Infusion of iloprost, a prostacyclin analogue, for treatment of Raynaud's phenomenon in systemic sclerosis. Effect of the dual endothelin receptor antagonist bosentan on Raynaud's phenomenon secondary to systemic sclerosis: a double-blind prospective, randomized, placebo-controlled pilot study. Oral iloprost as a treatment for Raynaud's syndrome: a double blind multicentre placebo controlled study. Sublingual and oral isoxsuprine in patients with Raynaud's phenomenon Successful treatment of Raynaud's Syndrome with prostacyclin. Oral iloprost in Raynaud's phenomenon secondary to systemic sclerosis: a multicentre, placebo-controlled, dose-comparison study. Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Treatment of severe Raynaud's syndrome by injection of autologous blood pretreated by heating, ozonation and exposure to ultraviolet light (H-O-U) therapy. Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: a double blind randomised study. Low level laser therapy for treatment of primary and secondary Raynaud's phenomenon. Successful treatment of patients with severe secondary Raynaud's phenomenon with the endothelin receptor antagonist bosentan. Losartan therapy for Raynaud's phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial. A double-blind placebo-controlled trial of antioxidant therapy in limited cutaneous systemic sclerosis. Placebo controlled study showing therapeutic benefit of iloprost in the treatment of Raynaud's phenomenon. The effect of electrical acupuncture-stimulation therapy using thermography and plasma endothelin (ET-1) levels in patients with progressive systemic sclerosis (PSS). Prolonged effect of CGRP in Raynaud's patients: a double-blind randomised comparison with prostacyclin. Sustained-release transdermal glyceryl trinitrate patches as a treatment for primary and secondary Raynaud's phenomenon. Double-blind, randomised, placebo controlled low level laser therapy study in patients with primary Raynaud's phenomenon. Low level laser therapy in primary Raynaud's phenomenon--results of a placebo controlled, double blind intervention study. Prostaglandin E1 infusions for vascular insufficiency in progressive systemic sclerosis. Use of prostaglandin E1 (lipo-PGE1) to treat Raynaud's phenomenon associated with connective tissue disease: thermographic and subjective assessment.
Iloprost , a stable prostacyclin analogue , was given by intravenous infusion to 29 patients with severe Raynaud 's phenomenon , 26 of whom had systemic sclerosis ( SS ) , and compared with placebo infusion in a double blind crossover trial . Iloprost significantly lessened the number and the severity of attacks compared with placebo . Nine patients expressed a preference for effectiveness of treatment , eight of these in favour of Iloprost .  Thermography failed to show any long term effect of Iloprost . Side effects of headache , flushing , nausea , and vomiting were common , and the inconvenience of intravenous administration may limit its routine use OBJECTIVE To investigate the efficacy of the endothelin receptor antagonist , bosentan , in patients with RP secondary to SSc without pre-existing digital ulcers . METHODS Single-centre , r and omized , prospect i ve , double-blinded comparison of bosentan and placebo . Patients received either 62.5 mg bosentan twice daily for 4 weeks , followed by 125 mg twice daily for 12 weeks or matching doses of placebo . RESULTS Of the 17 patients enrolled , 16 completed the study and 1 withdrew from the study due to the reversible development of peripheral oedema .  Compared with placebo , bosentan did not improve the frequency , duration , pain or severity of RP attacks . However , in contrast to placebo , bosentan significantly improved the functional scores . With respect to baseline , the scleroderma HAQ disability index changes were in favour of bosentan at Weeks 12 ( P = 0.03 ) and 20 ( P = 0.01 ) , and the United Kingdom functional score changes at Weeks 8 ( P = 0.038 ) and 16 ( P = 0.039 ) . CONCLUSIONS Bosentan is not effective in SSc-related RP without pre-existing digital ulcers , but it might benefit functional impairment in those patients . TRIAL REGISTRATION European Union Drug Regulating Authorities Clinical Trials , https://eudract.emea.europa.eu , EudraCT-Nr 2004 - 002686 - 21 OBJECTIVE --To compare the efficacy , tolerance and safety of 50 - 150 micrograms orally administered iloprost given twice a day versus placebo in patients with Raynaud 's syndrome . METHODS --The study was multicentre ( n = 3 ) , double blind and placebo controlled . Sixty three patients who had eight or more vasospastic attacks per week