Pachyonychia Congenita: A Research Agenda Leading to New Therapeutic Approaches.

Pachyonychia congenita (PC) is a dominantly inherited genetic disorder of cornification. PC stands out among other genodermatoses because despite its rarity, it has been the focus of a very large number of pioneering translational research efforts over the past 2 decades, mostly driven by a patient support organization, the Pachyonychia Congenita Project. These efforts have laid the ground for innovative strategies that may broadly impact approaches to the management of other inherited cutaneous and noncutaneous diseases. This article outlines current avenues of research in PC, expected outcomes, and potential hurdles.

SIG1273: a new cosmetic functional ingredient to reduce blemishes and Propionibacterium acnes in acne prone skin.

BACKGROUND: Propionibacterium acnes is a major contributing factor to the inflammatory component of acne. The interaction of P. acnes with keratinocytes leads to an innate immune response via activation of toll-like receptors (TLR2, TLR4) resulting in the production and secretion of pro-inflammatory mediators. SIG1273, an isoprenylcysteine small molecule modulates inflammatory signaling pathways and kills P. acnes. SIG1273 represents a novel cosmetic functional ingredient that provides relief from blemishes in acne prone skin. OBJECTIVE: To assess the keratinocyte response and microbial growth of SIG1273 in vitro and evaluate the tolerability of SIG1273 gel applied topically in acne prone subjects. METHODS: For in vitro studies, human keratinocytes were exposed in culture to live P. acnes and peptidoglycan (PGN) to induce IL-8 production. P. acnes were cultured to determine minimal inhibitory concentration and minimal bactericidal concentration values. A total of 30 subjects were randomized in a double-blind controlled trial receiving 3% SIG1273 gel or vehicle for 6 weeks. Evaluation included inflammatory lesions, noninflammatory lesions, microcomedones, Sebutape scores, and P. acnes counts. RESULTS: In vitro studies demonstrate SIG1273 inhibits P. acnes-induced IL-8 production and inhibits P. acnes growth. SIG1273 gel was well tolerated with no signs of stinging, redness, or itching. Furthermore, improvement in some aspects of acne was observed in subjects applying SIG1273 gel, including inflammatory lesions, microcomedone counts and Sebutape scores. Facial scrubs taken to measure P. acnes colony-forming units showed those applying SIG1273 gel had ~1.0 Log 10 colony reduction over the length of the study, a statistically significantly improvement when compared with vehicle. No significant effects above vehicle were observed for noninflammatory lesions. CONCLUSIONS: SIG1273 represents a novel cosmetic functional ingredient that provides a safe dual modulating benefit to individuals with acne prone skin by reducing P. acnes counts and reducing inflammation.

Reappraising the phototoxicity of tretinoin: a report of four controlled clinical trials.

BACKGROUND: Retinoids are photoreactive molecules found in skin and retinal tissue. The use of retinoids in pharmacologic doses, applied topically, raises the potential of phototoxicities. Recent review articles and current US drug labeling indicate that tretinoin is a phototoxin. In developing a new formulation of topical all-trans-retinoic acid (tretinoin), formal testing of dermal photoreactions was therefore undertaken. METHODS: Four prospective, randomized, and controlled trials were carried out in healthy volunteers at two independent research facilities. Two trials examined phototoxicity following 24 h of drug exposure under occlusion (combined n=51), and two examined photoallergenicity following a 3-week, six dose induction phase (combined n=72) followed by challenge. RESULTS: No phototoxic or photoallergic reactions occurred with tretinoin 0.05% in a new gel formulation. CONCLUSION: The findings in these studies are consistent with previous studies of tretinoin in various formulations, and support the conclusion that tretinoin appears to be neither phototoxic nor photoallergenic in vivo.

Influence of papain urea copper chlorophyllin on wound matrix remodeling.

The purpose of this study was to examine the dermal and epidermal alterations associated with wound healing in wounds treated with papain urea copper chlorophyllin (PUC), papain-urea, copper chlorophyllin, or urea base ointment and compare these with moist wound care using a porcine full-thickness infected wound model. All the wounds were evaluated postsurgery for erythema, transepidermal water loss, microscopic morphology, and changes in protein expression. Examination of stained paraffin sections revealed an increase in the number of keratinocytes present in the epidermis of the PUC and papain-treated pigs, relative to moist control. This increase in keratinocyte number corresponded to an increase in the movement of the keratinocytes into the underlying dermis in the form of rete pegs. In the dermis, there appeared to be an increase in blood vessel formation, collagen I deposition, and mature collagen in the papain and PUC treated tissues. The quality of healing appears to be enhanced based on the number of keratinocytes present in the epidermis, the extensive rete peg formation, the increase in vasculature, and the increase in collagen birefringence.

The position not the presence of the halogen in corticosteroids influences potency and side effects.

Many topical corticosteroids currently on the market contain a halogen substitution at the C6, C9, or the side-chain C21 position of the corticosteroid skeleton. These modifications have enhanced the efficacy of corticosteroids as compared to hydrocortisone as topical anti-inflammatory agents, but have often increased side effects such as skin atrophy, adrenal suppression, and telangiectasia. These side effects have been attributed to the presence of halogens in the corticosteroid molecule and have raised concerns regarding the safety of all halogenated corticosteroids. In this review, we assert that it is the position and nature of the halogen atom(s) in the corticosteroid molecule that determine potency/toxicity, rather than their mere presence. A greater understanding of the role of halogenation in determining corticosteroid potency and side effects will clarify why all halogenated steroids are not the same.

Multivesicular emulsion: a novel, controlled-release delivery system for topical dermatological agents.

Multivesicular emulsion systems are a new patented technology for topical delivery of pharmaceutical and over-the-counter actives. This novel technology involves the creation of a 2-phase, oil-in-water emulsion system that produces concentric multilamellar spheres of oil and water. Active ingredients can be released from their respective layers upon application to the skin. In addition to a controlled-release of active agents, the multivesicular emulsion base improves the biophysical properties of the skin by reducing transepidermal water loss and enhancing skin hydration. This technology has been applied to 6% salicylic acid formulations that in clinical experience show efficacy with high tolerance in several hyperkeratotic disorders. Subjects' self-assessment was clearly indicative of the excellent cosmetic elegance of the multivesicular emulsion system.