Ken Washenik

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.

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.

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.

A randomized, double‐blind, placebo‐controlled study of clobetasol propionate 0.05% foam in the treatment of nonscalp psoriasis

Background Topical corticosteroids are the primary treatment for mild to moderate psoriasis. Foam preparations of corticosteroids offer potential cosmetic and pharmacodynamic advantages over cream and ointment vehicles. A clobetasol propionate foam product is as effective as clobetasol propionate solution in the treatment of scalp psoriasis.

CD4+ T-cell-directed antibody responses are maintained in patients with psoriasis receiving alefacept: results of a randomized study.

BACKGROUND Alefacept, human LFA-3/IgG(1) fusion protein, selectively reduces memory-effector (CD45RO(+)) T cells, a source of the pathogenic mediators of psoriasis. OBJECTIVE To evaluate the effect of alefacept on immune function, T-cell-dependent humoral responses to a neoantigen (PhiX174) and recall antigen (tetanus toxoid) were assessed. METHODS Patients with psoriasis were randomized to the control group or to receive alefacept (7.5 mg intravenously weekly for 12 weeks). The alefacept group received PhiX174 immunizations at weeks 6, 12, 20, and 26 and tetanus toxoid at week 21; control subjects received PhiX174 at weeks 6 and 12 and tetanus at week 10. RESULTS Mean anti-PhiX174 titers were comparable in both groups. There was no difference in the percentage of responders (anti-PhiX174 IgG >/=30% of the total anti-PhiX174) between the alefacept group and the control group (86% and 82%, respectively; P =.73). The percentage of patients with anti-tetanus toxoid titer increases >/=2 times baseline also was similar (alefacept, 89%; control 91%). CONCLUSION A single 12-week course of alefacept did not impair primary or secondary antibody responses to a neoantigen or memory responses to a recall antigen. The selective immunomodulatory effect of alefacept against a potentially pathogenic T-cell subset is associated with maintenance of a significant aspect of immune function (antibody response) to fight infection and respond to vaccinations.

Imiquimod; an international update on therapeutic uses in dermatology.

Imiquimod, the first member of a new class of immune response modifiers, is approved for the treatment of external genital and perianal warts. The clinical effect of imiquimod stems from cytokine‐induced activation of the immune system. Topical application of imiquimod elevates the production of cytokines, including the principal cytokine for antiviral activity, interferon‐α. This is the initial event in an immunological cascade resulting in the stimulation of the innate immune response as well as the cell‐mediated pathway of acquired immunity. This immune modification mediates the indirect antiviral, antiproliferative and antitumor activity of imiquimod in vivo. These properties highlight the potential of imiquimod not only as an effective treatment for genital warts, but also as a treatment for other cutaneous viral infections and cutaneous neoplasms.

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.

Full-thickness skin with mature hair follicles generated from tissue culture expanded human cells.

The goal of regenerative medicine is to reconstruct fully functional organs from tissue culture expanded human cells. In this study, we report a method for human reconstructed skin (hRSK) when starting with human cells. We implanted tissue culture expanded human epidermal and dermal cells into an excision wound on the back of immunodeficient mice. Pigmented skin covered the wound 4 weeks after implantation. Hair shafts were visible at 12 weeks and prominent at 14 weeks. Histologically, the hRSK comprises an intact epidermis and dermis with mature hair follicles, sebaceous glands and most notably, and unique to this system, subcutis. Morphogenesis, differentiation, and maturation of the hRSK mirror the human fetal process. Human antigen markers demonstrate that the constituent cells are of human origin for at least 6 months. The degree of new skin formation is most complete when using tissue culture expanded cells from fetal skin, but it also occurs with expanded newborn and adult cells; however, no appendages formed when we grafted both adult dermal and epidermal cells. The hRSK system promises to be valuable as a laboratory model for studying biological, pathological, and pharmaceutical problems of human skin.

Future horizons in hair restoration.

This article reviews the history of hair follicle regeneration from follicular fragments and dissociated cells. The challenges of trichogenic in vitro culture and subsequent delivery into the patient are discussed, as well as cosmetic acceptance, recent achievements on regeneration of human hair follicles, and new potential cell sources for hair regeneration.

Objective Outcome Measures: Collecting Meaningful Data on Alopecia Areata

Background: Although alopecia areata is a common disorder, it has no US Food and Drug Administration–approved treatment and evidence‐based therapeutic data are lacking. Objective: To develop guidelines for the diagnosis, evaluation, assessment, response criteria, and end points for alopecia areata. Methods: Literature review and expert opinion of a group of dermatologists specializing in hair disorders. Results: Standardized methods of assessing and tracking hair loss and growth, including new scoring techniques, response criteria, and end points in alopecia areata are presented. Limitations: The additional time to perform the assessments is the primary limitation to use of the methodology in clinical practice. Conclusion: Use of these measures will facilitate collection of standardized outcome data on therapeutic agents used in alopecia areata both in clinical practice and in clinical trials.