Journal: Journal of drugs in dermatology : JDD
Mid-dermal injection of stabilized hyaluronic acid (HA) is well established as a treatment to reduce the effects of skin aging.
Epigenetic phenomena, including DNA methylation, histone modification, and genetic regulation by miRNAs, are potentially heritable genetic regulatory changes that are not attributed to direct alterations in the DNA sequence of base pairs. They may explain the link between psoriasis risk alleles and disease development, as alleles possess various potentials to undergo epigenetic modification. Multiple genes involved in psoriasis pathogenesis demonstrate abnormal methylation patterns including those involved in epidermal differentiation and proliferation, immunity, the cell cycle, apoptosis, inflammation, and IFN-γ and TNF-α signaling. Hypoacetylation of histone H4 is observed in peripheral blood mononuclear cells of psoriatic patients, and the degree of hypoacetylation of histone H4 is inversely correlated to the PASI score. Investigators have reported both increased and decreased expression of miRNAs in patients with psoriasis, and have described and speculated a number of possible mechanisms for their roles in pathogenesis. Interestingly, the altered methylation patterns observed in psoriasis appear to be normalized by treatment with biologics directed at TNF-α inhibition. However, attempts to directly correlate epigenetic regulatory mechanisms with expression of genes observed in psoriasis have been limited thus far, and correlating miRNA expression levels to disease phenotypes can be challenging and inconsistent. Hopefully, the goal of drawing clinically relevant conclusions about the role of epigenetics in psoriasis will be aided by recent methods that enable fast and sensitive epigenomic profiling. Drugs targeting epigenetic mechanisms are currently being explored, though not for psoriasis, but specificity to pathogenetic mechanisms remains elusive. However, the amenability of cutaneous disease to topical therapies may elevate their usefulness in the treatment of this common skin disorder.
J Drugs Dermatol. 2014;13(2):111-118.
Abdominal Cesarean sections (C-sections) are frequently associated with an increased risk of excessive or unpleasant scarring. A topical scar gel containing extract of Allium cepae, allantoin and heparin (Contractubex®; Merz Pharmaceuticals GmbH, Germany), has shown efficacy in improving the appearance of various scar types.
Calcium hydroxylapatite filler (CaHA; Radiesse) is a synthetic, non-animal derived product composed of minerals that occur naturally in bone and teeth. Following its development in the US, initial approval by the US FDA for non-aesthetic indications and CE marking in Europe, it was used off FDA-labeling for aesthetic purposes. Its use has grown further since its FDA approval in 2006 for long-lasting correction of moderate to severe wrinkles and folds. It is a popular filler for volume restoration to the face, and also to nonfacial areas such as the dorsum of the hands.
Dermal fillers are important for facial aesthetic enhancement as patients are favoring non-surgical procedures with minimal recovery time. Voluma is a volumizing hyaluronic acid filler, 20 mg/ml HA dermal filler, which was FDA-approved in 2013 as the first dermal filler for treatment of age-related volume loss in the midface.
Aesthetics continues to be a rapidly growing field within dermatology. In 2014, Americans spent 5 billion dollars on an estimated 9 million minimally invasive cosmetic procedures. Between 1997 and 2014, the number of aesthetic procedures performed on men increased by 273%. The approach to male aesthetics differs from that of females. Men have a squarer face, a more angled and larger jaw, and equally balanced upper and lower facial proportions. Facial muscle mass, subcutaneous tissue, and blood vessel density are also increased in men relative to women. While many of the same cosmetic procedures are performed in males and females, the approach, assessment, and treatment parameters are often different. Improper technique in a male patient can result in feminizing facial features and patient dissatisfaction. With an increasing number of men seeking aesthetic procedures, it behooves dermatologists to familiarize themselves with male facial anatomy and the practice of cosmetic dermatology in this population.
J Drugs Dermatol. 2015;14(9):1029-1034.
In the Comparative Study of Humira vs Methotrexate vs Placebo In Psoriasis Patients (CHAMPION) study, significantly more patients achieved ≥75% improvement in the Psoriasis Area and Severity Index (PASI75) and ≥90% improvement (PASI90) after 16 weeks of treatment with adalimumab (80 mg at week 0, then 40 mg every other week starting at week 1) compared with methotrexate (up to 25 mg/week orally) or placebo. In this exploratory analysis, the efficacy of adalimumab was evaluated in a subset of the CHAMPION patient population stratified by baseline body mass index (BMI).
METHODS: PASI responses and Dermatology Life Quality Index (DLQI) scores through 16 weeks of treatment were examined by baseline BMI category (<25 kg/m2 [normal], 25 to <30 kg/m2 [overweight], and ≥30 kg/m2 [obese]) in patients with psoriasis with a baseline PASI total score ≥12. Treatment differences between the adalimumab and the methotrexate or placebo groups were compared using Fisher’s exact test for PASI responses and 1-way analysis of variance for DLQI scores.
RESULTS: In all BMI categories, adalimumab treatment led to significantly greater rates of PASI75/90 responses at weeks 12 and 16 compared with methotrexate or placebo (P<0.05 for all). In normal weight, overweight, and obese patients at week 16, the respective PASI75 response rates were 85.0%, 85.7%, and 61.3% with adalimumab; 43.3%, 29.3%, and 26.1% with methotrexate; and 28.6%, 16.7%, and 0% with placebo. PASI90 response rates were 70.0%, 53.6%, and 35.5% with adalimumab; 26.7%, 7.3%, and 8.7% with methotrexate; and 9.5%, 16.7%, and 0% with placebo. Across all BMI subgroups, the greatest decreases in DLQI scores from baseline occurred in the adalimumab group.
