Use of permethrin in the treatment of rosacea fulminans during pregnancy: One case report

Rosacea fulminans (RF) is a rare dermatological condition which occurs exclusively in women and it is characterized by a sudden onset of painful papules, pustules, cysts, and nodules on the face. A 28‐year‐old woman was referred to our clinic due to a painful facial eruption within the 13th week of her second pregnancy. After physical examination, the diagnosis of RF during pregnancy was established. Several treatments were used: mupirocin ointment, topical zinc oxide, topical erythromycin, oral erythromycin, metronidazole gel, oral metronidazole, oral amoxiciline, and oral prednisone. Finally, the patient was started on 5% permethrin cream with complete clearing of the lesions. Nowadays, a wide range of treatments for rosacea is available: topical metronidazole, oral metronidazole, topical ivermectin, oral tetracyclines, oral isotretinoin, systemic steroids, photodynamic therapy, or pulsed dye laser. However, in pregnant patients, the treatment alternatives are limited. We consider that 5% permethrin cream could be an effective, cheap, and safe treatment not only in regular patients with rosacea but also in pregnant women, representing an important alternative in the context of pregnancy when therapeutic options are limited. To our knowledge, this is the first case of rosacea treated with 5% permethrin cream in monotherapy during pregnancy.     

特异性双链RNA对小鼠干细胞和转基因荧光蛋白的抑制作用

目的 研究特异性dsRNA对小鼠ES细胞中对核外基因和核内染色体基因的干扰作用，并对RNA干扰(RNAi)技术在皮肤病基因治疗领域中应用的可能性进行初步探讨。方法 选择荧光蛋白基因为靶基因，通过质粒或RNA直接转染技术，将荧光蛋白双链RNA(dsRNA—EGFP)转染小鼠胚胎干细胞(ES细胞)，从而观察该细胞中特异性RNAi作用。并通过皮肤局部注射dsRNA—EGFP和局部外用脂质体包裹的dsRNA—EGFP。观察EGFP转基因鼠皮肤EGFP的表达。结果 无论是转染质粒产生的dsRNA—EGFP或是直接转染的dsRNA—EGFP，均明显抑制ES细胞核外或染色体中EGFP基因的特异性表达。局部皮肤注射或皮肤外用脂质体-dsRNA—EGFP均特异性抑制EGFP转基因鼠皮肤EGFP的表达。结论 本研究证实了小鼠ES细胞中特异性RNAi的作用。     

Small-interfering RNA targeted at antiapoptotic mRNA increases keratinocyte sensitivity to apoptosis

Background Gene silencing RNA interference technology concentrates on downregulation of gene expression using specific double‐stranded RNA molecules (small‐interfering RNA, siRNA), which induce the degradation of complementary mRNA. SiRNA therapeutics is currently being tested in several clinical trials. Skin disorders are an attractive target for siRNA‐based technology because effective agents can be delivered by topical application. In several inflammatory skin disorders, the barrier function of the skin is markedly impaired and this may increase the delivery efficiency. Psoriasis is a very common skin disorder. The characteristics of this disorder are abnormal keratinocyte proliferation and inflammation. Keratinocytes from psoriatic epidermis express much higher levels of the antiapoptotic protein, Bcl‐xL, compared with normal keratinocytes. Insulin‐like growth factor 1 receptor (IGF‐1R) plays a major role in cell growth, differentiation and apoptosis in many cell types, including keratinocytes and IGF‐1R activation plays an important role in the pathogenesis of psoriasis. Keratinocytes from patients with psoriasis are more susceptible to IGF‐1‐stimulated proliferation compared with normal keratinocytes. IGF‐1R is expressed by proliferating basal and suprabasal keratinocytes and is more abundant in psoriatic lesions. Objectives To prove the validity of IGF‐1R and Bcl‐xL as useful targets for siRNA‐based therapeutics and to deliver siRNA selectively and efficiently to primary human keratinocytes; this is a primary essential step in the development of siRNA. Methods Primary normal human keratinocytes were transfected with various siRNA molecules, and transfection efficiency was monitored by fluorescent labelling. Cell growth and apoptosis induction were evaluated in the transfected cells. Results We were able to deliver efficiently siRNA targeting Bcl‐xL or IGF‐1R to primary human keratinocyte cultures. We also showed that siRNAs targeting Bcl‐xL and IGF‐1R induce growth inhibition, apoptosis and increased sensitivity to ultraviolet B in keratinocytes. Conclusions The present findings demonstrate that Bcl‐xL and IGF‐1R are valid, important targets for siRNA‐based technology directed at the suppression of keratinocyte hyperproliferation.     

