The new 8th edition of TNM staging and its implications for skin cancer: a review by the British Association of Dermatologists and the Royal College of Pathologists, U.K.

The 8th edition of TNM (tumour, node and metastasis) has numerous and important changes compared with the 7th edition. Public Health England and the Royal College of Pathologists, U.K., have adopted the 8th edition of TNM (TNM8) published by the Union for International Cancer Control for skin cancer staging. These changes will have an impact on the management and commissioning of melanoma and nonmelanoma skin cancer (NMSC). The T1-T3 categories for NMSC staging require the clinician to measure the maximum dimension (usually diameter) of every potential invasive cancer. For squamous, basal and adnexal carcinomas, but not Merkel cell carcinoma (MCC), the T1-T3 categories are defined by new 20-mm and 40-mm divisions based on the maximum dimension of the lesion. In addition, new risk factors upstage T1 or T2 to T3. For melanoma, mitotic index no longer influences separation of pathological stage (pT1). There is a new, additional stratification level at 0·8-mm Breslow thickness. Subdivision pT1b, with a negative sentinel lymph node biopsy (SLNB) of pN0, is now stage IA compared with the previous IB. For MCC, SLNB is now included specifically in the pN staging system. The pT1 subdivision requires clinical information as to whether histologically involved nodes were clinically occult or detectable. For both melanoma and MCC the clinician must state whether the lymph nodes are occult or clinically detectable. Eyelid carcinoma continues to have a staging system different from that in general skin and the system is substantially revised in TNM8.

A guide to anticoagulation and endocarditis prophylaxis during cutaneous surgery.

Management of perioperative antiplatelet/anticoagulation drugs and appropriate antibiotic prophylaxis for endocarditis are two controversial issues in the safe practice of cutaneous surgery. This article highlights the current best practice based on a literature review on these topics. Antiplatelet agents should be continued perioperatively whenever clinically possible, and discontinued only after consultation with the patient's cardiologist. The exception to this is primary cardiovascular disease, when antiplatelet drugs should be stopped for 1 week before surgery. Warfarin can be continued perioperatively when the international normalised ratio is controlled at < 3. The use of antibiotics in patients at risk of endocarditis has been recently reviewed by the National Institute of Health and Clinical Excellence (NICE), the American Heart Association, and the European Society of Cardiology. The advice has changed significantly over the past few years, and the routine use of antibiotics perioperatively should occur only when there is evidence of infection perioperatively at the site of surgery.

Comparison of parent knowledge, therapy utilization and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specialist dermatology nurse.

BACKGROUND: The failure of patients to take medicines in a way that leads to clinical benefit is a major challenge. A consensus has emerged that, on average, compliance sufficient to obtain therapeutic objectives occurs about half the time, with noncompliance contributing to therapeutic failure in the other half. These figures refer to simple oral regimens. There has been little work assessing compliance/concordance with complex treatment regimens for atopic eczema. Asthma schools led by specialist nurses have been shown to improve knowledge, use of therapies and clinical outcome. OBJECTIVES: To determine the effect of education and demonstration of topical therapies by specialist dermatology nurses on therapy utilization and severity of atopic eczema. METHODS: Fifty-one children with atopic eczema attending a paediatric dermatology clinic were followed for up to 1 year. At each visit the parent's knowledge about atopic eczema and its treatment and therapy utilization was recorded. The severity of the eczema was recorded using the six area, six sign atopic dermatitis severity score (SASSAD) and parental assessment of itch, sleep disturbance and irritability. At the first visit a specialist dermatology nurse explained and demonstrated how to use all of the topical treatments. This education was repeated at subsequent visits depending on the knowledge of the parent. RESULTS: At baseline less than 5% of parents had received/recalled receiving any explanation of the causes of eczema or demonstration of how to apply topical treatments. The eczema was poorly controlled in all children (mean SASSAD 42.9). Of the children, 24% were not being treated with any emollient cream/ointment; the mean use was 54 g weekly. Of the children, 25% were being inappropriately treated with potent or very potent topical steroids. Following repeated education and demonstration of topical therapies by a specialist dermatology nurse, there was an 89% reduction in the severity of the eczema. The main change in therapy utilization was an 800% increase in the use of emollients (to 426 g weekly of emollient cream/ointment) and no overall increase in the use of topical steroids, accounting for potency and quantity used. CONCLUSIONS: This study reinforces the importance of specialist dermatology nurses in the management of atopic eczema. It also confirms the opinion of patients, patient support groups, dermatologists and best practice guidelines that the most important intervention in the management of atopic eczema is to spend time to listen and explain its causes and demonstrate how to apply topical therapies.

Homozygous variegate porphyria: a compound heterozygote with novel mutations in the protoporphyrinogen oxidase gene.

Homozygous variegate porphyria results from mutations in both alleles of the protoporphyrinogen oxidase (PPOX) gene. Our patient, a 36-year-old woman, has severe cutaneous manifestations. Her clinical and biochemical features are similar to the few other reported cases, including onset before 18 months of age, photosensitivity, absence of acute porphyric attacks, and elevated erythrocyte protoporphyrin. Mutation analysis of the PPOX gene revealed an in-frame 12 bp insert (c. 657-658 ins AAGGCCAGCGCC) encoding lysine-alanine-serine-alanine (KASA), and a G to A transition at the splice donor site of exon 11 (IVS 11-1 G-->A). Neither of these mutations has been reported previously. Our patient's mother has the splice site mutation and has had acute porphyric episodes. A maternal first cousin has the same mutation but no clinical manifestations. The medical and family history of our patient's father is uncertain.

