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Acne vulgaris
... По данни oт 2010 г. то засяга около 650 милиона души в световен мащаб, което се равнява на 9,4% от насе-лението [6]. Близо 90% от хората в западните общества страдат от заболяването по време на тийнейджърските си години, но в някои случаи и в зряла възраст [2]. При лека до умерена форма на акне вулгарис, както и в периодите между терапевтичното лечение на тежка форма на акне, провеждането на подходящо козметично третиране може значително да подобри състоянието. ...
... В този случай не се изчислява инкрементално съотношение разход/ефективност (incremental cost-effectiveness ratio, ICER). Резултатите от сравненията са представени в решетка разход/ ефективност (Таблица 2), която дава възможност нагледно да се представи сравнението между алтернативите въз основа на получените от анализа резултати [2]. ...
... These glands produce sebum, an oily liquid. The sebum carries dead skin cells through the follicles to the surface of the skin (Zhao et al., 2012;Taylor et al., 2011;Dawson and Dellavalle, 2013). ...
The antimicrobial activities of O. basilicum (ethanol and methanol) extract against the main causative agents of acne were examined in the present study, and their potency were assessed by the presence or absence of inhibition zones and zone diameter. Results showed that the two extracts tested had antibacterial activity against P. aeruginosa, while ethanolic extract was observed to be more effective against Propionibacterium acnes in a wider spectrum when compared to methanol. Only methanolic extracts of O.basilicum showed antimicrobial activity against S.aureus.
It is well-known that the pilosebaceous unit is an elective androgen target tissue. In some areas of the skin, pilosebaceous units respond to androgens by forming sexual hair follicles, whereas in other areas they respond by forming sebaceous glands. Excessive androgen levels as well as their excessive local action on pilosebaceous units in different areas of the body may lead to different skin androgen-related disorders: hirsutism, acne, and androgenetic alopecia (male and female pattern hair loss). In the present chapter, definition, epidemiology, etiology, and pathogenesis of the aforementioned skin androgen-related disorders are briefly reported, and related hormonal treatment is extensively discussed.
Acne vulgaris, the most common form of acne, is characterized by a mixed eruption of inflammatory and noninflammatory skin lesions primarily affecting the face, upper arms, and trunk. The pathogenesis of acne is multifactorial and includes abnormal keratinization and plugging of the hair follicles, increased sebum production, proliferation and activation of Cutibacterium acnes (C. acnes; formerly Propionibacterium acnes, P. acnes), and finally inflammation. Recent studies have found that cannabidiol (CBD) may be beneficial in the treatment of acne. The aim of this study was to explore natural plant extracts that, when combined with CBD, act synergistically to treat acne by targeting different pathogenic factors while minimizing side effects. The first stage of the study investigated the capacity of different plant extracts and plant extract combinations to reduce C. acnes growth and decrease IL-1β and TNFα secretion from U937 cells. The results found that Centella asiatica triterpene (CAT) extract as well as silymarin (from Silybum marianum fruit extract) had significantly superior anti-inflammatory activity when combined with CBD compared to either ingredient alone. In addition, the CAT extract helped potentiate CBD-induced C. acnes growth inhibition. The three ingredients were integrated into a topical formulation and evaluated in ex vivo human skin organ cultures. The formulation was found to be safe and effective, reducing both IL-6 and IL-8 hypersecretion without hampering epidermal viability. Finally, a preliminary clinical study of this formulation conducted on 30 human subjects showed a statistically significant reduction in acne lesions (mainly inflammatory lesions) and porphyrin levels, thereby establishing a tight correlation between in vitro, ex vivo, and clinical results. Further studies must be conducted to verify the results, including placebo-controlled clinical assessment, to exclude any action of the formulation itself.
PurposeThe main view of the present research is to develop a simple, selective and sensitive method to quantify Sarecycline by LC–MS/MS method in rat plasma, using doxycycline as internal standard and to apply the validated method for pre clinical study.MaterialsChromatographic separation was achieved on Waters symmetry C18 column (50 × 4.6 mm, 3.5 µm) using water of 0.05% formic acid and acetonitrile as mobile phase in gradient mode. Mass detection was achieved by ESI/MS/MS positive ion mode, monitored for sarecycline and doxycycline at m/z488.4 → 302.4, 444.8 → 243.7 respectively.ResultsThe linear scope of the calibration curve was observed to be ranging between 1 and 2028 ng/mL with a coefficient of correlation 0.999 and the lower limit of quantification at 1 ng/mL. Both the precision (RSD, %) and accuracy (RE, %) were found to be within the limits and matrix effect was observed negligible. Sarecycline was found to be stable throughout the freeze thaw cycles, bench top studies and autosampler studies. The validated method was further applied to quantify Sarecycline as part of pharmacokinetic studies after oral treatment with 1 mg/kg sarecycline to rats.Conclusion
The developed method exhibited linearity, sensitivity, accuracy and precision with minimal matrix interference and its application to pharmacokinetic profile could assist advanced investigational and pharmacokinetic studies of sarecycline.Graphical Abstract
For decades research has centered on identifying the ideal balanced skin microbiome that prevents disease and on developing therapeutics to foster this balance. However, this single idealized balance may not exist. The skin microbiome changes across the lifespan. This is reflected in the dynamic shifts of the skin microbiome's diverse, inter-connected community of microorganisms with age. While there are core skin microbial taxa, the precise community composition for any individual person is determined by local skin physiology, genetics, microbe-host interactions, and microbe-microbe interactions. As a key interface with the environment, the skin surface and its appendages are also constantly exchanging microbes with close personal contacts and the environment. Hormone fluctuations and immune system maturation also drive age-dependent changes in skin physiology that support different microbial community structures over time. Here, we review recent insights into the factors that shape the skin microbiome throughout life. Collectively, the works summarized within this review highlight how, depending on where we are in lifespan, our skin supports robust microbial communities, while still maintaining microbial features unique to us. This review will also highlight how disruptions to this dynamic microbial balance can influence risk for dermatological diseases as well as impact lifelong health.
We report the discovery that anti-Stokes fluorescence emission can be induced from porphyrins by continuous wave (cw) laser excitation. An anti-Stokes spectroscopy and imaging technique with an integrated multimodal imaging system was developed to study cutaneous porphyrin in psoriasis, acne, and nasal skin. We experimentally demonstrated that under 785 nm cw laser excitation, photoporphyrin IX (PpIX) powder exhibited anti-Stokes fluorescence with its intensity linearly depending on the excitation power, confirmed that it is a single-photon process. Anti-Stokes fluorescence imaging of psoriasis scale, acne sebum smear, and nasal skin was performed. The results showed that Anti-Stokes fluorescence is sensitive and also specific for porphyrin detection without interference from other skin fluorophores.
Menstrual irregularities during isotretinoin therapy, including amenorrhea, can cause a great deal of health-status uncertainty such as the possibility of pregnancy. This study aimed to evaluate the effects of isotretinoin treatment on the menstrual cycle. This cross-sectional study was conducted among females aged between 15–45 years taking isotretinoin for acne. Descriptive statistics were used in the form of frequencies and percentages to represent categorical variables. Pearson’s chi-squared test was performed to assess the relationship between some of the variables with menstrual irregularities. A logistic regression model was performed to assess the risk factors for developing menstrual irregularities during isotretinoin therapy. Of participants with a known regular menstrual cycle, 10.4% were found to have irregularity in their cycle after starting the drug (p < 0.001). Amenorrhea was the most commonly reported menstrual irregularity in isotretinoin-treated females. Our results showed that single females, those who took isotretinoin for 10–12 months and who were concurrently taking hormonal contraceptives all have a statistically significant higher risk of developing menstrual irregularities than others. In conclusion, we found that a statistically significant number of participants with a regular menstrual cycle pre-isotretinoin intake developed irregularity in their cycle after starting the drug. The mechanism of how isotretinoin influences female hormonal imbalances, thereby affecting menstrual irregularities is still poorly understood and needs to be clarified in further clinical studies.
Background/Aim: Acne can occur in people of all ages, but mostly affects the population at puberty. Given the high prevalence and large impact that acne has on young people, the aim of this study was to assess adolescents' knowledge about factors that improve or worsen the clinical picture of acne, as well as to evaluate the sources used to obtain information on acne. Methods: This cross-sectional study was conducted on a sample of 460 high school pupils from the Medical School and Gymnasium in Kosovska Mitrovica. A self-administrated questionnaire was used. Univariate and multivariate logistic regressions were used to model the association between gender (males/females) or presence of acne (no/yes) and potential exacerbating and ameliorating factors, as well as sources of information. Results: 36.7 % of the respondents were male and 63.3 % were female. 48.9 % of high school pupils confirmed that they had acne. The main factors that worsen the condition of acne, were irregular face washing (88.7 %), hormones (87.0 %), fatty foods (80.9 %) and sweets (79.3 %). The majority of respondents believed that the intake of more water (83.9 %), cosmetic treatment (77.8 %), dietary changes (75.9 %), holiday (54.1 %) and sunbathing (39.3 %) affect improving acne. Taking more water (OR = 1.77; 95 % CI = 1.01-3.11) as a factor in improving acne was significantly more common in girls, while boys more often believed that sunbathing (OR = 0.62; 95 % CI = 0.41-0.94) and weight loss (OR = 0.53; 95 % CI = 0.32-0.88) affect the improvement of acne. The most important sources of information about acne were the Internet (73.0 %) followed by parents (62.6 %), friends (54.1 %), and a doctor (42.8 %). Conclusion: Acne was more common in women and those with a positive family history. The presence of misconceptions among young people regarding the factors that improve or worsen the condition of acne indicates the need for additional education.
Zinc is a trace nutrient essential for the normal growth and development of human body. The main aim was to evaluate the significant association between measured zinc status in relation to different skin disorders and their severity. PubMed®, Google® Scholar™ and Cochrane© Reviews databases were searched for studies from January 2017 to June 2021, using the terms; zinc serum levels, zinc plasma levels and different dermatosis in the review, only human studies in English language were reviewed and the studies designs were controlled, cross sectional, observational and analytic types. A total of forty-eight research studies were included in this review. All studies have evaluated serum zinc in skin diseases including psoriasis, atopic dermatitis, pityriasis alba, androgenetic alopecia areata, telogen effluvium, vitiligo, melasma, acne, seborrheic dermatitis and hidradenitis suppuritiva. It was found that 33 studies had validated statistically significant differences in serum zinc levels between patients and controls. There is a predominance of low serum zinc levels in all the dermatoses reviewed. The clinical significance of this finding highlights the possible value, and need to investigate, the use of Zinc supplementation as an adjuvant therapy in the management of chronic inflammatory and autoimmune skin diseases proven to manifest altered zinc levels.
Background
Cell surface glycosaminoglycans (GAGs) participate in many physiological and pathological processes, including infections and inflammatory response. Acne is a common chronic inflammatory skin disorder that affects the pilosebaceous unit and has a multifactorial etiology, including bacterial colonization of the hair follicle. This study aimed to investigate the participation of GAG in the adhesion of Propionibacterium acnes , Staphylococcus aureus and Staphylococcus epidermidis to keratinocytes and fibroblasts of the skin by competition experiments and cell surface removal using specific liases. The alteration in the transcription of the genes responsible for the synthesis of GAG induced by the adhesion of these bacteria was also analyzed by qRT-PCR.
Results
GAGs are involved in bacterial adherence to skin cells, especially fibroblasts, where chondroitin sulfate displayed the higher effect. Bacterial adherence produced different alterations in the transcription of the genes responsible for GAG structures. P. acnes induced mostly changes in keratinocytes, while S. epidermidis was the main cause of alterations in fibroblasts. These variations in gene expression affected all the stages in the biosynthesis of the main species of GAGs, heparan and chondroitin sulphate.
Conclusions
GAGs species are involved in the adhesion of acne-related bacteria to skin cells in a differential manner depending on each microorganism and cellular type, although other receptors seem to exist. Bacterial adherence led to variations on gene expression in skin cells affecting GAG chains structure what, consequently, should alter their interactions with different ligands, affecting the development of acne disease.
The review covers current concepts of the pathogenesis of acne. It presents the data of international and Russian clinical studies conducted to assess the efficacy and safety of drugs comprising 15% azelaic acid and used for the treatment of acne. The authors describe mechanisms of the effect of azelaic acid on major stages of the pathogenesis of acne. They substantiate the need in basic care in the treatment of acne by the example of products of the JOYSKIN line. The authors discuss the effect of different components of skin care products on the acne-prone skin.
