Volume 10 | Issue 7
Isotretinoin Does Not Prolong QT Intervals and QT Dispersion in Patients With Severe Acne: A Surprising Finding for a Drug With Numerous Side Effects
Background: Isotretinoin is a widely prescribed drug for the treatment of severe acne. Several adverse cardiac effects due to isotretinoin have been previously reported. However, no data exist on the effects of isotretinoin therapy on QT intervals.
Objective: To investigate the effects of isotretinoin therapy on QT intervals and QT dispersion, and also to see if it is related to serum lipids, homocysteine and lipoprotein (a) or not.
Methods: Forty-five patients with severe acne (mean age 21±6 years, range 14-38 years; 26 female) were included in the study. Twelve-lead surface electrocardiograms (ECGs) were acquired at three stages: before therapy and at the ends of the first and sixth months of 0.8 mg/kg/day of isotretinoin therapy. Serum levels of triglycerides, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, very low density lipoprotein cholesterol, homocysteine and lipoprotein (a) were also measured at the day of ECG recordings. Minimum and maximum QT intervals were measured and QT dispersion was calculated.
Results: Mean heart rates were similar throughout the isotretinoin therapy. Serum levels of lipids, homocysteine and lipoprotein (a) all increased significantly at the end of the first month and remained significantly elevated at the end of sixth month (P<0.05 for both stages). QT intervals and QT dispersion did not differ significantly throughout the six months of isotretinoin therapy (P>0.05).
Conclusions: In patients with severe acne, six months of 0.8 mg/kg/day of isotretinoin therapy neither prolongs QT interval, nor increases QT dispersion. This effect is not related to blood lipids, homocysteine or lipoprotein (a) levels. Our findings indicate that from the point of polymorphic ventricular tachycardia risk, 0.8 mg/kg/day of isotretinoin therapy is a safe choice in acne treatment.
J Drugs Dermatol. 2011;10(7):710-714.
A Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Efficacy of a Citrus Bioflavanoid Blend in the Treatment of Senile Purpura
Background: Senile purpura is a common, chronic skin condition affecting more than 10 percent of individuals over the age of 50. Despite being a benign condition, the continual development of purpura lesions in afflicted patients is frequently a source of significant visual and social concern. To date, there are no known effective treatments for this condition.
Objectives: To evaluate the efficacy of a novel nutraceutical citrus bioflavonoid blend in improving the skin's appearance in patients with senile purpura.
Methods: A six-week, randomized, multicenter, placebo-controlled, double-blind study was conducted to determine whether a uniquely formulated, oral citrus bioflavonoid supplement could treat active lesions of senile purpura while preventing new lesions from arising. Seventy patients with senile purpura were enrolled and 67 completed the study. Subjects were randomized into two groups receiving either a citrus bioflavonoid blend or placebo medication, which was taken orally twice daily for six weeks. Clinical evaluations were performed by blinded investigators at two locations.
Results: A statistically significant reduction in the number of new purpura lesions in the skin area undergoing clinical study was documented. At the end of six weeks, the citrus bioflavonoid blend treated group showed a 50 percent reduction in purpura lesions from baseline. Patient self-assessment of the effectiveness of the medication echoed the results of an investigator global assessment with a statistically significant improvement in the skin's appearance noted by the patients receiving the active medication. No adverse effects were noted by either the patients or investigators.
Conclusion: This new treatment appears to both safely and effectively diminish skin bruising in patients with senile purpura.
J Drugs Dermatol.2011;10(7):718-722.
Ted Rosen M.D.|
Within a relatively short period of time after the first antimicrobial drugs were introduced, bacteria began exhibiting varying degrees of resistance. The excessive use (and abuse) of antibiotics in agriculture, and in both human and veterinary medicine, has played a critical causative role in the development of antibiotic resistance, which is now recognized as a global public health threat. Increasing concern over this issue should impact the practice of cutaneous medicine and surgery, as dermatologists can easily adopt new healthcare delivery patterns that might reduce the development of antibiotic resistance and still achieve acceptable treatment outcomes. Dermatologists should seriously consider any and all alternative therapies before committing to an extended course of antibiotic therapy for disease entities that are almost certainly not infectious. Conversely, dermatologists should carefully and closely adhere to dosage and duration recommendations when using antibiotics to treat a bona fide infectious disorder.
