Christine Rønneberg Mehren MD,a Anders Clemmensen MD,a Anne Boe-Hansen Dall MD,a
Peter Philipsen PhD,a and Robert Gniadecki MDa,b
BACKGROUND: The negative impact of psoriasis on health related quality of life (HRQoL) has been well documented. An unanswered question is the relative contribution of different manifestations of psoriasis (skin, joint, nail involvement) to HRQoL.
AIM: To assess the relative contribution of the different symptom domains on HRQoL in psoriasis.
METHODS: 165 psoriasis patients (41.2 % with psoriasis arthritis (PsA)) were enrolled in a single-center cohort-study. For the assessment of HRQoL, patients completed EuroQoL (EQ-5D), the Short Form 36-item Health Survey (SF-36), the Health Assessment Questionaire (HAQ), and Dermatological Life Quality Index (DLQI) questionnaires. Multiple regression analysis was applied to determine the contribution of the measured parameters to the EuroQoL score (used as a reference measure for overall HRQoL).
RESULTS: Psoriasis arthritis (PsA) patients showed a higher impairment in all HRQoL measures than the patients without PsA. PASI, number of affected joints (PsA-score), DLQI and HAQ were significant predictors of HRQoL (R2=0.57). HAQ was the dominant contributor to HRQoL, both in patients with PsA and without PsA (partial eta 0.23 and 0.28, respectively.) Final model with improved R2 (0.61) was obtained by backward regression analysis, and included 6 parameters: PASI, PsA-score, and three questions from HAQ and one question from DLQI questionnaire.
CONCLUSION: Musculoskeletal symptoms are an essential component of HRQoL in psoriasis, even in patients without active PsA. A model consisting of PASI, PsA-score, and 4 questions derived from DLQI and HAQ seems to reflect total HRQoL impairment in psoriasis. This finding may further optimize drug therapy in psoriasis.
J Drugs Dermatol. 2014;13(3):246-250.
Alan Menter MD,a Kim A. Papp MD PhD FRCPC,b Huaming Tan PhD,c Steve Tyring MD PhD,dRobert Wolk MD PhD DSc,c and Marjorie Buonanno MSN RNc
INTRODUCTION: Tofacitinib is a novel, oral Janus kinase inhibitor currently under investigation for plaque psoriasis.
METHODS: This exploratory analysis of a Phase IIb, 12-week, dose-ranging study (clinicaltrials.gov identifier: NCT00678210) evaluated tofacitinib efficacy in four body regions of patients with moderate-to-severe chronic plaque psoriasis. Patients (n=197) were randomized to tofacitinib 2, 5, or 15 mg, or placebo, twice daily (BID). Psoriasis Area and Severity Index (PASI) score, body surface area values and change from baseline to week 12 were measured according to body region (head/neck, upper limbs, trunk and lower limbs). Change in Target Plaque Severity Score (TPSS) from baseline to week 12 was measured according to typically responsive as well as non-responsive treatment areas.
RESULTS: At week 12, mean improvements in PASI and body surface area values were significantly greater with tofacitinib doses vs placebo across all four body regions measured (P<0.0001). TPSS in responsive areas decreased (improved) with tofacitinib 2, 5, and 15 mg BID vs placebo: -4.35, -4.79 and -6.32, vs -2.06, respectively (P<0.0001). In non-responsive areas, TPSS decreased with tofacitinib 2, 5, and 15 mg BID vs placebo: -3.74, -4.60 and -6.15, vs -2.23, respectively (P<0.01).
CONCLUSION: Short-term (12-week) treatment with oral tofacitinib produced clinical improvement across all body regions assessed in patients with moderate-to-severe plaque psoriasis, including areas typically non-responsive to treatment.
J Drugs Dermatol. 2014;13(3):252-256.
Mototsugu Fukaya MDa and Hajime Kimata MD PHDb
BACKGROUND: Though topical corticosteroids (TC) are used for treating atopic dermatitis (AD) as a standard, there exist several problems including topical steroid addiction (TSA) or Red skin syndrome. Moreover, the number of patients, who refrain from using TC because of steroid-phobia, is increasing. Recently, topical PPAR alpha ligand application has been reported to improve experimental allergic dermatitis. The purpose of this study was to investigate the short-term efficacy and safety of topical clofibrate, one of PPAR alpha ligand, in such steroid-phobic patients with AD.
