Volume 11 | Issue 3
Elizabeth K. Hale MD|No abstract details for the moment.
An Update on the Long-Term Safety Experience of Ustekinumab: Results From the Psoriasis Clinical Development Program With up to Four Years of Follow-UpBackground: The efficacy and safety profile of ustekinumab with up to three years of exposure suggested a favorable benefit-risk profile in patients with moderate to severe psoriasis.
Objective: To evaluate the safety of ustekinumab in patients with moderate to severe psoriasis treated for up to four years.
Methods: Safety data were pooled across four Phase II/III randomized controlled trials. Rates over time and cumulative rates of adverse events (AEs), AEs leading to treatment discontinuation, serious adverse events (SAEs), serious infections, malignancies, and major adverse cardiovascular events (MACE) (i.e., cardiovascular death, myocardial infarction [MI], or stroke as adjudicated by an independent panel of academic cardiologists) were evaluated. Observed rates of AEs of interest were compared with those expected in the general (malignancies, MI, and stroke) and psoriasis (serious infections, MI, and stroke) populations.
Results: Overall, 3,117 patients were followed for up to four years (6,791 patient-years). Rates of AEs, AEs leading to treatment discontinuation, and SAEs remained stable over time, whereas cumulative rates were generally comparable between patients who received 45 mg and 90 mg of ustekinumab. The rates of AEs of interest also remained stable over time, and cumulative rates per 100 patient-years were 0.80 and 1.32 (serious infections), 0.70 and 0.53 (nonmelanoma skin cancer), 0.63 and 0.61 (other malignancies), and 0.56 and 0.46 (MACE) in patients treated with 45 mg and 90 mg, respectively. Rates of AEs of interest were consistent with those in the general and psoriasis populations.
Conclusion: The safety profile of long-term ustekinumab treatment with up to four years of continuous use remains consistent with previous reports, with no evidence of cumulative toxicity.
J Drugs Dermatol. 2012;11(3):300-312
Given the multifactorial and complex contributors to acne development, combination therapy is standard of care. By addressing multiple pathogenic factors, combination therapy provides a quicker and more efficacious treatment outcome than monotherapy. Topical retinoids normalize follicular keratinocyte differentiation and are anti-inflammatory. Their use is limited by the potential for cutaneous irritation. Antimicrobials reduce Propionibacterium acnes colonization on the skin and reduce the bacteria's proinflammatory effects. Topical antibiotics and benzoyl peroxide (BPO) are commonly employed in fixed-dose combination products or two separate medications. BPO has the added benefit of being comedolytic and can minimize the risk for bacterial antibiotic resistance. Like topical retinoids, BPO may cause skin irritation, burning, erythema, and peeling. Managing cutaneous side effects when using multiple products that cause irritation can be a challenge. Careful product selection, dose titration, and patient-directed regimens can help to optimize outcomes. This review presents the latest data on two topical acne products that have demonstrated excellent efficacy and tolerability profiles. In addition, their in vitro profiles suggest the potential for combination use, affording greater dosing flexibility.
J Drugs Dermatol. 2012;11(3):313-317.
Efficacy and Safety of Clindamycin-Tretinoin Gel Versus Clindamycin or Tretinoin Alone in Acne Vulgaris: A Randomized, Double-Blind,Vehicle-Controlled Study
Background: Topical combination therapy containing a retinoid and an antimicrobial is an effective treatment for acne vulgaris.
Objective: To evaluate the efficacy and safety of a new topical formulation containing clindamycin phosphate 1.2% and tretinoin 0.025% solubilized in an aqueous-based gel (CT gel).
Methods: 1,649 participants were randomized 2:2:2:1 to 12 weeks of double-blind treatment with CT gel, clindamycin, tretinoin, or vehicle gel administered once daily.
Results: Significantly more participants achieved 2-grade or greater improvement on the Investigator's Static Global Assessment score with CT gel versus clindamycin, tretinoin, or vehicle gel. CT gel produced a significantly greater reduction in absolute number of total lesions versus all other treatment groups, in total and noninflammatory lesions versus clindamycin, and in total and inflammatory lesions versus tretinoin. Local tolerability was similar to that of tretinoin alone; signs and symptoms of irritation were most notable at week 2. There were no more adverse events with CT gel than with tretinoin gel.
