Ingenol mebutate gel for actinic keratosis. Treatment of actinic keratoses with a novel betulin-based oleogel. A prospective, randomized, comparative pilot study. Role of menthol in treatment of candidial napkin dermatitis PEP005 (ingenol mebutate) gel, a novel agent for the treatment of actinic keratosis: Results of a randomized, double‐blind, vehicle‐controlled, multicentre, phase IIa study Effects of topical boswellic acid on photo and age-damaged skin: clinical, biophysical, and echographic evaluations in a double-blind, randomized, split-face study. Efficacy and safety of ingenol mebutate 0.015% gel 3 weeks after cryosurgery of actinic keratosis: 11-week results. Topical Boswellic acids for treatment of photoaged skin. PEP005 (ingenol mebutate) gel for the topical treatment of superficial basal cell carcinoma: Results of a randomized phase IIa trial Accelerating the aesthetic benefit of wound healing by triterpene.
BACKGROUND Actinic keratosis is a common precursor to sun-related squamous-cell carcinoma . Treating actinic keratoses and the surrounding skin area ( i.e. , field therapy ) can eradicate clinical and sub clinical actinic keratoses . Topical field therapy currently requires weeks or months of treatment . We investigated the efficacy and safety of a new topical field therapy for actinic keratosis , ingenol mebutate gel ( 0.015 % for face and scalp and 0.05 % for trunk and extremities ) . METHODS In four multicenter , r and omized , double-blind studies , we r and omly assigned patients with actinic keratoses on the face or scalp or on the trunk or extremities to receive ingenol mebutate or placebo ( vehicle ) , self-applied to a 25-cm(2 ) contiguous field once daily for 3 consecutive days for lesions on the face or scalp or for 2 consecutive days for the trunk or extremities . Complete clearance ( primary outcome ) was assessed at 57 days , and local reactions were quantitatively measured . RESULTS In a pooled analysis of the two trials involving the face and scalp , the rate of complete clearance was higher with ingenol mebutate than with placebo ( 42.2 % vs. 3.7 % , P<0.001 ) . Local reactions peaked at day 4 , with a mean maximum composite score of 9.1 on the local-skin-response scale ( which ranges from 0 to 4 for six types of reaction , yielding a composite score of 0 to 24 , with higher numbers indicating more severe reactions ) , rapidly decreased by day 8 , and continued to decrease , approaching baseline scores by day 29 . In a pooled analysis of the two trials involving the trunk and extremities , the rate of complete clearance was also higher with ingenol mebutate than with placebo ( 34.1 % vs. 4.7 % , P<0.001 ) . Local skin reactions peaked between days 3 and 8 and declined rapidly , approaching baseline by day 29 , with a mean maximum score of 6.8 . Adverse events were generally mild to moderate in intensity and resolved without sequelae . CONCLUSIONS Ingenol mebutate gel applied topically for 2 to 3 days is effective for field treatment of actinic keratoses . ( Funded by LEO Pharma ; Clinical Trials.gov numbers , NCT00742391 , NCT00916006 , NCT00915551 , and NCT00942604 . ) BACKGROUND Actinic keratoses ( AK ) are squamous cell carcinomas in situ and require treatment . Betulin-based oleogel prepared from a st and ardized triterpene dry extract from birch bark represents a new topical agent with anti-inflammatory and anti-tumor potential . PATIENTS AND METHODS In the prospect i ve , r and omized , monocentric phase 2a study 45 patients with < 10 AK were included and r and omly assigned to one of the three treatment groups . Intervention consisted of topical betulin-based oleogel twice daily versus cryotherapy with liquid nitrogen versus the combination of cryotherapy with topical betulin-based oleogel . Treatment response was assessed clinical ly after three months . The clinical response was grade d into complete clearing ( 100 % ) , therapy responders ( > 75 % clearing of the lesions ) and non-responders ( < 75 % clearing ) . Additionally , punch biopsies were obtained from some patients before and at the end of treatment . RESULTS Therapy with betulin-based oleogel was well tolerated . Three patients discontinued therapy because of personal reasons . After three months , the 100 % ( and > 75 % ) clearing rates of the lesions were as follows : 64 % ( 86 % ) with betulin-based oleogel ( n = 14),79 % ( 93 % ) with cryotherapy ( n = 14 ) , and 71 % ( 71 % ) with the combined therapy ( n = 14 ) . Histological analysis of biopsies taken before and after treatment ( n = 8) showed a reduced degree of dysplasia in the epidermis in all study arms . CONCLUSIONS Betulin-based oleogel seems to be an effective novel approach in the topical treatment of actinic keratoses . However , the clinical and histological findings of the present pilot study have to be verified against placebo with larger case numbers Background The antibacterial , antifungal and probable anti-inflammatory effects of menthol were evaluated in the treatment of napkin dermatitis ( ND ) . Methods A pilot clinical trial was conducted in Iran at the Tehran University of Medical Sciences . Eligible neonates with a diagnosis of c and idial ND who did not require critical care or systematic antifungal and anti-inflammatory drugs were included in the study . Overall , 84 patients were r and omly allocated into two groups : menthol group ( n=42 ) receiving st and ard therapy ( topical clotrimazole ) plus menthol drops applied topically and control group ( n=42 ) receiving st and ard therapy plus a placebo .  Thirty-five neonates in each group finished the course of study and were analyzed for skin rash using Munz and Concannon rash scoring methods before therapy and on the 1st , 3rd , 5th and 7th day after the treatments . Results Demographic data and the baseline total skin rash score were not significantly different between the menthol and control groups . The total course of therapy for complete healing was found to be shorter in the menthol group ( 4.3±1.6 vs. 6.9±1.8 days , P=0.0001 ) and erythema and pustules had a significant ( P=0.0001 ) relief in this group . During the study no severe adverse effects of the drug were observed . Conclusion Topical application of menthol may be effective in treatment of c and idial ND The sap of the plant Euphorbia peplus is a traditional remedy for skin conditions , including actinic keratosis . The active constituent of the sap is ingenol mebutate ( ingenol‐3‐angelate ) , formerly known as PEP005 . This r and omized , double‐blind , vehicle‐controlled , phase IIa study investigated the safety ( and secondarily the efficacy ) of two applications of ingenol mebutate gel in 58 patients with biopsy‐confirmed actinic keratosis . Five preselected lesions were treated with ingenol mebutate gel , 0.0025 % , 0.01 % or 0.05 % , or vehicle gel , on days 1 and 2 ( Arm A ) or days 1 and 8 ( Arm B ) . There were no significant differences in tolerability or efficacy between Arms A and B. Treatment was well tolerated . The most common local skin responses were dose‐related erythema , flaking/scaling/dryness and scabbing/crusting . Efficacy was greatest with ingenol mebutate gel , 0.05 % , which result ed in complete clinical clearance of 71 % of treated lesions ( P < 0.0001 vs vehicle gel ) . In addition , 67 % of patients treated with ingenol mebutate gel , 0.05 % had clinical clearance of at least four of five treated lesions ( P = 0.0185 vs vehicle gel ) . Ingenol mebutate gel is being developed as a short‐course topical therapy for actinic keratosis and non‐melanoma skin cancer Boswellic acids ( BAs ) are pentacyclic triterpenes with strong anti-inflammatory activity ; their most important source is the extract of the gum resin of Boswellia serrata , a tropical tree that grows in India and Africa . In the present r and omized , double-blind , split-face , comparative study we have assessed efficacy , tolerability , and safety of a base cream containing 0.5 % BAs as compared to the same cream without these active ingredients in the treatment of clinical manifestations of photoaging of facial skin . Fifteen female volunteers were enrolled ; they applied creams once daily for 30 days . At baseline , at the end of the treatment , and after a 2-month follow-up , clinical findings were assessed according to the Dover classification scale for photoaging and by biophysical and ecographic measurements . We registered a significant improvement of tactile roughness and fine lines in the half side of the face treated with BAs ; noninvasive instrumental diagnostic investigations showed an improvement of elasticity , a decrease of sebum excretion , and a change of echographic parameters suggesting a reshaping of dermal tissue . The treatment was always well tolerated without adverse effects . The present findings seem to indicate that the topical application of BAs may represent a suitable treatment option for selected features of skin photoaging INTRODUCTION Cryosurgery is the most common treatment for  actinic keratosis ( AK ) in the United States . Efficacy with cryosurgery is variable , and is a modality for treating individual , visible lesions while failing to treat sub clinical lesions . METHODS FIELD Study 1 ( NCT01541553 ) is a phase 3 , multicenter , r and omized , double-blind study that evaluated the short- ( 11-week ) and long- ( 12-month ) term efficacy and safety of sequential AK treatment using cryosurgery with liquid nitrogen followed by ingenol mebutate gel , versus cryosurgery followed by vehicle . RESULTS Overall , 329 patients were r and omized to ingenol mebutate 0.015 % gel ( n=167 ) or vehicle ( n=162 ) 3 weeks after cryosurgery . Baseline characteristics were balanced across groups . At week 11 , complete clearance rate ( 100 % ) in the treatment area was higher for ingenol mebutate gel compared with vehicle ( 60.5 % vs 49.4 % , respectively ; P=.04 ) . Mean percentage reduction in number of AKs versus baseline was also numerically higher for ingenol mebutate gel ( 82.7 % vs 75.6 % ) . A general reduction from baseline lesion count was observed 3 weeks after cryosurgery . Treatment after cryosurgery was well tolerated . CONCLUSIONS Short-term ( 11-week ) AK clearance rates on the face or scalp with ingenol mebutate gel after cryosurgery were higher than with cryosurgery alone Boswellic acids ( BAs ) are pentacyclic triterpenes extracted from the gum resins of the tropical tree Boswellia serrata . They are orally administered in traditional Indian medicine for the treatment of several inflammatory disease and cancer because of their anti-inflammatory and immunomodulatory activities as well as stimulatory effects on fibroblasts . The present authors have investigated efficacy , tolerability , and safety of a base cream containing 0.5 % BAs in the treatment of clinical manifestations of photoaging of facial skin with a r and omized , double-blind , placebo-controlled , split-face study . Fifteen female volunteers applied the creams with or without BAs on the half sides of the face once daily for 30 days . Significant improvements of the Dover 's global score for photoaging , tactile roughness , and fine lines , as well as , with noninvasive diagnostic techniques , an increase of elasticity , a decrease of sebum excretion , and a change of echographic parameters were observed with topical BAs in comparison with placebo . The treatment was always well tolerated without adverse effects . The present findings seem to indicate that topical application of BAs may represent a suitable treatment option for selected features of skin photoaging Objectives : To evaluate the safety of two applications of PEP005 ( ingenol mebutate ) gel in superficial basal cell carcinoma .  Efficacy was a secondary end‐point Intention of the study ( EudraCT No 2009 - 017418 - 56 ) is a proof of aesthetic benefit of triterpene treatment in superficial wounds . In an open , prospect i ve , controlled , r and omized , blindly evaluated multicentre phase II clinical trial a triterpene ointment ( OG-S10 ) is compared intra individually with a state-of-the-art moist wound healing dressing ( Mepilex ( ® ) ) in split thickness skin graft donor sites . The graft wound areas at the upper leg were divided into two equal halves , one proximal and one distal site . Decided by r and omization the one site was treated with triterpene and the other in comparison with moist dressing . Triterpene treatment went on for 14 days as covering the wound at every change of wound dressing with the ointment ( 100 mg/cm(2 ) ) . The comparative treatment went on as covering the site by this dressing alone . The outcome of these different treatments was evaluated by two blindly observing distant experts on the basis of photographs of the wound healing progress . Photographs were taken day 14 , 3 month and 1 year after treatment . The only criterion for evaluation of the two sites was similarity of the wound area to the surrounding skin in terms of colour and texture : which of the two sites , the proximal or the distal , was aesthetically superior in normal skin appearance after 14 days at the end of treatment , after 3 month of follow up and 1 year after treatment ? The descriptive comparison is demonstrating quite a remarkable advantage of the ointment versus the moist wound dressing in promoting wound healing : even having in mind the small number of 24 patients within the protocol , the superiority of aesthetic benefit by triterpene treatment after 14 days ( 22 out of 24 patients ) , after 3 month ( 15 out of 19 patients ) and after 1 year ( 8 out of 10 patients ) is obvious
BACKGROUND / OBJECTIVE Terpenoids demonstrate pharmacologic activities that address important mechanisms underlying the pathogenesis of several cutaneous diseases .
This review evaluated clinical trials of dermatology-specific terpenoid-based treatments .