METHODS: This study was conducted as a double-blind design to investigate the effects of random administration of topical clofibrate and base (placebo) on skin manifestation and blood parameters of patients for 2 weeks. Severity was digitized using severity scoring systems for atopic dermatitis by the Japanese Dermatological Association (SSS-JDA) before and after two weeks. Subjective severity of patients was evaluated using visual analog scale (Pt-VAS). Serum thymus and activation-regulated chemokine (TARC) and immunoglobulin E (IgE) were also investigated.
RESULTS: Twenty patients were enrolled, and 19 of 20 patients completed the study. In 19 patients, the value of severity score using SSS-JDA was decreased significantly after administration of topical clofibrate (P=0.001). Subjective evaluation using Pt-VAS (P=0.008) and serum TARC levels (P=0.03) were also significantly decreased after two weeks of topical clofibrate. There was not a significant difference in serum IgE levels. No adverse effect was observed.
CONCLUSIONS: Topical clofibrate is useful for patients with AD especially who are reluctant to use topical steroids.
J Drugs Dermatol. 2014;13(3):259-263.
Staci Brandt PA-C MBA MSa and Peter Lio MDb
Sensitive skin is a common skin complaint frequently associated with skin diseases or adverse reactions to cosmetic products. Manufacturers have produced numerous products targeted for patients with sensitive skin and frequently label these products as being hypoallergenic. This term implies that the product may be less likely to cause an allergic reaction and be better suited for those with sensitive skin. However, there is no federal regulatory definition of this term and products may not have clinical support of their claim. Patch testing ingredients is frequently done to identify potential irritants; however, patch-testing product formulations may provide more realistic expectations about potential skin sensitivity and help support claims of hypoallergenicity. Ten skincare products were assessed for their sensitizing potential and hypoallergenicity in 14 repeat insult patch test clinical studies, involving over 2,000 subjects. In these studies, the products were deemed to be hypoallergenic if there was no evidence of sensitization or allergic reactions. The results from these trials demonstrated that all ten products were well tolerated, showed no sensitization or allergic reactions, and support claims of hypoallergenicity.
J Drugs Dermatol. 2014;13(3):264-266.
Miriam S. Bettencourt MD
BACKGROUND: Ingenol mebutate gel is a topical field treatment for actinic keratosis (AK) approved for a 2- or 3-day duration of application.
OBJECTIVE: This chart review examined the efficacy and safety of ingenol mebutate gel for treatment of AK in patients from a community dermatology practice.
METHODS: A retrospective chart review was conducted for all patients with AK treated with ingenol mebutate gel.
RESULTS: A total of 135 patients with a prolonged history of AK were treated from April 2012 to January 2013. The majority received cryosurgery to all visible lesions, followed 2 weeks later by ingenol mebutate; areas treated with ingenol mebutate were typically >25 cm2 in size. Local skin reactions, consisting of mild to moderate erythema and flaking/scaling, were significantly improved by 1 week after peak inflammation and were not treated in most patients. At 1 to 4 months after treatment of AKs on the face, nearly all patients (99%) achieved ≥75% clearance of baseline and emergent AKs. After treatment of AKs on the scalp or forearm and/or hand, >80% of patients demonstrated ≥75% clearance.
LIMITATIONS: This was a retrospective chart review of patients from a single practice.
CONCLUSION: Ingenol mebutate is an effective, well-tolerated topical treatment for AK in sun-damaged skin.
J Drugs Dermatol. 2014;13(3):269-273.