Conclusion: CT gel is more effective than clindamycin or tretinoin monotherapy, with a safety and tolerability profile similar to that of tretinoin.
J Drugs Dermatol. 2012;11(3):318-326.
Background: The role of vitamin D in Atopic Dermatitis (AD) is ambiguous and clinical trials are needed to assess the role of vitamin D in the treatment of AD. The aim of this clinical trial study to evaluate the effect of vitamin D supplementation on patients with AD.
Material and Methods: sixty AD patients were included in a randomized, double-blind, placebo-controlled trial study. They were randomly divided into two groups and treated for 60 days: group vitamin D (n=30), and placebo group (n=30). The two groups were as follows: Group D, 1600 IU cholecalciferol (vitamin D) and second group placebo. The severity of AD was evaluated based on SCORAD (Scoring Atopic Dermatitis) and TIS (Three Item Severity score) value by the same trained physician before and after the trial.
Results: According to SCORAD and TIS value index in the vitamin D group showed significant improvement in patients with mild, moderate and severe AD (P<0.05) and in patients who the intake placebo, this improvement didn't showed (P>0.05).
Conclusion: Results mention that supplementation with oral vitamin D dramatically improved disease severity in AD patients.
J Drugs Dermatol. 2012;11(3):327-330.
A Randomized, Double-Blind, Placebo-Controlled, Pilot Study to Assess the Efficacy and Safety of Clindamycin 1.2% and Tretinoin 0.025% Combination Gel for the Treatment of Acne Rosacea Over 12 Weeks
Background: Papulopustular acne rosacea is a chronic inflammatory condition which can be difficult to treat. Many patients are unwilling to use systemic medications, and single topical agents alone may not address all the symptoms of rosacea. A combination topical clindamycin phosphate 1.2% and tretinoin 0.025% gel is efficacious for acne vulgaris, and may be helpful for rosacea, since acne vulgaris and rosacea shares many similar clinical and histologic features.
Objective: To assess the preliminary efficacy and safety of a combination gel consisting of clindamycin phosphate 1.2% and tretinoin 0.025% on papulopustular rosacea after 12 weeks of usage.
Methods: Randomized, double-blind, placebo controlled two site study of 79 participants with moderate to severe papulopustular acne rosacea using both physician and subjects' validated assessment tools. Primary endpoint consisted of statistically significant reduction in absolute papule or pustule count after 12 weeks of usage.
Results: There was no significant difference in papule/pustule count between placebo and treated groups after 12 weeks (P=0.10). However, there was nearly significant improvement in physicians' assessments of the telangiectasia component of rosacea (P=0.06) and erythematotelangiectatic rosacea subtype (P=0.05) in treated versus placebo group after 12 weeks. The only significant adverse event different was facial scaling, which was significantly increased in treated group (P=0.01), but this did not result in discontinuation of study drug.
Conclusions: A combination gel of clindamycin phosphate 1.2% and tretinoin 0.025% may improve the telangiectatic component of rosacea and appears to better treat the erythemotelangiectatic subtype of rosacea rather than papulopustular subtype. Our preliminary study suggests that future studies with much larger sample size might confirm our findings. Clinical Trials: NCT00823901.
J Drugs Dermatol. 2012;11(3):333-339.
A Phase 2, Open-Label, Investigator-Initiated Study to Evaluate the Safety and Efficacy of Apremilast in Subjects With Recalcitrant Allergic Contact or Atopic DermatitisObjective: Evaluate the efficacy and safety of apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, in subjects with recalcitrant moderate to severe atopic dermatitis (AD) or allergic contact dermatitis (ACD).
Research design and methods: This was a proof-of-concept, phase 2, open-label, single institution trial that evaluated the efficacy and safety of apremilast, 20 mg twice daily, for twelve weeks, in ten subjects with either AD and/or ACD. The primary endpoint was a ≥2 point improvement in Investigator Global Assessment (IGA) score after 12 weeks of treatment. Secondary endpoints included a 75% reduction in the Eczema Assessment Severity Index (EASI-75), EASI-50, and the maximum EASI response.