J Drugs Dermatol.2011;10(7):724-733.
A Bilateral Comparison Study of Pimecrolimus Cream 1% and a Topical Medical Device Cream in the Treatment of Patients With Atopic Dermatitis
Jason J. Emer MD, Amylynne Frankel MD, Andrew Sohn BS, Mark Lebwohl MD|Corticosteroids are the mainstay of therapy for atopic dermatitis, but long-term use is associated with adverse effects. We sought to evaluate the clinical efficacy of two steroid-sparing creams for atopic dermatitis. Twenty patients were enrolled in an investigatorblinded, bilateral comparison study. Patients applied pimecrolimus cream twice daily to a target lesion on one side of the body and also applied a topical medical device cream three times daily on a symmetrical target lesion on the opposite side of the body for four weeks. Clinical assessments including Physician Global Assessment (PGA), Target Lesion Symptom Score (TLSS), subject selfassessment and digital photography were performed at the baseline, 2 week, and 4 week visits. Seventy-five percent of patients (pimecrolimus, 15 of 20; topical medical device, 15 of 20) were rated "clear" (0) or "almost clear" (1) by PGA for both medications after four weeks. Percent improvement of the PGA from randomization for pimecrolimus cream and the topical medical device cream were 72.50 and 71.67 respectively (P=0.9283). PGA scores decreased significantly from baseline for both treatments (P=0.004). Overall, there was no statistically significant difference between treatment groups for PGA scores throughout the study (P=0.8236). No cutaneous side effects were noted. Our study was limited by a small sample size and lack of double-blinding; however, both treatments were found to be safe and effective in treating atopic dermatitis over four weeks. Significant improvements were noted for all efficacy variables. In conclusion, a lipid-rich, non-steroidal, topical medical device cream was as effective in improving atopic dermatitis as pimecrolimus cream.
J Drugs Dermatol. 2011;10(7):735-743.
A New Body Moisturizer Increases Skin Hydration and Improves Atopic Dermatitis Symptoms Among Children and Adults
Eric Simpson MD MCRa and Yves Dutronc MDb|
Moisturizers result in an increase of skin hydration and restoration of the skin barrier function and play a prominent role in the longterm management of atopic dermatitis (AD). Cetaphil Restoraderm™ Moisturizer (CRM) contains novel ingredients specifically designed for AD, and its effects on skin hydration, skin barrier function and signs of AD were assessed in four studies, three of which were evaluator-blinded, randomized and intra-individual comparison trials. A single application of CRM induced significantly greater hydration than the untreated control for at least 24 hours (P<0.001). After the skin was disrupted with 0.5% sodium dodecyl sulfate (SDS), applications of CRM led to a more rapid restoration of skin barrier function and maintained significantly greater skin hydration compared to the untreated control (both P<0.05). After four weeks of twice-daily CRM application among subjects with a history of AD, a significant decrease of itching/stinging scores compared to baseline was reported, as well as an improvement in the quality-of-life and a high level of satisfaction regarding the product. When CRM was used as an adjunctive treatment with topical steroid for four weeks among subjects with mild-to-moderate AD, a more rapid decrease of overall disease severity was observed on days 7, 14 and 21 by the blinded investigator (P<0.05), compared to steroid treatment alone. In summary, CRM is suitable for the specific needs of patients with AD and can be used either alone for long-term management or in adjunction with traditional treatment for both short and long-term disease control.
J Drugs Dermatol. 2011;10(7):744-749.
