Volume 16 | Issue 2
Jerry Tan MD,a/sup> Sewon Kang MD,b/sup> and James Leyden MDc|Although there have been few formal studies, scarring is a known bothersome companion of acne vulgaris. We performed a prospective study of subjects consulting a dermatologist for active acne to assess the frequency of acne scarring. Investigators performed a short questionnaire on all acne patients seen at their office for one consecutive 5-day work week to assess scar frequency. Additionally, the first four subjects with acne scars identified were enrolled for a second phase (scar cohort) of the study during which the investigator collected further medical history and performed a clinical evaluation and the patient completed a self-administered questionnaire about scar perceptions and impact on quality of life. A total of 1,972 subjects were evaluated by 120 investigators. Among these, 43 percent (n=843) had acne scarring. Subjects with acne scars were significantly more likely to have severe or very severe acne (P less than .01); however, 69% of the subjects with acne scars had mild or moderate acne at the time of the study visit. Risk factors correlated with increased likelihood of scarring were acne severity, time between acne onset and first effective treatment, relapsing acne, and male gender. Treatments that can completely resolve acne scars are not yet available – prevention and early treatment remain a primary strategy against scars. It is vital for clinicians who manage individuals with acne to institute effective therapy as early as possible, since treatment delay is a key modifiable risk factor for scarring.
J Drugs Dermatol. 2017;16(2):97-102.
Lawrence F. Eichenfield MD and Sheila Fallon Friedlander MD|
Fungal infection of the nails is an increasingly recognized disease in infants and children. However, it can be difficult to distinguish clinically from other nail dystrophies. In addition, many mistakenly believe that onychomycosis does not occur in childhood. Under-recognition of this infectious disorder therefore occurs. Although many consider “nail fungus” a trivial cosmetic concern, it can lead to discomfort, risk of secondary infection, and a more significant health threat in immunocompromised or diabetic individuals. It should always be considered in the differential diagnosis of nail plate disorders in children as it is one of the more common causes.
Here we review the latest data on prevalence of the disease, reasons for its relatively low incidence compared with adults, and important predisposing factors. It is important to confirm the clinical diagnosis of onychomycosis in children, and affected individuals should be examined for concomitant tinea pedis. As familial disease often occurs, it is important to check parents and siblings as well for onychomycosis and tinea pedis.
Treatment of onychomycosis is challenging, and recurrence appears to be more common in children than in adults. Prolonged systemic antifungal therapy is commonly required. However, pediatric practitioners and parents alike hesitate when asked to treat young children with a systemic drug that requires laboratory monitoring and can have systemic toxicities. Due to their thinner, faster-growing nails, children are theoretically more likely to respond to topical monotherapy than adults, and therefore good candidates for topical antifungal therapy.
The clinical data on the use of topical antifungals in pediatric onychomycosis is scarce. We review data that exist from case reports and small clinical trials. New topical antifungals are now available that afford better nail penetration and additional delivery routes to the site of infection. Pediatric trials are now on-going, and should clarify the usefulness of these agents in children.
J Drugs Dermatol. 2017;16(2):105-109.
Regression Analysis of Local Skin Reactions to Predict Clearance of Actinic Keratosis on the Face in Patients Treated With Ingenol Mebutate Gel: Experience from Randomized Controlled Trials
Shelbi Jim On MD,a Kim Mark Knudsen PhD,b Torsten Skov MD PhD,b and Mark Lebwohl MDa|
Ingenol mebutate gel, a topical field treatment for actinic keratosis (AK), elicits inflammatory application-site reactions in most patients. This analysis explored the relationship between the intensity of local skin reactions (LSRs) and AK clearance, measured by the reduction in AK count from baseline in 218 patients who were treated for AK on the face in the pivotal Phase 3 studies. The analysis modeled the AK count at week 8, adjusted for baseline count, with the composite LSR score at 1 day after the last treatment application for each patient as a predictor to estimate the mean and 90% prediction interval for the percent reduction in AK count. The predicted mean percent reduction in AK count was higher in patients with higher composite LSR scores. Lower composite scores demonstrated a variable, less predictive percentage reduction in efficacy. Therefore, a large inflammatory reaction from ingenol mebutate gives a more reliable prognosis for improved AK clearance.
