Guidelines for clinical trials of frontal fibrosing alopecia: consensus recommendations from the International FFA Cooperative Group (IFFACG).

BACKGROUND: Frontal fibrosing alopecia (FFA) has become one of the most common causes of cicatricial alopecia worldwide. However, there is a lack of clear aetiology and robust clinical trial evidence for the efficacy and safety of agents currently used for treatment. OBJECTIVES: To enable data to be collected worldwide on FFA using common criteria and assessment methods. METHODS: A multicentre, international group of experts in hair loss was convened by email to create consensus recommendations for clinical trials. Consensus was defined at > 90% agreement on each recommended part of these guidelines. RESULTS: Standardized diagnostic criteria, severity rating, staging, and investigator and patient assessment of scalp hair loss and other clinical features of FFA were created. CONCLUSIONS: These guidelines should allow the collection of reliable aggregate data on FFA and advance efforts in both clinical and basic research to close knowledge gaps in this condition.

Identification and characterization of an abundant ovarian interstitial gland protein associated with sexual maturity in rabbits.

An abundant ovarian protein with a relative mol wt (Mr) of 37K and an apparent pI of 8, associated with the onset of sexual maturity in the rabbit, has been identified. Ovaries from sexually mature (greater than 6 months old) rabbits contain large quantities of this 37K protein, while none can be detected in ovaries of immature (1 and 2 months) animals. Analysis of polyacrylamide gel electrophoresis (PAGE) gels of mature ovarian homogenates demonstrates that this protein is more abundant than actin in these preparations. It appears to be tissue specific, since it was not detected in 16 other rabbit tissues tested. Autoradiographic analysis of proteins labeled with 35S in ovarian organ culture demonstrates that a protein of identical Mr and charge to the 37K protein is synthesized in this tissue. Polyclonal sheep antiserum has been produced to the two-dimensional PAGE-purified protein. Immunoblotting of two-dimensional PAGE gels shows specific recognition of this protein and two slightly more acidic proteins of the same Mr by this antiserum. These three protein species also stain identical colors with a silver-based color stain, further suggesting that these are charge variants of the same protein. This protein is not present in corpora lutea isolated form sexually mature ovaries and is present in interstitial cell-enriched ovaries of rabbits which have been actively immunized with zona pellucida proteins. Immunocytochemical localization studies further demonstrate that this protein is localized in the interstitial gland cells. These findings suggest that this 37K protein is not associated with either follicular or luteal cells, but, rather, is linked with the 20 alpha-hydroxyprogesterone-secreting interstitial gland cell population.

A randomized, controlled trial of a low-dose contraceptive containing 20 microg of ethinyl estradiol and 100 microg of levonorgestrel for acne treatment.

OBJECTIVE: To evaluate the efficacy of a low-dose oral contraceptive (OC) containing 100 microg of levonorgestrel (LNG) and 20 microg of ethinyl estradiol (EE) compared with placebo for the treatment of moderate acne. DESIGN: Multicenter, randomized, double-blind, placebo-controlled clinical trial. SETTING: Outpatient dermatology clinics. PATIENT(S): Women (> or =14 years old; n = 350) with normal menstrual cycles and moderate acne were randomized to receive LNG/EE or placebo for six cycles. INTERVENTION(S): Twenty microg of EE and 100 microg of LNG. MAIN OUTCOME MEASURE(S): Acne lesion counts and clinician global assessment were performed at baseline and at each cycle. Patient self-assessment was carried out at baseline and at cycles 4 and 6; blood pressure and weight were measured at baseline and at cycles 1, 3, and 6. RESULT(S): Inflammatory, noninflammatory, and total lesion counts at cycle 6 with LNG/EE were significantly lower compared to placebo. Patients in the LNG/EE group also had significantly better clinician global and patient self-assessment scores than those in the placebo group at cycle. Changes in weight from baseline were similar between patients in the LNG/EE and placebo groups at all measured time points. CONCLUSION(S): This double-blind, placebo-controlled study demonstrates that a low-dose OC containing 20 microg of EE and 100 microg of LNG is an effective and safe treatment for moderate acne.

A role for leukotriene antagonists in atopic dermatitis?

Atopic dermatitis is a chronic, relapsing skin condition that affects over 2% of the population. The pathophysiology of this disease is not completely understood, but immunologic abnormalities and the subsequent release of inflammatory mediators play a central role. Treatment with glucocorticoids has long been the standard of care, but their use is limited by their adverse effect profile. Leukotrienes (LTB4, LTC4, LTD4, and LTE4) are metabolites of arachidonic acid produced through the 5-lipoxygenase pathway. They play an important role in inflammatory and atopic conditions. LT modulating agents have been used with success in asthma. Recently, there has been increased interest in the potential utility of LT antagonists in atopic dermatitis. In vitro and in vivo data have demonstrated that LTs may play a key role in atopic dermatitis. The 2 different types of LT-modulating agents are 5-lipoxygenase inhibitors and LT receptor antagonists. Since the 5-lipoxygenase inhibitor acts at an earlier step in the LT synthetic pathway, it has the ability to alter the production of all the LTs, including LTB4, while the receptor antagonists target only the cysteinyl LTs, LTC4, LTD4, and LTE4. This reduction of LTB4 activity may point to a therapeutic advantage in using LT synthesis inhibitors as opposed to LT receptor antagonists for atopic dermatitis. Clinical evidence of the use of LT agents in atopic dermatitis is limited, but initial results have been promising and these agents may one day serve as corticosteroid-sparing treatments for atopic dermatitis.

