and subcutaneous diseases affect millions of people worldwide causing significant morbidity.

and subcutaneous diseases affect millions of people worldwide causing significant morbidity. two weeks of starting treatment [22]. 2.4 Other Apremilast (CC-10004) is a novel biologic agent that specifically targets phosphodiesterase 4 (PD-4). Phosphodiesterase 4 is an intracellular enzyme that is expressed predominantly Raf265 derivative in immune cells including dendritic cells neutrophils and monocytes but also in keratinocytes. PD-4 causes degradation of the secondary messenger cyclic AMP (cAMP) leading to increased production of pro-inflammatory mediators such as TNF-α interleukins 2 12 and 23 and chemokine (C-X-C motif) ligands 9 (CXCL9) and 10 (CXCL10) [23]. Therefore inhibition of PD-4 by apremilast has the potential to reduce pro-inflammatory cytokine production and subsequent inflammatory signalling. A recent phase II RCT was carried out to assess the efficacy of apremilast for moderate to severe psoriasis [24]. Patients were randomised to receive placebo or apremilast at 10 20 or 30 mg twice daily over 12 weeks. The primary endpoint was the proportion of patients with a PASI 75 response at week 16. This was achieved in 6% of placebo patients and 11% 29 and 41% of patients assigned apremilast at 10 20 and 30 mg respectively. Apremilast appears to be efficacious Cryab and tolerable at doses of 20 or 30 mg twice daily and to date there is no evidence of serious adverse events. Further investigation of the safety profile with long-term use is needed and a phase III Raf265 derivative trial using apremilast at 30 mg twice daily is in progress. Efalizumab is a recombinant humanised monoclonal antibody against the CD11a Raf265 derivative subunit of the cell surface protein LFA-1 (lymphocyte Raf265 derivative function-associated antigen-1). Binding of LFA-1 to intracellular adhesion molecule (ICAM) 1-3 is an important step in the pathogenesis of psoriasis causing activation and migration of T-lymphocytes into the skin. Studies have also shown Raf265 derivative efalizumab to downregulate several other T-cell surface molecules. Unfortunately three cases of confirmed progressive multifocal leukoencephalopathy (PML) have been reported in patients who had received the treatment for three years or more. This has resulted in the treatment being withdrawn from use. 3 Autoimmune Blistering Disorders Pemphigus describes a group of uncommon autoimmune mucocutaneous blistering disorders which can be fatal if left untreated. The most common type of pemphigus is pemphigus vulgaris (PV) although many other less common variants exist. The pathogenesis of PV involves circulating immunoglobulin G (IgG) autoantibodies against desmogleins 1 and 3 (desmosomal cadherins involved in epidermal intercellular adhesion). Conventional treatments include systemic corticosteroids immunosuppressive and anti-inflammatory providers. Biologic agents are able to target specific pathways in the pathogenesis of the disorder and have been used effectively in the treatment of PV. Rituximab is a chimeric human being/murine IgG1 monoclonal antibody against the CD20 protein indicated on the surface of B-lymphocytes. Rituximab focuses on pre-B and adult B lymphocytes causing match and antibody-dependent cytotoxicity and apoptosis therefore preventing their development into antibody-producing plasma cells. The CD20 protein is not indicated on the surface of terminally differentiated plasma cells. Studies have shown rituximab to be an effective and safe treatment for PV at a dose of 4 × 375 mg/m2 as currently approved for the treatment of B-cell malignancies and more recently at the higher dose approved for the treatment of rheumatoid arthritis [25 26 In a study of 23 individuals with severe pemphigus treatment with a combination of immunoadsorption rituximab pulsed dexamethasone and..