Approaches to nutrition intervention in plaque psoriasis, a multi-system inflammatory disease-The Diet and Psoriasis Project (DIEPP).

Psoriasis is an immune-mediated inflammatory skin disease affecting approximately 2% of the UK population. Its pathogenesis is suggested to be an outcome of genetic and environmental interplay. People with psoriasis have an increased likelihood of developing other conditions such as type 2 diabetes and cardiovascular disease. Systemic inflammation is hypothesised to be the common link between psoriasis and cardio-metabolic diseases. Emerging evidence shows diet as a potential therapeutic adjunct in the management of psoriasis. The Diet and Psoriasis Project (DIEPP) aims to investigate whether dietary factors are related to psoriasis severity by conducting an observational study followed by a dietary intervention trial, to assess the effect of the Mediterranean diet (MedD) and time-restricted eating (TRE) on psoriasis. This review article will explore the potential mechanisms by which the MedD and TRE may exert protective effects on psoriasis, evaluate the current evidence, and outline the design of the DIEPP. Given the early-stage evidence, we hope to be able to build knowledge to derive medically approved dietary recommendations and contribute to the research gaps exploring the role of diet and psoriasis.

Connective tissue disease and sarcoidosis: a true association or a secondary granulomatous reaction?

Sarcoidosis occurs much more commonly in cohorts of connective tissue disease (1%) compared to the general population (0.01-0.04%). We present a case of concomitant connective tissue disease and cutaneous sarcoidal granulomas and discuss whether the observed granulomas represent a reactive phenomenon or true sarcoidosis. Click here for the corresponding questions to this CME article.

A characteristic rash caused by Shiitake mushrooms - An emerging concern?

Shiitake mushroom dermatitis is a striking rash that can present as an emergency. Despite the dramatic appearance, the rash is an idiosyncratic reaction which resolves spontaneously and does not progress to anaphylaxis.

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated.

Tylosis with oesophageal cancer: Diagnosis, management and molecular mechanisms.

Tylosis (hyperkeratosis palmaris et plantaris) is characterised by focal thickening of the skin of the hands and feet and is associated with a very high lifetime risk of developing squamous cell carcinoma of the oesophagus. This risk has been calculated to be 95% at the age of 65 in one large family, however the frequency of the disorder in the general population is not known and is likely to be less than one in 1,000,000. Oesophageal lesions appear as small (2-5 mm), white, polyploid lesions dotted throughout the oesophagus and oral leukokeratosis has also been described. Although symptoms of oesophageal cancer can include dysphagia, odynophagia, anorexia and weight loss, there may be an absence of symptoms in early disease, highlighting the importance of endoscopic surveillance in these patients. Oesophageal cancer associated with tylosis usually presents in middle to late life (from mid-fifties onwards) and shows no earlier development than the sporadic form of the disease. Tylosis with oesophageal cancer is inherited as an autosomal dominant trait with complete penetrance of the cutaneous features, usually by 7 to 8 years of age but can present as late as puberty. Mutations in RHBDF2 located on 17q25.1 have recently been found to be causative. A diagnosis of tylosis with oesophageal cancer is made on the basis of a positive family history, characteristic clinical features, including cutaneous and oesophageal lesions, and genetic analysis for mutations in RHBDF2. The key management goal is surveillance for early detection and treatment of oesophageal dysplasia. Surveillance includes annual gastroscopy with biopsy of any suspicious lesion together with quadratic biopsies from the upper, middle and lower oesophagus. This is coupled with dietary and lifestyle modification advice and symptom education. Symptomatic management of the palmoplantar keratoderma includes regular application of emollients, specialist footwear and early treatment of fissures and super-added infection, particularly tinea pedis. More specific treatment for the thick skin is available in the form of oral retinoids, which are very effective but commonly produce side effects, including nasal excoriation and bleeding, hypercholesterolaemia, and abnormal liver function tests. Genetic counselling can be offered to patients and family members once a family history has been established. The prognosis of tylosis with oesophageal cancer is difficult to determine due to the limited number of affected individuals. In the last 40 years of surveillance, five out of six cases of squamous oesophageal cancer in the Liverpool family were detected endoscopically and were surgically removed. Four of five patients had stage 1 disease at presentation and remain alive and well more than 8 years later. This suggests that the presence of a screening program improves prognosis for these patients.

Discovery in genetic skin disease: the impact of high throughput genetic technologies.

The last decade has seen considerable advances in our understanding of the genetic basis of skin disease, as a consequence of high throughput sequencing technologies including next generation sequencing and whole exome sequencing. We have now determined the genes underlying several monogenic diseases, such as harlequin ichthyosis, Olmsted syndrome, and exfoliative ichthyosis, which have provided unique insights into the structure and function of the skin. In addition, through genome wide association studies we now have an understanding of how low penetrance variants contribute to inflammatory skin diseases such as psoriasis vulgaris and atopic dermatitis, and how they contribute to underlying pathophysiological disease processes. In this review we discuss strategies used to unravel the genes underlying both monogenic and complex trait skin diseases in the last 10 years and the implications on mechanistic studies, diagnostics, and therapeutics.