Solasodine Glycosides: A Topical Therapy for Actinic Keratosis. A Single-Blind, Randomized, Placebo-Controlled, Parallel Group Study with Curaderm^BEC5

Background: Untreated actinic keratosis can advance to squamous cell carcinoma, which in turn is associated with a risk of metastasis. Current treatments for actinic keratosis have many shortcomings. This communication describes the efficacy and safety of a topical cream therapy, CuradermBEC5, containing solasodine glycosides (0.005%) for actinic keratosis.Methods: Randomly assigned patients with actinic keratosis on the face, trunk or extremities received so-lasodine glycosides cream (CuradermBEC5) or placebo (vehicle) that was self-applied to the lesions and covered with an occlusive dressing (micropore) twice daily for 3 consecutive days. Complete clearance and local reactions were as-sessed at 56 days with follow-up periods of 6 months and 1 year. Results: The rate of complete clearance at day 56 was higher with solasodine glycosides than with placebo (92% vs. 38%, P 0.001). The absolute success rates after 1 year follow-up were 82% for solasodine glycosides and 18% for placebo. No differences in local reactions were obtained when solasodine glycosides and placebo were compared. Local reactions in both groups peaked at days 2 and 3 with local pain as the major event. The pain associated with treatments lasted approximately 10 minutes after application of solasodine glycosides and placebo. Complete reepithelialization occurred two weeks after treatment. Adverse events were generally mild to moderate in intensity and resolved without sequelae. Conclusions: Solasodine glycosides cream applied topically twice daily with a dressing for 3 days is effective for the treatment of actinic keratoses.

Clinical outcomes and 5-year follow-up results of keratosis pilaris treated by a high concentration of glycolic acid

BACKGROUND Keratosis pilaris is a hereditary abnormal keratosis of the hair follicle orifice.Gray-brown keratotic plugs in the pores and dark red keratotic papules at the openings of hair follicles can be seen,which contain coiled hair and are often accompanied by perifollicular erythema and pigmentation.Glycolic acid can correct the abnormalities of hair follicular duct keratosis and eliminate excessive accumulation of keratinocytes.It also promotes skin metabolism and accelerates the melanin metabolism.The therapeutic effect is related to the glycolic acid concentration.AIM To evaluate the efficacy and safety of a high concentration of glycolic acid in the treatment of keratosis pilaris,and to observe the outcomes at 5-year of follow-up.METHODS Twenty-five participants were recruited and areas with typical keratosis pilaris were selected as testing sites.High concentrations of glycolic acid(50%or 70%)were applied to a circular area(d=8 cm,S=50 cm2)and repeated four times,on days 0,20,40 and 60.Before each treatment and 20 d after the last treatment,on days 0,20,40,60,and 80 and at a 5-year follow-up,The number of follicular keratotic papules were counted and the extent of perifollicular erythema and pigmentation was determined.At the same time,the participants provided subjective evaluations of treatment efficacy and safety.RESULTS Treatment effectiveness was indicated by the percentage of keratotic papules in the test site,on days 20,40,60 and 80,which were 8%,12%,36%,and 60%,respectively.Compared with day 0,each difference was significant(P<0.05).Compared with day 0,differences in melanin content(M)in the skin and skin lightness(L)on days 40,60 and 80,the were statistically significant(P<0.05);skin hemoglobin content(E)on days 60 and 80 was statistically different as compared with before treatment(P<0.05).There were no significant differences in the number of keratotic papules,M,L,and E in 9 participants at the 5-year follow-up compared with before treatment(P>0.05%).CONCLUSION A high concentration of glycolic acid significantly improved skin roughness as well as follicular hyperpigmentation of patients with keratosis pilaris.The treatment was relatively safe,but there was no significant difference at the 5-year follow-up compared to before treatment.

Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp

AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK).METHODS Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm^2 for 3 consecutive days.Local skin reactions were calculated at each follow up visit using a validated composite score.Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57,and classified as complete,partial and poor response.RESULTS A number of 130 patients were enrolled,of which 101(77.7%) were treated on the face,while 29 (22.3%) on the scalp.The great majority of our study population (n = 119,91.5%) reached at least a 75% clearance of AKs and,in particular,58 patients (44.6%) achieved a complete response while 61(46.9%) a partial one.Logistic backward multivariate analysis showed that facial localization,level of local skin reaction (LSR) at day 2,the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response.CONCLUSION Ingenol mebutate 0.015% gel,when properly applied,is more effective on the face than on the scalp and efficacy is directly associated to LSR score.