Results: The primary endpoint of improvement in IGA by two or more points was met by 20% of subjects. Ten percent of subjects achieved EASI-75 and another 10% reached EASI-50. All subjects tolerated apremilast well with no serious adverse events or withdrawal due to side effects. Common adverse events associated with apremilast included headache, nausea, and soft stool.
Limitations: This study was limited by its small sample size and lack of a comparison group to serve as a control.
Conclusions: Apremilast was well tolerated in all subjects. Apremilast was minimally effective in AD and ACD and results were inferior to previous trials of apremilast in psoriasis.
J Drugs Dermatol. 2012;11(3):341-346.
Combination of Essential Oil of Melaleuca alternifolia and Iodine in the Treatment of Molluscum Contagiosum in Children
Molluscum contagiosum is a common childhood viral skin condition and is increasingly found as a sexually transmitted disease in adults. Current treatment options are invasive, requiring tissue destruction and attendant discomfort. Fifty-three children (mean age 6.3+5.1 years) with the diagnosis of molluscum contagiosum were treated with twice daily topical application of either essential oil of Melaleuca alternifolia (TTO), a combination of TTO and organically bound iodine (TTO-I), or iodine alone. At the end of 30 days, 48 children were available for follow up. A greater than 90% reduction in the number of lesions was observed in 16 of 19 children treated with TTO-I, while 1 of 16 and 3 of 18 children met the same criteria for improvement in the iodine and TTO groups (P<0.01, ANOVA) respectively by intention-to-treat analysis. No child discontinued treatment due to adverse events. The combination of essential oil of M. alternifolia with organically bound iodine offers a safe therapeutic alternative in the treatment of childhood molluscum. Clinical Trial Registry ACTRN12610000984099.
J Drugs Dermatol. 2012;11(3):349-354. 2012;11(3):349-354.
Background: Many therapeutic modalities for scabies were available, topical sulfur ointment is a cost-effective and safe therapeutic agent. It is often applied for the whole body for three successive days.
Objective: To evaluate their therapeutic regimen of 8% and 10% topical precipitated sulfur in petrolatum ointment for single day, three successive nights or three successive days in management of scabies.
Patients and Methods: This single-blinded, comparative study was conducted in the Department of Dermatology-Baghdad Teaching Hospital from April 2008 through October 2009. A total of 97 patients with scabies were enrolled in this study. The diagnosis was established on clinical basis. The patients treated with 8% and 10% topical sulfur in petrolatum ointment were divided randomly into three groups: Group A: 33 patients treated for single day (24 hours); Group B: 32 patients treated for three successive nights (from 6 p.m. to 8 p.m. to 6 a.m. to 8 a.m. and bathing every day); and Group C: 32 patients treated for three successive days (bathing every 24 hours). The patients were seen regularly every two weeks for the duration of four weeks.
Results: Study included 58 (59.8%) males and 39 (40.2%) females, with a male to female ratio 1.4:1. The age range of males at presentation from 3 to 64 (26.74±15.98) years, while the females age ranged at presentation from 3 to 60 (24.05±14.53) years of age. At the end of the study, the response to treatment was: Group A, response in 14 (42.4%) patients and no response in 19 (57.6%); Group B, response in 29 (90.6%) patients and no response in 3 (9.4%); and Group C, response in 31 (96.9%) patients and no response in 1 (3.1%). There is significant statistical difference among the response of 3 groups with (P=0.00000011), but no statistically significant difference between the response of Group C and Group B, (P=0.6055). Mild burning sensation and irritating (sulfur) dermatitis were the only side effects of 8% and 10% sulfur. Pruritic rash occurred in Group C mainly, in 11 (34.4%) patients, 8 (25%) in Group B and 4 (12.1%) in Group A, with no significance (P=0.1058). Recurrence or relapse occurred in Group A mainly, with 4 (12.1%) patients, and in Group B, 1 patient, (3.1%), with no recurrence in group C, with significance (P=0.0060).