The review presents modern views on the pathogenesis of acne. The data of foreign and domestic clinical trials to study the efficacy and safety of drugs containing 1% clindamycin and 15% azelaic acid used to treat acne. The mechanisms of the effects of these drugs on the main elements of the pathogenesis of acne. Substantiates the appropriateness of the drug combination of clindamycin and azelaic acid in the treatment of acne patients.
Treatment of acne is one of the important problems of modern dermatology. The goal of the research. The study of clinical efficacy and safety of the 15% azelaic acid in the form of Azelik-gel in the treatment of patients with papulo-pustular acne, mild to moderate in severity. Material and methods. Open comparative study of 8 weeks, which was attended by 75 patients. To assess the safety and efficacy of the therapy was performed clinical and biochemical blood and urine tests, evaluation of dermatological status, measurement of pH, moisture and oiliness of skin and analysis of DLQI. Results. 82% of patients receiving the Azelik-gel, marked clinical improvement or significant improvement. Conclusions. The results of the study indicate a high level of safety and tolerability of the Azelik-gel and obtained clinical results have shown its therapeutic efficacy in the treatment of papulo-pustular acne mild to moderate in severity.
Purpose of the study. To determine the safety and efficacy of 20% azelaic acid cream in the treatment of patients with papulopustular acne vulgaris.
Materials and methods. 65 patients with acne vulgaris were examined. The control group consisted of 30 healthy individuals. Acne severity was evaluated according to G. Michaelsson et al. scale, Cook’s scale, absolute number of papules and pustules. Assessment of quality of life was performed. Facial skin microbiocenosis was assessed. All patients with acne vulgaris applied 20% azelaic acid cream during 15 ± 2 days.
Results and discussion. The use of 20% azelaic acid cream contributed to the rapid regression of inflammatory acne. After 10 days of treatment, the number of papulopustular elements decreased in 3 times. After 10 days of therapy acne score according to G. Michaelsson et al. decreased in 1,5 times and after 15 days of treatment – in 1,9 times. After 10 days of therapy the acne score on the Cook’s scale decreased in 1,4 times. At the end of the study the acne score on the Cook’s scale was 2,4 points. There was a significant decrease in the total number of bacteria, the number of coagulase-positive staphylococci, quantity of Propionibacterium acnes on facial skin in 15 days after the start of therapy. A significant difference in the average value of the DLQI was fixed before (18,9 ± 0,31) and at the end (8,1 ± 0,54) of treatment.
Conclusions. The high effectiveness of 20% azelaic acid cream in treatment of papulopustular acne vulgaris was proved. 20% azelaic acid cream provides a rapid regression of inflammatory forms of acne, reduction of total quantity of bacteria and Propionbacterium acnes on skin.
Acne affects women's wellbeing and must be taken seriously, writes Julie Brackenbury
Background
: Our clinical experience suggests that pretreatment of the original lesions may be crucial for enhancing the efficacy of 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) in moderate-to-severe acne vulgaris. We performed this randomized controlled trial (RCT) to validate this observation.
Methods
: Efficacy and therapeutic reactions between tri-needle-pretreatment with ALA-PDT (TP-PDT) and conventional ALA-PDT without pretreatment (NP-PDT) were compared. In TP-PDT group, tri-needle-pretreatment was performed using comedone extractors, fire needles, or plum-blossom needles, according to the lesion type. In the TP-PDT group, 5% ALA cream was applied to lesions 30 min before illumination (LED red light: 633±10 nm, 40 mW/cm², 150 J/cm²). In the NP-PDT group, 5% ALA cream was applied 1 h before illumination (60 mW/cm², 72 J/cm²). Patients underwent four sessions, at 1-week intervals. The efficacy was evaluated as the proportion of patients achieving a remarkable effective rate, based on the reduction in the number of lesions. A numeric rating scale was used to assess the severity of pain, erythema, and edema.
Results
: Forty-eight patients completed the trial. The proportion of remarkable effective rate was significantly greater and the pain score was significantly lower for the TP-PDT than NP-PDT group. The edema score was significantly higher for the TP-PDT than NP-PDT group. There was no difference in erythema scores between the two groups.
Conclusion
: The tri-needle-pretreatment can improve the efficacy of ALA-PDT, without an increase in pain, for the treatment of moderate-to-severe acne vulgaris. These qualities make the TP-PDT a promising gold standard pretreatment for ALA-PDT for acne vulgaris.
Acne vulgaris (AV) is a chronic skin disease of the pilosebaceous unit affecting both adolescents and adults. Its pathophysiology includes processes of inflammation, increased keratinization, sebum production, hormonal dysregulation, and bacterial Cutibacterium acnes proliferation. Common AV has been treated with antibiotics since the 1960s, but strain resistance has emerged and is of paramount concern. Macroalgae are known producers of substances with bioactive properties, including anti-viral, antibacterial, antioxidant, and anti-inflammatory properties, among several others. In particular, red algae are rich in bioactive compounds such as polysaccharides, phenolic compounds, lipids, sterols, alkaloids, and terpenoids, conferring them antioxidant, antimicrobial, and anti-inflammatory activities, among others. Thus, the exploration of compounds from marine resources can be an appealing approach to discover new treatment options against AV. The aim of this work is to provide an overview of the current knowledge of the potentialities of red macroalgae in the treatment of AV by reviewing the main therapeutic targets of this disease, and then the existence of compounds or extracts with bioactive properties against them.
Background:
Acne vulgaris is the most common skin disease that can lead to disfigurement and psychological distress. This article aims to provide a narrative updated review on the management of acne vulgaris.
Methods:
A PubMed search was performed with Clinical Queries using the key term "acne". The search strategy included clinical trials, meta-analyses, randomized controlled trials, observational studies and reviews. The search was restricted to articles published in English.
Results:
Treatments of acne include proper skin care, topical medications, oral medications and procedural therapies. Topical agents are the first-line treatment for mild-to-moderate acne and can be used as combination therapy for more severe acne. Systemic therapies are usually prescribed for the initial treatment of moderate-to-severe acne as well as for acne that is refractory to topical therapies.
Conclusion:
Topical retinoids are the drugs of choice for the treatment and maintenance therapy of patients with mild-to-moderate acne vulgaris. Depending on the severity of the acne, topical retinoids may be used alone or in combination with benzoyl peroxide and topical or oral antibiotics. Oral antibiotics are an important therapy for inflammatory acne unresponsive to topical therapy. Neither topical nor oral antibiotics should be used as monotherapy. Oral contraceptives and/or spironolactone are useful for many women with acne. Oral isotretinoin is the drug of choice for severe, extensive, nodular acne vulgaris but is also often used in moderate cases where scarring is evident, acne-related psychosocial distress is significant or other treatment modalities have failed.
Background
Acne vulgaris is a chronic, inflammatory skin condition of pilosebaceous units. The standard treatment involves topical and oral antibiotics, retinoids, benzoyl peroxide, and other synthetic compounds, mostly associated with adverse effects. Hence, herbal skincare products are considered nowadays.
Aim
To evaluate the safety and efficacy of Purifying Neem Face Wash (PNFW), an herbal skincare product in the prevention and/or reduction of mild-to-moderate acne.
Methods
An open-label, single-center, single-arm, four-week clinical study was conducted with subjects having either mild-to-moderate acne or oily skin and non-existent acne. The performance of PNFW in the reduction and/or prevention of acne was detected by counting cutaneous inflammatory and non-inflammatory acne lesions in each of the four visits. Sebum level and skin hydration of both cheeks were measured via sebumeter and corneometer, respectively. Self-assessment questionnaires were used to assess the subjects’ responses toward PNFW.
Results
Out of 120 study subjects, 79% and 72% showed either reduction or no new appearance of inflammatory and non-inflammatory acne lesions, respectively, from baseline to Visits 3 and 4. Skin sebum level and skin hydration showed a statistically significant decrease (p < 0.001) and increase (p < 0.001), respectively, in Visits 3 and 4. Self-assessment surveys showed the satisfaction of the subjects about the product in terms of condition improvement, ease in use, and fragrance.
Conclusion
The present study indicated the beneficial effect of the herbal ingredients (neem and turmeric) of Himalaya's PNFW in the prevention and reduction of mild-to-moderate acne with no side effects.
Acne vulgaris should be considered a chronic, inflammatory disease and treatment should be aimed at both settling the acute symptoms (papules, pustules, nodules, cysts, etc.) and preventing relapse. Acne occurs in 90% of teenagers and half of them continue to have acne as adults. Acne is particularly cruel as it occurs on the worst part of the body (the face) at the worst time in a person’s life (teens and young adult) as teenagers are very conscious about their looks. 20% of young people have moderate to severe acne which can have long lasting physical and psychosocial effects. Acne can be associated with low self-esteem, depression and anxiety. There are safe, effective treatments for all degrees of severity of acne.
Acne vulgaris (acne) is a multi-factorial chronic inflammatory skin disease that is encountered frequently in general practice, accounting for over 3 500 000 annual consultations in the UK. It has an estimated global prevalence of 9.4%; and is often considered a teenage affliction, impacting virtually all adolescents to some extent. Nevertheless, it is surprisingly common in the adult population, affecting 8% of those aged 25–34 years and 3% of adults aged 35–44 years. This article explores key aspects of diagnosis and management, and considers specific scenarios such as pregnancy and transgender patients as well as the importance of psychosocial support and holistic care.
Suneeta Kochhar explains how this common dermatological condition can be treated effectively
Background
Retinoid‐based therapies are commonly used in the treatment of disorders of keratinization and other skin disorders but can result in non‐specific effects and adverse reactions. Use of retinoic acid metabolism blocking agents (RAMBAs) such as DX308 may address these shortcomings.
Objectives
Characterize the therapeutic potential of recently discovered, CYP26‐selective RAMBA, DX308.
Materials and Methods
Preliminary in vitro assessment of potential off‐target activity, metabolic and toxicologic profiling. Studies to assess safety and efficacy of topical treatment in correcting abnormal skin morphology in rhino mice. Extensive gene expression profiling by RNA sequencing and qPCR in 3D epidermis grown with keratinocytes (KCs) from keratinization disorders and healthy controls, to investigate modulation of retinoid biopathways.
Results
In vitro, DX308 does not interact with off‐target nuclear receptors or CYP450s, is not genotoxic, and is stable in skin, despite vigorous hepatic metabolism. In vivo, topical DX308 induces comedolysis and epidermal thickening without apparent adverse effects. Gene expression profiling shows potent modulation of retinoid‐responsive genes by DX308 in both healthy and keratinization disorder KCs. Pathway analysis suggests DX308 may inhibit inflammatory and immune responses in KCs.
Conclusions
These preliminary studies suggest that DX308 is an efficacious topical therapeutic with a favourable metabolic and safety profiles. DX308 may present an improved therapeutic alternative for the treatment of keratinization disorders and other retinoid‐responsive skin ailments.
Background
Neutrophilic folliculitis is an inflammatory condition of hair follicles. In some neutrophilic folliculitis, such as acne and hidradenitis suppurativa, follicular hyperkeratosis is also observed. Neutrophilic folliculitis is often induced and/or exacerbated by high-fat diet (HFD). However, the molecular mechanisms by which HFD affects neutrophilic folliculitis are not fully understood.
Objective
To elucidate how HFD promotes the development of neutrophilic folliculitis.
Methods
Mice were fed with HFD, and the skin was subjected to histological, RNA-sequencing and imaging mass spectrometry analyses. Phorbol 12-myristate 13-acetate (PMA) was used as an irritant to the skin to examine the effect of HFD on neutrophil accumulation around the hair follicles.
Results
Histological analysis revealed follicular hyperkeratosis in the skin of HFD-fed mice. RNA-sequencing analysis showed that genes related to keratinization, especially in upper hair follicular keratinocytes, were significantly upregulated in HFD-fed mice. Application of PMA to the skin induced neutrophilic folliculitis in HFD-fed mice, but not in normal diet (ND)-fed mice. Accumulation of neutrophils in the skin and around hair follicles was dependent on CXCR2 signaling, and CXCL1, a CXCR2 ligand, was produced mainly by hair follicular keratinocytes. Imaging mass spectrometry analysis revealed an increase of fatty acids in the skin, including oleic acids and palmitoleic acids in HFD-fed mice. Application of these fatty acids to the skin induced follicular hyperkeratosis, and caused PMA-induced neutrophilic folliculitis even in ND-fed mice.
