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1.
Efficacy of Folic Acid and Vitamin B12 Replacement Therapies in the Reduction of Adverse Effects of Isotretinoin: A Randomized Controlled Trial.
Ghiasi, M, Mortazavi, H, Jafari, M
Skinmed. 2018;(4):239-245
Abstract
Previous studies have reported elevated homocysteine levels and folic acid and/or vitamin B12 deficiencies after isotretinoin therapy, which increase the risk of cardiovascular and neuropsychiatric disorders. Homocysteine is metabolized in the liver, a process requiring folate and vitamin B12. We conducted a randomized controlled trial to investigate whether folate and vitamin B12 replacement therapy with isotretinoin would be useful for preventing hyperhomocysteinemia. A total of 66 patients with acne were randomized into two groups: group A took isotretinoin, folic acid, and vitamin B12, whereas group B took isotretinoin alone. Treatment was continued for 2 months. Blood homocysteine, folic acid, and vitamin B12 levels were measured before and after treatment. In group A, a significant decrease in homocysteine level was observed after treatment (P=.0004), although it was still within the normal range. Folic acid and vitamin B12 levels significantly increased (P=.0026 and P=.0002, respectively). In group B, no significant changes were observed in the levels of homocysteine and vitamin B12, but folic acid levels decreased significantly (P=.02). We concluded that folic acid and vitamin B12 supplementation during isotretinoin therapy could be useful for preventing folate deficiency and improving blood homocysteine levels; this might as a result reduce the risks for cardiovascular and neuropsychiatric disorders in patients taking isotretinoin.
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2.
Inherited Nonsyndromic Ichthyoses: An Update on Pathophysiology, Diagnosis and Treatment.
Vahlquist, A, Fischer, J, Törmä, H
American journal of clinical dermatology. 2018;(1):51-66
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Abstract
Hereditary ichthyoses are due to mutations on one or both alleles of more than 30 different genes, mainly expressed in the upper epidermis. Syndromic as well as nonsyndromic forms of ichthyosis exist. Irrespective of etiology, virtually all types of ichthyosis exhibit a defective epidermal barrier that constitutes the driving force for hyperkeratosis, skin scaling, and inflammation. In nonsyndromic forms, these features are most evident in severe autosomal recessive congenital ichthyosis (ARCI) and epidermolytic ichthyosis, but to some extent also occur in the common type of non-congenital ichthyosis. A correct diagnosis of ichthyosis-essential not only for genetic counseling but also for adequate patient information about prognosis and therapeutic options-is becoming increasingly feasible thanks to recent progress in genetic knowledge and DNA sequencing methods. This paper reviews the most important aspects of nonsyndromic ichthyoses, focusing on new knowledge about the pathophysiology of the disorders, which will hopefully lead to novel ideas about therapy.
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3.
Can an app supporting psoriasis patients improve adherence to topical treatment? A single-blind randomized controlled trial.
Svendsen, MT, Andersen, F, Andersen, KH, Andersen, KE
BMC dermatology. 2018;(1):2
Abstract
BACKGROUND Topical corticosteroid or corticosteroid/calcipotriol preparations are recommended first-line topical treatments of psoriasis, but a main cause for the lack of efficacy of topical treatments is considered low rates of adherence to topical drugs. Patient support by the use of applications (apps) for smartphones is suggested to improve medical adherence. METHODS/DESIGN Design: An investigator-initiated, single-center, single-blind, parallel-group, phase-4 clinical superiority randomized controlled trial (RCT). PARTICIPANTS 134 patients 18 to 75 years of age with mild-to-moderate psoriasis, who are capable of reading English language, own a smartphone, and are candidates for the study drug calcipotriol and betamethasone dipropionate (Cal/BD) cutaneous foam once daily prn (pro re nata). INTERVENTION A 28-day adherence-supporting app providing compulsory daily treatment reminders that pop-up on the smartphone screen with a short alert sound. The app synchronizes through Bluetooth® to an electronic monitor (EM) attached to the medication canister. The EM contains a chip registering the amount of foam, day and time the patient use the foam dispenser. The information is displayed in a diary that shows the amount of Cal/BD cutaneous foam used and the number of applied treatment sessions. The app has an optional diary with the patient's rating of symptoms. Non-intervention: Use of Cal/BD cutaneous foam and EM without the app. All participants are prescribed Cal/BD cutaneous foam prn for the entire study period. Primary outcome obtained in week 4: rates of adherence measured by patient report, weight of medication canisters, and number of treatment sessions measured by the EM. Secondary outcomes obtained at baseline, weeks 4, 8, and 26: Lattice System Physician's Global Assessment (LS-PGA) and Dermatology Quality of Life Index (DLQI). DISCUSSION This trial tests of whether an app can improve rates of adherence to a topical antipsoriatic drug. If the app improves rates of adherence and reduces the burden of psoriasis in a clinically significant way, the app could easily be implemented as a standard routine of care in the clinic. TRIAL REGISTRATION NCT02858713 , registered on August 3, 2016. EudraCT number 2016-002143-42.