A simple,noninvasive and efficient method for transdermal delivery of siRNA

Effective delivery of therapeutic agents is the most challenging hurdle in the use of RNA interference for research and in the clinic. Here, we assessed whether a short synthetic peptide, ACSSSPSKHCG (TD-1), could be transported through rat footpad (follicle-free) skin and efficiently deliver small interfering RNA (siRNA) to knock down a target gene. Fluorescence microscopy revealed that topical co-administration of FITC-labeled TD-1 and FAM-labeled siRNA distributed uniformly from the epidermis to the subcutaneous tissue of rat footpad skin. Transmission electron microscopy revealed the absence of cell–cell junctions and enlarged spaces between epithelial cells in the TD-1-treated footpad skin. TD-1 delivery of anti-GAPDH siRNA significantly reduced the level of GAPDH in 72 h. TD-1 can create a transient opening in non-follicle rat skin for delivery of siRNA and reveal a novel mechanism of transdermal delivery of TD-1 and siRNA into the epidermis for gene knockdown. The system might have potential for siRNA delivery in skin for drug therapy.     

Pediatric rosacea

Rosacea is a condition most commonly associated with adults; however, various forms exist in the pediatric population and need to be considered when a child presents with a facial rash. Acne rosacea, steroid rosacea, granulomatous periorificial dermatitis, and other variants of rosacea are presented here and are distinguished from their numerous mimickers. Various topical and systemic therapeutic options exist for the treatment of rosacea with several adjustments and considerations that must be taken into account when treating a child.     

Laser‐assisted drug delivery: mode of action and use in daily clinical practice

Topical application of pharmaceutical agents is a basic principle of dermatological therapy. However, the effective barrier function of the skin significantly impairs the bioavailability of most topical drugs. Fractional ablative lasers represent an innovative strategy to overcome the epidermal barrier in a standardized, contact‐free manner. The bioavailability of topical agents can be significantly enhanced using laser‐assisted drug delivery (LADD). In recent years, the principle of LADD has become well established for various dermatological indications. Herein, we review the current literature on LADD and present potential future applications.     

Women commonly seek care for rosacea: dermatologists frequently provide the care

Rosacea is a common dermatosis affecting the central portion of the face. The purpose of this study is to describe the demographics of patients and the treatments prescribed. Data on rosacea visits from 1990 to 1997 were obtained from the National Ambulatory Medical Care Survey There were 1.1 million outpatient visits for rosacea annually in the United States. Most rosacea patients were Caucasian (96%). Most visits were by women (69%), and the mean age (SD) of patients was 50 +/- 17 years. Visits to dermatologists accounted for 78% of visits. Common comorbid diagnoses included actinic keratoses, acne and cysts, and seborrheic and contact dermatitis. Topical metronidazole was the most commonly prescribed treatment; tetracycline was the most commonly prescribed systemic therapy. Combination treatment with an oral and a topical agent was commonly used. Because rosacea appears most often in fair-skinned women, these patients may benefit from the textural features and safety profiles of certain topical metronidazole preparations newly available and from oral antibiotics (eg, tetracycline). People with rosacea should be aware of the experience that dermatologists have in treating this disorder.     

Rosacea and rhinophyma

Rosacea is a common and chronic inflammatory cutaneous disease with unknown etiology. The pathophysiology of rosacea is still poorly understood. Epidemiological studies indicate a genetic component, but a rosacea gene has not been detected yet. Recent molecular studies propose that an altered innate immune response is involved in the pathogenesis of the rosacea disease. Signs of rosacea are indicated by the presence of characteristic facial or ocular inflammation involving both the vascular and tissue stroma. A wide range of drug options is available for the treatment of rosacea, including several topical ones (metronidazole, antibiotics, azelaic acid, benzoyl peroxide, sulfacetamide/sulfur, retinoids) and oral ones (mainly tetracyclines, metronidazole, macrolides, isotretinoin). This review highlights the recent clinical and pathophysiological developments concerning rosacea.     

Interventions for rosacea: abridged updated Cochrane systematic review including GRADE assessments

Rosacea is a common chronic facial dermatosis. This update of our Cochrane review on interventions for rosacea summarizes the evidence, including Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group assessments, of the effects of the currently available treatments. Searches included the following: Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE, EMBASE, LILACS and the Science Citation Index, and ongoing trials registries (July 2014). We included 106 randomized controlled trials (RCTs) with 13 631 participants, a more than 80% increase since the last update in 2011. Pooling of data was feasible for a few outcomes, for topical metronidazole and azelaic acid and both appeared to be more effective than placebo (moderate and high‐quality evidence, respectively). Topical ivermectin was more effective than placebo based on two studies (high‐quality evidence), and slightly more effective than metronidazole in one study. Brimonidine was more effective than vehicle in reducing erythema in rosacea (high‐quality evidence). Ciclosporin ophthalmic emulsion was effective for ocular rosacea (low‐quality evidence). For oral treatments there was moderate‐quality evidence for the effectiveness of tetracycline based on two old studies, and high‐quality evidence for doxycycline 40 mg compared with placebo according to physician assessments. One study at high risk of bias demonstrated equivalent effectiveness for azithromycin and doxycycline 100 mg. Minocycline 45 mg may be effective for papulopustular rosacea (low‐quality evidence). Low‐dose isotretinoin appeared to be slightly more effective than doxycycline 50–100 mg (high‐quality evidence). Laser and light‐based therapies for erythema in rosacea were effective (low‐quality evidence). Further RCTs are required for ocular rosacea.     