were enrolled . After a one week run-in period , all patients received either iloprost or placebo treatment to a maximum tolerated dose of 150 micrograms twice a day for 10 days . Diary cards assessed the duration and severity of the vasospastic attacks . Side effects were monitored by direct question ing . A global assessment of treatment efficacy was made by the patient at the end of treatment and two weeks later . RESULTS --Patient opinion tended to favour iloprost at the end of the 10 day treatment phase ( p = 0.09 ) and this was significant at day 24 ( the follow up visit ) ( p = 0.011 ) . Although the duration and severity of attacks tended to decrease in the iloprost treated group , these results tended not to reach statistical significance ( for severity p = 0.06 at end of treatment , p = 0.09 on day 24 ) . CONCLUSION --Iloprost administered intravenously has been shown to be of benefit in the treatment of the Raynaud 's syndrome associated with systemic sclerosis , but this route of administration is inconvenient . This study evaluated the use of iloprost administered orally to patients with Raynaud 's syndrome . Patient documented improvement was significantly improved by iloprost . Diary card analysis showed a trend in favour of iloprost , but these results did not reach statistical significance Summary Oral and sublingual isoxsuprine 20 mg were compared with placebo in a double blind r and omised cross over trial in 7 patients with Raynaud 's phenomenon .  Skin thermography , plethysmography of the finger tips and direct temperature measurements showed that sublingual isoxsuprine was slightly but consistently superior to the oral form and to placebo ; no significant difference was observed between the latter two treatments . It is concluded that sublingual administration of isoxsuprine has advantages over other routes of administration , and that thermography is a suitable technique for qualitative , but less appropriate for quantitative , measurement of drug effects in patients with Raynaud 's phenomenon There is evidence to suggest that platelet activation occurs in Raynaud 's syndrome . We evaluated the effect of prostacyclin ( PGI2 ) a potent antiplatelet and vasodilator agent in 5 female patients with Raynaud 's syndrome . Outpatient visits were made at weekly intervals for 4 weeks . At the first visit buffer solution ( Wellcome Laboratories ) was infused intravenously for 5 hrs , thereafter three five hr infusions of PGI2 at a peak dose of 10 ng/Kg/min were given . Six weeks after the infusions patients were review ed . Symptomatic improvement , including healing of ischaemic ulcers , occurred in 4 out of 5 patients . Thermography confirmed an increase in h and temperature after PCI2 . Subjective and objective improvement has persisted for at least 6 weeks after the last treatment OBJECTIVE To identify the optimal dose of oral iloprost on the basis of efficacy and tolerability in patients with Raynaud 's phenomenon secondary to systemic sclerosis . DESIGN Multicentre , r and omized , parallel-group comparison of two different doses of oral iloprost and placebo . SETTING European university hospitals . PATIENTS A total of 103 patients with Raynaud 's phenomenon secondary to systemic sclerosis . INTERVENTION Patients received one of three treatments for 6 weeks : placebo , oral iloprost 50 microg or oral iloprost 100 microg . Each treatment was taken twice daily , giving total daily doses of iloprost of 100 and 200 microg . MEASUREMENTS The frequency , total daily duration and severity of Raynaud 's attacks were recorded in a specially design ed patient diary ; physician 's global assessment and adverse events were recorded at visits to the clinic . Analysis was performed on an intention-to-treat population . RESULTS A total of 103 patients were recruited , 89 completed the assessment s throughout the treatment period and 82 completed an additional 6 weeks of follow-up after treatment . Thirty-five patients received placebo , 33 received iloprost 50 microg and 35 received iloprost 100 microg . The mean percentage reductions in the frequency , total daily duration and severity of Raynaud 's attacks were numerically greater in the iloprost groups at the end of treatment and at the end of follow-up . At the end of treatment ( 6 weeks ) , there were significant treatment differences in the total daily duration of attacks ( P = 0.03 ) , but not in the severity ( P = 0.07 ) or the frequency of attacks ( P = 0.37 ) . At the end of follow-up ( 12 weeks ) , there were significant treatment differences in the total daily duration of attacks ( P = 0.001 ) and in the