Adverse events related to topical drug treatments for acne vulgaris.

Introduction: Acne vulgaris is a widespread skin disease. Topical therapy is a standard treatment for mild to moderate acne. Given the complex pathophysiology of acne, various agents with complementary action are nowadays frequently combined to increase the efficacy of therapy.Area covered: This review focus on safety profile of topical agents used for the treatment of acne vulgaris, including topical retinoids, benzyl peroxide, azelaic acid, topical antibiotic, and combined agents. Data from clinical trials but also metanalyses, systematic reviews, and other secondary analyses are presented.Expert opinion: In general, topical agents used for acne vulgaris have a favorable safety profile. The most commonly reported AEs were associated with local skin irritation, usually mild to moderate in intensity, intermittent, and rarely led to the cessation of therapy. Irritative potential seems to be highest for BPO and topical retinoids. Due to the possibility of development of Cutibacterium acnes resistance, topical antibiotics should not be used in monotherapy but as a part of combination therapy. In female adolescent and adults of childbearing potential, topical retinoids should be used with caution, because they are contraindicated in pregnant females (FDA Pregnancy category) C (adapalene, tretinoin) and X (tazarotene).

Cluster of Vacuolated Spinous Keratinocytes: A Clue to Cornoid Lamellation and a Case of Porokeratosis Disseminata.

Cornoid lamella is a definitive diagnostic feature of porokeratosis, a disorder of keratinization that has various different clinical presentations. A tiered column of parakeratosis and a diminished granular layer with dyskeratotic keratinocytes at the column base are all useful and known features of cornoid lamellation. We have found a cluster of vacuolated spinous cells to be a reliable fourth feature of cornoid lamellation and a feature when present alone to be a reliable sign of impending cornoid lamellation on deeper sections. Furthermore, we present a novel clinical phenotype of disseminated papular porokeratosis with effective clinical response to combination of phototherapy, oral and topical retinoids, and topical vitamin D derivative, which too contained all 4 features of cornoid lamellation.

Melasma: A critical analysis of clinical trials investigating treatment modalities published in the past 10 years.

BACKGROUND: Melasma is an acquired disorder of facial pigmentation which is a treatment challenge. AIMS: The aim of this article is to critically appraise the clinical trial evidence for different treatment modalities for melasma, published in peer-reviewed journals in the past 10 years. PATIENTS/METHODS: The literature review was conducted using PubMed and MEDLINE. The search was performed in July 2019, and search parameters were limited to all English language articles published in the past 10 years only. RESULTS: Eighty-nine clinical trials were found. Four clinical trials investigated topical hydroquinone, supporting its safety and efficacy as first-line treatment. Twelve studies showed tranexamic acid as very promising. Nineteen studies assessed various novel oral, injectable, and topical treatments and highlight some new potential future treatments. Forty-two studies investigated laser and light treatment in melasma: LFQS laser is still one of the best options, especially in darker skin types. However, the picosecond laser has shown excellent results. Finally, 11 studies looked at peels. Overall, peels have not been shown to be superior to the use of topical therapy alone. CONCLUSION: Topical therapy with a HQ and retinoid-based product should be first line for a minimum of 3 months with the addition of oral tranexamic acid at 250 mg BD if no contraindication. Second-line treatment with lasers includes the LFQS Nd:YAG, picosecond laser, and the pulsed dye laser in lighter skin types. Third-line therapy would be the addition of chemical peels to the above treatments, with GA or TCA peels having the most evidence for effectiveness.

Grover disease: review of subtypes with a focus on management options.

Grover disease (GD) is a benign eruption that causes a papulovesicular rash on the trunk and proximal extremities. It often resolves spontaneously but can follow a more chronic and fluctuating course that may last several years. Although the etiology remains unknown, several associated triggers have been identified including heat and sweating, cool and dry air, renal failure, malignancy, and the initiation of several drugs. Since the disease tends to resolve on its own, management is aimed at disease prevention and symptomatic relief. First-line therapy includes topical steroids and vitamin D analogues with adjuvant antihistamines. In more severe cases that are refractory to less aggressive therapy, systemic corticosteroids, retinoids, and phototherapy may lead to successful resolution. Novel therapies are few and have little evidence but involve innovative use of light therapy and immune modulators. Herein, we review the literature and new trends of GD with a focus on established and novel treatments.