Integrative concepts of rosacea pathophysiology,clinical presentation and new therapeutics

Rosacea is a chronic relapsing inflammatory skin disease with high prevalence worldwide. Recent research suggests that dysregulation of innate and adaptive immune pathways as well as neurovascular changes is present, with different degrees of importance in the various subtypes. Neither the aetiology, genetics nor pathophysiological basis of the vascular, inflammatory or fibrotic changes is well understood. The clinical spectrum comprises a huge variability from erythema (vasodilation) to papules/pustules (inflammatory infiltrate) to phymata (fibrosis, glandular hyperplasia) making it a valuable human disease model to understand the interplay between the neurovascular and immune systems as well as the progression from chronic inflammation to fibrosis in skin. The lack of appropriate animal models emphasizes the importance of further translational research validating observed molecular pathways under disease conditions. A wide spectrum of physical (UV, temperature), biological (microbiota, food) and endogenous (genetic, stress) stimuli has been discussed as “trigger factors” of rosacea. Novel findings implicate keratinocytes, smooth muscle cells, endothelial cells, macrophages, mast cells, fibroblasts, Th1/Th17 cells, antibody‐producing B cells and neurons in the pathobiology of rosacea. So far, pattern recognition receptors like TLR2, transient receptor potential ion channels, cytokines, chemokines and proteases have been implicated as critical receptors/mediators. However, our understanding of the interactive networks on the molecular level is very limited. Identification of critical molecular components of the inflammatory cascade including antimicrobial peptides, the IL‐1β inflammasome, TNF, IFN‐γ, proteases and neuropeptides may provide the basis for novel pathomechanism‐based therapeutic approaches for this frequent and bothersome skin disease.     

Picosecond alexandrite laser is superior to Q-switched Nd:YAG laser in treatment of minocycline-induced hyperpigmentation: A case study and review of the literature

Background: Minocycline is a commonly prescribed tetracycline antibiotic used for the treatment of a number of dermatological conditions including acne and rosacea. Long-term adverse effects of minocycline include cutaneous hyperpigmentation. Various treatment options have been suggested for the treatment of minocycline pigmentation. We report a case of a patient on long-term low-dose minocycline for the treatment of rosacea with type III minocycline hyperpigmentation. A comparison was made between Q-Switch Nd:YAG and picosecond laser over a nine 9-period with treatments spaced 1 month apart, with a clearance in the patient pigmentation after four treatments with picosecond laser.     

Current topical and systemic approaches to treatment of rosacea

Rosacea is a common, often overlooked, chronic facial dermatosis characterized by intermittent periods of exacerbation and remission. Clinical subtypes and grading of the disease have been defined in the literature. On the basis of a genetic predisposition, there are several intrinsic and extrinsic factors possibly correlating with the phenotypic expression of the disease. Although rosacea cannot be cured, there are several recommended treatment strategies appropriate to control the corresponding symptoms/signs. In addition to adequate skin care, these include topical and systemic medications particularly suitable for the papulopustular subtype of rosacea with moderate to severe intensity. The most commonly used and most established therapeutic regimens are topical metronidazole and topical azelaic acid as well as oral doxycycline. Conventionally, 100–200 mg per day have been used. Today also a controlled release formulation is available, delivering 40 mg per day using non-antibiotic, anti-inflammatory activities of the drug. Anti-inflammatory dose doxycycline in particular allows for a safe and effective short- and long-term therapy of rosacea. Topical metronidazole and topical azelaic acid also appear to be safe and effective for short-term use. There are indications that a combined therapy of anti-inflammatory dose doxycycline and topical metronidazole could possibly have synergy effects. Further interesting therapy options for the short- and long-term therapy of rosacea could be low-dose minocycline and isotretinoin; however, too little data are available with regard to the effectiveness, safety, optimal dosage and appropriate length of treatment for these medications to draw final conclusions.

Conflicts of interest

None declared.     