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Efficacy and Safety of Adapalene 0.3%/Benzoyl Peroxide 2.5% Gel Plus Oral Doxycycline in Subjects With Severe Inflammatory Acne Who Are Candidates for Oral Isotretinoin.
Del Rosso, JQ, Stein Gold, L, Johnson, SM, Rueda, MJ, Baldwin, H, Lain, EL, Landis, M, Rendon, M, Tanghetti, E, Weiss, J
Journal of drugs in dermatology : JDD. 2018;(3):264-273
Abstract
INTRODUCTION Acne treatment guidelines suggest a combination approach with topical therapy including a topical retinoid, benzoyl peroxide and an oral antibiotic, or oral isotretinoin (OI), as first-line treatment options for severe acne vulgaris (AV). This study evaluated the efficacy and safety of a daily regimen of 0.3% adapalene and 2.5% benzoyl peroxide (0.3% A/BPO) gel and oral doxycycline 100 mg twice daily in severe (nonnodulocystic, non-conglobate) inflammatory AV.
METHODS This was a phase 4, 12-week, single-arm, openlabel, multi-center investigational study. Subjects (males and females, 12 or older, with severe inflammatory AV, Investigator Global Assessment [IGA] 4, and less than equal to 4 nodulocystic lesions, n=186) were considered OI candidates at baseline by the investigator. OI candidacy was re-evaluated at each study visit. Efficacy endpoints included inflammatory lesion (IL) reduction (week 12), IGA success (defined as IGA 0 [Clear] or 1 [Almost Clear], weeks 4, 8, and 12), percent reduction in lesions (weeks 4, 8, and 12), and subject questionnaires (week 12). Safety assessments included adverse events (AEs) and tolerability.
RESULTS Mean IL counts were significantly reduced from baseline to the end of the study (mean [SD]; baseline, 44.8 (21.73); week 12, 14.8 (16.11); mean percent reduction, 66.2% [30.47]; P less than .0001). By week 12, 37.1% of subjects achieved IGA Success (n=69, P less than .0001). Most subjects self-reported at least moderate improvement in AV (90.2%), and were "Satisfied" or "Very Satisfied" with the study treatment overall (83.2%). 41.9% of the subjects were no longer considered by their investigator to be OI candidates at week 4. At 12 weeks, only 19.9% were still considered OI candidates.
CONCLUSION 0.3% A/BPO + DOX is an effective and safe treatment option for severe inflammatory AV, before starting OI treatment, or as an alternative when OI cannot be used. ClinicalTrials.gov identifier: NCT02899000
J Drugs Dermatol. 2018;17(3):264-273.
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5.
A Review on Pityriasis Rubra Pilaris.
Wang, D, Chong, VC, Chong, WS, Oon, HH
American journal of clinical dermatology. 2018;(3):377-390
Abstract
Pityriasis rubra pilaris (PRP) is an idiopathic, papulosquamous inflammatory dermatosis. It is characterized by hyperkeratotic follicular papules coalescing into orange-red scaly plaques, islands of sparing, and palmoplantar keratoderma. PRP can be subdivided into six clinical subtypes according to Griffiths' classification, based on age of onset, disease extent, prognosis, and other associated features. The sixth subtype of PRP occurs in individuals affected by HIV infection, and retroviral screening in all de novo cases of PRP is advised. Other reported associations include various infections, autoimmunity, drugs, and malignancies, although the true significance of these is still unclear. The genetic basis for familial cases, most commonly categorized under the fifth subtype, has been mapped to gain of function mutations in the caspase recruitment domain family, member 14 (CARD14) gene. Treatment of PRP remains a challenge to this day due to a paucity of high-quality evidence. Therapeutic regimens have been guided mostly by case reports and case series, with the mainstay of treatment being oral retinoids. Recently, biologics have emerged as a promising treatment for PRP. We present a review of the clinicopathologic features, pathogenesis, associated disorders, and treatment of PRP, with an emphasis and critical appraisal of the existing literature on the latter.