Weight change and adverse event incidence with a low-dose oral contraceptive: two randomized, placebo-controlled trials.

Changes in body weight and the incidence of estrogen-related side effects with low-dose oral contraceptives (OCs) containing 20 microg ethinyl estradiol (EE) have not been demonstrated in placebo-controlled trials. Two placebo-controlled, randomized trials demonstrated the efficacy of a low-dose OC for the treatment of acne in healthy females (n = 704; >or=14 years old) with regular menstrual cycles and moderate facial acne. Patients were randomized to receive 20 microg EE/100 microg levonorgestrel (LNG) or placebo for six cycles. Body weight was measured at baseline and during Cycles 1, 3, and 6. The occurrence of adverse events was recorded at each visit. Mean changes in weight from baseline were similar with 20 microg EE/100 microg LNG [0.72 kg +/- 2.64 (SD; n = 349)] and placebo [0.56 kg +/- 2.64 (SD; n = 355; p > 0.05)] for the last measured weight of each patient. Rates of headache, nausea, weight gain, and breast pain, side effects commonly attributed to OCs, were also similar between groups (p > 0.05). No serious, unexpected, drug-related adverse events occurred during the study. The low-dose OC containing 20 microg EE/100 microg LNG is safe, well tolerated, and does not cause weight gain.

Bioengineering the hair follicle.

The hair follicle develops from the primitive embryonic epidermis as a result of complex epithelial-mesenchymal interactions. The full follicle, consisting of epithelial cylinders under control of a proximal lying mesenchymal papilla, grows in cycles giving rise to a new hair shaft during each cycle. The ability to cycle endows the follicle with regenerative properties. The evolution of hair follicle engineering began with the recognition in the early 1960's that hair follicles could be transplanted clinically into a foreign site and still grow a shaft typical of the donor site. Since that time, it has been found that the follicular papilla has hair follicle inducing properties and that the hair follicle houses within it epithelial stem cells that can respond to hair inductive signals. These findings have laid the foundation for isolating hair-forming cells, for expanding the cells in culture, and for forming new follicles in vivo.

Rediscovering thalidomide: a review of its mechanism of action, side effects, and potential uses.

Thalidomide, a hypnosedative drug introduced in the 1950s, has been used in a variety of dermatologic conditions during the past few decades. Although originally withdrawn from the world market on discovery of its teratogenic effect, it has since been selectively reintroduced for use in various disorders thought to have an autoimmune or inflammatory basis. A review of the literature focused on clinical uses of thalidomide in the treatment of dermatologic diseases was performed. Diseases for which thalidomide has been found effective include erythema nodosum leprosum, prurigo nodularis, actinic prurigo, discoid lupus erythematosus, aphthous stomatitis, Behçet's syndrome, and graft-versus-host disease. Side effects such as teratogenicity and peripheral neuropathy remain its limiting factor. Thalidomide is a useful addition to the therapeutic armamentarium for treatment-resistant dermatoses as long as proper vigilance for adverse effects is maintained.

Rediscovering mycophenolic acid: a review of its mechanism, side effects, and potential uses.

Oral mycophenolic acid (MPA) therapy has been investigated in the treatment of moderate to severe psoriasis since the early 1970s and has been found to be both safe and effective. By inhibiting de novo purine biosynthesis, it functions as an antifungal, antibacterial, antiviral, and immunosuppressive agent. The recent availability of mycophenolate mofetil (MMF), a morpholinoester of MPA, has created renewed interest in the antipsoriatic properties of MPA. MMF is currently indicated for the prevention of organ rejection in transplant recipients and is used concomitantly with cyclosporine and corticosteroids. This review focuses on the pharmacology of MPA and MMF, studies of MPA in the treatment of psoriasis, and therapy with MMF. There is a potential application of MMF in the treatment of severe psoriasis and other inflammatory dermatoses, as well as topical MPA for the treatment of psoriasis.

Efficacy of topical sensitizers in the treatment of alopecia areata.

It has been more than 2 decades since the first report of the use of dinitrochlorobenzene to induce hair growth in 2 patients with alopecia areata. Other topical sensitizers, namely squaric acid dibutylester and diphenylcyclopropenone, have been used with variable success. This article reviews the efficacy and safety of the use of topical sensitizers in the treatment of alopecia areata.