Conclusion
HFD can facilitate the development of neutrophilic folliculitis with the induction of hyperkeratosis of hair follicles and increased neutrophil infiltration around the hair follicles via CXCR2 signaling.
Background
The association between isotretinoin administration and depression in acne patients remains controversial. We aim to estimate the prevalence of depression among patients with acne vulgaris before and after treatment with isotretinoin in Riyadh, Saudi Arabia.
Methods
This was a prospective study on patients attending the King Khalid University Hospital (KKUH), a tertiary institution, who were prescribed isotretinoin for the treatment of acne vulgaris for the first time. The Beck Depression Inventory (BDI) was used to screen for depressive symptoms.
Results
A total of 179 patients were included in the study. The patients were then divided into two groups based on the treatment modality that they received: one group taking isotretinoin and the other treatment group who used other medications, including Retin-A (tretinoin) and Tazorac (tazarotene). A total of 119 patients were in the isotretinoin group with 91.6%, 2.5%, 1.7%, and 3.4% of those patients having a normal mood, mild depression, moderate depression, and severe depression scores before starting isotretinoin treatment, respectively. After three months of treatment, 94.1%, 1.7%, 0.8%, and 2.5% of patients had normal mood, mild depression, moderate depression, and severe depression, respectively. Meanwhile, after six months of treatment, 95.8%, 0.8%, 0%, and 1.7% of patients had normal mood, mild depression, moderate depression, and severe depression, respectively. The mean BDI score at the baseline was 3.31 ± 6.98 for isotretinoin and 3.17 ± 6.27 for other treatments. Compared to the baseline, patients using the isotretinoin showed a significant reduction in depression scores at three months (2.64 ± 6.17; p-value < 0.001), six months (1.99 ± 5.08; p-value < 0.001), and across all follow-up points (p-value < 0.001). Similar results were also estimated for the other treatment group, including Retin-A (tretinoin), adapalene, benzoyl peroxide, and doxycycline; however, no significant difference was noticed between the two groups (p-value = 0.885).
Conclusion
Isotretinoin treatment for acne does not appear to be associated with a statistically significant increased risk of depression in our population. Therefore, more studies are needed to understand this reflection in Saudi Arabia.
Background
Oral isotretinoin is the first‐line treatment of severe nodular acne. However, patients presenting ineffective or poor effective to oral isotretinoin are still a clinical problem, and its molecular genetic mechanisms remain unclear.
Aims
To compare the transcriptome profiles of isotretinoin‐effective and isotretinoin‐ineffective severe acne vulgaris patients and analyze the potential physiological roles to better understand the mechanisms of isotretinoin efficacy differences.
Patients/Methods
Peripheral blood of 43 patients with severe acne was collected before treatment. After 8‐week isotretinoin, patients presented effective and ineffective to isotretinoin treatment were selected and their pretreatment peripheral blood was analyzed. High‐throughput sequencing was used to detect gene expression profiles. Gene Ontology and KEGG were used to perform functional annotation and pathway enrichment analysis.
Results
Ten acne patients (3 male and 7 female, age 31 ± 9.2) presented effectiveness by oral isotretinoin and 10 acne patients (4 male and 6 female, age 28 ± 7.7) presented ineffectiveness were included. Comparison of gene profiles of isotretinoin‐effective and isotretinoin‐ineffective patients revealed 2779 differentially expressed genes: 2723 upregulated and 56 downregulated. Differentially expressed genes were enriched in RNA degradation pathway, autophagy pathway, protein ubiquitination pathway, protein processing in endoplasmic reticulum pathway, T‐cell receptor signaling pathway, spliceosome pathway, mRNA surveillance pathway, cell cycle pathway, long‐term potentiation pathway, and FoxO signaling pathway.
Conclusion
Transcriptome expression differences not only participated in the acne pathogenesis, but also influenced the isotretinoin therapeutic effects. These findings might provide some evidence for exploring individualized therapy for acne patients.
Dapsone (DAP) is a long-established molecule that remains a promising therapeutic agent for various diseases mainly because it combines antimicrobial and anti-inflammatory activities. Its oral application, however, is limited by the dose-dependent hematological side effects that may rise from systemic exposure. As an alternative to overcome this limitation, the administration of DAP to the skin has witnessed prominent interest in the past 20 years, particularly when applied to the treatment of dermatological disorders. In this review, all technological strategies proposed to the topical delivery of DAP are presented. Most of the reported studies have been devoted to the clinical use and safety of a gel formulation containing both solubilized and microcrystalline drug, however, the technological characteristics of such preparation are still missing. In parallel, the incorporation of DAP into vesicular and particulate carriers (e.g. nano- and microemulsions, niosomes, invasomes, bilosomes, cubosomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanocapsules and polymer-lipid-polymer hybrid nanoparticles) appears to be an alternative to provide greater drug release control, enhanced drug solubilization and follicular targeting. Indeed, the main application of DAP topical formulations reported in the literature was the treatment of acne vulgaris, a disease located in the hair follicle. Other diseases affecting different regions of the skin (e.g. cutaneous lupus erythematosus and cutaneous leishmaniasis), however, may also benefit from a topical therapeutic regimen containing DAP. Therefore, the investigation of appendageal route in comparison to passive transmembrane diffusion as a function of targeted disease, as well as pharmacokinetic studies, are perspectives highlighted herein. Such studies may drive future efforts towards the rational development of safe and effective technologies to deliver DAP to the skin.
Graphical abstract
Many topical agents are available for treating the acute phase of acne; however, few agents have been proven beneficial during the maintenance phase. Objective. To evaluate the efficacy and safety of moisturizer containing licochalcone A, 1,2-decanediol, L-carnitine, and salicylic acid during the maintenance phase of mild to moderate acne in Thai patients. Methods. One hundred and ten patients with mild to moderate acne vulgaris were initially treated with a fixed combination of adapalene 0.1%/benzoyl peroxide 2.5% gel once daily for 8 weeks. Fifty patients who achieved at least 50% reduction in lesion counts or at least a 2-grade improvement in the Investigator's Global Assessment (IGA) grade from baseline were enrolled in the maintenance phase, which was an investigator-masked, left-right comparison, randomized, controlled, intraindividual study. Moisturizers with and without the active study ingredients were applied twice a day to each side of the face, respectively, for 12 weeks. Assessments included acne lesion counts, acne severity by IGA scoring, skin bioengineering measurements, and skin tolerability as assessed by both patient and physician. Results. The treatment group had a significant reduction in the mean counts of noninflammatory, inflammatory, and total lesions compared to the vehicle group at week 12 and also between baseline and week 12. There was no significant difference in the mean scores for skin dryness, stinging/burning, or pruritus at any time point between groups. Conclusions. Moisturizer containing licochalcone A, 1,2-decanediol, L-carnitine, and salicylic acid reduced acne lesions and prevented the development of new lesions during the maintenance phase. This trial is registered with ClinicalTrials.gov registration no. NCT04002024.
Acne is one of the most common skin diseases seen in clinical practice and is caused by multiple factors. Epidemiological data on acne are limited from developing countries. Using a questionnaire survey, the epidemiological data of acne were evaluated with a view to establishing possible contributing etiological factors in dermatology practice in India. Out of 6409 patients included in the study 45% were male and 55% were female. The mean age of the patients was 24.64 years. Smoking habit was reported in 14% of the patients while high glycemic diet (HGD) was seen in half of the cases. Of respondents, 41% knew that acne was due to increased sebum production and blockade of pilosebaceous units whereas 35% had due to excessive cosmetic use. Grade II acne was predominant (47%) and majority of the patients had inflammatory papular acne (51%). The presence of hyperpigmentation (35%) and scarring (29%) was considered to be a reflection of the severity of the acne. Moisturizers and cleansers were one of the most common supportive measure of acne management. Cleansers were prescribed for 53% of the patients whereas 43% of the patients were prescribed moisturizers. Amongst topical treatment, adapalene and BPO combination (34%) was the most commonly prescribed combination followed by adapalene & clindamycin combination (29%). Monotherapy was not commonly prescribed. Most of the patients were managed with combination therapy. Isotretinoin was most commonly prescribed medication in all grades of acne comprising of 40% of the patients. This study presents the demographic features and clinical characteristics of acne in dermatology office practice in India.
Background:
Purple variant of passion fruit (Passiflora edulis Sims var. edulis) is a tropical plant commonly used in the beverage industry. The seeds have high content of linoleic acid and piceatannol which has been reported and showed antibacterial, anti-inflammatory, and antioxidant activities. However, there is no report regarding its effect on acne vulgaris.
Objective:
To determine the efficacy of topical use of Passiflora edulis Sims var. edulis seeds extract on acne vulgaris.
Methods:
In this open-label uncontrolled trial, 45 subjects with acne vulgaris were given passion fruit purple variant seeds extract 10% cream for 8 weeks. Noninflammatory, inflammatory, and total acne lesions count along with ultraviolet-induced red fluorescence (UVRF) measurement were done at weeks 0, 2, 4, 6, and 8. All reported adverse events were documented, and patient satisfaction rates were determined at week 8. Paired T-test and Wilcoxon test were done with P ≤ 0.05 indicating significance.
Results:
There were significant reductions in noninflammatory (80.9%), inflammatory (71.1%), and total (73%) lesion count after 8 weeks of the cream application (P < 0.001). Significant reduction in UVRF spot quantity (36%) and percentage area (45.9%) were found at week 8 (P < 0.001). Only 2.2% of subjects experienced an adverse event of mild and transient peeling. Most of the subjects (77.8%) noticed significant improvement in their acne vulgaris and expressed good satisfaction rate.
Conclusion:
Topical use of passion fruit purple variant seeds extract improves acne vulgaris with reduction in lesion counts and UVRF, minimal adverse events, and good satisfaction rate. Additional prospective studies are required.
Social media is an underutilized method for the surveillance of the patient perspective regarding their pharmacologic therapies. The purpose of this study was to investigate the nature of content posted on the social media platform Instagram with respect to the systemic acne medication isotretinoin.
The search term “#accutane” was queried into Instagram to generate all public posts using this hashtag between February 1 and May 31, 2018. Four independent investigators then scrutinized posts for eligibility. Our inclusion criteria were posts written in English, accessible by URL, primarily focused on isotretinoin, and posted by users of the medication. Data regarding multiple variables (tone of post, reason for positive or negative elements, posting of a face or other body part, mention of side effects, etc.) from each individual post was then entered into a Microsoft Excel template.
Of 7,661 posts, 3,082 were eligible. Among posts that contained negative tone (n=1312), this element was more commonly due to the presence of side effects (65%) than lack of improvement in skin appearance (33%). Overall, 1,263 posters (41%) mentioned adverse effects of oral isotretinoin, most commonly dry facial skin (17%), dry/cracked lips (16%), or arthralgias/myalgias (8%). Neuropsychiatric side effects were also documented, with users reporting fatigue (4%), mood changes (3%), and headache (2%).
In conclusion, reported side effects of oral isotretinoin on Instagram closely tracked its known side effects in frequency. Social media may be a valuable tool to surveil the general pattern and burden of adverse effects for patients undergoing treatment of dermatologic conditions.
Hydrogels, swellable hydrophilic polymer networks fabricated through chemical cross-linking or physical entanglement are increasingly utilized in various biomedical applications over the past few decades. Hydrogel-based microparticles, dressings and microneedle patches have been explored to achieve safe, sustained and on-demand therapeutic purposes toward numerous skin pathologies, through incorporation of stimuli-responsive moieties and therapeutic agents. More recently, these platforms are expanded to fulfill the diagnostic and monitoring role. Herein, the development of hydrogel technology to achieve diagnosis and monitoring of pathological skin conditions are highlighted, with proteins, nucleic acids, metabolites, and reactive species employed as target biomarkers, among others. The scope of this review includes the characteristics of hydrogel materials, its fabrication procedures, examples of diagnostic studies, as well as discussion pertaining clinical translation of hydrogel systems.
Background
Acne vulgaris is a common skin disease primarily affecting young adults. Given that the internet has become a major source of health information, especially among the young, the internet is a powerful tool of communication and has a significant influence on patients.
Objective
This study aimed to clarify the features of patients’ interest in and evaluate the quality of information about acne vulgaris on the internet.