Conclusion: Three successive days and three successive nights of 8% and 10% sulfur ointment were effective regimens with no statistical difference in favor of three successive days, while single-day application was much less effective but with fewer side effects.
J Drugs Dermatol. 2012;11(3):357-364.
Comparative Trial of 5% Dexpanthenol in Water-in-Oil Formulation With 1% Hydrocortisone Ointment in the Treatment of Childhood Atopic Dermatitis: A Pilot StudyBackground: Atopic dermatitis (AD) is a common chronic relapsing disease particularly affecting children. The emollient used for protection of skin barrier function is the standard treatment for patients with AD. Currently, there is a growing interest in the use of nonsteroidal anti-inflammatory agents such as dexpanthenol (vitamin B5) as an alternative treatment.
Objective: To compare the effectiveness of 5% dexpanthenol (DT) ointment with 1% hydrocortisone (HC) ointment in childhood AD therapy.
Method: Patients were treated topically with 5% DT ointment on the right side of the body and 1% HC ointment on the other side twice daily for 4 weeks. The clinical responses were evaluated by SCORAD (Scoring Atopic Dermatitis index) with statistical analysis using paired t-test.
Result: Of the 30 children enrolled, 26 completed the protocol; mean age was 7.19 years. The average baseline SCORAD score of the DT-treated side and the HC-treated side was 30.95 and 30.54, respectively. There was no statistically significant difference in SCORAD score reduction between the 2 agents. The edematous score of the HC-treated side exhibited faster resolution than that of the DT-treated side, with a statistically significant difference at week 1 and without a statistically significant difference at weeks 2 to 4. The lichenification response rate of HC treatment was more rapid than that of DT treatment; however, there was no statistical group difference. No adverse events were observed with either agent.
Conclusion: The effectiveness of 5% DT ointment is equal to that of 1% HC ointment. DT ointment may be used as alternative treatment in mild to moderate childhood AD therapy.
J Drugs Dermatol. 2012;11(3):366-374.
Background: Defects of the nasal ala present a complex reconstructive challenge. Composite grafts comprise all layers required to successfully reconstruct these full thickness deformities making them the ideal reconstructive method, yet they are usually avoided because of unjustified disreputable failure rates.
Objective: The authors introduce a stepladder approach for alar reconstruction with a crus of helix composite graft according to the severity and complexity of the defect.
Methods: Data from 25 patients who underwent correction of full thickness alar defects with composite grafts was collected and reviewed.
Results: There were no complete graft failures in any of the cases. Ten patients (40%) had partial graft necrosis ranging from 5 to 50% (average 18%); two of them (20%) were heavy smokers.
Conclusions: Composite grafts should be considered for reconstruction of full thickness nasal ala defects, given the correct surgical technique is implemented.
J Drugs Dermatol. 2012;11(3):376-381.
Hypopigmented patches and plaques are a rare presentation of cutaneous sarcoidosis. We describe a case of generalized hypopigmented cutaneous sarcoidosis that showed good response to minocycline therapy.
J Drugs Dermatol. 2012;11(3):385-389.
Interferon- α has been associated with a wide range of adverse events (AEs). A lupus-like reaction at the injection site of subcutaneous (SC) interferon-α is exceptionally rare. A 60-year-old woman with recurrent metastatic melanoma repeatedly developed cutaneous lupus-like reactions at the SC interferon-α-2b injection sites on her thighs. Known features of lupus-like reactions at SC interferon-α injection sites are reviewed, and cutaneous injection site reactions to SC interferon-α are summarized.
J Drugs Dermatol. 2012;11(3):393-398.
Elephantiasis nostras verrucosa is a rare disorder characterized by dermal fibrosis, hyperkeratotic, verrucous, and papillomatous le- sions that result from both chronic filarial and nonfilarial lymphedema. Various treatment options have been reported for this disease. We present a 64-year-old man with erythrodermic psoriasis and elephantiasis nostras verrucosa in whom the lesions were resolved almost completely after acitretin treatment.
J Drugs Dermatol. 2012;11(3):402-405.