Skin cancer prevention: a review of current topical options complementary to sunscreens.

The incidence of non-melanoma skin cancer (NMSC) is dramatically increasing worldwide, despite the increased use of improved sunscreens. In 2014, the Surgeon General estimated that 2.2-5.0 million people were treated annually for NMSC. As the number of newly diagnosed skin cancers continues to rise, there is a need for additional preventative measures beyond sunscreens. Several newer topical products that focus on boosting DNA repair, modulating DNA transcription, decreasing inflammation and selectively targeting precancerous cells may play an important role in future skin cancer prevention.

An Anatomical Approach to Evaluating and Treating Cellulite.

Cellulite is the common rippling or dimpling of skin of the thighs and buttocks of women, formed from a confluence of skin laxity, tethering fibrous septa, and fat herniation. We describe an anatomical approach to evaluating the cellulite patient and selecting the best treatment from among available non-invasive, minimally invasive, and invasive therapies. It is crucial to consider the anatomy of the patient and the morphology of cellulite while choosing a treatment. Diffuse rippling represents increased adiposity and/or increased skin laxity which may stand to benefit from lipolytic and skin tightening modalities. Dimpling represents tethering by fibrous septa which may stand to improve from subcision by minimally invasive devices such as Cell na. Patients with both morphologies may be treated with a combination of treatments or Cellulaze. Careful evaluation of the patient can help identify the best therapeutic strategy. J Drugs Dermatol. 2017;16(1):58-61..

Interventions for the management of oral lichen planus: a review of the conventional and novel therapies.

OBJECTIVE: This narrative review focuses on the rationale and role of conventional and newer therapies in the management of oral lichen planus (OLP) with emphasis on randomized controlled trials (RCTs) reported over two decades. MATERIALS AND METHODS: Literature search was conducted to identify RCTs for the management of OLP from 1 January 1995 to 31 December 2015; Medline and Cochrane databases complemented with manual search were used. Primary outcome as resolution of pain was evaluated with the analysis of clinical resolution of erythema and ulceration as secondary outcome. RESULTS: The search provided 260 abstracts, of which 70 full-text articles were included. Majority of trials used topical steroids with very few trials on newer therapies. It was found that topical steroids are effective for symptomatic management of OLP with equal efficacy shown by topical calcineurin inhibitors and retinoids. However, the side effect of transient burning sensation with relapse was more with calcineurin inhibitors. CONCLUSION: Although the newer therapies offer advantage over steroids for the management of OLP in recalcitrant cases, extensive lesions, and cases unresponsive to steroids, but sufficient clinical data on their use are still lacking. Hence, more RCTs with large sample size, adequate treatment duration, and long-term follow-up are required for clinical utility.

Review of treatment for discoid lupus erythematosus.

Discoid lupus erythematosus (DLE) is a chronic cutaneous disease characterized by inflammatory plaques that, in the absence of prompt diagnosis and treatment, may lead to disfiguring scarring and skin atrophy. However, there is limited evidence for which treatments are most effective. Currently, no medications have been approved specifically for the treatment of DLE. Many of the drugs described in the literature were developed for use in other immune disorders. This review will summarize current therapeutic options for DLE and their supporting evidence with discussion of prevention, topical measures, physical modalities, and systemic therapies, including newer potential therapies.

Treatment of Acne in Pregnancy.