severity of attacks ( P = 0.007 ) , but not in the frequency of attacks ( P = 0.07 ) . Percentages of patients improved at the end of treatment as assessed by the physician were 44 % placebo , 57 % iloprost 50 microg and 64 % iloprost 100 microg ( not significant ) . Side-effects were reported by 80 % of patients on placebo , 85 % on oral iloprost 50 microg and 97 % on oral iloprost 100 microg . Premature discontinuations of treatment in each group were 9 , 30 and 51 % , respectively , with 6 , 27 and 51 % being due to adverse events . CONCLUSION The results on the daily duration of Raynaud 's attacks suggest that both 50 and 100 microg oral iloprost twice daily may be effective in the treatment of Raynaud 's phenomenon secondary to systemic sclerosis . The 50 microg iloprost dose was better tolerated in this patient group OBJECTIVE To compare fluoxetine , a selective serotonin reuptake inhibitor , with nifedipine as treatment for primary or secondary Raynaud 's phenomenon . METHODS Twenty-six patients with primary and 27 patients with secondary Raynaud 's phenomenon were assigned r and omly to receive 6 weeks of treatment with fluoxetine ( 20 mg daily ) or nifedipine ( 40 mg daily ) . Following a 2-week washout period , each group was crossed over to the other treatment arm . The primary outcome variable was the frequency of attacks of Raynaud 's phenomenon . Self-reported attack severity , thermographic recovery from cold challenge and plasma levels of von Willebr and factor and soluble P-selectin were also measured . RESULTS There was a reduction in attack frequency and severity of Raynaud 's phenomenon in patients treated with either fluoxetine or nifedipine , but the effect was statistically significant only in the fluoxetine-treated group ( P=0.0002 for attack severity and P=0.003 for attack frequency ) . Subgroup analysis showed that the greatest response was seen in females and in patients with primary Raynaud 's phenomenon . A significant improvement in the thermographic response to cold challenge was also seen in female patients with primary Raynaud 's phenomenon treated with fluoxetine but not in those treated with nifedipine . There was no significant treatment effect on von Willebr and factor or soluble P-selectin . No significant adverse effects occurred in the fluoxetine-treated group . CONCLUSION This pilot study confirms the tolerability of fluoxetine and suggests that it would be effective as a novel treatment for Raynaud 's phenomenon . Larger and placebo-controlled trials are warranted to assess fluoxetine 's therapeutic potential further in this vasospastic condition OBJECTIVE To determine the effect of re-injection of small sample s of autologous blood , pretreated with heat , ozone and ultraviolet light ( H-O-U therapy ) in patients with severe Raynaud 's syndrome . EXPERIMENTAL DESIGN Open trial in 4 patients . SETTING Temperature/humidity controlled vascular laboratory . PATIENTS Severe Raynaud 's syndrome of more than 5 years duration and defined as more than 5 attacks daily or 10 attacks in one week , at least half of which were painful and lasting for more than 30 minutes . Three patients were refractory to infusions of Iloprost . INTERVENTIONS Patients were treated daily or on alternate days for a two to three weeks period by re-injection of citrated autologous blood pre-treated with heat , ozone and ultraviolet light ( H-O-U therapy ) . MEASURES Clinical observations ; mean equilibrated h and temperature ( infrared thermography ) ; distributive and microcirculatory blood-flow ( venous occlusion strain-gauge plethysmography , infrared photoplethysmography , laser Doppler flowmetry ) iontophoresis of acetylcholine and sodium nitroprusside ; estimations : serum levels of 6-keto-PGF1alpha and serum levels of anti-hsp65 antibody . RESULTS Reduction or abolition of Raynaud 's attacks for at least three months after treatment . Mean equilibrated h and temperature increased but did not normalise . Blood flow parameters improved but did not reach statistical significance . Iontophoresis of acetylcholine showed an increase in laser Doppler flowmetry which was statistically significant . Serum levels of 6-keto-PGF1alpha , fell significantly in three patients . Serum levels of anti-hsp65 antibody fell in the one patient which was followed sequentially . CONCLUSIONS H-O-U therapy may prove useful in patients with severe Raynaud 's syndrome OBJECTIVE --To compare the long term effects of short term intravenous infusions of iloprost with those of oral nifedipine in patients with Raynaud 's phenomenon associated with systemic sclerosis . DESIGN --Double