D. Tsambaos

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:u2002 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.

Treatment of Porphyria cutanea tarda with Oral Thalidomide

Eight male patients with overt clinical and biochemical features of porphyria cutanea tarda (PCT) were orally treated with 300 mg/day thalidomide for 1 week and with 200 mg/day for 3 more weeks. Already after the first week of treatment no new vesicles and/or bullae could be observed. Spontaneous blisters completely disappeared, increased skin fragility subsided and skin hyperpigmentation receded about 2 months after completion of therapy, whereas hypertrichosis persisted. There was a rapid decrease in the urinary total porphyrin excretion which reached normal levels in all patients by the end of the fourth week of therapy, whereas the posttreament chromatographic pattern of urinary porphyrins revealed a slight reduction of higher carboxylated porphyrin metabolites and an increase in the amount of the excreted coproporphyrin, as compared to the pretreatment period. Somnolence, intermittent constipation and dry mouth occurred in all patients, 2 patients additionally experienced dizziness. No evidence of peripheral neuropathy could be detected and laboratory investigations revealed no abnormalities, as compared to the pretreatment period. During the 16- to 28-month follow-up of the patients, no clinical or biochemical relapse was observed. In view of the encouraging results of the present investigation, further studies are now warranted in order to definitely answer the question whether oral thalidomide may be regarded as an effective alternative approach to the treatment of PCT.

Disseminated erythematous and pityriasiform plaques caused by imatinib mesylate

Sir, Imatinib mesylate (formerly STI 571, now referred to as Glivec in Europe andGleevec in theUnited States) is a rationally developed, orally administered potent competitive inhibitor of the BCR-ABLprotein tyrosine kinase that reveals a significant efficacy and a favourable safety profile in patients with chronic myeloid leukaemia (CML) (1). This compound has been reported to be effective also in gastrointestinal stromal tumours unresponsive to standard chemotherapy (2) and in metastatic dermatofibrosarcoma protuberans (3). We report here a patient who developed a skin rash during treatment with imatinib mesylate.

Qualitative and quantitative alterations of cell surface carbohydrate residues during epidermal morphogenesis

The purpose of this study was to investigate the carbohydrate residue composition of cell surface in the developing epidermis and to define the chronological sequence of its alterations in human fetuses from the 10th to the 20th weeks of gestation and at the 23rd week of gestation, using a panel of six biotinylated lectins: Concanavalinxa0A, Ulex europaeus agglutinin-I, Ricinus communis agglutinin-I, Peanut agglutinin, Wheat germ agglutinin, and Dolichos biflorus agglutinin. Distinct qualitative and quantitative alterations in the expression of cell surface carbohydrate residues were found during epidermal morphogenesis prior to keratinization (10th to 20th weeks). At the 23rd week of gestation, the already keratinized fetal human epidermis revealed a pattern of cell surface glycosylation very similar to that of the adult human epidermis. Further studies are now warranted to answer the question regarding whether the glycosylation pattern in the developing human epidermis is disturbed in fetuses with genodermatoses and whether these disturbances might be important for prenatally diagnosing the latter.

Long-term remission of recurrent herpes labialis following topical imiquimod application on distant healthy skin: a clinical and immunological study.

BACKGROUNDnGiven the limitations of current antiviral therapies, safer and more effective approaches to the management of recurrent herpes labialis (RHL) are needed.nnnMETHODSnA patient with a 23-year history of RHL and 14 healthy individuals were studied. The patient applied imiquimod to distant healthy skin for 3 weeks. Peripheral blood (PB) samples were collected from the patient during treatment and 21 months after its discontinuation; samples were collected from the controls once. The distribution of lymphocyte populations in PB were analysed by flow cytometry and PB cytokine levels were measured using cytometric bead arrays.nnnRESULTSnThe patient showed long-term remission of the disorder subsequent to a 3-week imiquimod application to distant healthy skin. Imiquimod treatment induced the activation and proliferation of T-helper and cytotoxic T-cells, B-cells and T-regulatory cells. In addition, there was a very strong transient increase of T-helper 1 cells (resulting in interferon-γ secretion) and type 1 (pro-inflammatory) polarization of the immune response accompanied by a sustainable interferon-α production. At follow-up 21 months after treatment cessation, with the patient remaining relapse-free, the patient had control levels of all cytokines, increased levels of activated cytotoxic T-cells, continuous production of new T-helper cells and B-cells and near-to-normal levels of T-regulatory cells.nnnCONCLUSIONSnOur results indicate that topical application of imiquimod to healthy skin is capable of causing systemic immunomodulation. This treatment might represent a new and effective alternative to established therapeutic and prophylactic regimens for RHL.

Lectin‐binding pattern of primary malignant melanomas and melanocytic nevi

A panel of six biotinylated lectins was applied in order to study the composition and distribution of plasma membrane carbohydrate residues in 83 primary cutaneous melanomas (MMs) and in 85 melanocytic nevi (MN) with the avidin‐biotin peroxidase technique. No clear‐cut differences between MN and MMs were observed with regard to the staining with lectins. In MN and MMs derived from different patients, the lectin‐binding pattern was variable and heterogeneous even within the individual nevi or melanomas. It seems reasonable, therefore, to assume that the lectin‐binding pattern cannot be regarded as a reliable histochemical marker for the differentiation of MN from MMs. Moreover, because the pattern reveals no statistically significant correlation with the thickness or the depth of invasion of MM, it seems to lack prognostic significance.

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.