***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: Background Histamine‐releasing activity ( HRA ) is detectable in up to 50 % of patients with chronic ordinary urticaria . Objectives To determine the effect of cyclosporin on clinical features and HRA in patients with chronic urticaria . Methods Thirty patients with severe unremitting disease , responding poorly to antihistamines and showing a positive autologous serum skin test ( ASST ) as a marker of HRA , were r and omized to 4 mg kg−1 daily of cyclosporin ( S and immun ® , n = 20 ) or placebo ( n = 10 ) for 4 weeks . Non‐responders were offered open‐label cyclosporin for 4 weeks . All were followed for up to 20 weeks or until clinical relapse ; all took cetirizine 20 mg daily throughout the study . The primary measure of efficacy was a daily urticaria activity score ( UAS ) of weal numbers and itch ( maximum score 42 per week ) . A positive response was defined as a reduction to < 25 % of baseline weekly UAS and relapse as a return to > 75 % . The effect of cyclosporin  on serum HRA was assessed by in vitro basophil histamine release assays and ASSTs before and after treatment . Results Twenty‐nine patients ( 19 active , 10 controls ) completed the r and omized trial medication . Eight of 19 on active treatment but none on placebo had responded at 4 weeks ( P < 0·05 ) . Three others on active drug met the criterion for response at 2 weeks but not at 4 weeks . Mean reduction in UAS between weeks 0 and 4 was 12·7 ( 95 % confidence interval , CI 6·6–18·8 ) for active and 2·3 ( 95 % CI − 3·3–7·9 ) for placebo ( P = 0·005 ) . Seventeen non‐responders ( seven r and omized to active and 10 to placebo ) chose open‐label cyclosporin and 11 responded after 4 weeks . Six of the eight r and omized active drug responders relapsed within 6 weeks . Of the 19 responders to r and omized and open‐label cyclosporin , five ( 26 % ) had not relapsed by the study end‐point . Mean in vitro serum HRA fell from 36 % ( 95 % CI 22–49 % ) to 5 % ( 95 % CI 1–8 % ) after cyclosporin treatment ( n = 11 , P < 0·0001 ) . The ASST response to post‐treatment serum was also reduced ( P < 0·05 ) . Conclusions This study shows that cyclosporin is effective for  chronic urticaria  and provides further evidence for a role of histamine‐releasing autoantibodies in the pathogenesis of this chronic ‘ idiopathic ’ disease This study evaluates the effectiveness and safety of cyclosporine ( CsA ) in the treatment of patients with chronic idiopathic urticaria with a positive autologous serum skin test ( ASST ) , who fail to respond to conventional therapy , and requiring long-term oral steroid treatment . In a double-blind study , 40 adults were assigned r and omly to receive CsA ( 5 mg/kg per day for 8 weeks and then 4 mg/kg per day for 8 weeks ) or cetirizine ( 10 mg/day ) and then they were followed up for 9 months . After 2 weeks , the study was opened because 16 patients ( 40 % ) had daily severe relapses requiring systemic steroids treatment . All of these patients had been receiving antihistamines and , therefore , all patients also were assigned to the CsA treatment regimen ( 5 mg/kg per day for 8 weeks and then 4 mg/kg per day for 8 weeks ) . The ASST and clinical severity score were evaluated before and after treatment . All of the 40 patients completed the 16-week CsA course without dropping out because of relevant side effects . In three patients , CsA was reduced by 0.5 mg/kg per day after the 1st month of treatment for a mild and reversible increase in serum creatinine . During CsA treatment , 20 patients had relapses resolving spontaneously ( 8 patients ) or with antihistamines ( 12 patients ) . During the 9-month follow-up period , 22 patients had relapses resolving spontaneously ( 10 patients ) or with antihistamines ( 12 patients ) . Only two patients failed to complete the study because of severe symptoms occurring after 4 and 7 days of follow-up and requiring long-term steroid treatment . After 9 months of follow-up , 16 patients were still in full remission . The clinical severity score of chronic idiopathic urticaria dropped significantly by the end of the 4th month of treatment ( p = 0.002 ) as well as by the completion of follow-up ( p = 0.007 ) . The ASST was negative in 13 patients and positive in 3 of 16 patients , with total remission of symptoms . Significant score reduction also was observed in patients experiencing relapses that resolved spontaneously ( p = 0.005 ) or with antihistamines ( p = 0.03 ) . These results show the long-term efficacy and tolerability of CsA  in patients with severe chronic idiopathic urticaria  , unresponsive to conventional treatments The present study aim ed to evaluate the effectiveness of 2.5 mg/kg/day cyclosporin ( CsA ) treatment in patients with severe chronic idiopathic urticaria ( CIU ) and the impact of CsA treatment on several cytokines involved in the etiopathogenesis of CIU . Twenty-seven CIU patients and 24 healthy control subjects were included in the study . The  autologous serum skin test ( ASST ) for autoantibodies and urticaria activity scoring ( UAS ) were measured for the evaluation of the clinical severity and the response to therapy , and the serum levels of interleukin (IL)-6 , IL-8 , IL-2 receptor , IL-1beta , tumor necrosis factor (TNF)-alpha and IL-5 were measured . The mean UAS score was 32.07 + /- 7.05 and 6.22 + /- 3.84 before and after CsA treatment , respectively . The serum IL-2 receptor , TNF-alpha and IL-5 levels of patients before CsA treatment were statistically higher than those of the control group ( P = 0.001 ) , and after 4 weeks of CsA therapy the mean IL-2R , TNF-alpha and IL-5 levels were significantly decreased . The data