blind , placebo controlled , r and omised group comparison . SETTING --Dermatology outpatient clinic . PATIENTS --Twenty three patients with Raynaud 's phenomenon associated with well documented systemic sclerosis ( American Rheumatism Association criteria ) and with typical abnormalities in fingernail folds on capillaroscopy . INTERVENTIONS --Twelve patients were r and omised to receive intravenous infusions of iloprost starting at 0.5 ng/kg/min and increased by 0.5 ng/kg/min every 15 minutes to a maximum of 2.0 ng/kg/min for eight hours on three consecutive days with a further single infusion at week 8 . Placebo capsules were given concurrently . Eleven patients were r and omised to receive nifedipine , starting at 30 mg daily and increased to 60 mg daily after four weeks for another 12 weeks . Infusions of placebo were given in the same manner as the infusions of iloprost . One patient from each group withdrew because of social reasons and three patients receiving nifedipine withdrew because of side effects . END POINT -- Reduction in number , duration , and severity of attacks of Raynaud 's phenomenon , reduction in number of digital lesions , increase in digital blood flow . MEASUREMENTS AND MAIN RESULTS -- Measurements were taken at 0 , 4 , 8 , 12 , and 16 weeks . Both regimens produced a reduction in the number , duration , and severity of attacks of Raynaud 's phenomenon . The mean ( SE ) number of digital lesions was reduced with iloprost ( from 3.5 ( 1.6 ) to 0.6 ( 0.3 ] and with nifedipine ( from 4.3 ( 0.8 ) to 1.4 ( 0.5 ] after 16 weeks . H and temperature and digital and microcirculatory blood flow were increased with iloprost but not with nifedipine . CONCLUSION --Both iloprost and nifedipine are beneficial in the treatment of Raynaud 's phenomenon . With nifedipine , however , side effects are common . Short term infusions of iloprost provide longlasting relief of symptoms , and side effects occur only during the infusions and are dose dependent BACKGROUND We recently performed a pilot study which suggested that clinical and thermographic improvements occurred in patients with primary and secondary Raynaud 's phenomenon ( RP ) following treatment with low level laser irradiation ( LLLI ) .  In view of these findings , we have proceeded with a double blind , placebo-controlled study . METHODS Forty seven patients suffering from primary or secondary RP were r and omly assigned in a double-blind manner to receive either 10 sessions of distant LLLI ( 16 f , 8 m , median age 45 years ) or placebo irradiation ( 21 f , 2 m , median age 46 years ) during winter months . The attack frequency of RP was measured by a diary count ; its severity was assessed by means of visual analogue scale . Response to cold challenge test before and after LLL or placebo treatment was assessed by infrared thermography . RESULT Overall a significant reduction of the frequency as well as the severity of RP in patients with either LLLI ( frequency p < 0.0001 , severity p < 0.0001 ) or placebo treatment ( frequency p < 0.0001 , severity p = 0.02 ) was found , but patients in the LLLI group exhibited a statistically more significant improvement of the frequency at 6 weeks p = 0.007 and 3 months p = 0.02 and the severity p = 0.02 , p = 0.04 of RP . Thermographic response to cold challenge improved only in patients treated with LLL but not in those treated with placebo . CONCLUSION LLLI significantly lowers the frequency and severity of Raynaud 's attacks in patients with primary and secondary RP . Since this therapeutic modality is a safe , and non-invasive treatment , it might be considered as an alternative to existing therapeutic regimes Secondary Raynaud 's phenomenon ( RP ) in patients with systemic sclerosis ( SSc ) and other collagen vascular diseases is a serious manifestation of microvascular damage that may precede the onset of visceral and /or cutaneous sclerosis for years . Recent studies have demonstrated that the endothelin receptor antagonist bosentan prevents the development of new digital ulcers in SSc . We investigated the potential benefits of bosentan in patients with secondary RP associated with pre-scleroderma and with SSc , independent of digital ulcers . Three patients with secondary RP received bosentan 62.5 mg twice daily for 4 weeks followed by 125 mg twice daily for 12 weeks during the winter season .  