CONCLUSION: Significantly higher PASI75/90 response rates and more pronounced improvements in DLQI scores at week 16 were identified in patients treated with adalimumab, compared with methotrexate or placebo, regardless of baseline BMI category.
J Drugs Dermatol. 2015;14(8):864-868.
The treatment of cutaneous wounds in the clinical setting continues to be a clinical challenge and economic burden, with burn wounds being especially formidable. Direct mechanical injury coupled with the transfer of thermal energy leads to tissue necrosis, pro-inflammatory cytokine release and the eventual expansion of an initial wound. Our current therapeutic armamentarium falls short of options to help prevent wound expansion, and therefore new modalities are required. Nitrosating substances such as RSNOs have been proven to be effective in promoting wound closure due to their ability to modulate inflammation, cytokine production and vascular function.
Leflunomide (LEF) is an immune modulator used most commonly for rheumatoid arthritis (RA). The mechanisms of action of LEF also include anti-microbial effects, particularly anti-viral effects.
OBSERVATIONS: We present three patients with atopic dermatitis on azathioprine therapy who had multiple verrucae and in two molluscum contagiosum (MC) that were resistant to repeated conventional therapies. These patients were switched to LEF, and all the patients showed complete resolution of their verrucae and MC within 2 months of starting therapy. In addition, all three patients showed equivalent to better control of their atopic dermatitis with LEF.
CONCLUSIONS: LEF has previously been reported to be a useful immune modulator for the treatment of severe atopic dermatitis. The spectrum of anti-viral effects previously seen with leflunomide did appear beneficial in these patients in clearing verrucae and MC, which had been resistant to conventional therapies while the patients were on azathioprine.
J Drugs Dermatol. 2015;14(3):230-234.
Poly-ureaurethane has been previously described for the management of dry, brittle, and in general, dystrophic nails. The polymer yields a waterproof, breathable barrier to protect the nail plate and prevent further damage to the nail, while regulating transonychial water loss (TOWL). Because nail dystrophy and dessication are contributing factors to onychomycosis, a barrier that protects the nail but also allows a topical antifungal to permeate its shield is potentially an advantageous combination. Oral antifungals such as terbinafine, itraconazole, and fluconazole, as well as the newer topical antifungals efinaconazole and tavaborole (although formulated to penetrate the nail unit and work with the porosity and inherent electrical charge of the nail plate), do not take into account nail damage that has been created from years of harboring a dermatophyte infection. Up to 50% of cases presumed to be onychomycosis are in fact onychodystrophy without fungal infection, and laboratory testing for fungus should be obtained prior to initiating antifungal treatment. Whether a nail has onychomycosis, or onychodystrophy due to other causes, barrier function and structural integrity are compromised in diseased nails, and should be addressed. A poly-ureaurethane barrier that protects against wetting/drying, fungal reservoirs, and microtrauma, followed by the addition of oral or topical antifungals after laboratory fungal confirmation may optimize outcomes in the treatment of onychomycosis.
OBJECTIVE: The purpose of this work was to determine through in vitro release testing (IVRT) whether poly-ureaurethane 16% allows for penetration of efinaconazole 10% or tavaborole 5%. Results could spur subsequent clinical studies which would have implications for the addition of an antifungal based on fungal confirmation, after addresssing the underlying nail dystrophy primarily.
METHODS: A vertical diffusion cell system was used to evaluate the ability of efinaconazole 10% and tavaborole 5% to penetrate across poly-ureaurethane 16%. The diffusion cells had a 1.0 cm2 surface area and approximately 8 mL receptor volume. Poly-ureaurethane 16% was applied to a 0.45 μm nylon membrane and allowed to dry before use. Efinaconazole 10% or tavaborole 5% was then applied to the poly-ureaurethane 16% coated membrane, and samples were pulled from the receptor chamber at various times. Reverse phase chromatography was then used to assess the penetration of each active ingredient across the membrane.
RESULTS: The flux and permeability of efinaconazole or tavaborole across poly-ureaurethane 16% were determined from efinaconazole 10% or tavaborole 5%, respectively. The flux and permeability of efinaconazole were determined to be 503.9 +/- 31.9 μg/cm2/hr and 14.0 +/- 0.9 nm/sec. The flux and permeability of tavaborole were determined to be 755.5 +/- 290.4 μg/cm2/hr and 42.0 +/- 16.1 nm/sec.
CONCLUSION: In addition to the treatment of onychoschizia, onychorrhexis, and other signs of severe dessication of the nail plate, a barrier that regulates TOWL should be considered in the management onychomycosis to address barrier dysfunction and to promote stabilization of the damaged nail. Previously published flux values across the nail are reported to be 1.4 μg/cm2/day for efinaconazole and 204 μg/cm2/day for tavaborole. These values are substantially lower than the herein determined flux for both molecules across poly-ureaurethane 16%. A comparison of the data suggests that poly-ureaurethane 16%, if used prior to efinaconazole or tavaborole, would not limit the ability of either active ingredient to access the nail, and therefore, would be unlikely to reduce their antifungal effect. Onychodystrophy is inherent in, and often precedes onychomycosis, and consideration should be given for initiation of treatment in the same sequence: stabilizing and protecting the nail plate barrier primarily, and subsequently adding oral or topical antifungals after laboratory confirmation. Future clinical studies will be needed to determine combination efficacy for in vivo use.
J Drugs Dermatol. 2016;15(9):1116-1120.