Methods
We compared the search volumes on acne vulgaris with those of other dermatological diseases using Google Trends from January 2004 to August 2019. We also determined the search volumes for relevant keywords of acne vulgaris on Google and Naver and evaluated the quality of answers to the queries in KnowledgeiN.
Results
The regression analysis of Google Trends data demonstrated that the patients’ interest in acne vulgaris was higher than that for other dermatological diseases, such as atopic dermatitis (β=−20.33, 95% CI –22.27 to –18.39, P<.001) and urticaria (β=−27.09, 95% CI –29.03 to –25.15, P<.001) and has increased yearly (β=2.38, 95% CI 2.05 to 2.71, P<.001). The search volume for acne vulgaris was significantly higher in the summer than in the spring (β=–5.04, 95% CI –9.21 to –0.88, P=.018) and on weekends than on weekdays (β=–6.68, 95% CI –13.18 to –0.18, P=.044). The most frequently searched relevant keywords with “acne vulgaris” and “cause” were “stress,” “food,” and “cosmetics.” Among food, the 2 highest acne vulgaris–related keywords were milk and wheat in Naver and coffee and ramen in Google. The queries in Naver KnowledgeiN were mostly answered by a Korean traditional medicine doctor (53.4%) or the public (33.6%), but only 12.0% by dermatologists.
Conclusions
Physicians should be aware of patients’ interest in and beliefs about acne vulgaris to provide the best patient education and care, both online and in the clinic.
Gut microbiome can be defined as the microorganisms’ inhabitat in the gastrointestinal tract including bacteria, viruses, protozoa, and fungi and their collective genetic material present within it. The gut microbiota has long been of research interest due to their importance to human health, nutrition, and well-being. A healthy gut microbiota (properly balanced bacterial groups) is normally required for human health to maintain host immune homeostasis including skin, nutrient intake, as well as gut development. An unbalanced gut microbiota or dysbiosis in microbes often leads to occurrence of both acute and chronic diseases, such as infectious diarrhea, inflammatory bowel diseases, obesity, diabetes, colon cancer, and neonatal necrotizing enterocolitis; not only metabolism-related disease, but also skin diseases like acne vulgaris and atopic dermatitis, in addition to psychological problems such as depression and autism. The human and other genome projects that have been completed as well as the ongoing human microbiome project give rise to revolutionary technologies characterized by culture-independent, high-throughput, particularly next-generation DNA sequencing and bioinformatics analyses. These robust, powerful methods have enabled more comprehensive studies on the gut microbiota and their functions including interaction with host and diet. New knowledge on the modulation of gut microbiota by dietary fiber is critical for the development of effective strategies to improve human health and to treat microbiota-associated diseases. This chapter focuses on the significance and various factors affecting gut microbiota, along with associated disorders. Additionally, the gut microbiome brain and skin axis and various methodologies to study gut microbiota are also discussed.
Inhibition of cytochrome P450 (CYP)-mediated retinoic acid (RA) metabolism by RA metabolism blocking agents (RAMBAs) increases endogenous retinoids and is an alternative to retinoid therapy. Currently available RAMBAs (i.e. liarozole and talarozole) tend to have fewer adverse effects than traditional retinoids but lack target specificity. Substrate-based inhibitor DX314 has enhanced selectivity for RA-metabolizing enzyme CYP26B1 and may offer an improved treatment option for keratinization disorders such as congenital ichthyosis and Darier disease. In this study we use RT-qPCR, RNA sequencing, pathway, upstream regulator, and histological analyses to demonstrate that DX314 can potentiate the effects of all-trans-RA (atRA) in healthy and diseased reconstructed human epidermis (RHE). We unexpectedly discovered that DX314, but not atRA or previous RAMBAs, appears to protect epidermal barrier integrity. Additionally, DX314-induced keratinization and epidermal proliferation effects are observed in a rhino mice model. Altogether, results indicate that DX314 inhibits atRA metabolism with minimal off-target activity and shows therapeutic similarity to topical retinoids in vitro and in vivo. Findings of a barrier-protecting effect require further mechanistic study but may lead to a unique strategy in barrier-reinforcing therapies. DX314 is a previously unreported promising candidate compound for further study and development in the context of keratinization disorders.
Introduction: Acne vulgaris (AV) is one of the most common dermatological disorders. However, data of AV in Saudi Arabia are not well documented. Purpose: To determine the prevalence, potential risk factors, psychological impact, and treatment modality of AV in the Kingdom of Saudi Arabia and highlights the gaps of knowledge related to this disease. Methods: The literature search was performed using the keywords “acne vulgaris,” “Saudi Arabia,” and “KSA” in four electronic databases: PubMed, Google Scholar, Web of Science, and Embase. The search was restricted by the locational filter of Saudi Arabia and a timeframe of 2010–2019. Results: 453 potentially relevant titles and abstracts being identified, of which 18 articles met the inclusion criteria. AV is becoming more prevalent among the Saudi population, particularly among Saudi women. The knowledge and awareness of the public is relatively low. Conclusion: Community-based interventions on acne are needed to increase the awareness and to improve the perception and belief of acne patients. Further studies are needed to evaluate the effects and side effects of different complementary medicine and over-the-counter modalities.
Objective: Acne vulgaris, a chronic disorder of pilosebaceous units, is common in adolescents. Early detection and appropriate treatment of acne is essential in the prevention of severe acne and scarring, and the consequent adverse psychosocial disabilities resulting from feelings of embarrassment, frustration and poor self-esteem. Emotional issues in young individuals with acne must be identified appropriately. Material and method: This was a cross-sectional survey involving students applied to a University Medical Center. They were administered a questionnaire including socio-demographical properties, general knowledge about acne and Rosenberg Self-Esteem Scale’s first ten questions. SPSS 15.0 program was used for statistical analysis and p<0.05 was accepted as statistical significant. Results: Two hundred and forty seven students were included and 63.6% (n.157) were women. Mean age was 21.40±2.38. Majority of the students (99.3%) had acne but 41.3% of acne problems had lasted before three months. Acne was defined as an illness by 53.4% of the students and 38.1% visited a doctor for acne treatment. Conclusion: Despite the high prevalence of acne, there is still much deficiency of knowledge and wrong beliefs about acne. This indicates that there is a need for education about etiopathogenesis, potential complications and importance of effective treatment for acne. Amaç: Akne vulgaris, pilosebase birimlerin ergenlerde yaygın olarak görülen kronik bir hastalığıdır. Aknenin erken tanısı ve uygun tedavisi, şiddetli akne ile yara izi oluşumunun utanç, hayal kırıklığı, düşük benlik saygısı duygularından kaynaklanan, olumsuz psikososyal sorunların önlenmesinde önemlidir. Akneli genç bireylerde, duygusal konular, uygun teşhis edilmelidir. Yöntem: Bu çalışma, bir üniversitenin medikososyal hizmetler birimine başvuran öğrencilerin yer aldığı kesitsel bir çalışmadır. Katılımcılara, sosyodemografik özellikler, akne hakkında genel bilgiler ve Rosenberg Benlik Saygısı Ölçeği ilk on sorusunu içeren bir anket uygulanmıştır. Veri analizinde SPSS 15.0 kullanılmış ve p<0.05 anlamlı kabul edilmiştir. Bulgular: Çalışmaya 247 öğrenci dâhil edilmiş olup % 63,6’sı (n=157) kadındır. Yaş ortalaması 21.40±2.38 (Min=18, Maks=32) olan öğrencilerin çoğunluğunda (%99,3) akne görüldüğü, %41,3’ünde üç aydan az sürdüğü belirtilmiştir. Öğrencilerin %53,4’ü akneyi bir hastalık olarak tanımlamış ve %38,1’i akne tedavisi için doktora başvurmuştur. Sonuç: Üniversite öğrencileri arasında akne görülme sıklığı yüksek olmasına rağmen, akne hakkındaki bilgi düzeyleri düşük bulunmuştur. Konuyla ilgili olarak etiyopatogenez, potansiyel komplikasyonlar ve uygun tedavinin önemi açısından gerekli bilgilendirmenin yarar sağlayabileceği düşünülmektedir.
Acne vulgaris is a chronic inflammatory disease of the skin resulting from androgen‐induced increased sebum production and altered keratinization. Nicotinamide (NAM), an amide form of vitamin B3 with a well‐established safety profile, has shown good therapeutic potential in treating acne and its complications. NAM has anti‐inflammatory effects and reduces sebum but its function in androgen biosynthesis remains unknown. In this study, we used a widely used cell model, starved human adrenal NCI‐H295R cells, to examine the effects of NAM in androgen production and its mediated network changes. By treating NCI‐H295R cells with 1 mM to 25 mM of NAM, we found that cell viability was only slightly inhibited at the highest dose (25 mM). NAM reduced testosterone production in a dose‐dependent manner. Transcriptomic analysis demonstrated that key enzymes of androgen biosynthesis were significantly decreased under NAM treatment. In addition, gene set enrichment analysis (GSEA) showed that gene sets of cell cycle, steroid biosynthesis, TGFβ signalling, and targets of IGF1 or IGF2 were enriched in NAM treated cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis of the differentially expressed genes also suggested that steroidogenesis and SMAD signalling were affected by NAM. Overall, these crucial genes and pathways might form a complex network in NAM‐treated NCI‐H295R cells and result in androgen reduction. These findings help explain the potential molecular actions of NAM in acne vulgaris, and position NAM as a candidate for the treatment of other hyperandrogenic disorders.
Background:
Acne vulgaris (AV) is a common dermatological disease affecting almost 85% of teenagers. Patients with AV usually present at community pharmacies during the early stages of their disease.
Aim:
The aim of this study was to assess community pharmacists' knowledge, attitudes, and practice toward AV management in West Bank in Palestine.
Methods:
This study was a cross-sectional questionnaire-based study. The questionnaire included four sections: 1) demographic, 2) knowledge, 3) attitude and practice items related causes, and 4) treatment options and counseling during management of patients with AV. A convenience sampling method was implemented in this study. Parametric and non-parametric tests were used to compare different issues as appropriate. P < 0.05 were considered significant.
Result:
A total of 270 community pharmacists were interviewed, and more than half (54.1%) were males. The study revealed that community pharmacists had an inadequate level of knowledge on management of AV; only 7.7% had high levels of knowledge. Pharmacists have positive attitude regarding AV management, but inadequate knowledge was reflected on their treatment practices; only 10% of participants independently dealt with AV without referral. Pharmacists with a low level of knowledge showed five times more referrals than those with a high level of knowledge (OR: 5.3; P < 0.001), and those with a bachelor degree showed three times more referrals than postgraduates (OR: 3.3; P < 0.001).
Conclusion:
There is a demand to update dermatological knowledge of community pharmacists and encourage them to attend structured training programs about the management of AV.
Adapalene-loaded transfersome gel containing vitamin C as a combination therapy for the management of acne vulgaris was developed in the present study. The transfersome was prepared by reverse-phase evaporation, and the effect of various process parameters were investigated by the Design of Experiment (DOE) approach and optimized based on the particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). The selected tranfersomes were further evaluated for their thermal behavior and morphology by transmission electron microscopy and turbidity measurements and incorporated into a gel with/without vitamin C. The gel was evaluated and compared with the marketed product (Adiff gel) for various physicochemical parameters, and in vivo studies in testosterone-induced rat models of acne. The prepared transfersomes had PS in the range of 280 to 400 nm, PDI values of 0.416 to 0.8, ZP of − 38 to − 20 mV, and % EE of 32 to 70%. DSC studies confirmed a positive interaction of the components in the transfersome. Surface morphology confirmed that the vesicles were spherical, unilamellar, and discrete. A relative deformability study showed higher elasticity of the transfersomes compared with Adiff aqs gel. Ascorbyl-6-palmitate in adapalene-loaded transfersome gel containing vitamin C (ADVTG) was found to have a good antioxidant free radical–scavenging activity. An in vitro drug release study showed that the sustained release of the transfersomal formulations was attributed to the flexibility of the vesicles by which penetration was increased. ADVTG was found to be promising in treating acne compared with the marketed product.