Adrenergic Urticaria and Rheumatoid Arthritis in a Patient With Melanoma: An Intricate Medical ManagementA 45-year-old woman with marital and working troubles, a personal history positive for malignant melanoma, and a family history of vitiligo presented with adrenergic urticaria (AU), which at first responded to propranolol, but later became unresponsive to both β-blockers and antihistamines. Meanwhile, rheumatoid arthritis became apparent. Treatment with corticosteroids and methotrexate led to remission of neither the rheumatologic nor the dermatologic condition. Attempts to taper the immunosuppressive treatment were invariably followed by recurrence of adrenergic urticaria, which still proved unresponsive to propranolol, as did the rheumatoid arthritis. The courses of the diseases strictly paralleled each other. Rheumatoid arthritis could have triggered adrenergic urticaria by simply adding a supplemental stress, but also by systemically activating mast cells, which are known to be involved in the pathogenesis of chronic inflammatory diseases. A brief discussion of either the dermatological manifestations of, or treatments for rheumatoid arthritis is provided, in order to illustrate the kind of clinical difficulties that such atypical patients pose to physicians.
Adrenergic urticaria is an uncommon yet probably under-diagnosed form of urticaria,¹ which is considered a form of neurogenic acute reaction mainly triggered by acute stress.²,³ The author presents a case of AU, however, that is only partially explained by a stress setting, though it is strongly associated with the course of an autoimmune disease.
J Drugs Dermatol. 2012;11(3):409-412.
Long-Term Etanercept Use for Severe Generalized Psoriasis in an HIV-Infected Individual: A Case StudyThe treatment options for psoriasis in HIV-infected individuals are limited due to the immunosuppressive nature of the therapeutic modalities and the patient's immunocompromised state. Etanercept has been shown to be safe and effective in the non-HIV psoriasis population with nearly 20 years of experience. However, there is limited data on the safety of etanercept use in the HIV patient population. The authors report a case of an HIV-infected patient with psoriasis who has remained mostly clear on continuous, uninterrupted etanercept use for over six years.
J Drugs Dermatol. 2012;11(3):413-414.
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 National Capital Consortium Dermatology Residency Training 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]
No abstract details for the moment.
No abstract details for the moment.
Kendra Gail Bergstrom MD FAAD|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.
Clinical Trial Review is a JDD department designed to provide physicians with information on drugs and devices undergoing clinical testing. It is our goal to inform the reader of the status of select drug and device studies relevant to the practice of dermatology before this information is available through standard channels. To participate in or learn more about these and additional trials, visit www.clinicaltrials.gov.
Hema Sundaram MD, Gary D. Monheit MD, Mitchel P. Goldman MD, Corey S. Maas MD, Nowell Solish MD, Steven H. Dayan MD, John P. Arkins BS, Ellen Marmur MD, Joel Cohen MD, Oge Onwudiwe MD, Jonathan Sykes MD, Derek H. Jones MD, Jean Carruthers MD, Hugues Cartier MD, Berthold Rzany MD ScM, Laurie Casas MD, David J. Goldberg MD JD, Patrick Trévidic MD, Rhoda S. Narins MD, Marina Landau MD, Benjamin Ascher MD, Haideh Hirmand MD|Part I of this two-part supplement brings together experts from the U.S., Europe, Canada, and Israel to discuss the state-of-the-art in soft tissue fillers in a fair-balanced, CME-accredited format. It includes a roundtable discussion on hyaluronic acid (HA) fillers that charts the clinical and scientific path that has led dermatologists from wrinkle-chasing to true volumetry. International case vignettes with commentary highlight a variety of applications for fillers'some currently available in the U.S., and some available elsewhere and on the American horizon. Topics covered include single-product and multi-product volumetry, anatomic and safety considerations, and the use of blunt injection microcannulas. Quick poll surveys provide an engaging snapshot of the faculty's personal approaches, with the first three surveys focusing on the palette of HA fillers.
This is a CME supplement; visit the JDD Medical Education Library to participate in this activity and earn 2 AMA PRA Category 1 Credits.