Complementary Antioxidant Function of Caffeine and Green Tea Polyphenols in Normal Human Skin Fibroblasts
Jared Jagdeo MD MS and Neil Brody MD PhD|
The study of free radicals is particularly relevant in the context of human skin carcinogenesis and photoaging because of these oxidants´ ability to induce DNA mutations and produce lipid peroxidation byproducts, including 4-hydroxy-2-nonenal (HNE). Therefore, it is important to identify and evaluate agents with the ability to modulate intracellular free radicals and HNE. The purpose of this research is to investigate the ability of antioxidants green tea polyphenols (GTPs) and caffeine, alone and in combination, to modulate the hydrogen peroxide (H2O2)-induced upregulation of reactive oxygen species (ROS) free radicals and HNE in normal human skin fibroblast WS-1 cells in vitro. GTPs and caffeine were selected for evaluation because these compounds have demonstrated antioxidative properties in various skin models. Furthermore, GTPs and caffeine share a close natural botanical association as caffeine is present in green tea, as well. Hydrogen peroxide is a well-known generator of free radicals that is produced during endogenous and UV-induced oxidation processes in human skin and was used to upregulate ROS and HNE in normal human fibroblast WS-1 cells. Using a flow cytometry-based assay, the results demonstrate that at 0.001% concentration, green tea polyphenols alone, and in combination with 0.1 mM caffeine, inhibited the upregulation of H2O2-generated free radicals and HNE in human skin fibroblasts in vitro. Caffeine alone demonstrated limited anti-oxidant properties.
J Drugs Dermatol. 2011;10(7):753-761.
Corrugator Supercilii Muscle Terminal Nerve Ablation Using a Novel Thread Technique for the Treatment of Hyperdynamic Vertical Glabellar Furrows
Background: A novel percutaneous corrugator supercilii muscle terminal nerve CSMTN ablation technique is proposed for the treatment of hyperdynamic vertical glabellar furrows (HVGF).
Technique: Two surgical marks are placed on each eyebrow. One is placed at the level of the lateral canthus and the second at the outer border of the limbus. At each of the four marks, the following steps are carried out: (1) a guiding needle is used to punch the frontal skin at 3 mm above the eyebrow (orifice A) and will then travel deeply at the level of the supraperiostium and emerge outside the skin 3 mm below the eyebrow (orifice B) at the palpebral skin; (2) the needle is then reentered exactly at orifice B and will travel underneath the skin at a more superficial level in the subcutaneous layer and then emerge outside exactly at orifice A. Both ends of the thread are gently pulled in a sawing motion with counter tension until no more resistance is felt from the anatomical structures involved, and then the loops of thread are withdrawn from orifice A.
Results: Forty-seven subjects underwent bilateral CSMTN ablation. In the first 10 cases, the authors performed only one neurotomy per eye and observed a 50 percent HVGF recurrence rate. Then, the authors chose to perform two neurotomies per side and had a three percent recurrence rate (1/37) with a high degree of patient satisfaction. Major complications such as deforming hematomas, eyelid ptosis, abscess, scar formation or adhesions were not observed during follow up.
Conclusion: This novel technique may represent a simple and permanent solution for HVGF.
J Drugs Dermatol.2011;10(7):762-765.
Medication Choice and Associated Health Care Outcomes and Costs for Patients With Acne and Acne-Related Conditions in the United States
Palak Patel MS,a Hsien-Chang Lin PhD,b,c Steven R. Feldman MD PhD,d Alan B Fleischer Jr MD,d Milap C. Nahata MS PharmD,e Rajesh Balkrishnan PhDb,c|
Background: Acne is a common condition for which multiple treatment options are available. The patterns of pharmacotherapy for acne and similar conditions, and the effect of those patterns on cost, are not well characterized.
Objective: This study examined the impacts of patient demographics and medication choices on patients' health status and associated medication costs.
Methods: A retrospective cross-sectional study was conducted using the 2007 Medical Expenditure Panel Survey (MEPS) database. Information on patient demographics, health status, medication utilization and medication costs was obtained from the database representing 3,784,816 patients with acne and similar conditions.
Results: Weighted multiple linear regression analyses indicated that the use of topical retinoids was preferred in combination with other treatments rather than as monotherapy. Oral antibiotics were widely prescribed and their use was associated with a significant decrease in total annual prescription spending. Use of oral retinoids and oral contraceptives increased the annual prescription costs significantly. Increase in annual drug refills was not associated with the improvement in health status.