Enzo Emanuele MD PhD,a James M. Spencer MD MS,b and Martin Braun MDc
Non-melanoma skin cancers (NMSC) are the most common human neoplasms and continue to represent an important public health issue with greater than one million cases diagnosed each year. The primary factor contributing to the molecular pathogenesis of NMSC is unprotected skin exposure to ultraviolet (UV) radiation, ie, UVA (wavelength: 315-400 nm) and UVB rays (wavelength: 280-315 nm) with additional albeit less damaging factors of infrared radiation (wavelength: ~750 nm -1 mm) and environmental pollutants. Skin carcinogenesis by DNA damage is the current predominant paradigm of UV toxicity, which may be caused by direct damaging effects of energy deposited by photons or indirect oxidative action of short-lived reactive oxygen species (ROS) formed from water that reacts with biomacromolecules. UV rays are capable to induce direct both DNA damages, mainly consisting in the formation of helix-distorting photoproducts such as cyclobutane pyrimidine dimers (CPDs), as well as oxidative damage to DNA bases, including the formation of 8-oxo-7, 8-dihydro-2’-deoxyguanosine (8OHdG). Growing evidence also suggests that the efficiency of DNA repair after exposure to UV radiation is crucially dependent on the levels of oxidative protein damage, including but not limited to DNA repair proteins. Besides DNA lesions, UV-induced oxidative stress can indeed result in carbonylation of proteins, a major form of irreversible protein damage that inactivates their biological function. Interestingly, microorganisms characterized by extreme resistance to UV rays have an intrinsic capacity to protect their proteome, rather than genome, from radiation-induced damage, suggesting that protein carbonylation (PC) may serve as a reliable and innovative biomarker of UV photodamage. This review discusses the main DNA and protein markers of UV-induced damage (eg, CPDs, 8OHdG, and PC) and their relationship and importance to the current understanding of skin carcinogenesis. The identification of key DNA and protein signatures of photodamage may represent a therapeutic target for translational studies of innovative therapeutic and preventive approaches for reducing both skin aging and the morbidity and mortality associated with NMSC.
J Drugs Dermatol. 2014;13(3):274-281.
Qiuhong Yang MS,a* Daniel J. Aires MD JD,b* Shuang Cai PhD,a Garth R. Fraga MD,b
Da Zhang MD,b Cicy Z. Li MS,b and M. Laird Forrest PhDa
BACKGROUND: Melanoma is a deadly skin cancer with rapidly rising incidence. While localized melanoma can be treated with excision, there are at present no similarly effective treatments for regional and distant disease, so survival rates are low. One problem is that melanoma is chemo-resistant, and most chemotherapy doses are limited by systemic toxicity. A method for delivering high-dose chemotherapy directly to tumors and draining lymph nodes could have the advantage of allowing much higher effective doses with reduced systemic exposure.
METHODS: Human melanoma cell line A-2058 tumor cells were injected into athymic mice. After tumors grew to 50~100 mm3 mice were divided into five groups: (1) nontreated (2) intravenous (i.v.) cisplatin, (3) i.v. nano hyaluronan-conjugated cisplatin (HA-Pt), (4) subcutaneous (s.c.) peri-tumoral cisplatin, and (5) s.c. peri-tumoral HA-Pt. All treatment groups received 3 weekly doses of 10 mg/kg.
RESULTS: Tumors grew progressively in all control, i.v. cisplatin, and s.c. cisplatin groups. Tumors showed a trend toward slower growth in the i.v. HA-Pt group, but all animals died or were euthanized per protocol within 3 weeks of treatment. Tumors showed shrinkage only in the subcutaneous peri-tumoral HA-cisplatin group; one of these mice appeared to be cured.
CONCLUSIONS: Peri-tumoral HA-cisplatin may be shown potential as a therapeutic option in treatment of certain types of melanoma.
J Drugs Dermatol. 2014;13(3):283-287.
Audrey S. Wang MD,a,b Olubukola Babalola BS,a,b and Jared Jagdeo MD MSa,b,c
Injectable poly-L-lactic acid (PLLA) is a biodegradable, biocompatible, synthetic polymer that acts as a scaffold to promote collagen formation and is FDA-approved for the correction of facial lipoatrophy in patients with human immunodeficiency virus (HIV) infection. The safety and efficacy of injectable PLLA for the treatment of HIV-associated facial lipoatrophy has been demonstrated in clinical studies and is accompanied by improvement in patient quality of life. Volumization of the mid-face is regarded as complex. The importance of respecting patient mid-face differences at rest and in motion was highlighted in a study that demonstrated effectiveness of silicone microdroplets (0.01 mL) in a depot manner to treat HIV patients with facial lipoatrophy. One of the challenges of facial volume rejuvenation with these techniques is preserving and enhancing dynamic facial movements after treatment. To address this challenge, we developed an injection technique termed “smile-and-fill.” In this case series, we describe three patients treated by this technique to restore the malar aspect of the mid-face with improvement several months post-treatment.