Graphical Abstract
Objective: Two clinical studies were conducted to 1) assess the pharmacokinetic (PK) properties of tazarotene and tazarotenic acid in DFD-03 lotion (a 1-minute, short-contact formulation for the topical treatment of acne vulgaris) and tazarotene cream 0.1% and 2) to evaluate transepidermal water loss (TEWL) with DFD-03 lotion, tazarotene gel (0.1%), or vehicle. Design: The PK study included a single-center, randomized, multiple-dose, laboratory-blinded, open-label, parallel-design, and the TEWL study included a multiple-dose, within-subject comparison design. Participants: The PK study included healthy adult men aged 18 to 40 years (n=43), and the TEWL study included healthy adults, male or female, aged 18 to 40 years (n=24). Measurements: PK was assessed via Cmax, AUC0-12, AUC0-24, Tmax, Cmin, Tmin, and fluctuation. TEWL was assessed via evaporimetry. Results: Tazarotene levels were very low due to rapid esterase hydrolysis to the primary active metabolite, tazarotenic acid. Tazarotenic acid AUC0-24 ratios (%) were at least two times higher when the test product was applied twice daily (Treatment-1) versus once daily (Treatment-2) on Days 7 and 14 (268.73% and 254.42%, respectively). Tazarotenic acid AUC0-24 ratios (%) were nearly 100 percent for Treatment-1 versus once-daily tazarotene cream 0.1% (Treatment-3) (99.36% and 83.21%, on Days 7 and 14, respectively). Starting on Day 7, DFD-03 lotion TEWL readings were significantly greater than vehicle (p≤0.05), except for on one study day. DFD-03 lotion TEWL readings were numerically greater (nonsignificant) than tazarotene gel. Conclusion: DFD-03 lotion was well-tolerated, increased TEWL when applied twice daily for one minute, and had a PK profile with similar overall exposure as compared with commercially available tazarotene formulations applied once daily for 12 hours.
p class="abstract"> Background: Acne vulgaris is one of the commonest inflammatory skin disorders. It also has a psychosocial impact on patients, specially known in adolescents and hence needs effective treatment. The objectives of the study was to find out and ascertain different clinical presentations of acne vulgaris in both sexes of various age groups and to find out the outcome of treatment with various topical modalities in various clinical types.
Methods: A total of 150 patients with acne vulgaris were studied with age group >10 years. Detailed history, thorough physical examination and relevant investigations were done. Patients were divided into 2 groups of 75 each and each group received different treatment and were followed up at 4th, 8th and 12th week.
Results: At the end of 12 weeks there was significant improvement in grade-II patients treated with cindamycin 1% gel.
Conclusions: The results of the study show that different grades of acne vulgaris respond with different regimens. </p
Acne is a common skin affliction that involves excess sebum production and modified lipid composition, duct blockage, colonization by bacteria, and inflammation. Acne drugs target one or more of these steps, with antibiotics commonly used to treat the microbial infection for moderate to severe cases. Whilst a number of other acne therapies are purported to possess antimicrobial activity, this has been poorly documented in many cases. We conducted a comparative analysis of the activity of common topical acne drugs against the principal etiological agent associated with acne: the aerotolerant anaerobic Gram-positive organism Propionibacterium acnes (recently renamed as Cutibacterium acnes). We also assessed their impact on other bacteria that could also be affected by topical treatments, including both antibiotic-sensitive and antibiotic-resistant strains, using broth microdilution assay conditions. Drugs designated specifically as antibiotics had the greatest potency, but lost activity against resistant strains. The non-antibiotic acne agents did possess widespread antimicrobial activity, including against resistant strains, but at substantially higher concentrations. Hence, the antimicrobial activity of non-antibiotic acne agents may provide protection against a background of increased drug-resistant bacteria.
Background:
Depending on disease severity, standard acne treatments can vary from topical to systemic therapy. However, poor compliance caused by adverse events and antibiotic resistance is a major cause of treatment failure.
Aims:
To determine the effectiveness of photodynamic therapy (PDT) with intense pulsed light (IPL) in the treatment of acne when combined with a cream containing licochalcone A, L-carnitine and decanediol (so-called, 'active formulation') versus PDT alone.
Patients/methods:
Twenty-nine volunteers, aged 21-39 years (26 women and 3 men, mean age 29.41 ± 5.24 years), with mild to severe facial acne, were enrolled. Each subject's face sides were randomized in a split-face manner to either receive PDT (IPL with a 400-720 nm cut-off filter, at 4 sessions with two-week intervals) combined with the active formulation cream twice daily for 10 weeks on one face side; or PDT and the vehicle cream on the other side, with the same treatment protocol. Reduction in acne quantity, melanin index and erythema index were assessed 2 weeks after the second treatment (day 28), 1 week after the fourth treatment (day 49), and 1 month after the fourth treatment (day 70).
Results:
Compared to baseline, patients in the active formulation group demonstrated a faster onset of reduction in the number of lesions at 2 weeks after the second treatment (p=0.010 for inflammatory acne and p=0.001 for non-inflammatory acne). A significantly greater reduction in lesion count was observed in the active formulation group compared with the vehicle group at all timepoints of evaluation for noninflammatory acne (day 28, day 49, and day 70; p=0.003, 0.005 and 0.002 respectively), and at 1 month after the fourth treatment for inflammatory acne (p=0.036). Compared to the vehicle group, the melanin index of the active formulation group decreased significantly at 1 month after the fourth treatment (p=0.015).
Conclusion:
PDT is more effective in treating acne when combined with a topical cream containing licochalcone A, L-carnitine and decanediol, than PDT alone. Significant acne reduction and improvements in post-inflammatory hyperpigmentation were observed, which offers acne patients a better therapeutic option. It is a safe and effective combination treatment for patients with moderate and severe acne.
Retinoids play a vital role in the treatment of acne because they act on the primary lesion, the microcomedo. They are synthetic derivatives of vitamin A (retinol), and are selected for their effectiveness. Several compounds are used for acne, either in topical or systemic form.
We describe and compare the different topical retinoids, tretinoin (all-trans-retinoic acid), isotretinoin (13-cis-retinoic acid), adapalene (derived from naphthoic acid), and tazarotene (acetylenic retinoid). They act mainly as comedolytics, but anti-inflammatory actions have also been discovered recently. The retinoids have great beneficial effects, but also some adverse effects, the main one being teratogenicity. It is preferable not to use them in topical form for pregnant women, although a pregnancy test is only compulsory for tazarotene.
Only isotretinoin is used in systemic form. It acts on all the factors of acne and offers long remissions, and sometimes complete cures. Precautions must be taken for women of childbearing age due to its teratogenicity. It is also important to be aware of its other adverse effects, explain them to the patient and, if possible, deal with them in advance.
Topical antibacterial agents are an essential part of the armamentarium for treating acne vulgaris. They are indicated for mild-to-moderate acne, and are a useful alternative for patients who cannot take systemic antibacterials. Topical antibacterials such as clindamycin, erythromycin, and tetracycline are bacteriostatic for Propionibacterium acnes, and have also been demonstrated to have anti-inflammatory activities through inhibition of lipase production by P. acnes, as well as inhibition of leukocyte chemotaxis. Benzoyl peroxide is a non-antibiotic antibacterial agent that is bactericidal against P. acnes and has the distinct advantage that thus far, no resistance has been detected against it. Combined agents such as erythromycin/zinc, erythromycin/tretinoin, erythromycin/isotretinoin, erythromycin/benzoyl peroxide, and clindamycin/benzoyl peroxide are increasingly being used and have been proven to be effective. They generally demonstrate good overall tolerability and are useful in reducing the development of antibacterial resistance in P. acnes. The selection of a topical antibacterial agent should be tailored for specific patients by choosing an agent that matches the patient’s skin characteristics and acne type. Topical antibacterial agents should generally not be used for extended periods beyond 3 months, and topical antibacterials should ideally not be combined with systemic antibacterial therapy for acne; in particular, the use of topical and systemic antibacterials is to be avoided as far as possible.
Topical retinoids represent a mainstay of acne treatment because they expel mature comedones, reduce microcomedone formation, and exert anti-inflammatory effects. The first-generation retinoid tretinoin (all-trans retinoic acid) and the synthetic third-generation polyaromatics adapalene and tazarotene are approved for acne treatment by the US FDA, whereas topical tretinoin, isotretinoin (13-cis retinoic acid), and adapalene are accredited in Canada and Europe. Topical retinoids have a favorable safety profile distinct from the toxicity of their systemic counterparts. Local adverse effects, including erythema, dryness, itching, and stinging, occur frequently during the early treatment phase. Their impact varies with the vehicle formation, skin type, frequency and mode of application, use of moisturizers, and environmental factors such as sun exposure or temperature. The broad anti-acne activity and safety profile of topical retinoids justifies their use as first-line treatment in most types of non-inflammatory and inflammatory acne. They are also suitable as long-term medications, with no risk of inducing bacterial resistance, for maintenance of remission after cessation of initial combination therapy.
Health professionals must enquire about issues such as low self-esteem when reviewing patients with acne.
Minocycline is an oral antibiotic used for acne vulgaris. Its use has lessened due to safety concerns (including potentially irreversible pigmentation), a relatively high cost, and no evidence of any greater benefit than other acne treatments. A modified-release version of minocycline is being promoted as having fewer side-effects.
To assess new evidence on the effects of minocycline for acne vulgaris.
Searches were updated in the following databases to November 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We also searched trials registers and checked reference lists for further references to relevant randomised controlled trials (RCTs).The Cochrane Skin Group's Trials Search Co-ordinator undertook searches exploring minocycline's adverse effects in EMBASE and MEDLINE in February 2012.
We selected randomised controlled trials (RCTs) comparing minocycline, at any dose, to an active or a placebo control, in participants with inflammatory acne vulgaris. For adverse effects, we selected additional studies that reported the number of adverse effects and the number of participants treated.
Outcome measures used in the trials included lesion counts, acne grades/severity scores, doctors' and participants' global assessments, adverse effects, and dropout rates. Two authors independently assessed the quality of each study. Effect sizes were calculated, and meta-analyses were undertaken where possible.Sixteen studies met the inclusion criteria for the review of adverse effects.
We included 12 new RCTs for this update, giving a total of 39 RCTs (6013 participants). These additional 12 RCTs have not changed the original conclusions about the clinical efficacy of minocycline.The identified RCTs were generally small and poor quality. Meta-analysis was rarely possible because of the lack of data and different outcome measures and trial durations. Although minocycline was shown to be an effective treatment for moderate to moderately-severe acne vulgaris, there was no evidence that it is better than any of the other commonly-used acne treatments. One company-sponsored RCT found minocycline to be less effective than combination treatment with topical erythromycin and zinc. No trials have been conducted using minocycline in those participants whose acne is resistant to other therapies. Also, there is no evidence to guide what dose should be used.The adverse effects studies must be interpreted with caution. The evidence suggests that minocycline is associated with more severe adverse effects than doxycycline. Minocycline, but not other tetracyclines, is associated with lupus erythematosus, but the risk is small: 8.8 cases per 100,000 person-years. The risk of autoimmune reactions increases with duration of use. The evidence does not support the conclusion that the more expensive extended-release preparation is safer than standard minocycline preparations.
Minocycline is an effective treatment for moderate to moderately-severe inflammatory acne vulgaris, but there is still no evidence that it is superior to other commonly-used therapies. This review found no reliable evidence to justify the reinstatement of its first-line use, even though the price-differential is less than it was 10 years ago. Concerns remain about its safety compared to other tetracyclines.
This article discusses the effects of acne (sometimes referred to as acne vulgaris), how to diagnose it confidently and how to distinguish it from rosacea, and the options available for treatment, especially in primary care. We also suggest when referral to dermatology should be considered, and try to anticipate some frequently asked questions.
Acne vulgaris is classically considered a disease of adolescence. Although it most commonly occurs and has been best studied in that age group, it can develop at any time during childhood. It is important that health care practitioners recognize the manifestations of neonatal, infantile and childhood acne, as well as the differential diagnosis and best therapeutic approach in the younger child. Acneiform eruptions in infants and toddlers can occasionally be associated with scarring or with other significant disorders that may be life-threatening. In this article, the authors draw on their own clinical experience as well as the available literature to suggest an age-based approach to managing acne in children from the neonatal period through age 11 years.
Acne vulgaris affects most adolescents and two-thirds of adults and is associated with substantial psychosocial burden. Health-related quality of life (HRQOL) for patients with acne is an important factor of patient care, and several dermatologic and acne-specific measures have been created to assist in acne research, management, and care. This review describes several skin disease and acne-specific HRQOL measures and their applications in clinical care or research. The ideal HRQOL measure for the management of patients with acne is a concise questionnaire that places minimal burden on respondents and allows physicians to track improvement in HRQOL with successful treatment.