J Drugs Dermatol. 2017;16(2):112-114.
Scott A. Elman AB,a Joseph F. Merola MD MMSc,a,b April W. Armstrong MD MPH,c Kristina Callis Duffin MD,d John Latella,e Amit Garg MD,f Alice B. Gottlieb MD PhDg|
The International Dermatology Outcome Measures (IDEOM) group, comprising patients, physicians, health economists, industry partners, payers, and regulatory agencies, was established to develop unified and validated patient-centered outcome measures in dermatology in response to increasing demand to quantify effectiveness of treatments and performance outcomes among providers. IDEOM has chosen to start with psoriasis outcome measures, and then apply its methodology to other dermatologic diseases. In this paper, we review the background and progress to date of IDEOM, including an update of IDEOM activities as of our 2016 meeting in Washington DC, USA. Briefly, the progress-to-date of a Delphi process to create outcome measures for psoriasis was reviewed, including preliminary data from the first round of Delphi voting. Updates were also heard from industry partners including the National Psoriasis Foundation (NPF) and the US Food and Drug Administration (FDA). Furthermore, plans to establish outcome measures for hidradenitis suppurativa (HS) were discussed.
J Drugs Dermatol. 2017;16(2):119-124.
Randomized, Placebo- and Active-Controlled Crossover Study of the Safety and Efficacy of THVD-102, a Fixed-dose Combination of Oxybutynin and Pilocarpine, in Subjects With Primary Focal Hyperhidrosis
David M. Pariser MD FACP FAAD,a Janakan Krishnaraja MD,b Thomas M. Tremblay RN,d R. Michael Rubison PhD,c Ted W. Love MD,d and Benjamin F. McGraw III PharmDd|BACKGROUND: While muscarinic antagonists (anticholinergics) have shown efficacy in treating primary focal hyperhidrosis (PFH), side effects - most commonly dry mouth - are intolerable for most patients. THVD-102, a fixed-dose combination product has been developed combining oxybutynin, a muscarinic antagonist, and pilocarpine, a muscarinic agonist. The pilocarpine is at a dose level and release profile optimized to correct salivary flow impaired by oxybutynin yet not interfere with the therapeutic muscarinic antagonist effect of oxybutynin upon the sweat glands. OBJECTIVES: This study evaluated safety, efficacy, dry mouth and quality of life with THVD-102 (oxybutynin 7.5 mg / pilocarpine 7.5 mg) in subjects with axillary and / or palmar PFH. METHODS: After a 21-day open label treatment period with oxybutynin 5 mg twice daily to determine susceptibility of subjects to develop dry mouth, eligible subjects were randomized to 1 of 6 sequences of 3 study treatments (THVD-102, oxybutynin 7.5 mg, and placebo) in sequential 21day double-blind crossover treatment periods, each preceded by a washout period of at least 7 days. RESULTS: A total of 24 subjects were randomized and 19 finished all crossover treatments. Changes from baseline to end of treatment in symptoms associated with PFH were statistically significant for both THVD-102 versus placebo and for oxybutynin versus placebo as assessed by multiple measures. Beneficial trends, not statistically significant, for gravimetric measurements were also observed. There were no statistically significant differences between THVD-102 and oxybutynin in PFH efficacy. Fewer subjects reported moderate to severe dry mouth while receiving THVD-102 compared to oxybutynin and more subjects categorized their dry mouth as none or mild while receiving THVD-102 compared to oxybutynin. Differences in reported dry mouth were statistically significant. CONCLUSION: THVD-102 was generally well-tolerated. Both THVD-102 and oxybutynin 7.5 mg twice daily were effective in treating PFH. THVD-102 was associated with significantly reduced dry mouth compared to oxybutynin. J Drugs Dermatol. 2017;16(2):127-132.