J Drugs Dermatol. 2014;13(3):288-290.
Kateřina Fajkošová MUDr,a Alena Machovcová MD PhD MBA,b,c Meltem Onder MD,d and Klaus Fritz MDd,e
In this study, the efficacy of non-contact, selective radiofrequency (RF) were evaluated for body contouring as non-invasive fat and circumferential reduction of the abdomen. 40 healthy (36 female, 4 male) subjects showing significant volume of subcutaneous fat tissue on the abdomen and waistline were included. Once a week for 30 minutes, 4 sessions were performed. The applicator was placed on a supplied spacer covering the treatment area. Maximum power was 200W, which induced heat in the fat and connective tissue layer. The homogeneity of heat distribution and temperature of the skin surface were controlled. The circumferential reduction was measured at the baseline and after the last treatment. The photographs and adverse effects were recorded. Participants completed the self-evaluation questionnaires and rated their level of satisfaction. All subjects tolerated the treatments well. The only side effect was mild to moderate erythema. 35 subjects finished the protocol as planned and 5 subjects dropped off due to events not related to the study. 32 subjects had a 1-13 cm decrease in abdominal circumference and 3 subjects did not show significant response (0-1 cm). Most likely, a very thin fat layer was the reason for lack of response (the non-responding group was the thinnest patient group). No significant differences were found between men and women. The average decrease of 4.93cm was calculated as a result of circumferential reduction statistical evidence. This study demonstrates that the selective RF system designed for contactless deep tissue heating is a painless, safe, and effective treatment for non-surgical body contouring and circumferential fat reduction.
J Drugs Dermatol. 2014;13(3):291-296.
Robert H. Gotkin MD FACSa,c and Deborah S. Sarnoff MD FAAD FACPb,c
Building upon the fractional CO2 technology incorporated into the first generation SmartXide DOT (DEKA / ElEn, SpA, Calenzano, Italy) introduced in the U.S. in 2008, a second generation SmartXide Quadro has recently been introduced. This is a versatile device that has the ability to combine fractional CO2 laser output for skin resurfacing with the synchronous delivery of bipolar radiofrequency (RF) energy for deeper, more diffuse heating. A pilot study was undertaken to demonstrate the safety and efficacy of the SmartXide Quadro, employing both fractional CO2 laser output combined with the synchronous delivery of radiofrequency energy for the treatment of facial rhytides and acne scars.
Ten patients, all women, six with facial rhytides and four with acne scarring, were treated with the SmartXide Quadro, a variably pulsed CO2 laser with Pulse Shape Design® technology, a microablative DOT scanner and synchronized bipolar RF emission. Each patient was treated with a single fractional CO2 laser-RF treatment; laser and RF parameters varied according to the severity of the rhytides or acne scars and were based upon both manufacturer-recommended settings and surgeon experience. Follow-up was at three days, one week, 2 weeks, and one month, three months, and six months after treatment. Results were judged by comparison of preoperative and post-operative photos evaluated by independent physicians, preoperative and post-operative grading by treating physicians, subjective evaluation of results by the patients themselves, and tabulation and categorization of adverse events (AEs).
The SmartXide Quadro variably pulsed CO2 laser with a microablative DOT scanner, with synchronous delivery of bipolar RF energy emission, proved to be both safe and effective in the treatment of facial rhytides and acne scars. The single treatment protocol was well tolerated and recovery was similar to fractional CO2 laser skin resurfacing alone. The AEs were minimal and no significant complications occurred.
J Drugs Dermatol. 2014;13(3):299-304.
Anne Goldsberry MD MBA,a Alan Dinner PhD, and C. William Hanke MD MPHa
Limonia acidissima or Hesperethusa crenulata is a common tree in Southeast Asia. It is indigenous to the Republic of Myanmar (formerly Burma) as well as India, Sri Lanka, Java, and Pakistan. In English, the common names for Limonia acidissima are sandalwood, wood-apple, elephant-apple, monkey fruit, and curd fruit tree. The plant has a number of different names in different languages including bal or bael in Assamese, bael in Bengali, kaitha in Hindi, belingai in Malaysia, and thanaka in Burmese. Unique to the Burmese people, thanaka has been used as a cosmetic product for over 2000 years. Mention of thanaka has been traced back to ancient Burmese lyrics, and relics of equipment used by ancient royalty to grind thanaka can be found in museums.1
J Drugs Dermatol. 2014;13(3):306-307.