Acne vulgaris is a common disease of the pilosebaceous unit and affects adolescents and adults. Because high-quality guidelines regarding treatment of acne in pregnancy are scarce, management of this condition can be challenging. We describe the safety profile of common therapies and outline approaches based on available evidence. Topical azelaic acid or benzoyl peroxide can be recommended as baseline therapy. A combination of topical erythromycin or clindamycin with benzoyl peroxide is recommended for inflammatory acne. Oral erythromycin or cephalexin is generally considered safe for moderate to severe inflammatory acne when used for a few weeks. A short course of oral prednisolone may be useful for treating fulminant nodular cystic acne after the first trimester. In general, topical and oral antibiotics should not be used as monotherapy, but combined with topical benzoyl peroxide to decrease bacterial resistance. Oral retinoids are teratogenic and absolutely contraindicated for women who are pregnant or considering pregnancy. Although some complementary therapies including micronutrients and nonpharmacologic treatments seem to be well tolerated, limited data exist regarding their safety and efficacy, and they are not currently recommended during pregnancy. The risk-to-benefit ratio, efficacy, acceptability, and costs are considerations when choosing a treatment for acne in pregnancy.

Skin-Directed Therapies in Cutaneous T-Cell Lymphoma.

Early stage mycosis fungoides represents the most common clinical presentation of cutaneous lymphoma, with skin-directed therapies long established in its treatment. These therapies continue to change as new treatment regimens emerge. Other skin-directed treatments include light and radiation therapy. Therapies with higher levels of evidence and less systemic toxicity are usually preferred as first-line treatment. However, even these established therapies, like topical corticosteroids and carmustine, lack randomized clinical trials to establish their efficacy. Research is also needed to further define the role of combination topical therapies and how skin-directed therapies can be used as adjuvants to systemic medications.

100% Complete response rate in patients with cutaneous metastatic melanoma treated with intralesional interleukin (IL)-2, imiquimod, and topical retinoid combination therapy: results of a case series.

BACKGROUND: Patients with cutaneous melanoma metastases have experienced excellent responses to intralesional interleukin (IL)-2. This has led to its recent inclusion into the US National Comprehensive Cancer Network guidelines for management of cutaneous melanoma metastases. Despite this, intralesional IL-2 has not been highlighted in the US literature nor have US physicians adopted it. OBJECTIVE: We sought to evaluate the effectiveness of intralesional IL-2 combined with topical imiquimod and retinoid for treatment of cutaneous metastatic melanoma. METHODS: A retrospective case series of 11 patients with cutaneous metastatic melanoma were treated with intralesional IL-2 combined with topical imiquimod and retinoid. RESULTS: A 100% complete local response rate with long-term follow-up (average of 24 months) was seen in all 11 patients treated with this proposed regimen. Biopsy specimens of treated sites confirmed absence of malignant cells. The most common treatment-related adverse event was rigors. LIMITATIONS: Small number of patients, retrospective review of charts, and lack of a comparison group were limitations. CONCLUSION: Intralesional IL-2 administered concomitantly with topical imiquimod and a retinoid cream is a promising therapeutic option for managing cutaneous melanoma metastases. The regimen was well tolerated and should be considered as a reasonable alternative to surgical excision.

Focal epithelial hyperplasia by human papillomavirus (HPV)-32 misdiagnosed as HPV-16 and treated with combination of retinoids, imiquimod and quadrivalent HPV vaccine.

Focal epithelial hyperplasia (FEH) or Heck's disease is a rare, benign and asymptomatic mucosal proliferation associated with human papillomavirus (HPV) infection, mainly with genotypes 13 and 32. We report a florid case of FEH in an 11-year-old Haitian girl with systemic lupus erythematosus receiving immunosuppressive therapy. Cryotherapy was previously performed on numerous occasions with no results. We decided to prescribe a non-invasive and more comfortable treatment. A combination of topical retinoid and imiquimod cream was well tolerated and led to an important improvement. The evidence of infection by HPV-16 detected by polymerase chain reaction (PCR) technique, prompted us to prescribe the quadrivalent HPV vaccine (types 6, 11,16 and 18). Subsequent PCR sequencing with generic primers GP5-GP6 and further BLAST comparative analysis confirmed that genomic viral sequence in our case truly corresponded with HPV-32. This molecular misdiagnosis can be explained by the similarity between genomic sequences of both HPV-16 and -32 genotypes. At the 1-year follow up, we observed total clinical improvement and no recurrences of the disease. Complete healing in this case may correspond to a potential action of topical retinoid, imiquimod and the cross-protection mechanism of the quadrivalent HPV vaccine.