Topical antimicrobial treatment is indicated for mild to moderate acne vulgaris. Our literature review includes searches of Ovid, MEDLINE, EMBASE, and the databases of the Cochrane Library. A detailed search strategy is included. All searches were limited to controlled trials and systematic reviews. No year limits were applied to the searches, but we focused on trials, guidelines, and reviews published since 2004, the year that the last review of topical antimicrobials was published in this journal. Several controlled trials demonstrate that benzoyl peroxide, topical antibiotics, and topical retinoids used in combination provide the greatest efficacy and safety profile for the treatment of mild to moderate acne, but there are few trials directly comparing different combinations of these topical therapies with one another. Additionally, robust studies comparing cost and efficacy of generic combinations of the above agents with proprietary fixed-dose combination therapies that may increase compliance are also lacking. Although they have not been extensively studied, alternative agents including dapsone, salicylic acid, azelaic acid, and zinc are safe and efficacious when combined with traditional therapies.
Acne vulgaris is a common skin condition with substantial cutaneous and psychologic disease burden. Studies suggest that the emotional impact of acne is comparable to that experienced by patients with systemic diseases, like diabetes and epilepsy. In conjunction with the considerable personal burden experienced by patients with acne, acne vulgaris also accounts for substantial societal and health care burden. The pathogenesis and existing treatment strategies for acne are complex. This article discusses the epidemiology, pathogenesis, and treatment of acne vulgaris. The burden of disease in the United States and future directions in the management of acne are also addressed.
This review summarizes important clinical developments in acne treatment identified in five systematic reviews and two significant primary research studies, published between March 2010 and February 2011. Although evidence showing a direct link between development of bacterial resistance and oral antibiotic therapy for acne is not convincing, prescribers can still tailor their practice to minimize future risks by stopping treatment when appropriate, using benzoyl peroxide, and avoiding combining topical and systemic antimicrobials. A systematic review evaluating combination products containing benzoyl peroxide did not show convincing evidence that such products are superior to monotherapies. A systematic review of combined oral contraceptives confirmed their efficacy for acne in women. However, another systematic review of botanical products for acne failed to provide any good-quality evidence of benefit. A large, well-reported retrospective cohort study attempted to clarify the potential link between isotretinoin and depression/suicide. Although suicide risk peaked 6 months after isotretinoin treatment, an increased risk was present before initiation of isotretinoin, making it difficult to attribute the increased risk to isotretinoin alone. However, those with a history of suicide attempts before treatment made fewer new attempts than those whose behaviour started during treatment. This suggests that patients with severe acne with a history of attempted suicide should not automatically be refused isotretinoin. Another randomized controlled trial of 60 patients from Korea suggested that low-dose isotretinoin dose than might provide a better long-term outcome with minimal side-effects for people with moderate acne.
Acne vulgaris is common throughout the world and often perceived by both patients and clinicians as an inconsequential disease of adolescence. In reality, however, acne is a chronic medical disease that lasts for years and causes a considerable impact on quality of life. Many patients with acne experience emotional problems due to their disease, which can lead to reduced social interactions and even a lower likelihood of employment. Little has been written specifically about acne in Asian patients in the English-language medical published work, perhaps due to an assumption that the management of acne is the same in all populations. A group of acne experts from nine Asian countries and the USA met to review and discuss acne care within the Asia-Pacific region, focusing on evidence-based medicine. This group developed a care algorithm using results of clinical trials as well as knowledge of practice patterns.
Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from androgen-induced increased sebum production, altered keratinisation, inflammation, and bacterial colonisation of hair follicles on the face, neck, chest, and back by Propionibacterium acnes. Although early colonisation with P acnes and family history might have important roles in the disease, exactly what triggers acne and how treatment affects the course of the disease remain unclear. Other factors such as diet have been implicated, but not proven. Facial scarring due to acne affects up to 20% of teenagers. Acne can persist into adulthood, with detrimental effects on self-esteem. There is no ideal treatment for acne, although a suitable regimen for reducing lesions can be found for most patients. Good quality evidence on comparative effectiveness of common topical and systemic acne therapies is scarce. Topical therapies including benzoyl peroxide, retinoids, and antibiotics when used in combination usually improve control of mild to moderate acne. Treatment with combined oral contraceptives can help women with acne. Patients with more severe inflammatory acne usually need oral antibiotics combined with topical benzoyl peroxide to decrease antibiotic-resistant organisms. Oral isotretinoin is the most effective therapy and is used early in severe disease, although its use is limited by teratogenicity and other side-effects. Availability, adverse effects, and cost, limit the use of photodynamic therapy. New research is needed into the therapeutic comparative effectiveness and safety of the many products available, and to better understand the natural history, subtypes, and triggers of acne.
Affecting over 80% of adolescents, acne is a widespread condition with substantial negative physical and emotional effects, and significant societal cost. Cleansing the acne patient involves several considerations, including matching skin type to the right type of cleanser, optimal times and methods of cleansing, treating parts of the body other than the face, and patient perceptions of the cause and treatment of acne. Moisturizing prevents and alleviates skin irritation, soothing the skin by slowing the evaporation of water. Many liquid face cleansers also moisturize, which may be all that is needed for a patient with oily skin. Protection from sun and environmental damage is important for all patients. While sunscreens are often irritants, the best options for young, oily, acne-prone skin tend to have a water or light liquid base. Moisturizing sunscreens are appropriate for patients with dry, sun-damaged skin, as well as those who wear makeup, have other skin diseases, or are easily irritated by products. Overall, treating acne patients should include education in patient-friendly terms and promoting healthy daily skin care practices, including cleansing and protection against environmental damage.
Severe nodular acne, defined as grade 4 or 5 acne on the Investigator's Static Global Assessment scale, is a skin condition characterized by intense erythema, inflammation, nodules, cysts, and scarring. Both the well known risk of physical scarring and the more recent recognition that acne can be a chronic, psychologically distressing disease with significant adverse effects on a patient's quality of life, have prompted earlier, more aggressive treatment with more effective medications, in the hope of preventing progression to more severe, nodular forms of the disease. Oral antibacterials, primarily tetracyclines, have long been the first-line therapy for severe nodular acne, which frequently remained refractory to therapy. However, concerns of antibacterial adverse effects, patient adherence, and antimicrobial resistance prompted the search for alternate therapies and combinations thereof in order to target the multifactorial pathogenesis of the disease. Isotretinoin, an oral retinoid introduced in 1982, has since become the gold standard therapy in severe acne and has revolutionized its treatment. Several adjunctive agents exist. Oral antibacterials are indicated as an alternative for patients with severe acne who cannot tolerate oral retinoids, or for whom a contraindication exists. In order to prevent bacterial resistance, antibacterials should always be used in combination with benzoyl peroxide, a nonantibiotic antimicrobial agent with anti-inflammatory activity. Topical retinoids are often added to this regimen. In women, hormonal agents, which include oral contraceptives, spironolactone, and oral corticosteroids, and, in Europe, cyproterone acetate, may be used as monotherapy or concomitantly with isotretinoin. For rapid treatment of inflammatory nodules, intralesional corticosteroids are effective. These treatment modalities have been studied, refined, and combined in novel ways in order to target the multifactorial pathogenesis of the disease, and in this article we review each of their roles.
This review highlights clinically important findings about acne treatment identified in nine systematic reviews published or indexed in the period March 2009 to February 2010. A systematic review of dietary influences on acne suggested that a possible role of dietary factors in acne cannot be dismissed, as the studies to date have not been sufficiently large or robust. Another review looked at benzoyl peroxide, which may be enjoying a comeback because of increasing bacterial resistance to antibiotics, and suggested that there was a lack of evidence that stronger preparations were more effective than weaker ones. The same team also carried out a systematic review addressing the question of whether topical retinoids cause an initial worsening of acne. They found no evidence to suggest initial worsening of acne severity, although there was evidence of skin irritation that typically settled by 8-12 weeks. A review of oral isotretinoin and psychiatric side-effects reinforced a possible link between the two, although it pointed out that the better-quality primary studies were still inconclusive. An updated Cochrane Review confirmed the efficacy of combined oral contraceptives (COCs) in reducing acne lesion counts. It also found that the evidence to support COCs containing cyproterone acetate over others was very limited. Another Cochrane Review failed to show any benefit of spironolactone for acne, based on limited studies. Three reviews examined laser and light therapies, and found some evidence of superiority only for blue or blue/red light treatment over placebo light, but a general absence of comparisons against other acne treatments. Photodynamic therapy had consistent benefits over placebo but was associated with significant side-effects and was not shown to be better than topical adapalene.
This 16-week study evaluated once-daily tazarotene 0.1% cream and adapalene 0.3% gel in patients with moderate-to-severe acne. Patients treated with tazarotene 0.1% cream performed better in many acne efficacy measures (reduction in lesion counts, percentage of patients achieving a 50 percent lesion count reduction, overall disease severity, investigator's global assessment) than did patients treated with adapalene 0.3% gel. Reduction in postinflammatory hyperpigmentation (PIH) was also significantly greater with tazarotene 0.1% cream than with adapalene 0.3% gel (P < or = 0.018). Irritation was infrequent, generally mild and similar between treatment groups. In conclusion, both tazarotene 0.1% cream and adapalene 0.3% gel were effective and well tolerated in patients with at least moderate acne. Tazarotene 0.1% cream appeared to be more effective and nearly as well tolerated as adapalene 0.3% gel in reducing acne lesions and was more effective than adapalene 0.3% gel in reducing PIH.
There is a paucity of treatment options for severe acne vulgaris aside from oral isotretinoin. This randomized, vehicle-controlled, multicenter, double-blind study evaluated the efficacy and safety of combination therapy using adapalene 0.1%-benzoyl peroxide 2.5% (A/BPO) fixed-dose combination gel with doxycycline hyclate 100 mg in the treatment of severe acne vulgaris. A total of 459 participants were randomized in a 1:1 ratio to receive oral doxycycline hyclate 100 mg once daily and either A/BPO or vehicle once daily for 12 weeks. Efficacy in the A/BPO with doxycycline group was demonstrated as early as week 2 compared with the vehicle arm for total, inflammatory, and noninflammatory lesions (all P < .005). At week 12, this combination was superior to vehicle with doxycycline in reducing total, inflammatory, and noninflammatory lesion counts (an added incremental benefit of 23%, 24%, and 21%, respectively), as well as for global success and overall participant satisfaction (all P < .001). Digital UV fluorescence photography demonstrated a rapid reduction in Propionibacterium acnes in the A/BPO with doxycycline group, particularly within the first 4 weeks. These findings provide evidence on the efficacy of combining A/BPO and the oral antibiotic doxycycline in the treatment of severe acne vulgaris.
Historically, the relationship between diet and acne has been highly controversial. Before the 1960s, certain foods were thought to exacerbate acne. However, subsequent studies dispelled these alleged associations as myth for almost half a century. Several studies during the last decade have prompted dermatologists to revisit the potential link between diet and acne. This article critically reviews the literature and discusses how dermatologists might address diet when counseling patients with acne. Dermatologists can no longer dismiss the association between diet and acne. Compelling evidence exists that high glycemic load diets may exacerbate acne. Dairy ingestion appears to be weakly associated with acne, and the roles of omega-3 fatty acids, antioxidants, zinc, vitamin A, and dietary fiber remain to be elucidated. This study was limited by the lack of randomized controlled trials in the literature. We hope that this review will encourage others to explore the effects of diet on acne.
This review summarizes clinically important findings from 3 systematic reviews, 1 updated guideline and a selection from the 62 randomized controlled trials (RCTs) published between February 2007 and January 2009 on the topic of acne vulgaris. Low glycaemic-load diets might reduce acne severity but this remains unproven. Written patient information leaflets have not been surpassed by other communication methods. New combination topical treatments have not shown convincing advantages over current combination products such as clindamycin/benzoyl peroxide. Topical dapsone is superior to placebo but has yet to be compared with standard topical treatments. Long-term topical tretinoin to prevent nonmelanoma skin cancer in elderly men was associated with higher all-cause mortality, but there is currently no evidence of increased mortality for topical retinoid use when treating acne. All oral tetracyclines have similar efficacy, yet minocycline is the most costly. Oral isotretinoin monotherapy remains the gold-standard treatment for severe acne. Flutamide plus the oral contraceptive pill is beneficial for acne associated with polycystic ovary syndrome. Photodynamic therapy, phototherapy and laser therapy cannot be recommended universally for acne until minimal postinflammatory pigmentation and longer-term benefit can be shown, especially with current high costs. Development of non-antibiotic therapies is preferable to minimize the risk of community antibiotic resistance. Future trials should use active comparators at optimum doses and avoid noninferiority comparisons unless appropriately powered. Trials need to shift from using multiple, unvalidated outcome measures to including patient-reported and quality-of-life outcomes, and all trials should be registered on a public clinical-trials database.