Pain ( visual analogue scale ) , Raynaud 's disease activity ( Scleroderma Health Assessment Question naire ) , number and severity of daily Raynaud 's attacks ( diary ) and peripheral thermoregulation ( thermography ) were assessed during treatment periods . Pain , Raynaud 's disease activity , number and severity of Raynaud 's attacks significantly decreased during treatment periods . Thermography after 16-week treatment demonstrated improved peripheral thermoregulation . Although this is a small observational study , treatment with bosentan appears to measurably reduce the daily impact of Raynaud 's disease and improve peripheral thermoregulation in patients with secondary RP , independent of digital ulcers OBJECTIVE To compare the efficacy and tolerability of losartan , an antagonist of angiotensin II receptor type 1 , with nifedipine for the treatment of primary and secondary Raynaud 's phenomenon ( RP ) in a pilot study . METHODS In a r and omized , parallel-group , controlled trial , patients with primary RP ( n = 25 ) or RP secondary to systemic sclerosis ( SSc [ scleroderma ] ; n = 27 ) were allocated to receive 12 weeks ' treatment with either losartan ( 50 mg/day ) or nifedipine ( 40 mg/day ) . Primary outcome variables were the severity and frequency of RP episodes and findings on vascular measurements , including thermography and laser Doppler flowmetry . Serum levels of soluble adhesion molecules , endothelin 1 , fibrinogen , von Willebr and factor , and procollagen type I N-terminal propeptide ( PINP ) were also measured . RESULTS There was a reduction in the severity of RP episodes following treatment with losartan and with nifedipine , but this effect was greater in the losartan arm of the study ( P<0.05 ) : episode frequency was reduced only in the losartan group ( P<0.01 versus baseline ) . Symptomatic improvement was associated with a significant reduction in soluble vascular cell adhesion molecule 1 and PINP ( P<0.01 ) . Subgroup analysis suggested that although these biochemical changes occurred mainly in SSc patients , the clinical benefit was greater in the primary RP group . CONCLUSION This study confirms the tolerability of short-term treatment of RP with losartan , and our data suggest its clinical benefit . Further evaluation of this drug as a long-term treatment for SSc-associated RP should be considered , since it may have additional disease-modifying potential OBJECTIVE To evaluate the effects of a combination of micronutrient antioxidants ( selenium , beta-carotene , vitamin C , vitamin E and methionine ) with allopurinol in patients with limited cutaneous systemic sclerosis ( SSc ) . METHODS The study was design ed as a placebo-controlled double-blind crossover study . A carryover effect was detected retrospectively for some of the prescribed antioxidants , and so the data were analysed as : ( a ) a between group comparison of the first 10 week treatment period ; and ( b ) a within group comparison of the first and second 10-week periods in those who received placebo treatment first . Study end-points were plasma von Willebr and factor ( vWF ) , thermographic response to a st and ard cold challenge , frequency and duration of Raynaud 's attacks , patient opinion , and specialised biochemical parameters ( fatty acid profiles , antioxidants and markers of free radical injury ) . RESULTS Thirty-three patients were recruited . The median duration of Raynaud 's phenomenon was 10 years ( range 2 to 50 years ) in the active-first group and 10 years ( range 4 to 53 years ) in the placebo-first group . In the 10-week study , there were no differences between the active and placebo groups in the change from baseline for vWF , for the parameters of the rewarming curve , or for patients ' symptoms . Despite a rise in circulating antioxidant levels , there was no fall in markers of free radical mediated injury . In the 20-week cross-over study , patients did not experience any clinical benefit from active treatment compared to placebo . CONCLUSION No clinical benefit could be demonstrated from active treatment . There are several possible explanations for this negative result , including the short duration of therapy . It is possible that antioxidant therapy , to be effective , needs to be given early in the SSc disease process , before the onset of irreversible tissue damage Iloprost is a chemically stable analog of prostagl and in I2 showing the same properties as the naturally occurring substance , but with advantages of ease of h and ling and administration to patients . A double blind within patient comparison of intravenous iloprost and placebo was undertaken in 13 patients with Raynaud 's phenomenon severe enough to warrant short term hospitalization for intravenous dilator therapy ; thermography was used as one form of assessment . Our results , while showing improvements in frequency of Raynaud 's attacks