Congenital fibrosarcoma in complete remission with Somatostatin, Bromocriptine, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow up.

At birth, a male child presented a 6 cm tumour in the right leg. The tumour was partially removed after just 12 days. Histology showed a congenital fibrosarcoma associated with reactive lymphadenitis. A first cycle of adjuvant chemotherapy did not prevent the rapid progression of the disease. Subsequent evaluation for surgical removal raised serious concerns due to the need for a major operation involving total amputation of the right leg and hemipelvectomy. Since surgery could not exclude the possibility of disease recurrence and since the traditional cycles of chemotherapy did not offer any possibility of a cure, the parents opted for the Di Bella Method. The combined use of Somatostatin, Melatonin, Retinoids solubilized in Vit. E, Vit. C, Vit. D3, Calcium, and Chondroitin sulfate associated with low doses of Cyclophosphamide resulted in a complete objective response, still present 14 years later, with no toxicity and without the need for hospitalization, allowing a normal quality of life and perfectly normal adolescent psycho-physical development.

Trends in systemic psoriasis treatment therapies from 1993 through 2010.

BACKGROUND: Moderate-to-severe psoriasis generally requires systemic therapy, and is often undertreated. OBJECTIVE: To determine and analyze what courses of treatment and in what frequency are being utilized to combat psoriasis in the United States. METHODS: Analysis of data from the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) of the National Center for Health Statistics. Data were analyzed to examine the prevalence of different therapy techniques to combat psoriasis from 1993 through 2010. The trends for phototherapy, methotrexate (MTX), retinoids, cyclosporine A (CSA), systemic steroids, and biologics were all analyzed over the entire 18-year period and independently before and after the introduction of biologics in 2002. RESULTS: From 1993 to 2010, the trend for total systemic treatments has not significantly increased (P=0.5). Frequency of phototherapy treatments significantly decreased from 1993 to 2010 (P<0.001). Since the introduction of biologics in 2002, their frequency has significantly increased, becoming the most frequently used treatment from 2008-2010 (P<0.0001). LIMITATIONS: Severity of psoriasis was not recorded in the NAMCS and NHAMCS. CONCLUSIONS: The frequency of systemic treatments to treat psoriasis has not significantly increased from 1993 to 2010. Despite the introduction of biologics, it appears that little progress has been made in reducing under-treatment of moderate-to-severe psoriasis.

Systematic review of combination therapies for mycosis fungoides.

BACKGROUND: A variety of therapeutic options are available for mycosis fungoides, the most prevalent subtype of cutaneous T cell lymphomas, but thus far, no regimen has been proven to be curative. A combination of treatments is a well-established strategy to increase the therapeutic efficacy. However, data from clinical trials analyzing such combinations for the treatment of mycosis fungoides are scarce. OBJECTIVE: To analyze the available evidence on combination therapies with emphasis on the combination of psoralen with UVA phototherapy (PUVA), interferon-alpha and bexarotene with another treatment. METHODS: Systematic literature review of the databases Embase, Cochrane, Medline, and Medline in Process. RESULTS: Combination of PUVA with interferon-alpha or retinoids did not result in an increased overall response rate. Addition of methotrexate but not retinoids to interferon-alpha may increase the overall response rate. Bexarotene was investigated in one trial each with vorinostat, methotrexate or gemcitabine, whereby only methotrexate possibly enhanced the effect of bexarotene. CONCLUSION: For mycosis fungoides, no combination treatment has been demonstrated to be superior to monotherapy. Based on our analysis, we conclude that in certain clinical situations, patients may benefit from a combination of PUVA with interferon-alpha or a retinoid or a combination of the latter two. Furthermore, patients in advanced stages may benefit from the combination of methotrexate and interferon-alpha or bexarotene. Finally, the combination of bexarotene with either vorinostat or gemcitabine did not increase the overall response rate but resulted in more pronounced side effects and cannot be recommended.

Topical retinoids in skin ageing: a focused update with reference to sun-induced epidermal vitamin A deficiency.