from this study demonstrate that CsA therapy is efficient and safe for CIU patients . Increase in clinical efficacy and marked decreases in serum cytokine levels suggest that inhibition of cytokine generation is involved in the action of the drug in this clinical setting BACKGROUND Chronic idiopathic urticaria is sometimes difficult to treat , with little response to antihistamine therapy . OBJECTIVE In a limited number of severe chronic idiopathic urticaria patients , cyclosporine A ( CsA ) therapy was found to be effective . In this study , we compared the clinical efficacy and safety of short- and long-term CsA applications . METHODS Twenty patients with severe disease , unresponsive to antihistamines and showing a positive autologous serum skin test ( ASST ) were r and omized to 4 mg/kg per day of CsA for 4 or 12 weeks . The clinical efficacy was measured with a daily activity score of weal numbers and itch ( UAS ) . The two groups were compared in terms of mean reduction in UAS and ASST response to pre- and post-treatment sera . RESULTS The clinical improvement was dramatic in the first month of treatment in both groups . There was no significant difference in the frequency of responses , side effects and the reduction of UAS in either group . CONCLUSION The preliminary results of our study suggest that CsA is clinical ly effective for chronic urticaria . The prolonged use of this therapy for more than 1 month provides little benefit in the clinical improvement Background : Because of specific method ological difficulties in conducting r and omized trials , surgical research remains dependent predominantly on observational or non‐r and omized studies . Few vali date d instruments are available to determine the method ological quality of such studies either from the reader 's perspective or for the purpose of meta‐ analysis . The aim of the present study was to develop and vali date such an instrument Chronic Idiopathic Urticaria ( CIU ) is a cutaneous disorder for which there is no identifiable specific etiologic agent . Some recent evidence s suggest that CIU might be an autoimmune disease . We analyzed immunological features occurring in CIU and evaluated effectiveness and tolerance of Cyclosporin A ( CsA ) treatment in patients unresponsive to antihistaminic treatment . Twenty patients with CIU were recruited after a selective diagnostic protocol and were divided into two groups . CsA was prescribed for group 1 and Prednisone for group 2 as control , for 8 weeks . Before and after the therapy we performed on all patients immunological studies . For all patients symptoms disappeared after a few days of therapy . Before therapy all patients showed activated B cells ( CD19+CD23 + cells ) and among B CD19 + cells , about 20 % were CD5 + ( cells that synthesize natural autoantibodies ) . After treatment with Prednisone in group 2 , a significant reduction of CD4 + lymphocytes ( p + 0,01 ) was observed . Our findings might support the CIU autoimmune pathogenetic hypothesis . The clinical remission in the CsA-treated group confirmed the therapeutic effectiveness of this therapy in antihistaminic unresponsive CIU and , at dosage used , side effects were rare , mild and reversible . Thus , CsA might be a good therapeutic alternative in CIU patients unresponsive to conventional treatments Patients with autoimmune urticaria ( AIU ) and positive autologous serum skin test ( ASST ) represent a more serious type of chronic urticaria that does not respond to treatment with antihistamines , but responds completely to systemic corticosteroids . Because of the chronic course of the disease , there is a risk of side-effects .  Cyclosporin A ( CsA ) is an alternative treatment for patients with AIU . In order to determine the efficacy of CsA at the lowest possible dose in patients with chronic idiopathic urticaria and positive ASST , 30 patients were included in a 5-month study with a follow-up one year after the end of treatment . All patients had positive ASST before treatment and autoantibodies were present in 73 % . Twenty- three patients completed the study and responded to low-dose CsA treatment . Three patients did not respond to a dose of 2.5 mg/kg CsA , and 4 patients dropped-out due to side-effects . After the first month of treatment , an improvement of 31 % was noted , reaching 88 % after the fifth month of treatment . The mean dose of CsA was 2.16 mg/kg for the first month and 0.55 mg/kg for the fifth month . Three to 6 months after the end of the study , the ASST was repeated and was negative in 78.3 % of patients . At the one-year follow-up , 20 patients were symptom-free ( 87 % ) and 3 had relapsed ( 13 % ) . CsA , even in low-doses , can be an effective and short-term treat- ment with minimum side-effects in patients with AIU 
    Output:
    
Our systematic review showed that positive autologous serum skin test results , positive baseline basophil histamine release assays , positive baseline basophil activation test responses , elevated baseline plasma D-dimer levels , elevated baseline serum interleukin (IL)-2 , IL-5 , and tumor necrosis factor-alpha ( TNF-α ) levels , and low baseline serum IgE levels might assist in predicting favorable CsA responses in CSU patients .
Decreased plasma D-dimer levels ; and decreased serum IL-2 , IL-5 , and TNF-α levels were reported to be correlated with clinical improvement after CsA treatment .
Since most positive results were from non- RCT articles and some data were still inconsistent , this systematic review identified no reliable practical biomarker for predicting CsA treatment response in patients with CSU .
There were no positive predictors with good consistency and mechanical plausibility