after iloprost compared with placebo , show no significant effects on other variables In all 11 patients with progressive systemic sclerosis ( PSS ; Barnett type I , 2 ; type II , 5 ; type III , 4 cases ; male 1 ; female 10 cases ; 45.2 + /- 10.2 years-old ) , 6 cases of scleroderma spectrum disorders ( SSD , male 1 ; female 5 cases ; 51.2 + /- 13.2 years-old ) and 7 healthy controls ( HC , male 1 ; female 6 cases ; 43.1 + /- 8.4 years-old ) were entered to be examined . The plasma endothelin-1 ( ET-1 ) levels of PSS , SSD and HC were 1.98 + /- 0.69 , 1.76 + /- 0.39 and 1.15 + /- 0.38 pg/ml , respectively . After the stimulation with the low frequency electrical current , electrical acupuncture , for unilateral side of h and /arm ( 30 min ) , the plasma ET-1 levels decreased in 10 cases of PSS treated ( 1.61 + /- 0.45 pg/ml ) , but no change of plasma serotonin levels . In 4 of 6 cases of SSD , plasma ET-1 levels increased ( 2.06 + /- 0.39 pg/ml ) , however , nitrate levels increased and serotonin decreased in 3 of 5 cases of SSD . In 6 cases of HC treated with the electrical acupuncture , the plasma ET-1 levels increased ( 1.72 + /- 0.58 pg/ml ) . Thermographically , 9 of 11 cases of PSS and 5 of 6 cases of SSD showed temporally temperature-elevation of h and /fingers not only in treated sides , but also in non treated sides , although none of 7 HC showed temperature-elevation of h and s/fingers . The decrease in plasma ET-1 levels due to the electrical acupuncture was thought to induce the vasodilatation and elevate the surface temperature in patients with PSS . These results will provide an excellent basis to study the efficacy of electrical acupunctural stimulation 1 . Calcitonin gene related peptide ( CGRP ) is a potent endogenous vasodilator to which we have previously demonstrated a specific hypersensitivity in skin blood flow in the h and s in patients with Raynaud 's disease . 2 . We have now investigated whether long infusion of CGRP can relieve symptoms of patients with Raynaud 's disease using prostacyclin as a control . 3 . Six patients were r and omised to receive intravenous infusion of either human alpha-CGRP on one occasion , or prostacyclin ( PGI2 ) on another occasion in a double-blind and cross-over design . The dose of each agent was initially titrated up to 8 ng kg-1 min-1 or to a maximum increase in heart rate of 25 beats min-1 . 4 . In addition to blood pressure , heart rate and skin blood flow measurements , infrared thermography and cold stress challenge was performed before , immediately after infusion and at 3 and 14 days post-infusion . 5 . CGRP caused an increase in h and skin blood flow throughout its infusion , whilst PGI2 caused only a short lived increase . The thermographic results showed significant improvement in h and rewarming 3 days after CGRP but not after PGI2 . 6 . We conclude that 3 h infusion of CGRP was better tolerated than PGI2 and caused objective improvement up to 3 days . CGRP may be an alternative to PGI2 in some patients A r and omized , double-blind , placebo controlled , cross-over study was conducted to determine the clinical efficacy of and patient tolerance to sustained-release glyceryl trinitrate ( GTN ) patches in the treatment of Raynaud 's phenomenon . The patients studied were those with primary Raynaud 's disease ( n = 21 ) and patients with Raynaud 's phenomenon secondary to systemic sclerosis ( n = 21 ) .  GTN patches ( 0.2 mg/h ) were found to be effective in reducing the number ( P < 0.05 ) and severity of Raynaud 's attacks ( P < 0.05 ) in both groups of patients . Objective assessment s by infrared thermography did not show any significant improvement when the patients were on GTN patches ( P > 0.05 ) . Headaches , refractory to treatment , led to the withdrawal of eight patients from the study and occurred in approximately 80 % of the remaining patients . Thus , in spite of the subjective efficacy , the frequent headaches will limit the use of GTN patches in Raynaud 's phenomenon . Elucidating the mechanism of action of the beneficial and adverse effects of GTN at the molecular level may shed light on the pathogenesis of Raynaud 's phenomenon and its treatment BACKGROUND No causal treatment of primary Raynaud 's phenomenon is available due to its unclear aetiology . Low level laser therapy ( LLLT ) is applied in a multitude of medical conditions often without sufficient evidence of efficacy and established mechanisms . To asses the effect of this therapy in patients with primary Raynaud 's phenomenon a r and omised , double blind , placebo controlled cross over study was design ed . PATIENTS AND