Identifying the causes of contact dermatitis.

Contact dermatitis results from skin contact with an exogenous substance. It can be caused by direct contact, airborne particles, vapours or light. Individuals of any age can be affected. The two most common variants are irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). ICD is more common and has a worse prognosis. Other less common forms of contact dermatitis include photocontact allergy and, in food handlers, protein contact dermatitis. ICD is a form of eczema and is induced by direct inflammatory pathways without prior sensitisation. Classical ACD is mediated by type 4 cell-mediated immunity. Sensitisation occurs within 5 to 16 days of skin contact with a potential allergen but at this first exposure there is no inflammation. Frequent exposure and high concentrations of potential allergens increase the risk of sensitisation. If eczema is recurrent/persistent, or occurs in an individual with no previous history of eczema, contact dermatitis should be considered. Dorsal aspects of the hands are most often affected by ICD, usually with involvement of the finger webs. Cumulative effects of water, soaps and detergents are the most common cause of ICD which affects the hands more often than any other site. Nickel, fragrances, rubber accelerators and biocides are the most common sensitisers in ACD. Patients with leg ulcers and stasis eczema are at especially high risk of developing allergies to ingredients of their topical treatments, dressings and bandages. If ACD is suspected the patient should be referred to secondary care for patch testing. Age should not be a deterrent to patch testing. Accurate diagnosis, avoidance of identified allergens and protection from irritants are the key to successful treatment.

Sole dermatitis in children: patch testing revisited.

Although dermatoses affecting the soles of the feet in children are regularly encountered in dermatology clinics, the relationship with allergic contact dermatitis affecting this part of the foot is not well established. The aim of this study was to evaluate the relevance of patch testing children with sole dermatoses. We reviewed the results of all patch tests performed in children (<18 years) presenting with dermatoses involving the soles between 1997 and 2009 from our departmental patch test database. Forty-one children were identified: 27 children with an inflammatory dermatitis affecting the sole and 14 children with juvenile plantar dermatosis (JPD). Seventeen (41%) children had at least one clinically relevant positive patch test reaction. Rubber additives and potassium dichromate were the most frequent allergens identified. Forty-eight percent of children with inflammatory dermatitis affecting the sole and 29% of children with JPD had at least one relevant reaction. Of the children with relevant reactions, 76% had a personal or family history of atopy. Our results demonstrate the importance of patch testing children with dermatoses affecting the soles and indicate that a history of atopy or a diagnosis of JPD should not deter investigation.

Haploinsufficiency for AAGAB causes clinically heterogeneous forms of punctate palmoplantar keratoderma.

Palmoplantar keratodermas (PPKs) are a group of disorders that are diagnostically and therapeutically problematic in dermatogenetics. Punctate PPKs are characterized by circumscribed hyperkeratotic lesions on the palms and soles with considerable heterogeneity. In 18 families with autosomal dominant punctate PPK, we report heterozygous loss-of-function mutations in AAGAB, encoding α- and γ-adaptin-binding protein p34, located at a previously linked locus at 15q22. α- and γ-adaptin-binding protein p34, a cytosolic protein with a Rab-like GTPase domain, was shown to bind both clathrin adaptor protein complexes, indicating a role in membrane trafficking. Ultrastructurally, lesional epidermis showed abnormalities in intracellular vesicle biology. Immunohistochemistry showed hyperproliferation within the punctate lesions. Knockdown of AAGAB in keratinocytes led to increased cell division, which was linked to greatly elevated epidermal growth factor receptor (EGFR) protein expression and tyrosine phosphorylation. We hypothesize that p34 deficiency may impair endocytic recycling of growth factor receptors such as EGFR, leading to increased signaling and cellular proliferation.

Epidermolysis bullosa simplex in Scotland caused by a spectrum of keratin mutations.

Epidermolysis bullosa simplex (EBS) is an inherited skin disorder caused by mutations in keratins K5 (keratin 5) and K14 (keratin 14), with fragility of basal keratinocytes leading to epidermal cytolysis and blistering. Patients present with widely varying severity and are classified in three main subtypes: EBS Weber-Cockayne (EBS-WC), EBS Köbner (EBS-K), and EBS Dowling-Meara (EBS-DM), based on distribution and pattern of blisters. We could identify K5/K14 mutations in 20 out of the 43 families registered as affected by dominant EBS in Scotland; with previous studies this covers 70% of all Scottish EBS patients, making this the most comprehensively analyzed EBS population. Nine mutations are novel. All mutations lie within five previously identified rod domain hotspots and the severest blistering was associated with mutations in the helix boundary motifs. In some cases, the same mutation caused symptoms of EBS-WC and/or EBS-K, both within and between families, suggesting a contribution of additional factors to the phenotype. In some patients, no mutations were found in K5, K14, or K15, suggesting involvement of other genes. The results confirm that EBS is best considered as a single disorder with a spectrum of phenotypic variations, from severe EBS-DM at one extreme to mild EBS-WC at the other.