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6.
Tatami Mats: A Source of Pitted Keratolysis in a Martial Arts Athlete?
Balić, A, Bukvić Mokos, Z, Marinović, B, Ledić Drvar, D
Acta dermatovenerologica Croatica : ADC. 2018;(1):68-70
Abstract
Dear Editor, Pitted keratolysis (PK), also known as keratosis plantaris sulcatum, is a non-inflammatory, bacterial, superficial cutaneous infection, characterized by many discrete superficial crateriform ''pits'' and erosions in the thickly keratinized skin of the weight-bearing regions of the soles of the feet (1). The disease often goes unnoticed by the patient, but when it is noticed it is because of the unbearable malodor and hyperhidrosis of the feet, which are socially unacceptable and cause great anxiety to many of the patients. PK occurs worldwide, with the incidence rates varying based on the environment and occupation. The prevalence of this condition does not differ significantly based on age, sex, or race. People who sweat profusely or wash excessively, who wear occlusive footwear, or are barefoot especially in hot and humid weather are extremely prone to this condition (2). Physicians commonly misdiagnose it as tinea pedis or plantar warts. Treatment is quite simple and straightforward, with an excellent expected outcome if treated properly. We report a case of a 32-year-old male patient with skin changes of approximately one-year duration diagnosed as plantar verrucae, who was referred to our Department for cryotherapy. The patient presented with asymptomatic, malodorous punched-out pits and erosions along with hyperkeratotic skin on the heel and metatarsal region of the plantar aspect of both feet. The arches, toes, and sides of the feet were spared (Figure 1). Except for these skin changes, the patient was healthy and denied any other medical issues. He was an athlete active in martial arts and had a history of sweating of feet and training barefoot on the tatami mat for extended periods of time. The diagnosis of PK was established based on the clinical findings (crateriform pitting and malodor), negative KOH test for hyphae, and a history of prolonged sweating in addition to contact of the skin with tatami mats, which are often a source of infection if hygiene measures are not adequately implemented. Swabs could have been helpful to identify causative organisms, but they were not crucial for the diagnosis and treatment. The patient was prescribed with general measures to prevent excessive sweating (cotton socks, open footwear, and proper hygiene), antiseptic potassium permanganate foot soaks followed by clindamycin 1% and benzoyl peroxide 5% in a gel vehicle twice daily. At the one-month follow-up visit, the skin changes, hyperhidrosis, and malodor were entirely resolved (Figure 2). Pitted keratolysis is common among athletes (3,4). The manifestations of PK are due to a superficial cutaneous infection caused by several bacterial Gram-positive species including Corynebacterium species, Kytococcus sedentarius, Dermatophilus congolensis, Actynomices keratolytica, and Streptomyces that proliferate and produce proteinase and sulfur-compound by-products under appropriate moist conditions (5-7). Proteinases digest the keratin and destroy the stratum corneum, producing the characteristic skin findings, while sulfur compounds (sulfides, thiols, and thioesters) are responsible for the malodor. Athletes and soldiers who wear occlusive footwear for prolonged periods of time or even barefooted people that sweat extensively and spend time on wet surfaces such as laborers, farmers, and marine workers are more prone to this problem (3,4,8-11). Martial arts athletes are at greater risk of skin infections due to the constant physical contact that can lead to transmission of viral, bacterial, and fungal pathogens directly but also indirectly through contact with the mat and the skin flora of an another infected individual. A national survey of the epidemiology of skin infections among US high school athletes conducted by Ashack et al. supported the prevalent theory that contact sports are associated with an increased risk of skin infections. In this study, wrestling had the highest skin infection rate of predominantly bacterial origin (53.8%), followed by tinea (35.7%) and herpetic lesions (6.7%), which is consistent with other literature reporting (12). Being barefoot on the tatami mat in combination with excessive sweating and non-compliance with hygiene measures makes martial arts athletes more susceptible to skin infections, including PK. The diagnosis is clinical, by means of visual examination and recognition of the characteristic odor. Dermoscopy can be useful, revealing abundant pits with well-marked walls that sometimes show