***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: The effect of hydroxychloroquine ( HCQ ) on dry eye has not been fully determined . This study aim ed to compare the 12-week efficacy of HCQ medication with that of a placebo in the management of dry eye in primary Sjögren 's syndrome ( pSS ) . A double-blind , r and omized control study was conducted in 39 pSS subjects from May 2011 through August 2013 . pSS was diagnosed based on the classification criteria of the American-European Consensus Group . Subjects received 300 mg of HCQ or placebo once daily for 12 weeks and were evaluated at baseline , 6 , and 12 weeks , with a re-visit at 16 weeks after drug discontinuance . The fluorescein staining score , Schirmer test score , tear film break-up time ( TBUT ) , and ocular surface disease index ( OSDI ) were measured , and tears and blood were collected for ESR , IL-6 , IL-17 , B-cell activating factor ( BAFF ) , and Th17 cell analysis . Color testing was performed and the fundus was examined to monitor HCQ complications . Twenty-six subjects completed the follow-up . The fluorescein staining score and Schirmer test score did not differ significantly . The OSDI improved with medication in the HCQ group but was not significantly different between the groups . TBUT , serum IL-6 , ESR , serum and tear BAFF , and the proportion of Th17 cells did not change in either group . HCQ at 300 mg daily for 12 weeks has no apparent clinical benefit for dry eye and systemic inflammation in pSS ( Clinical Trials.gov . NCT01601028 ) OBJECTIVE To define the clinical manifestations , autoantibody associations , optimal treatment , and prognosis of hypergammaglobulinemic purpura associated with systemic autoimmune rheumatic diseases . METHODS Of 303 consecutive patients with systemic autoimmune rheumatic diseases evaluated over 5 years , 17 French Canadian patients with hypergammaglobulinemic purpura with systemic lupus erythematosus ( SLE ) ( n = 12 ) or another systemic autoimmune rheumatic disease ( n = 5 ) were identified and followed prospect ively . Mild secondary Sjörgren 's syndrome developed in 9 ( 53 % ) patients . RESULTS Sixteen ( 94.1 % ) patients were women . Attacks of hypergammaglobulinemic purpura occurred in the pretibial ( 76.5 % ) or perimalleolar ( 70.5 % ) areas or the dorsal aspect of the feet ( 52.9 % ) . Triggering factors included walking , prolonged st and ing , and alcohol intake . The mean duration of attacks was 6.1 days . Systemic manifestations consistent with a flare of the underlying systemic autoimmune rheumatic diseases accompanied hypergammaglobulinemic purpura attacks in 15 ( 88 % ) patients . Arthralgias ( n = 13 , 86.6 % ) , arthritis ( n = 9 , 69.2 % ) , and periarthritis were characterstically localized adjacent to the purpura . Anti-Ro antibodies were expressed in all ( 100 % ) patients with hypergammaglobulinemic purpura with SLE , but in only 11 ( 28.9 % ) of 38 consecutive patients with SLE without hypergammaglobulinemic purpura ( P < 0.000001 , odds ratio 84 , 95 % confidence interval 4.6 , 1525 ) . The positive predictive values for hypergammaglobulinemic purpura in SLE were : anti-Ro plus anti-La 73 % , anti-La 57 % , and anti-Ro 52 % . The negative predictive value of anti-Ro was 100 % . Although 11 ( 92 % ) patients with SLE with anti-Ro expressed anti-52 kDa Ro [ 4 ( 36.3 % ) of whom also expressed anti-60 kDa Ro ] , this frequency was not greater than in anti-Ro positive patients with SLE without hypergammaglobulinemic purpura . The effects of indomethacin or hydroxychloroquine were assessed over 6 months in 8 patients with recurrent incapacitating hypergammaglobulinemic purpura . Complete ( n = 4 ) or partial ( n = 4 ) remission of hypergammaglobulinemic purpura occurred . In 5 additional patients with severe hypergammaglobulinemic purpura , attacks stopped with prednisone 25 to 60 mg daily . The mean duration of hypergammaglobulinemic purpura followup