corticosteroids are a versatile option for treatment of many pathologies , including dermatological conditions , due to their availability in a wide range of potencies and formulations.13 betamethasone valerate ( bmv ) is a medium - potency corticosteroid without mineralocorticoid properties.4 bmv has been successfully used in a lotion formulation for treatment of seborrheic dermatitis and scalp psoriasis.57 furthermore , the bmv foam formulation has been found effective and safe for treatment of several dermatological pathologies , such as moderate - to - severe scalp psoriasis,4 scalp seborrheic dermatitis,8 mild - to - moderate plaque psoriasis ( not affecting the scalp),9 alopecia areata,10 and stasis dermatitis.11 a ready - to - use medicated plaster for continuous and sustained transdermal delivery of bmv , betesil ( ibsa farmaceutici italia , lodi , italy ) , has recently been developed to treat several cutaneous inflammatory conditions . the transdermal therapeutic system is a very popular modality of drug administration whose pharmacokinetics has gained wide acceptance by avoiding hepatic first - pass metabolism and fluctuation in plasma drug concentration observed following oral therapies . the administration is easier , and it is possible to interrupt treatment immediately , if necessary . although the transdermal therapeutic system is an attractive alternative to oral administration , only a limited number of drugs are available in the form of transdermal plasters.12 many studies have confirmed the superiority of bmv plasters over the cream formulation . in 2006 , pacifico et al13 enrolled 42 patients with mild - to - moderate psoriasis . the patients involved in this study were treated , in a half - side distribution , with a bmv 0.1% tape and bmv 0.12% cream for 30 days . after a 4-week therapy , both bmv 0.1% tape and bmv 0.12% cream were found effective in decreasing lesion size , but the tape caused a greater decrease in psoriasis area and severity index ( pasi ; 39.5% reduction ) , if compared with the bmv 0.12% cream ( 62% reduction ) , indicating a higher efficacy of the tape formulation . in a prospective , randomized , assessor - blind , parallel - group , active - controlled , multicenter phase iii study , naldi et al14 evaluated the efficacy and safety of a new plaster containing bmv 0.1% and a bmv 0.1% cream , in patients affected by mild - to - moderate chronic plaque psoriasis . a total of 231 patients were randomized to receive bmv 0.1% plaster ( 116 patients ) or bmv 0.1% cream ( 115 patients ) for 35 weeks . plasters were applied once daily , and they were worn for at least 20 consecutive hours . the plaster displayed a greater efficacy in decreasing the total size of target plaques , if compared with the cream . bmv plaster was also used with positive results in subjects with relapses of chronic tendinopathies , as shown by salini and abate.15 in that study , 15 patients affected by this condition were treated with a bmv plaster applied to the affected tendon . after 28 days of treatment , pain significantly decreased either at rest or during activities , and a significant improvement in functional limitation was also observed . saraceno et al investigated the effects of bmv 0.1% tape in patients with prurigo nodularis , a chronic skin condition characterized by pruriginous nodules.16 twelve patients were treated with the bmv tape or a moisturizing itch - relief cream containing feverfew , over a period of 4 weeks . the tape was applied once a day for 24 hours to the nodular lesions in the left side of the body and changed every morning , while the cream was applied to the lesions present in the right side twice a day . over the 4-week treatment period , lesions treated with the tape showed a greater reduction in itching , excoriation , and infiltration from baseline , if compared with those lesions treated with the cream . to date , no study has investigated the clinical efficacy of bmv medicated plaster in improving facial swelling , edema , inflammation , ecchymosis , and hematoma following facial rejuvenation procedures . in the present study we tested the hypothesis that a new bmv medicated plaster can safely reduce facial swelling , edema , inflammation , ecchymosis , and hematoma in a series of healthy patients who underwent an intradermal hyaluronic acid - based facial rejuvenation procedure with the aim of erasing facial wrinkles of the perioral and nasolabial folds and improving chin and eye contour . addressing the above mentioned complications is crucial due to the increase in the clinical use of hyaluronic acid , not only in the aesthetic medicine clinic,17,18,19 but also in restorative medicine20 and for the treatment of other pathologies , such as lower - leg telangiectasia,21 premature ejaculation,22 and osteoarthritis.23,24,25 the present study was performed at the poliambulatorio del secondo parere ( modena , italy ) . this study was designed and performed according to the declaration of helsinki and approved by the local