Antibiotic resistance of Propionibacterium acnes (P. acnes) is a growing phenomenon in the wake of widespread use of topical and systemic antibiotics for acne vulgaris. Benzoyl peroxide has a proven track record of safety and efficacy, and can decrease reliance on antibiotics in the treatment of acne.
To review the literature for methods to increase the efficacy and tolerability of benzoyl peroxide (BPO).
A PubMed literature search was done using the terms "benzoyl peroxide," "vehicle," "mechanism," and "delivery system." Relevant papers were reviewed for methods of increasing BPO efficacy and tolerability.
BPO in concentrations of 2.5%, 5% and 10% are equally effective at treating inflammatory acne. However, higher concentrations are associated with more adverse effects. The efficacy of BPO may be enhanced by the presence of Vitamin E and tertiary amines. BPO is also more efficacious if used in combination with topical retinoids than as a monotherapy. Novel vehicles including a microparticle delivery system and those with a hydrophase or urea base increase the tolerability of BPO without sacrificing efficacy.
Benzoyl peroxide has a proven track record of safety and efficacy for the treatment of acne. Recent discoveries have provided new methods of increasing the efficacy and tolerability of topical BPO, making it useful as monotherapy for mild acne or as an adjunct in the treatment of moderate to severe acne vulgaris.
The Global Alliance to Improve Outcomes in Acne published recommendations for the management of acne as a supplement to the Journal of the American Academy of Dermatology in 2003. The recommendations incorporated evidence-based strategies when possible and the collective clinical experience of the group when evidence was lacking. This update reviews new information about acne pathophysiology and treatment-such as lasers and light therapy-and relevant topics where published data were sparse in 2003 but are now available including combination therapy, revision of acne scarring, and maintenance therapy. The update also includes a new way of looking at acne as a chronic disease, a discussion of the changing role of antibiotics in acne management as a result of concerns about microbial resistance, and factors that affect adherence to acne treatments. Summary statements and recommendations are provided throughout the update along with an indication of the level of evidence that currently supports each finding. As in the original supplement, the authors have based recommendations on published evidence as much as possible.
Oral isotretinoin is a highly effective agent for the treatment of moderate to severe acne, but ever since oral isotretinoin was introduced as a modality for acne, the relationship between oral isotretinoin therapy and psychiatric problems, especially depression, has been controversial. The purposes of this study were to know the acute effects of oral isotretinoin therapy on psychiatric symptoms and to investigate the relationships among them, which have not been reported in the published work. This cohort study included 38 acne patients who started oral isotretinoin therapy. Individual patients were examined before administering oral isotretinoin and 2 and 8 weeks after commencement. Acne severity was graded using the Leeds revised acne grading system. Acute psychiatric effects of oral isotretinoin were assessed using a questionnaire authorized by two psychiatrists. This questionnaire included assessments of acne-related quality of life (Assessment of the Psychological and Social Effects of Acne [APSEA]), depression (Beck's depression inventory [BDI]), anxiety (Beck's anxiety inventory [BAI]) and psychopathology (Symptomchecklist-90-revised [SCL-90-R]). Acne grading and APSEA showed similar change patterns. Both improved after 8 weeks of oral isotretinoin treatment. On the other hand, the severity of depression decreased after 2 weeks of treatment. A significant correlation was found between BDI and APSEA, but no correlation was found between BDI and acne grade. These results indicate that oral isotretinoin therapy alleviates depressive symptoms. Improvements in depression are directly related to acne-related life quality improvements rather than to improvement in acne grade.
Oral antibiotics are commonly used to treat acne vulgaris, primarily in patients presenting with moderate to severe facial or truncal disease severity. These agents are most appropriately used in combination with a topical regimen containing benzoyl peroxide and a topical retinoid. The most common oral antibiotics for treating acne vulgaris are the tetracycline derivatives, although macrolide agents such as erythromycin have also been used extensively. Over the past 4 decades, as the sensitivity of Propionibacterium acnes to several oral and topical antibiotics has decreased, the efficacy of oral tetracycline and erythromycin has markedly diminished, leading to increased use of doxycycline, minocycline, and other agents, such as trimethoprim/sulfamethoxazole.
Resistance to topical antibiotics is increasingly relevant in dermatology. This article discusses emerging patterns of resistance and the implications for clinical practice. Emergence of resistance is complicating decolonization of the skin and nares in patients infected with methicillin-resistant Staphylococcus aureus. In the setting of acne treatment, adding topical benzoyl peroxide has been shown to reduce the emergence of strains resistant to topical antibiotics. Other agents, such as zinc salts, are promising in this regard. This article discusses alternatives to antibiotics and mechanisms to stem the emergence of resistance.
This article reviews the anti-inflammatory and nonantimicrobial effects of antibiotics in acne and other diseases and examines issues relating to the emergence of decreased bacterial sensitivity to antibiotics and how these issues relate to clinical practice. It includes an overview of the inflammatory activities of some antibiotic agents and their potential for use in various dermatologic and nondermatologic diseases. It demonstrates that P. acnes-resistant organisms may be associated with therapeutic failure in some patients with acne, and that the prudent use of antibiotics is necessary to ensure that we can continue to use these drugs to combat disease effectively. It concludes that there are treatment strategies that can effectively minimize the potential for development of resistant P. acnes organisms.
Acne affects more than 40 million people, of which more than half are women older than 25 years of age. These women frequently fail traditional therapy and have high relapse rates even after isotretinoin. Recent advances in research have helped to delineate the important role hormones play in the pathogenesis of acne. Androgens such as dihydrotestosterone and testosterone, the adrenal precursor dehydroepiandrosterone sulfate, estrogens, growth hormone, and insulin-like growth factors may all contribute to the development of acne. Hormonal therapy remains an important part of the arsenal of acne treatments available to the clinician. Women dealing with acne, even those without increased serum androgens, may benefit from hormonal treatments. The mainstays of hormonal therapy include oral contraceptives and antiandrogens such as spironolactone, cyproterone acetate, or flutamide. In this article, we discuss the effects of hormones on the pathogenesis of acne, evaluation of women with suspected endocrine abnormalities, and the myriad of treatment options available.
Acne is the most common disease of the skin, yet only a fraction of acne sufferers are treated with prescription products by physicians. There is, however, a large and expanding market for over-the-counter (OTC) medications, many of which are not only effective but also well tolerated and cosmetically elegant. Given the presence of OTC acne medications on the television, the Internet, and store shelves, patients will be acutely aware of these OTC remedies and will have questions. Patients will expect dermatologists to advise them regarding products to use either as a sole therapy or in combination with prescription drugs. Recently, combinations of OTC acne medications in treatment regimens or "kits" have gained popularity and appear to have increased patient compliance. Quality-of-life outcomes from OTC medication use, in at least one study, have demonstrated good benefit. The most common OTC ingredients include benzoyl peroxide, a potent antibacterial agent, and salicylic acid, a mild comedolytic and antiinflammatory medication. Other, less-common OTC ingredients include sulfur, sodium sulfacetamide, and alpha hydroxy acids. Zinc, vitamin A, tea tree oil, and ayurvedic therapies also are available OTC for acne. Additional and better studies are needed to clarify the benefit of these latter medications.
There is widespread misunderstanding of acne amongst both the medical and lay community, who often perceive the condition to be a simple, self-limited affliction of adolescents. Because many think that the disease "will go away on its own," they do not feel an urgency to aggressively treat acne. However, very often the reality is that acne treatment can be quite difficult. Furthermore, acne can be a devastating disease for the patient, since it manifests on visible body parts and in children near puberty, who are vulnerable both socially and psychologically. Most typically, acne is not an acute disease but rather a condition that continuously changes in its distribution and severity. Usually, acne treatment is necessary for many months and sometimes years. Despite treatment, acne may cause scarring and associated negative psychological effects. It is important for both patients and physicians to be aware that very effective treatments are available. It is also important to realize that new studies have proven the benefit of maintenance therapy with topical retinoids; these agents can minimize the potential for relapse, which is part of the natural history of acne. This article reviews the evidence suggesting that acne is a chronic disease in at least a subset of individuals. The members of the Global Alliance to Improve Outcomes in Acne believe that acne should be recognized and investigated as a chronic disease. This will change expectations of clinical trial design and treatment and will highlight gaps in the knowledge of acne epidemiology. The result should be an improvement in patient outcomes.
A double-blind, randomized study comparing isotretinoin gel (Isotrex-®), its vehicle base, and benzoyl peroxide was performed on 77 patients with mild to moderate acne vulgaris.
The effect of treatment was assessed by acne grade and lesion count. The vehicle base had no effect, bur both active groups produced significant improvements. Benzoyl peroxide and isotretinoin significantly reduced non-inflamed lesions at 4 (P 0.05), 8 (P < 0.01), 12 (P < 0.01) weeks. Benzoyl peroxide had a more rapid effect on inflamed lesions, their being significant reductions at 4, 8 and 12 weeks (P < 0.01), whereas with isotretinoin there was a significant improvement at 12 weeks (P < 0.01). In addition, compared to placebo, both active treatments significantly reduced inflamed and non-inflamed lesions. Acne grade had improved significantly in the benzoyl peroxide group by 4 weeks (P < 0.01) and in the isotretinoin group by 8 weeks (P < 0.05). No significant change in haematological or biochemical parameters occurred. An irritant dermatitis occurred equally with both treatments but was well tolerated by the patients.
This data confirms the clinical benefit of benzoyl peroxide in acne.
The initial effect of isotretinoin on non-inflamed lesions in this study suggests that the prime mode of action is on comedone formation or separation whereas benzoyl peroxide has an effect on both comedones and inflammation.
We investigated 299 patients treated 5-10 years ago with isotretinoin, and followed them for 5 years post-treatment. Of the 299 patients 22·7% required repeat courses of treatment; 17% had two courses, 5% had three courses and 1% had 4-5 courses. Response to further treatment was predictably successful, was not associated with any additional adverse reactions, and produced no persistent side-effects.
Factors contributing to the need for further courses of treatment included lower dose regimens (0·1 and 0·5 mg/kg), the presence of severe acne, being a female over the age of 25 at the onset of therapy, and having a prolonged history of acne.
To consider whether oral isotretinoin (Roaccutane/Accutane) represents good value compared with typical alternative treatments for moderate or severe acne.
Published reports were reviewed on the comparative effectiveness of oral isotretinoin and its alternatives and on their relative costs.
Observational studies of clinical and patient-assessed outcomes suggest that oral isotretinoin is much more effective than available alternatives. The costs of treatment with isotretinoin are greater in the first year, but substantial cost savings accrue in subsequent years.
Isotretinoin is more cost-effective than long-term antibiotic therapy mainly because of its greater efficacy but also because of long-term cost savings. MESSAGE: The costs and benefits of alternative treatments for acne should be assessed over a period of at least 2 years, preferably longer. The higher initial cost of oral isotretinoin should not be a barrier to its use where the drug is clinically indicated.
It has previously been shown that a combination of erythromycin and benzoyl peroxide is superior to either ingredient when used alone in the treatment of acne. A clindamycin/benzoyl peroxide combination gel might have an advantage over erythromycin/benzoyl peroxide gel because the former does not require refrigeration after it is dispensed.
Our purpose was to determine the efficacy and safety of a combination clindamycin/benzoyl peroxide gel when compared with benzoyl peroxide, clindamycin, or vehicle gels.
In two double-blind, randomized, parallel, vehicle-controlled trials, patients were treated for 11 weeks with once-nightly application of one of the above preparations. Evaluations were performed at 2, 5, 8, and 11 weeks and included lesion counts and assessment of global responses and irritant effects.
A total of 334 patients completed the study. All three active preparations were significantly superior to the vehicle in global improvement and in reducing inflammatory lesions and noninflammatory lesions. The combination gel was significantly superior to the two individual agents in global improvement and reduction of inflammatory lesions and also to the clindamycin gel in reducing noninflammatory lesions. There was no significant difference in tolerance to the active gels versus the vehicle gel.