was 5.4 years ( range 1 - 6 years ) . At last followup , hypergammaglobulinemic purpura had resolved in 11 ( 64.7 % ) patients despite persistently abnormal serology . CONCLUSION In the absence of anti-Ro antibodies , a presumptive diagnosis of hypergammaglobulinemic purpura secondary to SLE should be question ed . Prednisone should be used only in severe hypergammaglobulinemic purpura . Indomethacin and hydroxychloroquine are of value in the treatment of milder hypergammaglobulinemic purpura Objectives To analyze the clinical and immunological characteristics at enrollment in a large prospect i ve cohort of patients with primary Sjögren 's syndrome ( pSS ) and to investigate the association between serum BAFF , beta2-microglobulin and free light chains of immunoglobulins and systemic disease activity at enrollment . Methods Three hundred and ninety five patients with pSS according to American-European Consensus Criteria were included from fifteen centers of Rheumatology and Internal Medicine in the “ Assessment of Systemic Signs and Evolution of Sjögren 's Syndrome ” ( ASSESS ) 5-year prospect i ve cohort . At enrollment ,  serum markers were assessed as well as activity of the disease measured with the  EULAR Sjögren 's Syndrome Disease Activity Index ( ESSDAI ) . Results Patient median age was 58 ( 25th–75th : 51–67 ) and median disease duration was 5 ( 2–9 ) years . Median ESSDAI at enrollment was 2 ( 0–7 ) with 30.9 % of patients having features of systemic involvement . Patients with elevated BAFF , beta2-microglobulin and kappa , lambda FLCS had higher ESSDAI scores at enrollment ( 4 [2]–[11 ] vs 2 [ 0–7 ] , P = 0.03 ; 4 [1]–[11 ] vs 2 [ 0–7 ] , P < 0.0001 ) ; 4 [2]–[10 ] vs 2 [ 0–6.6 ] , P < 0.0001 and 4 [ 2–8.2 ] vs 2 [ 0–7.0 ] , P = 0.02 , respectively ) . In multivariate analysis , increased beta2-microglobulin , kappa and lambda FLCs were associated with a higher ESSDAI score . Median BAFF and beta2-microglobulin were higher in the 16 patients with history of lymphoma ( 1173.3(873.1–3665.5 ) vs 898.9 ( 715.9–1187.2 ) pg/ml , P = 0.01 and 2.6 ( 2.2–2.9 ) vs 2.1 ( 1.8–2.6 ) mg/l , P = 0.04 , respectively ) . Conclusion In pSS , higher levels of beta2-microglobulin and free light chains of immunoglobulins are associated with increased systemic disease activity OBJECTIVES --In 1985 and 1988 a positive effect of treatment of primary Sjögren 's syndrome with hydroxychloroquine was reported in two small open studies . To investigate further the clinical and laboratory effects of hydroxychloroquine in primary Sjögren 's syndrome a two year study was performed . METHODS --The design of the study included a prospect i ve , placebo controlled , two year double blind crossover trial in 19 patients . RESULTS --A significant decrease in IgG and IgM and a tendency for a decrease in the erythrocyte sedimentation rate ( ESR ) during treatment with hydroxychloroquine compared with treatment with placebo were found . No beneficial clinical effect of the use of hydroxychloroquine as expressed in preference for treatment with hydroxychloroquine or placebo with regard to symptoms and signs of primary Sjögren 's syndrome could be shown , however , nor any relevant change in tear gl and activity and sequelae of peripheral tear function deficiency , nor salivary gl and scintigraphy . CONCLUSIONS --The use of hydroxychloroquine at a dose of 400 mg daily taken over a 12 month period does not have a worthwhile clinical benefit in patients with primary Sjögren 's syndrome despite an improvement of hyperglobulinaemia and slight changes in the ESR and The dysregulated cytokine network in Sjögren 's Syndrome ( SS ) is reflected by local and systemic overexpression of pro-inflammatory cytokines and absent or low levels of anti-inflammatory cytokines . To date , the use of cytokine based therapies in SS has been disappointing . Oral administration of low dose interferon ( IFN ) α showed inconsistent efficacy in