .
The findings are congruent with the suggested stepwise approach to treating CindUs .
However , the data do not allow for drawing specific conclusions for specific subtypes of