METHODS Absolute and relative frequency and intensity of vasospastic attacks during three weeks of either LLLT or placebo therapy and results of  infrared thermography  before onset and at the end of both therapy sequences were evaluated in 15 patients with primary Raynaud 's phenomenon . RESULTS Frequency of Raynaud 's attacks was not significantly affected by low level laser therapy . Compared to placebo a significantly lower intensity of attacks during laser irradiation was observed , but no transfer effect occurred . Additionally the mean temperature gradient after cold exposure was reduced after laser irradiation , while the number of fingers showing prolonged rewarming was unaffected . CONCLUSION Though further studies are necessary to confirm these results we could demonstrate for the first time in a double blind placebo controlled clinical trial that low laser therapy is a potential c and i date for an effective therapy of Raynaud 's phenomenon , although effects seem to be of short duration OBJECTIVE To assess the efficacy of low level laser therapy in patients with primary Raynaud 's phenomenon and predict the success of laser therapy by clinical characteristics . METHODS Forty-eight patients were included in a r and omized  placebo controlled , double blind crossover study . Laser and sham therapy each were applied 5 days a week for 3 weeks . Clinical symptoms , exposure to triggers , and frequency and intensity of attacks were recorded in diaries . Results of infrared thermography before onset and at the end of both irradiation sequences were evaluated . Primary endpoint was the average intensity of attacks ; secondary endpoints were average number of attacks and thermography results . Age , sex , duration of symptoms , age at onset of symptoms , evoking conditions other than cold , maximum temperature drop after cold provocation , and rewarming time after cold provocation were tested as potential predictors . RESULTS Number of attacks and their intensity were significantly reduced during laser therapy compared to sham treatment .  Thermographic parameters did not reach statistical significance . In a stepwise multiple regression analysis , evoking conditions other than cold ( stress , wetness as additional triggers ) , rewarming time , and temperature decrease after cold provocation were significant predictors of therapeutic efficacy . CONCLUSION Low level laser therapy reduces frequency and severity of Raynaud attacks . The effect is most pronounced in patients with signs of decreased threshold for vasospasm and less effective in patients with delayed hyperemia Twelve patients with systemic sclerosis ( SS ) and severe Raynaud 's phenomenon received infusions of prostagl and in E1 ( PGE1 ) at a dose of 6 - 10 ng/kg/min , with either saline or 5 % dextrose , for 72 hours in a single-blind cross-over study . The infusions were administered intravenously by central ly positioned catheters . Infusions were well tolerated with only mild side effects . Following the PGE1 infusion cold tolerance improved and attacks of Raynaud 's phenomenon were less frequent , less severe , and shorter in duration . This subjective improvement was maintained for several weeks in most patients , and 2 noted healing of ischaemic ulcers . There was no significant change in objective measurements of h and function after either infusion . However , pain measured on a 10 cm visual analogue scale improved 2.19 cm with PGE1 and only 0.91 cm with normal saline ( P less than 0.05 ) . Temperature of the fingers and h and s recorded by thermography did not change significantly with saline infusions , but did rise during PGE1 infusions ( mean rise 2.0 degrees C at 48 hours , p less than 0.001 ) , and was maintained when measured again 2 weeks later ( mean rise 1.56 degrees C , p less 0.001 ) . PGE1 may therefore be suitable treatment for Raynaud 's phenomenon and the vascular insufficiency of systemic sclerosis and other connective tissue diseases Four patients with connective tissue disease who had been suffering from severe Raynaud 's phenomenon were treated with an intravenous infusion of prostagl and in E1 ( PGE1 ) and its effectiveness was assessed by thermography and a question naire approach . PGE1 in a lipid microsphere formulation ( lipo-PGE1 ) produced a significantly greater increase in lesional skin temperature compared with treatment with PGE1 clathrated in alpha-cyclodextrin 12 months previously in the same group of patients . These results were supported by the subjective assessment obtained from the patients by question naire
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