Longitudinal Tracking of Autoantibody Levels in a Pemphigus Vulgaris Patient: Support for a Role of Anti-Desmoglein 1 Autoantibodies as Predictors of Disease Progression
Nadia Y. Abidi MD, Irene Lainiotis BS, Gretchen Malikowski MD, Kristina Seiffert-Sinha MD, and Animesh A. Sinha MD PhD|Anti-desmoglein (Dsg) 1 and -Dsg3 antibody titers have an established role in the diagnosis of the autoimmune blistering skin disease pemphigus vulgaris (PV). However, their usefulness for disease monitoring has been controversial. A recent large-scale immunoprofiling study by our group indicated that anti-Dsg1 levels may be a better predictor of disease activity than anti-Dsg3 levels, with declining levels predicting progression from active phase of disease to early remission, irrespective of lesional subtypes. Here, we report an illustrative case of a PV patient with mucocutaneous disease that was followed longitudinally for >2.5 years clinically and by serum serology. Autoantibody levels directed against both Dsg1 and -3 showed a moderate correlation with PDAI scores, supporting a correlation of Dsg1 and 3 levels with disease severity. However, while both anti-Dsg3 and -Dsg1 antibody levels demonstrated a steady parallel decline after initiation of rituximab therapy, only anti-Dsg1 antibodies fell to levels below detectability with the progression to remission, while anti-Dsg3 levels remained elevated. This case illustrates the potential key role and clinical benefit of tracking anti-Dsg1 levels to monitor and conceivably predict disease activity in patients with PV. J Drugs Dermatol. 2017;16(2):135-139.
Halobetasol Propionate Lotion, 0.05% Provides Superior Hydration Compared to Halobetasol Propionate Cream, 0.05% in a Double-Blinded Study of Occlusivity and Hydration
Gary Grove PhD,a Charles Zerweck PhD,a Tim Houser MS,a Anthony Andrasfay BS,b Bob Gauthier MS,b Charles Holland PhD,b and Daniel Piacquadio MDb|BACKGROUND: This study measured skin hydration and occlusivity of two test products [halobetasol propionate lotion, 0.05% (HBP Lotion) and Ultravate® (halobetasol propionate) cream, 0.05% (HBP Cream)] at 2, 4, and 6 hours after application to skin test sites previously challenged by dry shaving, which was performed to compromise the integrity of the stratum corneum barrier. METHODS: Trans-epidermal water loss (TEWL), an indicator of skin barrier function, was measured using cyberDERM, inc. RG-1 evaporimeter. Skin hydration was evaluated using IBS SkiCon-200 conductance meter. Test products were applied bilaterally on dry-shaved sites on the volar forearm sites, according to a randomization scheme, with two test sites untreated to serve as “dry-shaved” controls. TEWL and conductance were measured at 2, 4, and 6 hours post-treatment. RESULTS: HBP Lotion displayed a significant increase in skin hydration at 2, 4, and 6 hours post-treatment compared to the baseline values and dry-shaved controls (each, P less than 0.001). However, HBP Cream produced statistically significant increased skin hydration only after 6 hours (P less than 0.05). HBP Lotion was significantly more effective than HBP Cream in increasing skin hydration at 2 and 4 hours post-treatment (each, P less than 0.001), and had a directional advantage (not statistically significant) at 6 hours. Neither test product had a significant occlusive effect as measured by TEWL at 2, 4, and 6 hours post-application. CONCLUSION: Both formulations of HBP (Lotion and Cream) contributed to skin moisturization, as measured by skin conductance. HBP Lotion produced a significantly more rapid onset and higher level of moisturization at 2 and 4 hours post-application compared to HBP Cream. The TEWL results indicate that neither HBP Lotion nor HBP Cream provided any significant occlusivity to the skin.
J Drugs Dermatol. 2017;16(2):140-144.