In the treatment of acne, topical clindamycin/benzoyl peroxide combination gel is well tolerated and superior to either individual ingredient.
The purpose of this meta-analysis was to determine if adapalene 0.1% gel (Differin) provided superior efficacy and better tolerability than tretinoin 0.025% gel in the treatment of acne vulgaris. All comparative studies, both published and unpublished, from the United States and Europe, that fulfilled rigorous protocol criteria (multicentre, randomized, investigator-blind) were used. Five comparative studies met these criteria. In total, the meta-analysis evaluated 900 patients (450 treated with adapalene 0.1% gel, 450 treated with tretinoin 0.025% gel) with mild-to-moderate acne from the combined clinical trials. To avoid study bias, the meta-analysis used an intention-to-treat analysis. Statistical methodology for the meta-analysis included analysis of covariance, analysis of variance and Cochran-Mantel-Haenszel test. All statistical tests were two-sided, with the 0.05 probability level used to establish statistical significance, and 95% confidence intervals used to assess equivalence. Adapalene demonstrated equivalent efficacy to tretinoin in terms of reducing total lesion count. Adapalene demonstrated more rapid efficacy, as evidenced by a significant difference in the reduction of inflammatory and total lesions at week 1. Adapalene also demonstrated considerably greater local tolerability at all evaluation periods. The findings from this meta-analysis suggest that adapalene 0.1% gel constitutes a pharmacologic advance over such classic retinoids as tretinoin for the treatment of acne vulgaris.
Adapalene 0.1% gel (Differin gel) is a recently introduced topical treatment for mild to moderate acne which has been demonstrated to be much better tolerated and at least as effective as tretinoin 0.025% gel. We compared the tolerance of adapalene 0.1% gel with six different formulations and concentrations of tretinoin. A total of 55 healthy human subjects were enrolled in two controlled, randomized, observer blinded, intraindividual comparison studies. In the first study, adapalene 0.1% gel was evaluated for its 21-day cumulative irritation potential compared with tretinoin 0.025%, 0.05% and 0.1% cream, tretinoin 0.01% and 0.025% gel, and petrolatum (control). In the second study, adapalene 0.1% gel was evaluated for its 21-day cumulative irritation potential compared with tretinoin 0.025%, 0.05% and 0.1% cream, tretinoin 0.1% gel microsphere, and petrolatum (control). In both studies, cumulative irritation scores helped to define three groups of common irritancy potential, with significant differences between each group. In study A, the three groups were in descending order of irritancy: tretinoin 0.1% cream and tretinoin 0.05% cream; tretinoin 0.025% gel, tretinoin 0.01% gel and tretinoin 0.025% cream; adapalene 0.1% gel and petrolatum (control). In study B, the three groups were in descending order of irritancy: tretinoin 0.1% cream; tretinoin 0.05% cream, tretinoin 0.025% cream and tretinoin 0.1% gel microsphere; adapalene 0.1% gel and petrolatum (control). The experimental results show that adapalene 0.1% gel is significantly better tolerated than any of six formulations of tretinoin, including two gels, three creams and a microsphere formulation, ranging in potency from 0.01% to 0.1%.
This paper reports the results of a meta-analysis of isotretinoin treatment in moderate to severe acne. It forms part of a comprehensive investigation into the cost-effective treatment of acne in South Africa and as such establishes the clinical foundation for an economic model of acne management. This foundation includes an evaluation of the daily dosages, treatment durations, success rates, clinical effectiveness and relapse rates reported in published trials since 1981.
A predetermined protocol for the study established the scope, appropriate inclusion and exclusion criteria for peer-reviewed data, and the statistical rigour that would be applied to the selected data. Following an extensive literature search, data reflecting the effectiveness of isotretinoin were extracted, statistically assessed, described and reported. The combinability of the data was confirmed using analyses of variance and chi-square tests, as applicable.
Isotretinoin consistently proved to be a highly effective agent in the treatment of moderate to severe acne vulgaris. The response rate determined by the meta-analysis indicated a clinical cure in 84.22% to 86.71% of patients treated. From the data considered, the average treatment duration was calculated to be 17.9 weeks (4 months). The relapse rate was low (21.45%) and dose-dependent. Optimal results were achieved by treating patients with a daily dose of 1 mg/kg and treating to a target cumulative dose of 120 mg/kg over the treatment duration.
The results of this meta-analysis support the continued use of isotretinoin in the treatment of acne. The results are important in the field of pharmaceutical benefit management where they will assist in the optimal management of this health condition. The results will be used to develop a pharmaco-economic model to evaluate the various treatment regimens used for acne in South Africa.
Systemic retinoids represent a growing armamentarium in the treatment of a wide range of skin disorders and malignancies. Although these drugs can have substantial toxicities, their wise use can result in safe and efficacious therapy that can alter dramatically the lives of individuals with severe skin disorders.
This paper examines the existing literature and MedWatch reports concerning a proposed relationship between isotretinoin and depression and suicide. The authors provide a brief overview of the biology of isotretinoin and depressive disorder and find no basis for a putative molecular mechanism linking the two. They also address the complexities of Substance-Induced Mood Disorder (SIMD) as a psychiatric diagnosis and its relevance to isotretinoin. Based on this review, the authors conclude that there is no evidence to support a causal connection between isotretinoin and major depression or suicide, because reported cases do not meet the established criteria for causality. The authors also conclude, however, that it is important for dermatologists to be aware of the risk factors for suicide and to monitor patients who exhibit depressive symptoms.
The efficacy and tolerability of tazarotene 0.1% gel and adapalene 0.1% gel were compared in a multicenter, double-blind, randomized, parallel-group study in 145 patients with mild-to-moderate facial acne vulgaris. Both treatments were applied once daily in the evenings for up to 12 weeks. Compared with adapalene, treatment with tazarotene was associated with a significantly greater incidence of treatment success (> or = 50% global improvement) (78% vs 52%; P=.002) and significantly greater reductions in overall disease severity (P<.0001), noninflammatory lesion count (P<.0001), and inflammatory lesion count (P=.0002). In the early weeks of treatment, tazarotene was associated with transiently greater levels of burning, pruritus, erythema, and peeling compared with adapalene (P<.01). However, mean levels of these parameters were consistently less than mild in both treatment groups and, at the end of treatment, patients considered both treatments to be comparably well tolerated (the proportion of patients in each group who rated the comfort of their treated skin as comfortable or very comfortable was 76% with tazarotene and 69% with adapalene). Mean usage of study medication was 0.32 g per application of tazarotene and 0.42 g per application of adapalene, which resulted in cost-effectiveness ratios of $79.95 per treatment success for tazarotene and $107.88 per treatment success for adapalene. Sensitivity analyses suggest that these cost-effectiveness results are robust across a range of cost and efficacy assumptions. In conclusion, tazarotene 0.1% gel was more effective than adapalene 0.1% gel and was also a more cost-effective treatment option.
The efficacy and tolerability of tazarotene 0.1% gel and tretinoin 0.1% microsponge gel were evaluated in a multicenter, double-blind, randomized, parallel-group study in patients with mild-to-moderate inflammatory facial acne vulgaris. A total of 169 patients were randomized to once-daily applications of one of these topical retinoids for 12 weeks. Both agents were associated with significant reductions from baseline in the noninflammatory and inflammatory lesion counts. Tazarotene treatment was associated with a significantly greater incidence of treatment success (defined as > or = 50% global improvement [67% vs 49%; P=.03]) and significantly greater reductions in overall disease severity (36% vs 26%; P=.02) and noninflammatory lesion count (60% vs 38% at week 12; P=.02) than tretinoin microsponge treatment. Both drugs were well tolerated, with mean levels of dryness, burning, pruritus, erythema, and peeling generally being no more than trace throughout the study. There were no clinically significant between-group differences in these measures of tolerability. Two patients in each group (2%) discontinued because of treatment-related adverse events. The mean amount of medication applied by the patients was 0.28 g per application with tazarotene and 0.41 g per application with tretinoin microsponge, resulting in cost-effectiveness ratios of $81.45 per treatment success with tazarotene and $108.24 per treatment success with tretinoin microsponge. Tazarotene was observed to have greater efficacy and comparable tolerability and to be a cost-effective alternative to tretinoin 0.1% microsponge gel.
Previous clinical trials have shown that adapalene gel produces less irritation than tretinoin gels and tretinoin 0.025% cream. Short term results have shown that adapalene is less irritating than tretinoin gels and creams. This study is the first to compare the 0.1% formulation of adapalene gel with the 0.05% strength of tretinoin cream in a formal clinical trial.
To investigate the efficacy and tolerability of adapalene gel 0.1% compared with tretinoin cream 0.05% in patients with mild-to-moderate acne vulgaris.
Ten-week, multicentre, randomised, investigator-masked, active-controlled, parallel group study in 409 patients with acne vulgaris.
Adapalene gel 0.1% demonstrated equivalent efficacy in reduction of acne lesion counts and global improvement of acne severity over 10 weeks' treatment and was significantly better tolerated than tretinoin cream 0.05% in terms of erythema, dryness, desquamation and stinging/burning.
Adapalene gel 0.1% showed equivalent efficacy and was significantly better tolerated than tretinoin cream 0.05% in patients with mild-to-moderate acne vulgaris.
One approach to suppressing the overgrowth of antibiotic-resistant bacteria is to develop combination products composed of active constituents with complementary but distinct mechanisms of antibacterial action.
The purpose of this study was to compare the antimicrobial and clinical efficacy and tolerability of clindamycin phosphate 1%/benzoyl peroxide 5% gel formulation with matching clindamycin 1% gel in the treatment of acne vulgaris.
This 16-week, single-center, double-blind, randomized, parallel-group study compared the combination gel with clindamycin monotherapy applied BID in patients 13 to 30 years of age with mild to moderate acne and facial Propionibacterium acnes counts > or = 10(4) colony-forming units per square centimeter of skin.
Seventy-nine patients were enrolled and randomly assigned to receive the combination gel (n = 40) or clindamycin monotherapy (n = 39). Seventy patients (50 males, 20 females; mean age, 18.2 years) were included in the intent-to-treat group. The combination gel treatment produced significantly greater reductions (P < or = 0.046) from baseline in total lesion counts and in numbers of inflammatory lesions and comedones compared with clindamycin monotherapy. Greater reductions in the severity of acne also were observed in the physician's and patient's Clinical Global Improvement scale scores and in other secondary efficacy measurements. Reductions in clindamycin-resistant P acnes counts were observed relative to baseline in the combination gel group; in contrast, P acnes counts increased by >1,600% in the clindamycin monotherapy group at week 16 (P = 0.018 vs combination gel). Reductions in inflammatory (r2 = 0.31; P = 0.016) and total (r2 = 0.28; P = 0.027) lesions were correlated with decreases in clindamycin-resistant bacteria. Also, significant correlations were observed between the percent change from baseline in total lesion counts (r2 = 0.44; P < 0.001) and comedo counts (r2 = 0.50; P < 0.001) and the log10 change from baseline in total P acnes counts.
The total P acnes count (P = 0.002) and the clindamycin-resistant P acnes count (P = 0.018) were significantly reduced after 16 weeks of treatment with combination gel compared with clindamycin monotherapy. These reductions in total P acnes and clindamycin-resistant P acnes counts correlated with reductions in total acne lesions.
A comparison of efficacy, safety and cost-effectiveness of lymecycline and minocycline in the treatment of acne vulgaris has been addressed. This was a multicenter, randomized, investigator-masked, parallel group trial involving patients with moderate to moderately severe acne vulgaris, receiving either lymecycline or minocycline for 12 weeks. Efficacy and safety evaluation was performed at baseline and at weeks 4, 8, and 12 and completed by a pharmacoeconomic analysis including week 12 data. One hundred and thirty-six patients were enrolled. At week 12, the mean percent reductions in inflammatory count were 63 % and 65 %, and for total lesions counts 58 % and 56 % for lymecycline and for minocycline respectively. Median percent reduction in non-inflammatory count were 54 % and 47 % for lymecycline and for minocycline respectively. Eighty-seven per cent of all patients tolerated the treatments well. Treatment with lymecycline was found to be 4 times more cost-effective than with minocycline. Results showed that lymecycline has a comparable efficacy and safety profile to minocycline while being 4 times more cost-effective.