Enzo Emanuele MD PhD,a James M. Spencer MD MS,b and Martin Braun MDc
The exposure to ultraviolet radiation (UVR) is a major risk factor for skin aging and the development of non-melanoma skin cancer (NMSC). Although traditional sunscreens remain the mainstay for the prevention of UVR-induced skin damage, they cannot ensure a complete protection against the whole spectrum of molecular lesions associated with UVR exposure. The formation of helix-distorting photoproducts such as cyclobutane pyrimidine dimers (CPD), as well as oxidative damage to DNA bases, including the formation of 8-oxo-7,8-dihydro-2’-deoxyguanosine (8OHdG) are among the key DNA lesions associated with photoaging and tumorigenesis. Besides DNA lesions, UVR-induced formation of free radicals can result in protein carbonylation (PC), a major form of irreversible protein damage that inactivates their biological function. This study compares a complex novel topical product (TPF50) consisting of three actives, ie, 1) traditional physical sunscreens (SPF 50), 2) a liposome-encapsulated DNA repair enzymes complex (photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]), and 3) a potent antioxidant complex (carnosine, arazine, ergothionine) to existing products. Specifically, we assessed the ability of TFP50 vs those of DNA repair and antioxidant and growth factor topical products used with SPF 50 sunscreens in preventing CPD, 8OHdG, and PC formation in human skin biopsies after experimental irradiations. In head-to-head comparison studies, TPF50 showed the best efficacy in reducing all of the three molecular markers. The results indicated that the three TPF50 components had a synergistic effect in reducing CPD and PC, but not 8OHdG. Taken together, our results indicate that TPF50 improves the genomic and proteomic integrity of skin cells after repeated exposure to UVR, ultimately reducing the risk of skin aging and NMSC.
J Drugs Dermatol. 2014;13(3):309-314.
Linda Stein Gold MD,a Leon Kircik MD,b Joseph Fowler MD,c Jerry Tan MD,d Zoe Draelos MD,e Alan
Fleischer MD,f Melanie Appell MD,g Martin Steinhoff MD,h Charles Lynde MD,i
Hong Liu MSc,j and Jean Jacovella MDk
on behalf of the Ivermectin Phase III Study Group
BACKGROUND: Treatments for papulopustular rosacea (PPR) are limited.
OBJECTIVE: To demonstrate the efficacy and safety of once-daily ivermectin 1% cream in subjects with moderate to severe PPR.
METHODS: Two identically designed, randomized, double-blind, controlled studies of ivermectin 1% cream (IVM 1%) or vehicle once daily for 12 weeks were conducted in subjects with moderate to severe PPR. Efficacy assessments were Investigator's Global Assessment (IGA) of disease severity and inflammatory lesion counts. Safety assessments included incidence of adverse events (AEs) and local tolerance parameters. Subjects evaluated their rosacea and completed satisfaction and quality of life (QoL) questionnaires.
RESULTS: In both studies, a greater proportion of subjects in the IVM 1% group achieved treatment success (IGA “clear” or “almost clear”): 38.4% and 40.1% vs 11.6% and 18.8% for vehicle (both P<.001), respectively. Ivermectin was superior to vehicle in terms of reduction from baseline in inflammatory lesion counts (76.0% and 75.0% vs 50.0% for both vehicle groups, respectively). For all endpoints, starting at week 4 and continuing through week 12, IVM 1% was statistically significantly superior (P<.001). Fewer subjects treated by IVM 1% reported dermatologic AEs, and a higher proportion of subjects were observed to have no skin dryness or itching compared to vehicle. Significantly more subjects receiving IVM 1% reported having an “excellent” or “good” improvement, along with an improved QoL.
CONCLUSION: Ivermectin 1% cream was effective and safe in treating inflammatory lesions of papulopustular rosacea.
J Drugs Dermatol. 2014;13(3):316-323.