Effects of a New Human Recombinant MnSOD in the Treatment of Photoaging and Actinic Keratosis

Physiological processes, as aerobic metabolism and inflammatory response, generate reactive oxygen species (ROS) that may induce cellular injury when their amount is increased and antioxidant defense mechanisms are overwhelmed. Also, ROS are generated following UV skin irradiation able to deplete the natural antioxidant defenses in the skin. The increase in exposure to UV may lead to photoaging and precancerous skin lesions (actinic keratosis). New antioxidant strategies in the prevention and therapy of skin lesions are urgently needed. In this study, we evaluated the antioxidant efficacy of a recombinant form of human manganese superoxide dismutase able to inhibit reactive oxygen species production in some patients affected by severe photoaging and actinic keratosis.

Holistic Approach in the Treatment of Actinic Keratosis: Benefits and Disadvantages of 5-Fluorouracil, Imiquimod, Diclofenac and Curaderm

Background Actinic keratosis is the most prevalent premalignant skin disorder in the white population. Current guidelines provide no clear recommendations about preferred treatments. Methods The parameters;effectiveness, treatment duration, recurrence, side effects and cost of treatment were investigated for three frequently used topical therapies which were then compared with a most recent developed topical therapy. Published clinical data obtained from the literature was used to compare these parameters for 5-fluorouracil, imiquimod and diclofenac and relate them with the newly developed Curaderm. Results A wide variation in the concentrations of the active anti-keratotic ingredients, application frequency, duration of treatment, recurrence rates and cost of treatment exist between the different topical therapies. The efficacy rates and side effects were less variable. Overall, Curaderm is the most suitable treatment for actinic keratosis. Clinical evidence is presented illustrating the effects of Curaderm on field-directed treatments and solitary treatments of actinic keratoses. Conclusions Current medical guidelines do not provide clear recommendations on which treatment approach for actinic keratosis is preferred. Direct head-to-head comparison between treatments with emphasis on efficacy, safety, treatment duration, compliance, convenience, cosmetic outcome, patient acceptance and cost should be available to the patient, the practising physician, healthcare system and should assist in therapeutic treatment guidelines and policymaking. Given the very favourable profiles of these parameters with Curaderm when compared with other home-based treatments, it should be considered that Curaderm is first-in-line.

Discussion on the Treatment of Palmoplantar Keratosis by TCM Soaking and Washing

By combing the mechanism and advantages of traditional Chinese medicine(TCM)soaking and washing and combining TCM syndrome differentiation with western medicine differentiation of diseases,guided by the view that"the principle of external treatment is that of internal treatment",this article discusses the differentiation and treatment ideas of palmoplantar keratosis by TCM soaking and washing,which will provide a reference for clinical treatment.

A rare interesting case of seborrheic keratosis of pinna

Seborrheic keratosis is a benign tumour of external ear originating from proliferative epithelial cells. Its most common site ranges from the retroauricular region to the helical rim. Diagnosis is made on the basis of clinical & histopathological examination. Here, we discuss the clinical presentation, differential diagnosis, pathological diagnosis and management of such a case.

Cryotherapy versus Hydrogen Peroxide in the Treatment of Seborrheic Keratosis

Seborrheic keratosis has a varying degree of pigmentation. In pigmented seborrheic keratosis, the proliferating keratinocytes trigger the activation of neighboring melanocytes by secreting melanocyte-stimulating cytokines. The etiology of seborrheic keratosis is not known. Epidermal growth factors or their receptors have been implicated in the development of seborrheic keratosis. Seborrheic keratoses can safely be left alone, but ugly or easily traumatized ones can be removed with cryotherapy, electrodesiccation, curettage, or shave excision. The present work aims to compare two modalities of treatment for seborrheic keratosis, namely cryotherapy and hydrogen peroxide (30%). Methods: 30 patients with seborrheic keratosis were included in this study. They were divided into two groups, each with 15 patients. The treatment modalities that have been used include cryotherapy and hydrogen peroxide in three different concentrations (30%, 35%, and 40%). Result: The cryotherapy group consisted of 15 patients, 7 males and 8 females. Their ages ranged from 38 to 80 years, with a mean of 56.1 ± 11.4. Clinical and photographic assessments showed complete removal in all 15 patients in this group (100%). As regards the hydrogen peroxide group, this group included 15 patients, distributed among 7 males and 8 females. Their ages ranged from 39 to 90 years, with a mean of 53.9 ± 14.4. Clinical and photographic assessments showed response in only one small superficial lesion in one patient (6.7%) and no response in 14 patients (93.3%). Conclusion: Cryotherapy is an effective, easy, and relatively cheap method for treating seborrheic keratosis.