The mechanism of action and clinical benefits of soy for the treatment of hyperpigmentation

Background Hyperpigmentation disorders are common and diverse conditions that may require treatment for medical and/or cosmetic reasons. Hyperpigmented lesions can reduce patients’ quality of life, self‐perception, and social and vocational functioning. The most commonly used treatments for hyperpigmentation include topical agents, such as hydroquinone, retinoids and azelaic acid. Objectives Current topical treatments have significant limitations; they often do not produce adequate results and may be limited by adverse effects, such as dermatitis. Soy and soy‐based products have demonstrated a wide range of potential benefits for health and nutrition, including a range of dermatological effects. Methods Research from the last decade has identified multiple mechanisms by which soy‐derived products may affect skin pigmentation, as well as photodamage and photoaging, overall skin health, and even the risk for and progression of skin cancer. Results Preclinical evidence has demonstrated that soy‐derived serine protease inhibitors affect skin pigmentation by inhibiting protease‐activated receptor‐2‐mediated phagocytosis of melanosomes by keratinocytes. Conclusion Soy‐based products containing these serine protease inhibitors may represent a new therapeutic option for dermatological treatment. Indeed, recent evidence from randomized clinical studies supports the safe and effective use of soy products for the treatment of hyperpigmentation.     

A case of granulomatous rosacea successfully treated with pimecrolimus cream

A 43-year-old male attended with lesions on his face that had been present for 3 months. On dermatological examination, multiple papules and pustules were seen on the forehead, nose, bilateral cheeks and lower eyelids. The patient used systemic clindamycin and doxycycline and topical benzoyl peroxide therapies, but the lesions did not regress. Routine laboratory tests were normal. Histopathological examination of the lesions confirmed the diagnosis of granulomatous rosacea. Pimecrolimus cream 1% was applied to the lesions. The regression of lesions began in the first month and complete improvement was observed at the end of the fourth month of therapy. Rosacea is a chronic, inflammatory skin disorder characterized by remissions and relapses. Although it is known that the disease is a treatable disorder, it may be resistant to standard therapies and there is a need for new therapy alternatives in some patients. We present a case of granulomatous rosacea successfully treated with pimecrolimus cream and believe that pimecrolimus may be a good alternative for the treatment of granulomatous rosacea.     

Idiopathic facial aseptic granuloma

Idiopathic facial aseptic granuloma (IFAG) is a condition that is commonly encountered in clinical practice, but is rarely reported. It appears in childhood and its pathogenesis is still unknown. It has a benign course with resolution within a few months without aggressive treatment. Microbiological tests are negative and histological findings are nonspecific. It is possible that this condition is part of the spectrum of granulomatous rosacea in childhood. We present two cases in which diagnosis of IFAG was established and resolved without sequelae following topical antibiotic treatment.     

Tacrolimus ointment for the treatment of steroid-induced rosacea: a preliminary report

BACKGROUND: Excessive topical corticosteroid application to facial areas commonly leads to steroid-induced rosacea. This may be a recalcitrant problem that requires months of antibiotic and anti-inflammatory therapy before it resolves. OBJECTIVE: The purpose of this article is to review the use of tacrolimus ointment, a macrolide anti-inflammatory ointment for the treatment of 3 patients with steroid-induced rosacea. METHODS: Three patients with steroid-induced rosacea applied tacrolimus ointment, 0.075% twice daily for 7 to 10 days. Patients were also instructed to avoid topical corticosteroid use and other rosacea-aggravating substances including caffeine, spicy foods, alcohol, hot fluids, and fluoride. Patients were observed for tenderness, erythema, and relief of pruritus. RESULTS: Pruritus, tenderness, and erythema were resolved in all 3 patients after 7 to 10 consecutive days' use of tacrolimus 0.075% ointment in conjunction with avoidance of topical steroids, caffeine, spicy food, alcohol, hot fluids, and fluoride. CONCLUSION: This preliminary study demonstrates that tacrolimus 0.075% ointment may be effective for patients with steroid-induced rosacea, when combined with avoidance of topical steroid use, as well as avoidance of other agents known to aggravate rosacea (caffeine, spicy foods, alcohol, hot fluids, and fluoride).     

Incidental control of rosacea by somatostatin

BACKGROUND: The precise pathomechanism of rosacea remains elusive. The disease commonly requires long-term treatments using topical or oral therapies. OBJECTIVE: This report presents incidental findings about the possible modulatory role of somatostatin in the outcome of rosacea. METHOD: Four patients presenting long-standing recalcitrant facial rosacea were treated with octreotide for diabetic retinopathy. RESULTS: Rosacea improved rapidly and even cleared without any recurrence in 3 of the patients. CONCLUSION: The beneficial effect might be attributed to inhibitory actions on the sebaceous gland, the neovascularization and/or on the inflammatory process.