Dow Stough

Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis

BACKGROUND There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus, is being evaluated as a topical therapy for actinic keratosis. OBJECTIVE Assess the efficacy and safety of ingenol mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis. METHODS Patients with non-facial actinic keratoses applied vehicle gel for 3 days, ingenol mebutate gel, 0.025% for 3 days, or ingenol mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period. RESULTS All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with ingenol mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel (P = .0002 to P < .0001 vs vehicle). The complete clearance rate was also significantly higher (P < or = .0006) for patients in the ingenol mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for ingenol mebutate gel compared with 13.3% for vehicle, P < .0001 to .0007 vs vehicle). The median percentage reduction in baseline actinic keratosis lesions for patients treated with ingenol mebutate gel ranged from 75% to 100% compared with 0% for vehicle gel (P < .0001 vs vehicle). Active treatment was well tolerated at all dosages. The mechanism of action of this agent is the localized induction of necrosis followed by a transient inflammatory response, and this was manifested in most patients as transient local skin responses consisting primarily of erythema, flaking/scaling, and crusting. There was no evidence of treatment-related scarring. LIMITATIONS Local skin responses may have suggested active treatment to investigators. CONCLUSIONS Short-course, field-directed therapy with ingenol mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.

Philosophy and technique in hair restoration surgery

Hair restoration surgeons can now evaluate the results of 25 years of hair restoration techniques. With the advent of total micrografting and a sharp decline in scalp reduction procedures, a new era of hair restoration has begun. These changes call for a reevaluation of patient selection and procedure planning. Surgeons need no longer to struggle for coverage of the entire bald scalp, because new techniques use the visual qualities of hair and varying design patterns to create the optical illusion of more hair than is actually present. The creation of a high, mature, static hairline with prominent frontoparietal recessions and a thin, albeit natural, look has revolutionized the way hair restoration surgery is approached. This new approach affects philosophic issues, candidate selection, hairline design, and surgical technique. The main impetus for recent changes in hair restoration surgery has been twofold: (1) the use of one to four hair grafts, which allows a natural, undetectable hairline, and (2) the transplantation of large numbers of these small grafts during a single session. Older techniques were milestones in their time but were often unnatural in appearance, disfiguring, and did not address long-term concerns. Newer philosophies and techniques are geared towards naturalness and undetectability for the lifetime of the patient. The driving force that has led to the use of smaller grafts and a more natural product has been a study of outcome assessment of previous hair restoration procedures. Instead of short-term goals, the surgeon and patient are now beginning to consider the long-term outcomes of various techniques and procedures. A cosmetically pleasing, long-lasting, undetectable transplant has become the ultimate goal regardless of how dense or complete the transplant is. In our reevaluation of the philosophies and techniques in hair restoration surgery, we address each aspect of the process leading to the desired final product — a natural, undetectable transplant that withstands the test of time.

Core curriculum for hair restoration surgery, recommended by the International Society of Hair Restoration Surgery (ISHRS).

BACKGROUND Because hair restoration surgery (HRS) has changed so significantly, the International Society of Hair Restoration Surgery (ISHRS) presents the recently developed Core Curriculum for Hair Restoration Surgery (CCHRS). Physician competence in HRS demands a sound understanding of all of the alternate pathologic causes of hair loss, as well as their risks and treatments. OBJECTIVE The CCHRS defines the knowledge, didactic information, medical insights, and surgical techniques that are essential to physician competence in the correct diagnoses and treatment of hair loss problems, in a manner consistent with patient safety and sound esthetic results. The ISHRS hopes that all existing surgical and dermatology training programs that teach HRS procedures will find the CCHRS useful in developing their curriculum relative to HRS and that this will facilitate the development of a new standard of training within the profession. METHODS Developed and reviewed by a committee of experienced hair restoration surgeons. RESULTS The CCCHRS clearly defines the diagnosis and treatment of hair loss as a multidimensional specialty requiring knowledge of several medical disciplines, including genetics, endocrinology, dermatology, and surgery. CONCLUSION The ISHRS believes that the CCHRS is an important contribution to physician education in HRS and that a clearly defined core curriculum will facilitate achieving contemporary results and higher patient satisfaction.

Commentary on A New Subtype of Lichen Planopilaris Affecting Vellus Hairs and Clinically Mimicking Androgenetic Alopecia.

In the journal article by Drs. Abbasi and colleagues, they present data on a cross-sectional study ofmen and women who were undergoing hair transplantation. The sampling of participants was limited to men and women with no knowledge of any hair pathology other than typical androgenetic alopecia; thus, this was not a referred subset with preexisting known lichen planopilaris (LPP). Of the 650 patients in this study, 58 had clinical biopsies which were identical to LPP. Specifically, the histology demonstrated classical histopathological features seen in LPP. Even more impressive than the large sampling size and statistical data was the findings of predominantly terminal hair and a significant decrease in vellus hair. In addition, there were minute “punctate scars” present. Dr. Abbasi and colleagues have confirmed what many transplant surgeons have encountered over the years, that is a subtype of patients who have subtle folliculitis who may develop a more fulminant manifestation of LPP after transplantation. Thus, it is crucial that we use every tool available to identify this subset of patients before transplantation. By identifying these patients before surgery, we can warn our patients of future problems and perhaps prevent adverse outcomes through better therapeutic regimens. Finally, the questionmust be asked “Is this a new subset of LPP with distinctive characteristics, or is this a variant of androgenetic alopeciapresenting aspatternbaldness?” Only time will sort out this question. We look forward to future findings from Dr. Abbasi and colleagues.