Actinic keratosis and field cancerization

While actinic keratoses(AKs) have been considered precancerous until recently for being able to turn into squamous cell carcinomas(SCCs), it is now agreed that it would be more appropriate to call them cancerous. Although not all AKs turn into SCC and some of them may even have a spontaneous regression, there is an obvious association between SCC and AK. Approximately 90% of SCs have been reported to develop from AKs and AKs are the preinvasive form of SCCs. The presence of two or more AKs on a photodamaged skin is an indicator of field cancerization and represents an increased risk of invasive SCC. All lesions should be treated since it cannot be foreseen which of the lesions will regress and which will progress to SCC. AK can be a single lesion or it can involve multiple lesions in a field of cancerization; thus, AK treatment is grouped under two headings:(1) Lesion-specific treatment; and (2) Field-targeted treatment. Lesion-specific treatments are practicable in patients with a small number of clinically visible and isolated lesions. These treatments including cryotherapy, surgical excision, shave excision, curettage and laser are based on physical destruction of the visible lesions. Field-targeted treatments are effective in the treatment of visible lesions, subclinical lesions and keratinocyte changes in the areas surrounding the visible lesions. Field targeted treatment options are topical imiquimod cream, 5% 5-fluorouracil cream, ingenol mebutate, diclofenac gel, resimiquimod and photodynamic therapy.

Application of topical gentamicin ointment in the treatment of Nagashima-type palmoplantar keratosis in children with a nonsense mutation

Importance:Nagashima-type palmoplantar keratosis(NPPK)is a hereditary dermatosis mostly caused by a nonsense mutation in SERPINB7.Despite the increasing interest in readthrough gentamicin treatment of NPPK,clinical evidence for this treatment is limited.Objective:This study aimed to provide further evidence for the use of topical gentamicin in the treatment of NPPK in children with nonsense mutations.Methods:We designed a bilaterally controlled study of topical gentamicin ointment.Children diagnosed with NPPK carrying nonsense mutations were enrolled in this study.A 0.1%gentamicin ointment was applied to one hand and an emollient to the other for 3 months.A bilateral comparison of the visual analog scale scores for clinical manifestations and safety was performed.Results:Ten children with NPPK were included in this study.In comparison with the emollient side,the topical gentamicin side showed significant improvements in hyperkeratosis,erythema,maceration,and desquamation after 1 and 3 months of treatment(P<0.05).However,hyperhidrosis and odor did not improve significantly.No adverse events were observed during the systemic safety monitoring examinations.Interpretation:Topical gentamicin ointment showed good safety in the treatment of NPPK with nonsense mutations,indicating that it is a promising therapeutic choice in children with NPPK.

Concurrence of Merkel Cell Carcinoma and Squamous Cell Carcinoma in A Patient with Generalized Actinic Keratosis: A Case Report

Introduction:Merkel cell carcinoma(MCC)is a rare,aggressive cutaneous malignancy,and its pathogenesis might relate to ultraviolet light and Merkel cell polyomavirus infection.MCC in the Chinese population is uncommon.Here,we present a case of MCC that occurred based on widespread actinic keratosis(AK)in a Chinese female.Case report:An 82-year-old woman presented with two rapidly enlarging and rupture lesions on the face for 1 year.Biopsy was suggestive of squamous cell carcinoma(SCC)on the forehead and MCC on the left cheek.The patient had a history of generalized AK for 3 years.The lesion on the left cheek was also revealed as an AK by histopathological examination 1 year ago.Complete surgical resection was performed to remove the two malignancies.Discussion:The co-occurrence of AK,SCC,and MCC in a Chinese woman is unusual.Immunohistopathological examination is vital for correct diagnosis.The three tumors,in this case,may originate from two different precursor cells and are affected by the same carcinogen.Alternatively,they may come from the same pluripotent epidermal stem cells,and chronic exposure to ultraviolet light and Merkel cell polyomavirus lead to the formation of different types of tumors.The coexist of MCC with other cutaneous tumors provided a train of thought for exploring the origin of MCC.Conclusion:We reported a rare co-existence phenomenon of MCC associated with AK and SCC.Hence,long-term follow-up and early treatment are imperative for patients with premalignant lesions,such as widespread AK.