various studies and failed to achieve the primary endpoint in a pivotal r and omised controlled trial . Similarly , neither of the two tumour necrosis factor (TNF)-α blockers tested ( etanercept and infliximab ) showed efficacy in placebo controlled trials . Although the rationale for low dose oral IFN treatment has not been firmly established , TNF blockade was based on solid pre clinical data . Therefore , the reason for the lack of efficacy is unclear , but recent data suggest that unexpected biological effects of TNF antagonists may have contributed to this . Cytokines , given their central role in the pathogenesis of SS , remain attractive targets for future treatments , despite the disappointing early results . Inflammatory cytokines are obvious c and i date s , and agents against several of them are available or under development for other autoimmune diseases similar to SS . New c and i date cytokines such as IL-17 and IL-12 and /or IL-23 may provide promising targets for SS . Additionally , as an alternative to systemic treatment , which has the risk of potentially severe side effects , the use of local cytokine directed therapy should be explored OBJECTIVE To evaluate the effect of hydroxychloroquine treatment on interleukin 6 ( IL6 ) , hyaluronic acid ( HA ) , and soluble interleukin 2 receptor ( sIL2R ) concentrations in the saliva and serum of patients with primary Sjögren ’s syndrome ( SS ) . METHODS Fourteen SS patients treated with hydroxychloroquine 200 mg/day for 12 months were investigated in an open prospect i ve study . Clinical parameters of efficacy and routine biochemical and haematological data to assess drug safety and tolerability were determined every three months . Salivary and serum IL6 , sIL2R , and HA values were determined at study entry , 6 and 12 months , using ELISA and radiometric assays . RESULTS After hydroxychloroquine treatment , salivary IL6 concentrations decreased from 13.2 ( 1.2 ) to 7.3 ( 1.1 ) pg/ml ( mean ( SEM ) ) ( p < 0.0001 ) . Similarly , salivary HA concentrations were also reduced from 577.8 ( 120 ) to 200 ( 34 ) ng/ml ( mean ( SEM ) ( p < 0.003 ) . Serum IL6 concentrations decreased from 5.4 ( 0.6 ) to 2.9 ( 0.2 ) pg/ml ( mean ( SEM ) ( p < 0.001 ) , while serum HA concentrations remained unchanged . No change has been detected in salivary or serum sIL2R concentrations after 12 months of treatment with hydroxychloroquine . Treatment also result ed in significant reduction in erythrocyte sedimentation rate , serum γ globulin , and C reactive protein values while only partial clinical improvement was noted in some patients . A more pronounced decrease of salivary IL6 and HA levels was found in the two patients in whom a reduction in the swelling of the parotid gl and was noted . CONCLUSION In this open label study of hydroxychloroquine treatment for SS a significant reduction of some salivary inflammatory markers was seen at the end of 12 months . Although during the treatment period only a partial clinical effect could be noted , the findings suggest that a double blind controlled study of hydroxychloroquine in SS is indicated OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity 
    Output:
    
For dry mouth and dry eyes , the effectiveness of HCQ treatment was essentially the same as placebo treatment .
For fatigue , the effectiveness of HCQ was lower than placebo .
The efficacy  of HCQ in treating pain associated with pSS was superior to that of the placebo .
There was no significant difference between HCQ-treated groups and controls in terms of Schirmer test results , but HCQ could reduce the erythrocyte sedimentation rate compare with placebo .
A descriptive safety assessment showed that gastrointestinal adverse effects were the most common adverse effects associated with HCQ .
Conclusions This systematic review showed that there is no significant difference between HCQ and placebo in the treatment of dry mouth and dry eye in pSS .