Conclusion: We observed an association with medication choice for acne and acne-related conditions on medication spending. Pharmacologic treatment of acne significantly adds to acne-related annual healthcare costs compared to non-pharmacologic treatment.
J Drugs Dermatol.2011;10(7):766-771.
Introduction: Acitretin is a systemic retinoid drug used in the treatment of severe psoriasis. It has also been used for a spectrum of other difficult-to-treat dermatoses, including hyperkeratotic and inflammatory dermatoses and non-melanoma skin cancers. Here we review the available data regarding both FDA-approved and off-label uses of acitretin, clinically relevant adverse events, precautions and monitoring.
Methods: A PubMed literature search was conducted utilizing the search term "acitretin," which yielded 714 hits. Results were further limited to English language clinical trials in human subjects. Of 78 articles evaluated for relevance, 60 were included for review.
Results: Acitretin is effective as monotherapy and in multidrug therapeutic regimens for the treatment of psoriasis and other hyperkeratotic and inflammatory disorders, as well as for malignancy chemoprevention. Its use is limited by its teratogenic potential and other adverse effects, including mucocutaneous effects and hepatotoxicity. Potential adverse effects may be reduced or avoided by using lower doses of acitretin or in combination with other therapies.
Limitations: The reviewed studies include many small trials and case reports of the use of acitretin for psoriasis. Studies of acitretin therapy for the treatment of other cutaneous disorders are limited.
Conclusion: Acitretin is a beneficial treatment for psoriasis, and should be considered when not contraindicated. Particularly when used in combination with ultraviolet (UV) phototherapy, is a safe and cost effective therapeutic strategy.
J Drugs Dermatol.2011;10(7):772-782.
Clinical Evidence for the Role of a Topical Anti-Inflammatory Agent in Comedonal Acne: Findings From a Randomized Study of Dapsone Gel 5% in Combination With Tazarotene Cream 0.1% in Patients With Acne Vulgaris
Emil Tanghetti MD,a Sunil Dhawan MD,b Lawrence Green MD,c Mark Ling MD PhD,d Jeanine Downie MD,e Marguerite A. Germain MD,f J. Scott Kasteler MD,g Leon Kircik MD,h Michael G. Oefelein MD,i Zoe Draelos MDj|
Background: Acne pathogenesis is multifactorial and includes inflammation. Combining drugs targeting multiple components of acne pathogenesis is standard practice.
Objective: To assess the safety and efficacy of dapsone gel 5%, an anti-inflammatory agent, in combination with tazarotene cream 0.1% for treatment of acne vulgaris.
Methods: Patients were randomized to receive combination therapy (dapsone gel 5% twice-daily plus tazarotene cream 0.1% daily) or monotherapy (tazarotene cream 0.1% daily). Efficacy and safety data were collected after 1, 2, 4, 8, and 12 weeks of treatment.
Results: Patients in both arms (n=86, dapsone + tazarotene; n=85, tazarotene) showed significant reductions from baseline in inflammatory, noninflammatory and total lesion counts (P<.001 for all). At 12 weeks, patients treated with dapsone plus tazarotene showed a greater reduction from baseline in noninflammatory (comedonal) and total lesion counts than tazarotene-treated patients (noninflammatory, 59.7 percent vs. 46.5 percent, P=.01; total, 63.3% vs. 53.6%, P=.02). The percentage of patients achieving treatment success (an investigator subjective score of 0 [none] or 1 [minimal]) was greater in dapsone plus tazarotene-treated patients (42.2%) than in tazarotene-treated patients (21.8%;P=.01). Both treatments were well tolerated.
Conclusion: Combination therapy with dapsone gel 5% plus tazarotene cream 0.1% was more effective than tazarotene monotherapy for treatment of comedonal acne. The results suggest that anti-inflammatory agents such as dapsone can effectively treat early stages of acne (both comedonal and noncomedonal) when used in combination with a retinoid.
