Prominent skin involvement is a defining characteristic of autoinflammatory disorders caused by abnormal IL-1 signaling. However, the pathways and cell types that drive cutaneous autoinflammatory features remain poorly understood. We sought to address this issue by investigating the pathogenesis of pustular psoriasis, a model of autoinflammatory disorders with predominant cutaneous manifestations. We specifically characterized the impact of mutations affecting AP1S3, a disease gene previously identified by our group and validated here in a newly ascertained patient resource. We first showed that AP1S3 expression is distinctively elevated in keratinocytes. Because AP1S3 encodes a protein implicated in autophagosome formation, we next investigated the effects of gene silencing on this pathway. We found that AP1S3 knockout disrupts keratinocyte autophagy, causing abnormal accumulation of p62, an adaptor protein mediating NF-κB activation. We showed that as a consequence, AP1S3-deficient cells up-regulate IL-1 signaling and overexpress IL-36α, a cytokine that is emerging as an important mediator of skin inflammation. These abnormal immune profiles were recapitulated by pharmacological inhibition of autophagy and verified in patient keratinocytes, where they were reversed by IL-36 blockade. These findings show that keratinocytes play a key role in skin autoinflammation and identify autophagy modulation of IL-36 signaling as a therapeutic target.

In this small survey, the first of its kind to focus on elderly patients, phototherapy appears to be well-tolerated, safe and efficacious in the short term. Further thought and investigation should be given to delivering phototherapy to an ageing population.

We report this case of fatal disseminated cowpox infection to highlight an increasing risk of this illness in the post-transplant population and to detail some unusual features not previously described, such as tonsillar involvement, disseminated skin lesions and multiorgan failure.

Chronic idiopathic urticaria (CIU) may be severe and refractory to standard therapies. We describe two patients with CIU, neither of whom had detectable autoantibodies, in whom control of the disease was achieved with methotrexate.

A retrospective study of the referral patterns to a specialist vulval clinic was performed. A total of 200 clinical records were reviewed of new patients seen between January 2004 and June 2005. A provisional diagnosis was stated in 45.5% of referrals, of which 27.5% had the diagnosis changed at the clinic. The majority of referrals were from general practitioners (GPs) (77%) and smaller proportions from gynaecologists (11%), dermatologists (9%) and others (3%). The most common conditions seen were lichen sclerosus (39%), eczema/lichen simplex (30.5%), lichen planus (11.5%), pain syndromes (10.5%) and others (8.5%). Lichen sclerosus was accurately diagnosed in 54.5% of referrals but for eczema/lichen simplex it was only recognised in 11.5% of referrals. Nine cases of lichen sclerosus had been referred by gynaecologists after histological confirmation, for advice on management. Education of vulval diseases to non-specialists should focus on conditions that they are most likely to encounter and find difficult to manage. This study illustrates an effective method to define what the local teaching requirements are.