the bacterial colonies (13). Cultures, if taken, show Gram-positive bacilli or coccobacilli. Because of the ease of diagnosis on clinical findings, biopsy of pitted keratolysis is rarely performed. Skin scraping is often performed to exclude tinea pedis, which is one of the main differential diagnosis, the others including verrucae, punctate palmoplantar keratoderma, keratolysis exfoliativa, circumscribed palmoplantar hypokeratosis, and basal cell nevus syndrome. If unrecognized and left untreated, skin findings and smelly feet can last for many years. Sometimes, if unrecognized, PK can be mistreated with antifungals, or even with aggressive treatment modalities such as cryotherapy. Appropriate treatment includes keeping feet dry with adequate treatment of hyperhidrosis, preventive measures, and topical antibiotic therapy. Topical forms of salicylic acid, sulfur, antibacterial soaps, neomycin, erythromycin, mupirocin, clindamycin and benzoyl peroxide, clotrimazole, imidazoles, and injectable botulinum toxin are all successful in treatment and prevention of PK (14,15). Topical antibiotics are the first line of medical treatment, among which fusidic acid, erythromycin 1% (solution or gel), mupirocin 2%, or clindamycin are the most recommended (14). As in our case, a fixed combination of two approved topical drugs - clindamycin 1%-benzoyl peroxide 5% gel, had been already demonstrated by Vlahovich et al. as an excellent treatment option with high adherence and no side-effect (16). The combined effect of this combination showed significantly greater effect due to the bactericidal and keratolytic properties of benzoyl peroxide. Additionally, this combination also lowers the risk of resistance of causative microorganisms to clindamycin. Skin infections are an important aspect of sports-related adverse events. Due to the interdisciplinary nature, dermatologists are not the only ones who should be aware of the disease, but also family medicine doctors, sports medicine specialists, and occupational health doctors who should educate patients about the etiology of the skin disorder, adequate prevention, and treatment. Athletes must enforce the disinfecting and sanitary cleaning of the tatami mats and other practice areas. Keeping up with these measures could significantly limit the spread of skin infections that can infect athletes indirectly, leading to significant morbidity, time loss from competition, and social anxiety as well.
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A smartphone application supporting patients with psoriasis improves adherence to topical treatment: a randomized controlled trial.
Svendsen, MT, Andersen, F, Andersen, KH, Pottegård, A, Johannessen, H, Möller, S, August, B, Feldman, SR, Andersen, KE
The British journal of dermatology. 2018;(5):1062-1071
Abstract
BACKGROUND Adherence to topical psoriasis treatments is low, which leads to unsatisfactory treatment results. Smartphone applications (apps) for patient support exist but their potential to improve adherence has not been systematically evaluated. OBJECTIVES To evaluate whether a study-specific app improves adherence and reduces psoriasis symptoms compared with standard treatment. METHODS We conducted a randomized controlled trial (RCT, clinicaltrials.gov registration: NCT02858713). Patients received once-daily medication [calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam] and were randomized to no app (n = 66) or app intervention (n = 68) groups. In total, 122 patients (91%) completed the 22-week follow-up. The primary outcome was adherence, which was defined as medication applied ≥ 80% of days during the treatment period and assessed by a chip integrated into the medication dispenser. Secondary outcomes were psoriasis severity measured by the Lattice System Physician's Global Assessment (LS-PGA) and quality of life, measured using the Dermatology Life Quality Index (DLQI) at all visits. RESULTS Intention-to-treat analyses using regression was performed. More patients in the intervention group were adherent to Cal/BD cutaneous foam than those in the nonintervention group at week 4 (65% vs. 38%, P = 0·004). The intervention group showed a greater LS-PGA reduction than the nonintervention group at week 4 (mean 1·86 vs. 1·46, P = 0·047). A similar effect was seen at weeks 8 and 26, although it did not reach statistical significance. CONCLUSIONS This RCT demonstrates that the app improved short-term adherence to Cal/BD cutaneous foam treatment and psoriasis severity.
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Ixekizumab treatment shows a neutral impact on cardiovascular parameters in patients with moderate-to-severe plaque psoriasis: Results from UNCOVER-1, UNCOVER-2, and UNCOVER-3.
