Effective strategies for the management of pyoderma gangrenosum: a comprehensive review.

Pyoderma gangrenosum (PG) is an inflammatory disease characterized by painful skin ulcerations with undermined and erythematous borders. The etiology of PG is not well understood, but it is generally considered to be an aberrant immune response characterized by a dermal neutrophilc infiltrate. Given the existence of only a few PG clinical trials, treatment options are largely based upon anecdotal data and small case studies. In addition to classic immunosuppressive medications, PG has been reported to respond well to the anti-TNF agents, infliximab, etanercept, adalimumab. Newer biologics such as ustekinumab (anti-IL-23), ixekizumab (anti-IL-17) and brodalumab (anti-IL-17R) are promising given the effect of IL-17 on neutrophil migration. However, the effectiveness of these newer agents remains to be rigorously evaluated. Multi-drug regimens have not been well described in the literature but are an excellent alternative for patients with refractory disease. Herein, we provide a comprehensive review of the pathophysiology of PG and of the different treatments available for managing PG patients, including the theoretical benefit of initiating multidrug regimens. We also provide one possible treatment algorithm for patients with refractory disease and give examples of refractory PG cases successfully treated with multidrug regimens.

Metastatic melanoma - a review of current and future treatment options.

Despite advances in treatment and surveillance, melanoma continues to claim approximately 9,000 lives in the US annually (SEER 2013). The National Comprehensive Cancer Network currently recommends ipilumumab, vemurafenib, dabrafenib, and high-dose IL-2 as first line agents for Stage IV melanoma. Little data exists to guide management of cutaneous and subcutaneous metastases despite the fact that they are relatively common. Existing options include intralesional Bacillus Calmette-Guérin, isolated limb perfusion/infusion, interferon-α, topical imiquimod, cryotherapy, radiation therapy, interferon therapy, and intratumoral interleukin-2 injections. Newly emerging treatments include the anti-programmed cell death 1 receptor agents (nivolumab and pembrolizumab), anti-programmed death-ligand 1 agents, and oncolytic vaccines (talimogene laherparepevec). Available treatments for select sites include adoptive T cell therapies and dendritic cell vaccines. In addition to reviewing the above agents and their mechanisms of action, this review will also focus on combination therapy as these strategies have shown promising results in clinical trials for metastatic melanoma treatment.

NKG2C, HLA-E and their association with psoriasis.

Natural killer (NK) cell activation is regulated by the integration of signals from inhibitory and activating cell surface receptors. Both NKG2A and NKG2C pair with CD94 to form inhibitory and activating receptors specific for the HLA-E-canonical peptide complex. HLA-E is a non-classical MHC class Ib molecule with limited polymorphism. It preferentially binds to and presents leader sequence peptides derived from classical MHC class I molecules. Wilson et al. have identified an association between NKG2C deficiency and psoriasis. They have also discovered an HLA-C-dependent association between HLA-E and psoriasis. Their research highlights the importance of NK cells in the pathophysiology of psoriasis. Herein, we propose two different models to explain the association between NKG2C, HLA-E and psoriasis. In the first model, we hypothesize that NKG2C deficiency and/or HLA-E O1:01 can inhibit the ability of NK cells to regulate autoreactive T cells, predisposing to psoriasis. The second model proposes that HLA-E 01:03 can disrupt the presentation of the psoriasis-inducing self-determinant by HLA-C, thereby protecting against psoriasis.

Pathophysiology of Autoimmune Bullous Diseases: Nature Versus Nurture.

Pemphigus and pemphigoid are the prototypical immunobullous diseases. Although it has been well established that they are caused by deposition of autoreactive antibodies directed against adherence proteins within the skin, the specific genetic and environmental factors leading to development of these diseases continue to be an area of investigation. Herein, we discuss several of the potential environmental triggers that may induce patients to develop immunobullous diseases including medications, viral infections, UV exposure or other radiation injury and dietary factors. In addition, the potential genetic and immunologic mechanisms contributing to the pathogenesis of pemphigus and pemphigoid will be reviewed. The multifactorial nature of these diseases contributes to their complexity and highlights the importance of a detailed personal and family history when caring for these patients.