institutional review board . forty patients ( 8 males and 32 females ) , aged between 37 and 65 ( mean 52.04  1.4 years ) , participated in the study . the patients underwent a rejuvenation procedure to erase facial wrinkles of the perioral and nasolabial folds and improve chin and eye contour . after this procedure , the patients were randomized to receive either a bmv plaster ( betesil ; n=20 ) applied immediately after the procedure for 12 hours or an aescin 10% cream ( ndema crema gel ; agave farmaceutici , prato , italy ; n=20 ) applied immediately after the procedure , in the evening and the morning after ( control group ) . aescin cream was chosen since this compound possesses well - documented anti - edematous and anti - inflammatory properties.26 after cooling the skin , the subjects were injected ( total of 5.21  0.2 injections varying according to the individual patient s medical needs ) with 2 ml of cross - linked hyaluronic acid ( aliaxin global performance ; ibsa farmaceutici italia ; 25 mg / ml ; molecular weight 10002000 kda ; extrusion force 23  3 newton ) with free contents of 1,4-butanediol diglycidyl ether ( bdde ) ( < 0.1 ppm ) , using a 27 g needle and cannula , in the deep malar areas , followed by a single mesotherapy injection , using a 27 g needle , into the cheeks , chin , and mandible line , with 2 ml of a compound composed of 32 mg non - cross - linked hyaluronic acid ( 700800 kda ) plus a complex including ammonium molybdate , ammonium metavanadate , calcium chloride , iron sulphate , potassium chloride , copper sulphate , magnesium chloride , manganese sulphate , sodium acetate , sodium hydrogen carbonate , sodium chloride , sodium hydrogen phosphate , sodium metasilicate , sodium selenite , stannous chloride , zinc sulphate , alanine , arginine , asparagine , aspartic acid , cysteine , glutamine , glutamic acid , glycine , histidine , isoleucine , leucine , lysine , methionine , phenylalanine , proline , serine , threonine , tryptophan , tyrosine , valine , adenine ( vitamin b4 ) , biotin ( vitamin b8 ) , calcium pantothenate ( vitamin b5 ) , choline chloride , folic acid ( vitamin b9 ) , inositol ( vitamin b7 ) , nicotinammide ( vitamin b3 ) , pyridoxine ( vitamin b6 ) , riboflavin ( vitamin b2 ) , thiamine ( vitamin b1 ) , vitamin b12 , deoxythymidine , glucose , putrescine , sodium pyruvate , and lipoic acid ( viscoderm skinko e ; ibsa farmaceutici italia ) . a mesotherapy injection of the same compound was repeated once a month for 2 months with the aim of prolonging the effect of the first injection of cross - linked hyaluronic acid . this particular combination of the two different hyaluronic acid products had produced successful results in previous unpublished rejuvenation procedures performed at the poliambulatorio del secondo parere ( modena , italy ) . at the end of the procedure , a betesil ( ibsa farmaceutici italia ) plaster was applied to the face over the treated areas , and cut to shape to adequately cover the injected surfaces ( figures 1 and 2 ) , and no other oral or topical medication was allowed . betesil is a 75  100 mm transparent medical plaster , with an adhesive layer containing 30 g / cm bmv . the plaster is self - adhesive and waterproof and can be cut in order to be properly adapted to the treated skin area . the adhesive layer of the plaster contains sodium hyaluronate , 1,3-butylene glycol , glycerol , disodium edetate , tartaric acid , aluminum glycinate , polyacrylic acid , sodium polyacrylate , hydroxypropylcellulose , caramellose sodium , methyl parahydroxybenzoate , propyl parahydroxybenzoate , and purified water . the day after the procedure , the patients were individually admitted to a follow - up examination where the following parameters were quantitatively evaluated : overall facial swelling / edema / inflammation ( scored on a 04 scale ) : 0 = no swelling / edema / inflammation ; 1 = minimal swelling / edema / inflammation ; 2 = slight swelling / edema / inflammation ; 3 = moderate swelling / edema / inflammation ; and 4 = severe swelling / edema / inflammation . ecchymosis and hematoma around the needle injection track ( scored on a 04 scale ) : 0 = no ecchymosis / hematoma ; 1 = minimal ecchymosis / hematoma ; 2 = slight ecchymosis / hematoma ; 3 = moderate ecchymosis / hematoma ; and 4 = severe ecchymosis / hematoma . subjective satisfaction of the patient after the procedure ( scored on a 03 scale ) : 1 = not satisfied ; 2 = quite satisfied ; and 3 = very satisfied . time out from daily activities due to adverse reactions and patients compliance with the plaster , based on adhesiveness , skin reaction , and comfort , were also documented . forty patients ( 8 males and 32 females ) , aged between 37 and 65 ( mean 52.04  1.4 years ) , participated in the study . the patients underwent a rejuvenation procedure to erase facial wrinkles of the perioral and nasolabial folds and improve chin and eye contour . after this procedure , the patients were randomized to receive either a bmv plaster ( betesil ; n=20 ) applied immediately after the procedure for 12 hours or an aescin 10% cream ( ndema crema gel ; agave farmaceutici , prato , italy ; n=20 ) applied immediately after the procedure , in the evening and the morning after ( control group ) . aescin cream was chosen since this compound possesses well - documented anti - edematous and anti - inflammatory properties.26 after cooling the skin , the subjects were injected ( total of 5.21  0.2 injections varying according to the individual patient s medical needs ) with 2 ml of cross - linked hyaluronic acid ( aliaxin global performance ; ibsa farmaceutici italia ; 25 mg / ml ; molecular weight 10002000 kda ; extrusion force 23  3 newton ) with free contents of 1,4-butanediol diglycidyl ether ( bdde ) ( < 0.1 ppm ) , using a 27 g needle and cannula , in the deep malar areas , followed by a single mesotherapy injection , using a 27 g needle , into the cheeks , chin , and mandible line , with 2 ml of a compound composed of 32 mg non - cross - linked hyaluronic acid ( 700800 kda ) plus a complex including ammonium molybdate , ammonium metavanadate , calcium chloride , iron sulphate , potassium chloride , copper sulphate , magnesium chloride , manganese sulphate , sodium acetate , sodium hydrogen carbonate , sodium chloride , sodium hydrogen phosphate , sodium metasilicate , sodium selenite , stannous chloride , zinc sulphate , alanine , arginine , asparagine , aspartic acid , cysteine , glutamine , glutamic acid , glycine , histidine , isoleucine , leucine , lysine , methionine , phenylalanine , proline , serine , threonine , tryptophan , tyrosine , valine , adenine ( vitamin b4 ) , biotin ( vitamin b8 ) , calcium pantothenate ( vitamin b5 ) , choline chloride , folic acid ( vitamin b9 ) , inositol ( vitamin b7 ) , nicotinammide ( vitamin b3 ) , pyridoxine ( vitamin b6 ) , riboflavin ( vitamin b2 ) , thiamine ( vitamin b1 ) , vitamin b12 , deoxythymidine , glucose , putrescine , sodium pyruvate , and lipoic acid ( viscoderm skinko e ; ibsa farmaceutici italia ) . a mesotherapy injection of the same compound was repeated once a month for 2 months with the aim of prolonging the effect of the first injection of cross - linked hyaluronic acid . this particular combination of the two different hyaluronic acid products had produced successful results in previous unpublished rejuvenation procedures performed at the poliambulatorio del secondo parere ( modena , italy ) . at the end of the procedure , a betesil ( ibsa farmaceutici italia ) plaster was applied to the face over the treated areas , and cut to shape to adequately cover the injected surfaces ( figures 1 and 2 ) , and no other oral or topical medication was allowed . betesil is a 75  100 mm transparent medical plaster , with an adhesive layer containing 30 g / cm bmv . the plaster is self - adhesive and waterproof and can be cut in order to be properly adapted to the treated skin area . the adhesive layer of the plaster contains sodium hyaluronate , 1,3-butylene glycol , glycerol , disodium edetate , tartaric acid , aluminum glycinate , polyacrylic acid , sodium polyacrylate , hydroxypropylcellulose , caramellose sodium , methyl parahydroxybenzoate , propyl parahydroxybenzoate , and purified water . the day after the procedure , the patients were individually admitted to a follow - up examination where the following parameters were quantitatively evaluated : overall facial swelling / edema / inflammation ( scored on a 04 scale ) : 0 = no swelling / edema / inflammation ; 1 = minimal swelling / edema / inflammation ; 2 = slight swelling / edema / inflammation ; 3 = moderate swelling / edema / inflammation ; and 4 = severe swelling / edema / inflammation . ecchymosis and hematoma around the needle injection track ( scored on a 04 scale ) : 0 = no ecchymosis / hematoma ; 1 = minimal ecchymosis / hematoma ; 2 = slight ecchymosis / hematoma ; 3 = moderate ecchymosis / hematoma ; and 4 = severe ecchymosis / hematoma . subjective satisfaction of the patient after the procedure ( scored on a 03 scale ) : 1 = not satisfied ; 2 = quite satisfied ; and 3 = very satisfied . time out from daily activities due to adverse reactions and patients compliance with the plaster , based on adhesiveness , skin reaction , and comfort , were also documented . all data are represented as the means  standard error of the mean ( sem ) and were checked for normality using the anderson  darling test , using minitab 15 ( minitab inc , state college , pa , usa ) . data were then analyzed using graphpad prism 5 software ( graphpad software inc , san diego , ca , usa ) . facial swelling / edema / inflammation , ecchymosis / hematoma , and patient satisfaction score data were analyzed using a two - sample unpaired student s t - test . betesil application resulted in a significant improvement in the swelling / edema / inflammation score ( 0.3  0.17 ) , if compared with aescin 10% cream ( 1.3  0.28 ) ( p < 0.01 ) ( figure 3 ) . among the 20 patients receiving betesil , a patient presented minimal inflammation , a