Evaluation of the Physician Global Assessment and Body Surface Area Composite Tool for Assessing Psoriasis Response to Apremilast Therapy: Results from ESTEEM 1 and ESTEEM 2
Kristina C. Duffin MD MS,a Kim A. Papp MD PhD,b Jerry Bagel MD,c Eugenia Levi PharmD BCPS,d Rongdean Chen PhD,d and Alice B. Gottlieb MD PhDe|BACKGROUND: The Physician Global Assessment and Body Surface Area (PGAxBSA) composite tool is a simple, effective alternative for measuring psoriasis severity. OBJECTIVE: To evaluate the product of PGAxBSA as a sensitive alternative to the Psoriasis Area and Severity Index (PASI) for assessing disease severity and therapeutic response with data collected from the phase 3 ESTEEM 1 and 2 trials. METHODS: This post hoc analysis included 836 patients randomized to apremilast 30 mg BID at baseline (ESTEEM 1, n=562; ESTEEM 2, n=274). Spearman correlation coefficients were used to compare PGAxBSA, PASI, and the Dermatology Life Quality Index (DLQI). Concordance between PGAxBSA and PASI was evaluated for 50%/75%/90% improvement from baseline at week 16. RESULTS: In ESTEEM 1 and 2, PGAxBSA and PASI exhibited significant positive correlations for measuring disease severity at baseline (r≥0.757) and week 16 (r≥0.807). At week 16, ≥79% concordance was observed between PGAxBSA and PASI for 75% and 90% improvement from baseline; greater concordance (>88.0%) was observed using 50% improvement from baseline. At week 16, PGAxBSA and PASI were moderately correlated with DLQI. Limitations: Analysis was limited to patients with baseline BSA ≥10% and static PGA ≥3. CONCLUSIONS: In patients with moderate to severe psoriasis, PGAxBSA is correlated with PASI and sensitive to therapeutic response.
J Drugs Dermatol. 2017;16(2):147-153.
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Patrick Micheels MD,a Didier Sarazin MD,b Stéphanie Besse MD,c and Badwi Eliasd|The aim of this paper is to compare 2 hyaluronic acid gel fillers from the same Swiss manufacturer and with the same indications: filling of line wrinkles and folds. The products differ by their cross-linking process. With very simple easy-to-reproduce tests, cohesivity and resistance to traction forces were examined. Also, both gels were injected under ultrasound control in the mid reticular dermis of three subjects. The papules were controlled under ultrasound and biopsies at D0 and D15. Results showed significant differences between the 2 gels in all the tests. The new gel, manufactured with a lower-crosslinking density, seems to benefit from better integration in the tissue of the mid reticular dermis and to have a more cohesive nature than its comparator from a previous crosslinking technology. Under clinical observation, the range of new products present excellent tissue integration properties.
J Drugs Dermatol. 2017;16(2):154-161.
Ifedayo O. Kuye BAa and Gideon P. Smith MD PhDb|There is growing adoption of rituximab in the treatment of dermatomyositis patients whose disease is refractory to steroids. However, the effects have not been extensively studied. This is a retrospective study of 25 patients with dermatomyositis who were treated with rituximab. Data from January 2000 to July 2014 was obtained from a clinical data repository, which yielded results from two tertiary centers in the United States. We analyzed information on muscle weakness, skin disease, enzyme levels, and immunosuppressive medication use before and after treatment with rituximab. The follow-up time was six months. Among the patients with skin disease before treatment with rituximab, 72.2% had a clinical improvement in their skin disease at the follow-up visit (P less than0.01). Among the patients with proximal muscle weakness before treatment with rituximab, 81.8% had clinical improvement in their symptoms at the follow-up visit (P less than0.01). The average prednisone dose before rituximab therapy was 18.9 mg, and this dropped to 11.0 mg at follow up (P less than 0.05). The average number of immunosuppressive medications taken by patients dropped from 2.04 to 1.74 (P less than0.05). These changes were less in magnitude and significance among the subset of patient that had an additional connective tissue autoimmune condition.
J Drugs Dermatol. 2017;16(2):162-166.