Hilary Baldwin MD,a Diane Berson MD,b Maria Vitale MS,c Margarita Yatskayer MS,c
Nannan Chen PhD,c and Christian Oresajo MD PhDc,d
Rosacea is a condition most commonly characterized by central facial erythema and pupulopustules. There are highly effective drugs, both oral and topical, for papulopustular disease. At the present time, consistently effective pharmacologic therapy for erythematotelangiectatic rosacea is lacking. Patients whose papulopustular disease has been adequately treated are often still bothered by central facial erythema for which there is no adequate treatment short of laser and light. We present a study utilizing a novel topical composition evaluated for its ability to reduce background erythema remaining after adequate care of papulopustular disease. Patient, investigator and photographic evidence of erythema reduction was seen in 24/25 patients in this 8-week study.
J Drugs Dermatol. 2014;13(3):326-331.
Andrew Alexis MD MPH,a Selena R. Daniels PharmD MS,b Nathan Johnson MPH,c*
Farrah Pompilus MA,d Somali Misra Burgess PhD,e* and Julie C. Harper MDf
OBJECTIVE: Facial acne has been associated with impaired health-related quality of life, which is an essential patient outcome for evaluating the success of acne treatment. In consideration of the US Food and Drug Administration’s (FDA) new recommendations on patient reported outcome (PRO) measures, the objectives of this study were to (1) establish the need for a new PRO measure that assesses facial acne outcomes and satisfies the criteria set forth by the FDA and (2) develop the content of a new facial acne PRO measure appropriate for use in both adolescents and adults as well as adherent to the FDA PRO Guidance.
METHODS: A literature and PRO review, patient interviews (concept elicitation), and input from clinical experts were used to develop a conceptual framework for the outcomes deemed important to facial acne patients, and to construct items for a preliminary PRO measure: the Acne Symptom and Impact Scale (ASIS). Cognitive interviews were conducted to pilot test the ASIS.
RESULTS: A review of the literature and PROs revealed that, of the 34 measures identified, no suitable PRO measure for the population of interest was available. The conceptual framework comprised two main themes: symptoms and psychosocial impacts. Concept elicitation interviews included a diverse set of patients (n=48) with facial acne, of various ages: 12-17 years (n=15), 18-25 years (n=20), and 26-50 years (n=13). The most frequently reported symptoms were: pimples, oily skin, scabs/scars/marks, blackheads, acne, and whiteheads. The most frequently reported impacts were impacts on appearance, self-consciousness, annoyance, bothersomeness, mood, social criticism, embarrassment, confidence, and social withdrawal. These reported symptoms and impacts constituted the 15-item draft ASIS. The draft ASIS was modified following the analysis of 20 cognitive interviews, resulting in the current 17-item ASIS.
CONCLUSIONS: Results from both the concept elicitation and cognitive interviews demonstrated that the ASIS is content valid in both adolescents and adults with facial acne. The ASIS will undergo psychometric evaluation to further support its validity in both adolescents and adults with facial acne.
J Drugs Dermatol. 2014;13(3):333-340.
Ethan C. Levin MD,a Maya Debbaneh BA,b John Koo MD,a and Wilson Liao MDa
BACKGROUND: The efficacy of biologic therapy in treating plaque-type psoriasis is well documented. However, there is less data for use in other psoriasis subtypes, such as erythrodermic and generalized pustular psoriasis.
OBJECTIVE: We sought to review the safety and efficacy of biologic medications in the treatment of these severe subtypes of psoriasis and to identify strategies to help clinicians optimally manage these patients.
METHODS: We searched Pubmed for English language literature that assessed the use of biologic medication to treat erythrodermic or generalized pustular psoriasis.
RESULTS: The primary literature included cases reports, cases series, and open-label, uncontrolled trials. There were no head-to-head studies or other controlled trials. In both erythrodermic and generalized pustular psoriasis, infliximab was used to treat over half of the reported cases. Other biologic medications that were successfully used included etanercept, ustekinumab, adalimumab, and anakinra. Most cases reported improvement with biologic therapy. Serious adverse events were reported in 10-12% of the patients.
CONCLUSION: Although the evidence is limited, biologic therapy appears to be effective in treating erythrodermic and generalized pustular psoriasis. In order to assess the comparative efficacy and safety of the biologic medications, larger controlled studies are needed.
J Drugs Dermatol. 2014;13(3):342-354.