Oculocutaneous Albinism with Squamous Cell Carcinoma, Bowen’s Disease and Actinic Keratosis: A Case Report

IntroductionOculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by defects in melanin synthesis that affect the skin,eyes,ears,and hair to varying degrees.Because of the melanin deficiency,albino patients are at high risk for sun-induced skin cancers.Herein,we report a rare case of an OCA type 4 combined with a progressive carcinogenesis for precancerous (actinic keratosis,AK),in situ (Bowen's disease),and invasive status of squamous cell carcinoma (SCC).

The Value of Excipients and the Required Understanding of the Biological System in Product Development: An Impactful Example of Curaderm, a Topical Skin Cancer Treatment

The incidences of nonmelanoma skin cancer are increasing worldwide, and the ongoing war on its treatment necessitates the development of effective and non-invasive methods. Through basic and clinical research, non-invasive treatments like Curaderm have been developed, leading to improved quality of life for patients. Excipients, previously considered inactive ingredients, play a crucial role in enhancing the performance of topical formulations. The development of Curaderm emphasizes the importance of understanding the interactions between active ingredients, excipients, and the biological system to create effective and affordable pharmaceutical formulations. The systematic approach taken in the development of Curaderm, starting from the observation of the anticancer activity of natural solasodine glycosides and progressing through toxicological and efficacy studies in cell culture, animals, and humans, has provided insights into the pharmacokinetics and pharmacodynamics of solasodine glycosides. It is crucial to determine these pharmacological parameters within the skin’s biological system for maximal effectiveness and cost-effectiveness of a skin cancer treatment. Curaderm, as a topical treatment for nonmelanoma skin cancer, offers benefits beyond those obtained from other topical treatments, providing hope for improved quality of life for patients.

Gold Standard for Skin Cancer Treatment: Surgery (Mohs) or Microscopic Molecular-Cellular Therapy (Curaderm)?

Non-melanoma skin cancers or keratinocyte cancers such as basal cell carcinoma and squamous cell carcinoma make up approximately 80% and 20% respectively, of skin cancers with the 6 million people that are treated annually in the United States. 1 in 5 Americans and 2 in 3 Australians develop skin cancer by the age of 70 years and in Australia it is the most expensive, amassing $1.5 billion, to treat cancers. Non-melanoma skin cancers are often self-detected and are usually removed by various means in doctors’ surgeries. Mohs micrographic surgery is acclaimed to be the gold standard for the treatment of skin cancer. However, a novel microscopic molecular-cellular non-invasive topical therapy described in this article, challenges the status of Mohs procedure for being the acclaimed gold standard.

莱泽-特雷拉综合征

1临床资料 例1,女性,49岁。发现右侧颈部肿块8个月。体检右侧甲状腺可触及一大小约3.5cm×3.0cm、质偏硬、界清、随吞咽上下活动的肿块,左耳轮脚有一褐色0.9cm×0.7cm大小、周边呈细小颗粒状、中央呈疣状、界清、形态不规则的斑块。左耳廓病变近期才出现。

Pigmented hidroacanthoma simplex:A diagnostic pitfall

Hidroacanthoma simplex(HAS) is a rare skin appendage tumor and is recognized as an intraepidermal variant of poroma. Pigmented HAS is an extremely rare variant with dendritic melanocytes and/or melanin pigment in the tumor cells and a few cases of pigmented HAS have been reported in the English literature. We herein report a case of pigmented HAS and discuss the clinicopathological features of pigmented HAS and the pitfall in the diagnosis of black lesions.

Comparison of photodynamic therapy for skin cancers and pre-cancers with δ-aminolevulinic acid