J Drugs Dermatol. 2011;10(7):783-792.
Decrease of Insulin Growth Factor-1 as a Novel Mechanism for Anti-Androgen Effect of Isotretinoin and Its Reported Association With Depression in Some Cases
Isotretinoin and its desirable effects have received tremendous attention in recent years by scientists. This article reviews the evidence that decrease of insulin growth factor-1 is implicated as a novel mechanism of anti androgenic effect and its reported association with depression in some cases.
J Drugs Dermatol. 2011;10(7):793-794.
Michael McLeod|No abstract details for the moment.
Jason J. Emer MD, Mary L. Stevenson MD, Orit Markowitz MD|
Female-pattern androgenetic alopecia is a very common disorder that has been associated with extreme psychological morbidity. Few treatments have documented utility and many physicians are often overwhelmed with how little is pharmacologically available to treat this condition. Novel treatments that are effective, safe, less costly and simple are in high demand. We report a case of female-pattern androgenetic alopecia that failed to respond to a novel treatment with injected bimatoprost solution. Hypothetically, the treatment should have been effective and although we did not have success, this report suggests critical points to consider in the future of prostaglandin analogs, as well as other therapies being considered for the treatment of female-pattern hair loss.
J Drugs Dermatol. 2011;10(7):795-798.
Tamoxifen, a triphenylethylethylene, is an adjuvant therapy used for the treatment of oestrogen-receptor positive breast carcinoma due to its oestrogen receptor antagonist effect.1 We report here a case of rapid onset of hirsutism following administration of tamoxifen.
J Drugs Dermatol. 2011;10(7):799-801.
Natalie A. Wright MDa and Philip R. Cohen MDb-d|
Fixed drug eruption, a medication-associated mucocutaneous reaction, rarely presents as a delayed adverse reaction to intravenous non-ionic contrast media. We describe a 57-year-old woman with a history of metastatic renal cell carcinoma who repeatedly developed a sharply demarcated, erythematous patch on her left breast after receiving the iodinated non-ionic contrast media iohexol for staging computed tomography scans. Recurrent fixed drug eruption may be avoided by using another contrast medium. Prophylactic treatment with systemic corticosteroids may prevent repeated fixed drug eruption if an alternative contrast agent cannot be used.
J Drugs Dermatol. 2011;10(7):802-804.
Sheila M. Greenlaw MD,a Mariko Yasuda MD,a Karen Wiss MDa,b|
Resident Rounds is a section of the JDD dedicated to highlighting various dermatology departments with residency training programs. Resident Rounds includes three sections: (1) a program spotlight, highlighting pertinent information about the department and residency training program; (2) a section presenting study materials used by residents at the program; and (3) a section designed to highlight recent interesting cases seen at the institution. This issue of Resident Rounds features the University of Massachusetts Medical School Dermatology Residency Program. The editor of Resident Rounds is Omar A. Ibrahimi, MD, PhD. He is currently the Director of Cutaneous Laser and Cosmetic Surgery and a Mohs surgeon at the University of Connecticut. Dr. Ibrahimi is also a Visiting Scientist at the Wellman Center for Photomedicine at Massachusetts General Hospital/Harvard Medical School. If you are interested in highlighting your training program in a future issue, please contact Dr. Ibrahimi at [email protected]
Andrea Pearson MD, Maryanne Makredes MD, Nikki A. Levin MD PhD|No abstract details for the moment.
Pipeline Previews brings to you information on the newest drugs and medical products as they become available to the dermatologic community. This department may include additional information from the manufacturers, plus reports from physicians who wish to share their clinical experience with these new products. In addition, we will inform our readers about the latest drugs receiving Food and Drug Administration (FDA) approval.
Elizabeth Foley MD,a Sheila M. Greenlaw MD,a Jason Givan MD,b April Deng MD,c Mary Maloney MD,a David E. Geist, MDa|No abstract details for the moment.
Kendra Gail Bergstrom, MD, FAAD|News, Views and Reviews provides focused updates, topic reviews and editorials concerning the latest developments in dermatologic therapy.