Egeberg, A, Wu, JJ, Korman, N, Solomon, JA, Goldblum, O, Zhao, F, Mallbris, L
Journal of the American Academy of Dermatology. 2018;(1):104-109.e8
Abstract
BACKGROUND The impact of ixekizumab treatment for psoriasis on cardiovascular-related parameters in patients is unknown. OBJECTIVE To investigate cardiovascular-related parameters in patients with psoriasis treated with ixekizumab. METHODS In phase 3 trials, patients with moderate-to-severe psoriasis were randomized and treated with placebo, ixekizumab, or etanercept during the induction period (weeks 0-12; UNCOVER-1, UNCOVER-2, and UNCOVER-3). At week 12, responders were rerandomized to receive placebo or ixekizumab through the maintenance period (weeks 12-60; UNCOVER-1 and UNCOVER-2). Laboratory measures (fasting lipid profiles, glucose level, or high-sensitivity C-reactive protein [hsCRP] level), weight, blood pressure, and electrocardiograms were obtained through 60 weeks. RESULTS Baseline parameters were within normal ranges with the exception of elevated triglyceride and hsCRP levels. After maintenance dosing, no significant changes were observed versus placebo for total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, triglyceride, apolipoprotein A1, apolipoprotein B, or fasting glucose levels or for systolic/diastolic blood pressure at 60 weeks. Importantly, low-density lipoprotein-to-high-density lipoprotein ratios remained stable during the induction and maintenance periods. HsCRP concentrations were significantly reduced versus placebo at 12 weeks and remained reduced at 60 weeks, although not significantly. Although transient changes were observed for some parameters during the induction period, these changes did not persist into the maintenance period. LIMITATIONS A lack of echocardiogram evaluations. CONCLUSIONS Ixekizumab had a neutral impact on cardiovascular-related parameters in patients with psoriasis.
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Low-dose calcipotriol can elicit wound closure, anti-microbial, and anti-neoplastic effects in epidermolysis bullosa keratinocytes.
Guttmann-Gruber, C, Tockner, B, Scharler, C, Hüttner, C, Common, JE, Tay, ASL, Denil, SLIJ, Klausegger, A, Trost, A, Breitenbach, J, et al
Scientific reports. 2018;(1):13430
Abstract
Recessive dystrophic epidermolysis bullosa (RDEB) patients suffer from chronic and repeatedly infected wounds predisposing them to the development of aggressive and life-threatening skin cancer in these areas. Vitamin D3 is an often neglected but critical factor for wound healing. Intact skin possesses the entire enzymatic machinery required to produce active 1-alpha,25-dihydroxyvitamin D3 (calcitriol), underscoring its significance to proper skin function. Injury enhances calcitriol production, inducing the expression of calcitriol target genes including the antimicrobial peptide cathelicidin (hCAP18), an essential component of the innate immune system and an important wound healing factor. We found significantly reduced hCAP18 expression in a subset of RDEB keratinocytes which could be restored by calcipotriol treatment. Reduced scratch closure in RDEB cell monolayers was enhanced up to 2-fold by calcipotriol treatment, and the secretome of calcipotriol-treated cells additionally showed increased antimicrobial activity. Calcipotriol exhibited anti-neoplastic effects, suppressing the clonogenicity and proliferation of RDEB tumor cells. The combined wound healing, anti-microbial, and anti-neoplastic effects indicate that calcipotriol may represent a vital therapeutic option for RDEB patients which we could demonstrate in a single-patient observation study.
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10.
Cyclosporine for corticosteroid-refractory acute generalized exanthematous pustulosis due to hydroxychloroquine.
Castner, NB, Harris, JC, Motaparthi, K
Dermatologic therapy. 2018;(5):e12660
Abstract
Acute generalized exanthematous pustulosis most often manifests 1-2 days following exposure to a characteristic drug, such as aminopenicillins, calcium-channel blockers, or terbinafine. Recovery is usually rapid following drug withdrawal, and systemic corticosteroids represent the historic treatment of choice. Herein, acute generalized exanthematous pustulosis incited by hydroxychloroquine is briefly reviewed: a prolonged latency and recalcitrance to corticosteroids are noteworthy. In this unique context, cyclosporine tapered over several months is an effective therapeutic option.