Objective:The aim of the study was to compare the effects of photodynamic therapy(PDT) with δ-aminolevulinic acid(ALA) for patients with different kinds of skin cancers and pre-cancers.Methods:The present study enrolled seventyfive cases,which included 17 cases of actinic keratosis(AK),9 cases of Bowen's disease,11 cases of superficial basal cell carcinomas(BCC),23 cases of nodule basal cell carcinomas and 15 cases of squamous cell carcinomas(SCC),and every patient had single lesion.All patients were treated with 20% ALA topically and He-Ne laser weekly for three times,and followed up 1-3 years.Results:After therapy,the rates of complete reaction(CR) were 100% in AK lesions,77.8% in Bowen's diseases,90.9% in superficial BCCs,47.8% in nodule BCCs,and 50.3% in SCCs,which had significant differences among these five kinds of lesions(H = 18.27,P < 0.05).The therapeutic effectiveness of ALA-PDT for AK was superior to that of Bowen's disease(Q = 4.364,P < 0.05),superficial BCC(Q = 5.55,P < 0.01),SCC(Q = 8.94,P < 0.01) and nodule BCC(Q = 17.91,P < 0.01);the effect of Bowen's disease was better than that of SCC(Q = 7.8,P < 0.01),nodule BCC(Q = 13.44,P < 0.01);the effect of superficial BCC was better than that of SCC(Q = 9.73,P < 0.01),nodule BCC(Q = 16.28,P < 0.01),but similar with Bowen's disease(Q = 0.96,P > 0.05);the effect of SCC was better than that of nodule BCC(Q = 17.74,P < 0.01).Conclusion:Our study shows that therapeutic effectiveness of ALA-PDT for AK is best in five diseases,and Bowen's disease and superficial BCC are secondary,while nodule BCC and SCC are at the bottom.

Evaluation of the Therapeutic Response and Improvement in the Quality of Life of the Patient with Darier Disease to Acitretin through an Analogy between Close Relatives

Darier disease (DD), also known as follicular keratosis, is a rare autosomal dominant hereditary acantholytic dermatosis caused by a mutation in the ATP2A2 gene. Skin lesions are characterized by persistent confluent papules, preferentially located on the seborrheic areas of the face, chest and back. The hands, feet and nails are also commonly affected. DD has a chronic course with frequent relapses. Their treatment is often difficult and unsatisfactory. We present the case of a 54-year-old male with a history of keratotic papules with a brownish-black color, with a foul-smelling, pruritic and ardent appearance on the back and trunk, since the age of 19, which worsen in the summer. His 27-year-old daughter has a similar picture with her skin lesions started at age of 17 in the region below the breast, back, trunk, feet and hands. After the skin biopsy, the diagnosis was confirmed and acitretin 30 mg/day was instituted. The importance of this case report is to alert health professionals that the diagnosis of DD should be considered in family members of patients, especially those in the first degree, and also in patients with follicular keratolytic dermatoses, being an important differential diagnosis of this group of patients diseases.

Photodynamic Therapy/Assisted Photorejuvenation

Photodynamic therapy (PDT) shows great efficacy and high tolerability for the treatment of non-melanoma skin cancer (actinic keratosis, basal cell carcinoma, Bowen’s disease) especially in patients with large and multiple lesions, in poor-healing sites and patients immunosuppressed or with co-morbidities. Besides, more recently, PDT has been used, widely and with great success, for many off-label diseases and in cosmetic dermatology, especially on photorejuvenation, therefore further and larger prospective studies with long-term follow-up are required to verify its efficacy and safety in treating these condition. The treatment of ageing skin remains a very hot topic, and many systems have been reported as having varying degrees of success. Nowadays our experience and literature data show how topical PDT can be considered a new non-invasive device for the treatment o photoaging skin with no/minimal side effects and able to bridge the world of medical and cosmetic dermatologic surgery.

Application of topical gentamicin-a new era in the treatment of genodermatosis

Background The clinical use of gentamicin always lies in its antimicrobial activity in the past as an aminoglycoside antibiotic.However,in the past decade,there were considerable interests in therapeutic approaches in treating hereditary diseases.Some of the genodermatosis is caused by nonsense mutations that create premature termination codons and lead to the production of truncated or non-functional proteins.Gentamicin could induce readthrough of nonsense mutations and enable the synthesis of full-length proteins.We focus on previous publications on topical application of gentamicin and review its utility in genetic skin diseases.Data sources We search the MEDLINE through PubMed,EMBASE databases,and the Clinical Trials Registry Platform from January 1960 to July 2020 using the key search terms"gentamicin,topical gentamicin,genodermatosis,genetic skin diseases".Results The application of gentamicin in genodermatosis yielded promising results,both in vivo and in vitro,including Nagashima-type palmoplantar keratosis,epidermolysis bullosa,Hailey-Hailey disease,hereditary hypotrichosis simplex of the scalp,etc.Conclusions Topical gentamicin is a potential treatment option for genodermatosis caused by nonsense mutation.