George Badavanis

Calcipotriol Plus Short-Contact Dithranol: A Novel Topical Combination Therapy for Chronic Plaque Psoriasis

The purpose of this double-blind randomised parallel-group study was to compare the efficacy and safety of short-contact treatment with dithranol ointment (2%) with its combination with calcipotriol ointment (50 µg/g) in 2 groups of in-patients with chronic plaque psoriasis. The patients of the first group (n = 23) topically applied dithranol once daily for 30 min and the vehicle of calcipotriol twice daily. The patients of the second group (n = 23) used a single topical application of dithranol for 30 min daily and additionally applied calcipotriol twice daily. The extent and the severity of psoriasis were assessed by means of psoriasis area and severity index score (PASI score) before the onset of the 6-week therapy and weekly thereafter. The difference between the two groups with regard to the mean PASI score became statistically significant already after the first week of treatment and remained so until the end of the trial. No significant differences were observed between the two groups with respect to the cutaneous adverse events. These findings indicate that the addition of calcipotriol ointment to short-contact dithranol markedly augments the therapeutic efficacy of the latter in chronic plaque psoriasis and impressively accelerates the response of psoriatic plaques to this well-tolerated regimen.

Reduced expression of the antiapoptotic proteins of Bcl-2 gene family in the lesional epidermis of patients with Darier’s disease

Background:  Dyskeratotic cells in Darier’s disease (DD) are thought to represent apoptotic keratinocytes. Bcl‐2 gene family proteins play a major role in the regulation of apoptosis of epidermal keratinocytes and reveal pleiotropic interactions with intracellular Ca2+ homeostasis. The latter is impaired in DD because of mutations of ATP2A2 gene that encodes the type 2 isoforms of the sarcoplasmic/endoplasmic reticulum (ER) Ca++ ATPase 2 (SERCA2) pump.

Gianotti-Crosti Syndrome after Hepatitis A Vaccination

Gianotti-Crosti syndrome (GCS) is a relatively common skin disorder characterized by a distinctive, self-limiting, non-recurrent erythematous or skin-coloured papulo-vesicular eruption symmetrically distributed mainly on the extremities, buttocks and face of infants and young children and, infrequently, of adults. A wide spectrum of infectious agents, mostly viruses [hepatitis A, B and C, cytomegalovirus (CMV), Epstein-Barr, HIV, human her-pes virus 6, Coxsackie, rota-, echo- and parvovirus, para-influenza, mumps,

Successful treatment of granuloma annulare with imiquimod cream 5%: a report of four cases.

Sir, Granuloma annulare (GA) is a benign and usually asymptomatic granulomatous dermatosis characterized by erythematous, violaceous or skin-coloured necrobiotic papules, often fused into annular arrangements, that most commonly affect the extremities. Although it may resolve spontaneously, GA is frequently resistant to treatment. A variety of topical or systemic therapeutic modalities has been used in its management with varying success (1–3). To our knowledge, there is only one case report of imiquimod, a novel immune response modifier, being therapeutically active in GA (4). We therefore conducted a pilot study to evaluate the efficacy and safety of imiquimod 5% cream in the treatment of this disorder.

Topical application of imiquimod induces alterations in peripheral blood lymphocytes in healthy individuals.

The aim of this study was to determine whether imiquimod, a Toll-like receptor-7/8 agonist, in addition to its well-known topical action on the cutaneous immune response, might also induce alterations in the peripheral blood lymphocytes. A 62.5 mg quantity of imiquimod (5% cream) was applied topically under occlusion once daily every second day for 3 weeks to the skin of 10 healthy volunteers, age range 30-57 years. Ten sex- and age-matched healthy controls applied corresponding quantities of the vehicle under occlusion. Before, and one and 3 weeks after the start of treatment, peripheral blood lymphocyte subpopulations were measured by flow cytometry. Statistically significant alterations in the percentage or absolute numbers of peripheral blood lymphocyte subpopulations were found in the imiquimod-treated group compared with the control group. These alterations indicate for the first time that topical application of imiquimod induces alterations in peripheral blood lymphocyte subsets in healthy individuals, which may be of importance in the immunotherapy of neoplastic and infectious disorders and should be taken into careful consideration in patients who are treated with imiquimod.

Hsp27 expression coincides with epidermal stratification during human epidermal morphogenesis.

Heat shock protein 27 (Hsp27), apart from its protective function in response to stress, is implicated in the regulation of cell growth, differentiation and apoptosis. Data on the expression of Hsp27 in the developing human epidermis are sparse and partially conflicting. Thus, the purpose of the present study was to investigate Hsp27 expression during the morphogenesis of human epidermis. Skin biopsies and dispase-separated epidermal sheets obtained from 7 human embryos (7 and 8 weeks estimated gestational age, EGA), from 79 human fetuses (9-23 weeks EGA) and from 10 healthy adult volunteers were investigated by immunohistochemistry and Western blotting, respectively. The earliest detection of Hsp27 expression was found by immunohistochemistry at the 12th week EGA (basal and intermediate layer) and by Western blotting at the 9th week EGA. From the 16th to the 23rd week EGA immunoreactivity was not detectable in the basal layer, whereas in the overlying layers it revealed a differentiation-related pattern. The simultaneous onset of epidermal stratification and Hsp27 expression (9th week EGA) and the alterations of the latter in the subsequent stages of development, suggest that this stress protein may be involved in the molecular events underlying human epidermal morphogenesis.

Safety of Systemic Biologic Agents in the Treatment of Non-malignant Skin Disorders

The recent significant breakthroughs in the understanding of the pathogenetic mechanisms of psoriasis and other immune-mediated inflammatory disorders, have led to the emergence of a wide array of biologic agents or biologics, that are especially designed to target selective intracellular or extracellular components and pathways of the dysregulated immune response. These targeted biologic agents have altered the landscape in dermatotherapy aiming to offer higher therapeutic efficacy and an alternative in patients who either failed on conventional systemic regimens or have no other therapeutic options. In the last two decades, the number of the commercially available biologic agents and the extent of their use have dramatically increased; today, these compounds represent a substantial part of modern dermatologic armamentarium. Due to the immunosuppressive potential of biologics, serious concerns were raised about their safety profile, already during the pre-approval period. These concerns did not subside after the incorporation of the postmarketing experience, particularly after the withdrawal of a biologic agent (efalizumab) due to its serious and even fatal side effects. The purpose of the present article is to review the cutaneous and systemic side effects of all biologic agents used so far in modern systemic dermatotherapy and to contribute to a better and updated awareness of their safety risks among clinicians, which will enable the latter to make the best informed and personalized drug selection and therapeutic decisions. This review was mainly based on data derived from Medline and Scopus databases and from manufacturing companies, as well.