[Dermatology]. / Dermatologie.

We are going over therapeutic acquisitions in a club-journal including relevant publications in different fields: mecanisms of action, therapeutic perspectives in a near future, and side effects.

Proposed mechanisms of action for retinoid derivatives in the treatment of skin aging.

Skin aging (intrinsic aging) and photoaging (extrinsic aging) involve a similar process that leads to the typical creased appearance of the skin, with the progressive loss of its physical and biologic properties. Photoaging is a premature skin aging caused by long-term exposure to the ultraviolet B radiations of the sun, and is more frequently associated to skin cancer than intrinsic aging. Retinoids are natural and synthetic vitamin A derivatives. They are lipophilic molecules and penetrate the epidermis easily. Their biologically active forms can modulate gene expression by binding to nuclear receptors and then to specific DNA sequences. Because of their ability to modulate genes involved in cellular differentiation and proliferation, they appear as good candidates to treat and prevent photoaging. Hyaluronate and collagen, two major constituents of the dermis, are progressively decreased and altered during aging. Various retinoids were shown to increase their synthesis and concentration in the skin and reduce their rate of degradation. Furthermore, retinoids share a common chemical structure containing several conjugated double bonds that enable them to trap free radicals and absorb UV radiations from the sun, thereby protecting cellular targets such as DNA, lipid membranes, or proteins by preventing direct photochemical damage or UV-induced oxidative stress. Therefore, retinoids may be beneficial in treating skin aging and photoaging because of their biologic, chemical, and physical properties, which act at several levels.

Peroxisome proliferator-activated receptors as new molecular targets in psoriasis.

While psoriasis is upon the age of biological treatments, additional researches have led to other new therapies for psoriasis, including targets aimed at nuclear receptors. PPARs are members of the nuclear-hormone-receptor superfamily, including retinoid receptors and vitamin D receptors. Recent works have highlighted the role of PPARs, which transduce a wide variety of signals into a set of cellular responses at the level of gene transcription, as critical regulators of cutaneous homeostasis in regulating differentiation, proliferation, and inflammatory responses of the skin. PPAR agonists or antagonists may therefore, hold promise as interesting compounds for the treatment of various epidermal disorders characterized by inflammation, hyperproliferation and aberrant differentiation, such as psoriasis.

Childhood bullous pemphigoid: report of a case with life-threatening course during homeopathy treatment.

Bullous pemphigoid (BP) is an autoimmune blistering disorder that may very rarely occur in childhood. We describe a 9-month-old child who developed bullous pemphigoid while she was being treated for presumptive atopic eczema with a homeopathic regimen comprising sulfur, mercury, cantharides, and Rhus (Toxicodendron). She had generalized bullae and a progressive worsening of her general condition with asthenia, dehydration, malnutrition. While the role of homeopathy in triggering the disease remains unclear, our observation attests to the potential life-threatening course of childhood BP in instances where appropriate treatment is withheld.

Effect of topical PPARbeta/delta and PPARgamma agonists on plaque psoriasis. A pilot study.

BACKGROUND: Ligands of nuclear hormone receptors such as glucocorticoid, retinoid and vitamin D are useful antipsoriatic drugs. Peroxisome proliferator-activated receptors (PPARs), which also belong to the nuclear hormone receptor superfamily, are pleiotropic regulators of growth and differentiation in many cell types, including the keratinocytes. Recent reports have dealt with the involvement of PPARalpha in epidermal processes such as barrier development, proliferation and differentiation. In a pilot study of topical clofibrate, a PPARalpha ligand, we did not find any antipsoriatic activity. No study on the effect of topical application of other PPAR subtype ligands (PPARbeta/delta and gamma) has been published. OBJECTIVES: The purpose of this pilot study is to explore the clinical efficacy of the topical application of potent PPARbeta/delta and gamma agonists on plaque psoriasis, tetradecylthioacetic acid (TTA) and rosiglitazone, respectively. METHODS: In a pilot study on psoriatic patients, 8 individuals (5 male/3 female) were treated twice daily for 30 days with vehicle (n = 14 plaques), rosiglitazone 0.5% (n = 18) and TTA 0.5% (n = 18). Assessments of the PASI plaque score were carried out on days 0, 4, 7, 11, 14 and 30. RESULTS: No statistically significant difference was found at any of the examination times, between vehicle, rosiglitazone and TTA in terms of reduction of the PASI plaque score for total, scale and infiltration scores. Treatments were well tolerated, and skin irritation, adverse drug-related symptoms and dropouts did not occur. CONCLUSIONS: With the reservations due to the limited nature of this pilot trial, it seems that these topical PPARbeta/delta and gamma agonists do not exert a strong antipsoriatic effect when used alone at 0.5%.