patient showed slight edema , and a patient displayed moderate swelling . among the 20 patients receiving aescin 10% cream , seven reported no swelling , edema , or inflammation , five reported minimal edema and inflammation , four patients showed slight swelling , three had moderate swelling and inflammation , and a patient reported a severe degree of inflammation that resolved with ice application within 24 hours . when analyzing ecchymosis and hematoma around the needle injection track , using the ecchymosis / hematoma score , no difference was observed between the groups ( figure 4 ) . in the group treated with betesil plaster , 18 patients did not show any ecchymosis or hematoma around the needle injection track a day after treatment , while two patients had minimal ecchymosis and hematoma ( 0.1  0.06 ) ( figure 4 ) . in the control group , 15 patients did not show any ecchymosis or hematoma , while two patients had minimal ecchymosis and three patients slight hematoma ( 0.4  0.16 ) ( figure 4 ) . patient satisfaction score was significantly higher in patients receiving betesil ( 2.9  0.06 ) versus subjects receiving aescin 10% cream ( 2.4  0.16 ) ( p < 0.01 ) ( figure 5 ) . among 20 patients from the betesil group , 18 were very satisfied with the procedure and two were quite satisfied . in the control group , eleven patients were very satisfied with the procedure , six were quite satisfied , and three were not satisfied ( figure 5 ) . in the betesil-treated group , there was no withdrawal from daily activities , while in the control group , treatment caused absence from work activity for a day in two patients due to a severe degree of skin inflammation ( first case ) and ecchymosis ( second case ) . the plaster was well tolerated by all patients except for a case of skin rash , which resolved without any treatment within 24 hours . all the patients declared that the plaster was comfortable to wear and showed good adhesiveness to the skin . the present study shows that betesil plaster can be safely applied to the skin of patients undergoing facial rejuvenation procedures . its application significantly reduced facial swelling , edema , and inflammation compared with aescin 10% cream . in the betesil group , only two patients showed minimal ecchymosis and hematoma , while in the control group , two patients had minimal ecchymosis and three slight hematoma , with no significant difference between groups . the few cases presenting ecchymosis and hematoma in both groups are explained by the safety profile of aliaxin global performance and viscoderm skinko e that we previously observed in our clinic ( unpublished observation ) . in the present study , this is the first study testing the clinical effectiveness of the betesil plaster in cosmetic medicine . the scientific interest in transdermal therapeutic systems has significantly increased in the last two decades because it represents a valid alternative to oral and hypodermic administration . however , currently , only a limited number of drugs are available as transdermal plasters . indeed , the necessity for the drug released from a transdermal plaster to permeate through the stratum corneum and epidermis , in order to be taken up by capillary loops in the dermal papillae for systemic distribution , represents a rate - limiting step.27 furthermore , previous studies also reported adverse effects caused by transdermal plasters , such as contact dermatitis , sensitization , and delayed hypersensitivity.2844 as far as bmv plaster safety is concerned , pacifico et al13 reported no serious local or systemic treatment - related adverse effects during 30 days of treatment in patients affected by mild - to - moderate psoriasis . no adverse effects were also reported by saraceno et al16 in patients affected by prurigo nodularis treated for 4 weeks with bmv plasters , and by naldi et al14 in patients affected by mild - to - moderate chronic plaque psoriasis treated with bmv plaster for 35 weeks . in our experience , betesil medicated plaster was well tolerated and contributed to the prevention of swelling , edema , and inflammation after hyaluronic acid - based facial rejuvenation procedure . bmv plaster has the advantages of an occlusive therapy , such as increased local hydration and rapid therapeutic response . bmv can also be applied to areas where the use of conventional occlusive bandages would not be possible . the plaster can be cut to fit specific areas that need pharmacological treatment . in this way , it is possible to avoid the use of cosmetically unappealing ointments that may also stain clothes . furthermore , the high adherence of the plaster to the skin results in a longer persistence of the active ingredient in this location , without the need for continuous application of cream or ointment that can also be absorbed by clothing . in conclusion , the present study supports the use of betesil plaster immediately after facial cosmetic procedures in order to safely control facial swelling , edema , and inflammation .