Annular Elastolytic Giant Cell Granuloma Successfully Treated With Adalimumab Subsequently Complicated by Drug-Induced Lupus
Adele Haimovic MD, Hideko Kamino MD, and David E. Cohen MD MPH|We report a 51-year-old female with a 3-year history of recalcitrant annular elastolytic giant cell granuloma (AEGCG) who was effectively treated with the anti-tumor necrosis factor (TNF)-alpha antibody, adalimumab. Her disease was refractory to topical glucocorticoids, intralesional glucocorticoids, narrow-band ultraviolet light (UV)-B phototherapy and cyclosporine. During her treatment with adalimumab she developed a positive anti-nuclear-antibody and double-stranded-DNA antibody and her treatment was terminated. Our findings suggest that adalimumab is an efficacious therapeutic alternative for the treatment of annular elastolytic giant cell granuloma unresponsive to standard therapies, however drug-induced lupus is a potential side effect that clinicians must be cognizant of. To our knowledge, this is the first time adalimumab has successfully been used in the treatment of AEGCG.
J Drugs Dermatol. 2017;16(2):169-171.
Joshua D. Fox MD,a Sander R. Dubovy MD,b Sara T. Wester MD,c and Keyvan Nouri MDa|A variety of tumors may involve the eyelid, most of which are primary, but rarely can be metastatic. Previously reported eyelid primary carcinomas with neuroendocrine features include Merkel cell carcinoma, apocrine and eccrine gland carcinoma, sebaceous gland carcinoma, and one report of primary “well-differentiated neuroendocrine tumor.” Herein we report the first case of primary cribriform carcinoma of the eyelid with neuroendocrine features. The patient is a 75-year-old black man who presented to the clinic with a 5-year history of a slowly growing, non-painful, non-exudative lesion of his left lower eyelid. Examination disclosed a non-tender 8 mm by 9 mm ovoid, firm, euchromic subdermal non-adherent nodule involving the left lower eyelid with no madarosis or loss of lid margin architecture, but with overlying induration. An incisional biopsy demonstrated nodules and aggregates of tumor composed of cuboidal hyperchromatic basoloid cells with occasional mitotic figures within sheets in a mostly cribriform and occasionally papillary pattern. The tumor was diffusely positive for cytokeratin, Epithelial Membrane Antigen, and p40 and focally positive for synaptophysin. The tumor was negative with antibodies for Cytokeratin 20 (CK20), p63, CD10, Thyroid Transcription Factor-1, Cytokeratin 7, Prostate Specific Antigen, and Epithelial Specific Antigen. Oncologic evaluation was negative for metastases. The patient underwent a complete excision of his eyelid tumor with 5 mm margins using Mohs surgery, with subsequent reconstruction using a Hughes tarsoconjunctival flap, myocutaneous advancement flap, and lateral canthal tendon plication.
J Drugs Dermatol. 2017;16(2):173-174.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS) in a Psoriasis Patient Treated With Ustekinumab
Lauren Dickson MD and Alan Menter MD|The use of monoclonal antibodies against interleukin (IL)-12 and -23, such as ustekinumab, has considerably reduced the disease burden in many patients with moderate to severe psoriasis. Reversible posterior leukoencephalopathy syndrome (RPLS) is a neurologic disorder that has been documented with increased frequency with the use of systemic and biologic agents. We report a case of a 58-year-old man with psoriasis who presented with confusion and memory difficulties after being on treatment with ustekinumab for over six years. Imaging with CT and MRI revealed mild parenchymal edema with the typical appearance and distribution of RPLS, confirming the diagnosis of this condition. This case reports the second case of RPLS associated with ustekinumab treatment, with the only other known case reported during clinical trials. With the increasing use of biologics in patients with moderate to severe psoriasis, it is critical that clinicians are cognizant of this potential associated adverse event.
J Drugs Dermatol. 2017;16(2):177-179.
Laura F. Sandoval DOa and Howard Steinman MDb|Microcystic adnexal carcinoma is a rare cutaneous tumor that is often misdiagnosed and has the potential to be aggressive. Mohs surgery is the treatment of choice to prevent recurrences. We present a case of a large recurrent microcystic adnexal carcinoma on the sternum, initially diagnosed as a basal cell carcinoma. This tumor infiltrated the muscle and bone and was unresectable with Mohs surgery.
J Drugs Dermatol. 2017;16(2):180-181.
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.