Ultra-low dose rituximab for refractory pemghigus vulgaris: a pilot study.

Background: Pemphigus vulgaris is an autoimmune blistering disease affecting the skin and mucous membranes. Current treatments for pemphigus vulgaris include anti-inflammatory and immunosuppressive agents. Rituximab, an anti-CD20 monoclonal antibody, has been shown to be effective for the treatment of pemphigus vulgaris. However, the optimal dosage of rituximab for the treatment of this autoimmune bullous disease has not been clearly defined.The aim of this study was to investigate the clinical efficacy and adverse effects of an ultra-low dosage regimen of rituximab for pemphigus vulgaris.Methods: We performed a prospective non-randomized open case series including eight patients affected by pemphigus vulgaris. Patients were treated with an ultra-low dosage of rituximab (a single infusion of 200 mg).Results: All patients had a positive response after infusion. At the end of the follow-up period, 5 patients achieved a complete remission and 3 a partial remission. Except for one case of sepsis due to Citrobacer freundii and a pneumonia due to Haemophilus influenzae, no adverse events were documented in our patients.Conclusions: Data from our study suggest that an ultra-low dosage of rituximab could be an effective treatment for pemphigus vulgaris. Consequently, there is a need for a larger, confirmatory, randomized, multicenter trial.

Successful treatment of pyoderma gangrenosum with granulocyte and monocyte adsorption apheresis.

Pyoderma gangrenosum is a neutrophilic dermatosis clinically characterised by the presence of painful skin ulcerations with erythematous and undetermined borders and histologically by the presence of neutrophilic infiltrates in the dermis. Granulocyte and monocyte adsorption apheresis, also called granulocytapheresis, is a therapeutic strategy for extracorporeal immunomodulation that selectively removes activated granulocytes and monocytes/macrophages from the peripheral blood. Here, we report a case of a 73-year-old patient affected by a severe form of pyoderma gangrenosum presenting with multiple painful ulcers and pustules on his trunk and extremities. The disease was resistant to high doses of methylprednisolone and methotrexate and successfully treated by granulocyte and monocyte adsorption apheresis. To the best of our knowledge, this is the first report on the efficacy of granulocyte and monocyte adsorption apheresis in pyoderma gangrenosum in Europe.

Toll-like receptors and cutaneous melanoma.

Innate immune cells recognize highly conserved pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). Previous studies have demonstrated that PRRs also recognize endogenous molecules, termed damage-associated molecular patterns (DAMPs) that are derived from damaged cells. PRRs include Toll-like receptors (TLRs), scavenger receptors, C-type lectin receptors and nucleotide oligomerization domain-like receptors. To date, 10 TLRs have been identified in humans and each receptor responds to a different ligand. The recognition of PAMPS or DAMPs by TLRs leads to the activation of signaling pathways and cellular responses with subsequent pro-inflammatory cytokine release, phagocytosis and antigen presentation. In the human skin, TLRs are expressed by keratinocytes and melanocytes: The main cells from which skin cancers arise. TLRs 1-6 and 9 are expressed in keratinocytes, while TLRs 2-5, 7, 9 and 10 have been identified in melanocytes. It is hypothesized that TLRs may present a target for melanoma therapies. In this review, the involvement of TLRs in the pathogenesis and treatment of melanoma was discussed.