Vitamin A is an important constituent of the epidermis, where it plays a crucial role in epidermal turnover. A deficiency of epidermal vitamin A may be the consequence of nutritional vitamin A deficiency, exposure to sunlight or any UV source, oxidative stress or chronological ageing. As a consequence, any treatment aiming at increasing epidermal vitamin A would exert a protective effect against these deleterious conditions. Retinoids may counteract some deleterious actions of UV radiation by physical and biological mechanisms. Topical natural retinoic acid precursors such as retinaldehyde or retinol are less irritant than acidic retinoids and may prevent epidermal vitamin A deficiency due to nutritional deficiency, exposure to sunlight or any condition leading to free radical production. Retinoids may be combined with other compounds with complementary actions against ageing, nutritional deficiency and cancer, such as antioxidants, to potentiate their beneficial effects in the skin.

Treatment of acne vulgaris during pregnancy and lactation.

Acne vulgaris is a common problem encountered by pregnant and lactating women. Unfortunately, in clinical practice, treatment is often not optimized as a result of the lack of safety data and unified recommendations on the use of the various anti-acne therapies. In this narrative review, current data on their safety is summarized. We recommend the use of topical medications as first-line treatment for acne vulgaris in pregnant and lactating women. These include antibiotics (erythromycin, clindamycin, metronidazole and dapsone), benzoyl peroxide, azelaic acid and salicylic acid. Oral agents and/or light-based therapy may be considered as second-line treatment. The former consists of oral macrolides (erythromycin and azithromycin), cephalexin or zinc compounds. Blue-violet or red light phototherapy may be used as monotherapy or in addition to topical and/or oral therapies. Hormonal therapy, antibiotics consisting of tetracyclines, co-trimoxazole and fluoroquinolones, and both oral and topical retinoids should be avoided.

Vitamin A and its derivatives in experimental photocarcinogenesis: preventive effects and relevance to humans.

The 1925 classical observation that vitamin A deficiency leads to squamous metaplasia and epithelial keratinization, coupled with the later finding that excess vitamin A inhibits keratinization of chick embryo skin, set the foundation for the potential therapeutic use of retinoids in cutaneous conditions of keratinization. Significant progress has since been made understanding the molecular biology, biochemistry, pharmacology, and toxicology of vitamin A and its derivatives, collectively named retinoids. Natural and synthetic retinoids are now routinely used to treat acne, psoriasis, skin keratinization disorders, and photodamage. Retinoids also inhibit tumor formation and skin cancer development in experimental systems and in humans. Retinol and retinyl palmitate (RP) are found in cosmetic products and in foods and dietary supplements, which are all considered safe, by inclusion in the Generally Recognized as Safe Substances Database. However, the safety of topical retinoids was questioned in one publication and in a recent National Toxicology Program report of RP-containing topical preparations, suggesting the possible earlier onset of ultraviolet-induced squamous cell carcinomas in the hairless mouse photocarcinogenesis model. This suggestion contradicts a large body of data indicating that topical retinoids are chemoprotective in humans, and it was immediately challenged by new reviews on the safety of RP in general and within sunscreens. This paper will review the preclinical and clinical data supporting the safety and chemopreventive activity of retinoids, with an emphasis on RP, and will examine the experimental systems used to evaluate the safety of topical vitamin A preparations in order to provide perspective relative to human skin.

Systemic retinoids in the management of ichthyoses and related skin types.

The term retinoid includes both natural and synthetic derivatives of vitamin A. Retinoid-containing treatments have been used since ~1550BC by the early Egyptians. Treatment of ichthyosiform disorders with retinoids dates back at least to the 1930s. Early use of high-dose vitamin A demonstrated efficacy, but because vitamin A is stored in the liver, toxicity limited usefulness. Interest turned to synthetic retinoids in an effort to enhance efficacy and limit toxicity. Acetretin, isotretinoin and, in the past etretinate, have provided the most effective therapy for ichthyosiform conditions. They have been used for a variety of ages, including in newborns with severe ichthyosis and for decades in some patients. Careful surveillance and management of mucous membrane, laboratory, skeletal, and teratogenic side effects has made systemic retinoids the mainstay of therapy for ichthyosis and related skin types.