Laryngeal involvement in the Dowling-Meara variant of epidermolysis bullosa simplex with keratin mutations of severely disruptive potential.

The clinical features of the Dowling-Meara variant of epidermolysis bullosa simplex (EBS-DM) can, in an infant, be indistinguishable from other severe forms of epidermolysis bullosa (EB). Two unrelated infants with no family history of skin disease are described who, within hours of birth, developed extensive blistering of skin and oral mucosae and who both subsequently developed hoarse cries. Despite this superficial resemblance to other forms of EB, electron microscopy revealed a basal cell rupture and keratin aggregates characteristic of EBS-DM in the skin of both infants and in the vocal cord epithelium of one. Molecular analysis confirmed the diagnosis by identification of mis-sense point mutations in basal cell keratin genes in both cases. One patient carries a point mutation in keratin 14 (converting arginine at position 125 to histidine) and the other has a novel point mutation in keratin 5 (converting serine at position 181 to proline). Hoarseness is not a well documented feature of EBS-DM and is usually associated with junctional EB. These two patients demonstrate that the presence of a hoarse cry in an infant affected by severe EB does not necessarily indicate a poor prognosis.

Novel genetic association between the corneodesmosin (MHC S) gene and susceptibility to psoriasis.

Psoriasis is an inflammatory skin disease of unknown origin, but with a clear genetic component. The strongest genetic association has been found with the major histocompatibility complex (MHC) region, and specifically between susceptibility to familial early onset psoriasis and human leukocyte antigen (HLA)-Cw6. The basis of this association of the HLA-C locus with disease pathogenesis is, however, not clear, and it is possible that other genes, or a combination of genes, in the HLA region are of functional importance. The MHC S gene is expressed specifically in keratinocyte differentiation and, being located 160 kb telomeric of HLA-C, is a plausible candidate gene. We analysed the allelic distribution of two polymorphisms in the MHC S gene (at +619 and +1243) in a case-control association study. We could confirm a significant association between psoriasis and HLA-Cw6 [odds ratio (OR) = 7.75]. No association was found between disease (or any subtypes) and the MHC S gene polymorphism at position +619, despite its close proximity to HLA-C and the strong linkage disequilibrium between the loci. However, a significant trend with the rarer allele at MHC S (+1243) and psoriasis was detected in the overall data set (OR = 2. 66; P = 2 [times] 10(-)9). This effect was most pronounced in the type 1a (early onset) psoriatics (OR = 3.43). Furthermore, homozygosity for the associated allele at MHC S (+1243) increased the risk of disease over that for carriage of HLA-Cw6 alone (OR = 9. 38), suggesting that allele 2 of MHC S (+1243) provides an additional risk in psoriasis susceptibility. The strong association found here, coupled with the biological involvement of the MHC S gene product corneodesmosin in skin physiology, implicates this locus (or a haplotype across HLA-C and MHC S ) in the impaired desquamation characteristic of psoriasis.

Atopic and non-atopic individuals react to nickel challenge in a similar way. A study of the cytokine profile in nickel-induced contact dermatitis.

The influence of atopy on delayed-type hypersensitivity remains unclear. The expression of cytokine mRNA was assessed by reverse transcription-polymerase chain reaction (RT-PCR) in biopsy skin taken 24 h after the application of a 5% NiSO4 patch to five patients with atopic dermatitis and seven non-atopic subjects with previously proven contact allergy to nickel. Control specimens were obtained from untested and vehicle-tested skin from the same individuals. There was a significant increase in the mRNA expression for interferon-gamma (IFN-gamma), interleukin (IL)-2 and IL-4 together after nickel challenge in both patients (analysis of variance P = 0.007) and non-atopic-individuals (P = 0.005). In contrast, IL-10 mRNA increased in the non-atopic group only. These results show that atopic patients and normal subjects have a similar immunological reaction to nickel challenge. Moreover, it is suggested that both Th1- and Th2-type cytokines are involved in the immunopathogenesis of contact dermatitis.

Leukaemia inhibitory factor: induction in the early phase of allergic contact dermatitis.

It has been suggested that leukaemia inhibitory factor (LIF), may be involved in the pathogenesis of cutaneous inflammation. In 5 patients with previously proven contact allergy to nickel, LIF mRNA and protein expression were assessed by reverse transcription-polymerase chain reaction and immunohistochemistry in 5% nickel sulfate patch test biopsies 24 h after application of the patch. Control specimens were obtained from non-tested and vehicle-tested skin from the same individuals. LIF mRNA expression was significantly increased in nickel-tested skin compared with both vehicle-tested (p = 0.045) and non-tested skin (p = 0.041). All biopsies showed similar patterns of LIF immunoreactivity, with no significant differences between nickel-tested, vehicle-tested and non-tested skin. Immunostaining was cytoplasmic and was present in the epidermis and hair follicles. No dermal staining was observed. This study suggests that LIF may play a role in the early phase of allergic contact dermatitis.

Minoxidil, hypercoagulability and thromboembolic disease of the lung.

Minoxidil is a potent antihypertensive agent used in the treatment of resistant hypertension. A case is presented which illustrates a probably fatal interaction between minoxidil and a coagulation disorder.

Milia en plaque--a new site and novel treatment.

Milia en plaque is an unusual eruption typically occurring in the retroauricular area. Two cases of this disorder occurring in a novel position and treated with oral minocycline are now reported.