Abstract: Despite the well-documented action of growth hormone-releasing hormone (GHRH) on the stimulation of production and release of growth hormone (GH), the effects of GHRH in peripheral tissues are incompletely explored. In this study, we show that GHRH plays a role in wound healing and tissue repair by acting primarily on wound-associated fibroblasts. Mouse embryonic fibroblasts (MEFs) in culture and wound-associated fibroblasts in mice expressed a splice variant of the receptors for GHRH (SV1). Exposure of MEFs to 100 nM and 500 nM GHRH or the GHRH agonist JI-38 stimulated the expression of α-smooth muscle actin (αSMA) based on immunoblot analyses as well as the expression of an αSMA-β-galactosidase reporter transgene in primary cultures of fibroblasts isolated from transgenic mice. Consistent with this induction of αSMA expression, results of transwell-based migration assays and in vitro wound healing (scratch) assays showed that both GHRH and GHRH agonist JI-38 stimulated the migration of MEFs in vitro. In vivo, local application of GHRH or JI-38 accelerated healing in skin wounds of mice. Histological evaluation of skin biopsies showed that wounds treated with GHRH and JI-38 were both characterized by increased abundance of fibroblasts during the early stages of wound healing and accelerated reformation of the covering epithelium at later stages. These results identify another function of GHRH in promoting skin tissue wound healing and repair. Our findings suggest that GHRH may have clinical utility for augmenting healing of skin wounds resulting from trauma, surgery, or disease.
Abstract: BACKGROUND: Infliximab, a chimeric monoclonal antibody, has been shown to be effective for moderate to severe psoriasis. Clinical experience with long-term infliximab therapy for psoriasis is accumulating, and it is therefore important to share our experience with its use in real-life clinical practice. OBJECTIVES: To report our experience with infliximab (Remicade; Schering Plough, Kenilworth, NJ, U.S.A.) for the treatment of moderate to severe plaque psoriasis (and/or arthritis) from a single clinic in Greece. PATIENTS AND METHODS: Between August 2004 and March 2008, 62 patients presenting to our clinic with moderate to severe psoriasis were treated with infliximab. Disease phenotype, clinical course, disease severity and adverse events were assessed throughout the treatment period. RESULTS: Infliximab resulted in a reduction of median Psoriasis Area and Severity Index (PASI) of 70% at week 6 and 84.4% at week 14. Nineteen patients who have completed 1 year on infliximab treatment experienced sustained efficacy with a median PASI improvement of 92.16% and a Physician's Global Assessment (PGA) of 'clear' or 'almost clear', while nine patients have reached approximately 20 months of continuous therapy. All patients with psoriatic arthritis showed marked improvement in their clinical symptoms following the first infusion. Eight patients (12.9%) experienced adverse events that required discontinuation of treatment. There were no statistically significant differences in PASI and Dermatology Life Quality Index (DLQI) scores between patients with arthritis and those with only skin lesions, or between those who received methotrexate, either from the beginning or during infliximab therapy, and those who did not receive methotrexate at all. Selected patients of interest are discussed. CONCLUSIONS: The above data confirm previous reports that treatment with infliximab is an efficacious and safe option for patients with moderate to severe plaque psoriasis (and/or arthritis). Long-term follow-up, continued pharmacovigilance, and controlled comparative studies will be required to fully evaluate its use in the treatment of psoriasis.
Abstract: BACKGROUND: Anti-tumor necrosis factor (anti-TNF) biologic agents have been associated with a number of adverse events. OBJECTIVE: To review the cutaneous reactions that have been reported in patients receiving anti-TNF therapy. METHODS: We performed a systematic MEDLINE search of relevant publications, including case reports and case series. RESULTS: Reported cutaneous events included infusion and injection site reactions, psoriasiform eruptions, lupus-like disorders, vasculitis, granulomatous reactions, cutaneous infections, and cutaneous neoplasms. Infusion reactions and injection site reactions were definitely associated with anti-TNF administration, whereas all other events had a varying strength of association and severity, not necessarily requiring drug discontinuation. LIMITATIONS: Most information was derived from spontaneous case reports, where ascertainment biases and frequency of reporting may impair detection methodology and causal relationships. CONCLUSIONS: As anti-TNF biologic agents are progressively being used in clinical practice, cutaneous adverse events will be encountered more frequently. Until more data are accumulated with respect to their pathogenesis and potential association with anti-TNF therapy, dermatologists should become more familiar with the clinical presentation and management of such events.
Abstract: BACKGROUND: Efalizumab (anti-CD11a antibody) targets T cell-mediated steps important in the immunopathogenesis of psoriasis. As efalizumab is intended to be administered on a continuous long-term basis in psoriasis, it is important to share experience concerning issues commonly occurring during its use in real daily practice. OBJECTIVE: To evaluate the efficacy and safety of efalizumab treatment in Greek patients with moderate-to-severe plaque psoriasis, and to investigate whether there are specific characteristics that predict the clinical outcome of therapy. PATIENTS: Seventy-two patients with moderate-to-severe plaque psoriasis, who had failed to respond to, or had a contraindication to, or were intolerant to other systemic therapies, received efalizumab (1 mg kg(-1) per week) for 12 weeks or more. RESULTS: After 12 weeks of efalizumab treatment, 65% of patients achieved 50% or more improvement from baseline Psoriasis Area and Severity Index (PASI) and 39% achieved at least 75% reduction in PASI score. The mean percentage PASI improvement from baseline was 62%. The most common side effects were a flu-like syndrome, a transient localized papular eruption, leucocytosis and lymphocytosis. There was no correlation between the occurrence of these side effects and the clinical response. Patients with a past history of unstable types of psoriasis were likely poor responders to efalizumab, and at an increased risk of developing generalized inflammatory flare. CONCLUSION: These results confirm previous reports suggesting that treatment with efalizumab is an efficacious and safe option for patients with moderate-to-severe plaque psoriasis. A detailed previous history of psoriasis is important in order to select possible candidates for efalizumab therapy.
