False-negative rate of intraoperative frozen section margin analysis for complex head and neck nonmelanoma skin cancer excisions.

INTRODUCTION: Intraoperative frozen section analysis (IFSA) is traditionally performed for complex and high-risk non-melanoma skin cancer (NMSC) resections, particularly when surgery under a general anaesthetic and a complex reconstruction is required, and where Mohs micrographic surgery (MMS) is not available. METHODS: A retrospective audit of 253 cases between 1999 and 2009 was undertaken, investigating the accuracy and efficacy of IFSA for the treatment of NMSC in our tertiary skin tumour unit based in a university hospital setting. RESULTS: The combined incomplete and very narrow (<1 mm) excision margin rates were 28.7% and 27.5% for basal cell and squamous cell carcinoma, respectively. Unrepresentative sampling of the excision margins intraoperatively was the overwhelming cause of error (94%). CONCLUSION: After a thorough audit of our data, IFSA has been abandoned for the treatment of NMSC in our unit. MMS is practised intraoperatively, even in advanced cases. We believe that IFSA no longer has any role in our complex, multidisciplinary skin cancer practice.

Severe lower limb cellulitis is best diagnosed by dermatologists and managed with shared care between primary and secondary care.

BACKGROUND: Cellulitis is responsible for over 400,000 bed days per year in the English National Health Service (NHS) at the cost of £96 million. OBJECTIVES: An audit following transfer of care of lower limb cellulitis managed in secondary care from general physicians to dermatologists. METHODS: Review of patient details and work diaries from the first 40 months of implementation of the new model of care. RESULTS: Of 635 patients referred with lower limb cellulitis 33% had other diagnoses which did not require admission. Four hundred and seven of 425 patients with cellulitis were managed entirely as outpatients, many at home. Twenty-eight per cent of patients with cellulitis had an underlying skin disease identified and treated, which is likely to have reduced the risk of recurrent cellulitis, leg ulceration and lymphoedema. Only 18 of 635 patients referred with lower limb cellulitis required hospital admission for conventional treatment. CONCLUSIONS: This new way of managing suspected lower limb cellulitis offered substantial savings for the NHS, and benefits of early and accurate diagnosis with correct home treatment for patients.

A comparison of the stimulatory effects of cytokines on normal and psoriatic keratinocytes in vitro.

Keratinocytes from normal and psoriatic skin were tested for their in vitro proliferative response to a range of concentrations of rIL-6, rTGF alpha, rIL-8 and rGM-CSF using a serum-free culture system. With one exception, all normal cultures (11/12) were stimulated by 1000 ng/ml IL-6 (P < 0.001). Six out of ten psoriatic keratinocyte cultures were also stimulated at this concentration, but this just failed to reach significance (P = 0.05). As a group, the response by psoriatic keratinocytes to IL-6 was significantly less than that of normal keratinocytes (P = 0.02). TGF alpha at 1 ng/ml induced proliferation in approximately 60% of both normal (8/12, P < 0.05) and psoriatic (6/10, P < 0.01) keratinocyte cultures; there was no significant difference between the responses of the two groups to this cytokine. In addition, small numbers of both normal and psoriatic cultures responded to TGF alpha over a concentration range of 0.1 to 100 ng/ml. Approximately half of the normal and psoriatic cultures were stimulated by 10-1000 ng/ml IL-8. However, the effect was not significant for the group at any of the concentrations tested. GM-CSF had minimal to no effect on most of the normal and psoriatic cultures tested. This study showed that psoriatic keratinocytes are equally responsive to the stimulatory effects of TGF alpha and IL-8, but are less susceptible to IL-6 compared to keratinocytes from normal skin. These findings are consistent with a role for these cytokines in the maintenance of a hyperproliferative epidermis in psoriasis.

Induction of cutaneous lymphocyte-associated antigen expression by group A streptococcal antigens in psoriasis.

The cutaneous lymphocyte-associated antigen (CLA) has been proposed as a homing receptor for the selective migration of memory T cells into the skin. To investigate the effect of group A streptococci (GAS) on the migration of T cells in psoriasis, CLA expression was assessed by double-staining for CD3 and the HECA-452 epitope on peripheral blood T cells from 13 patients with psoriasis, 10 patients with other inflammatory skin diseases and 12 normal controls before and after 7 days culture with a GAS sonicate, Candida albicans (control antigen) or medium. In addition, CLA+, and CLA-, CD3+ CD45RO+ subsets were isolated from individuals in each group and V beta 2 expression and proliferation to GAS studied. Mean CLA expression by freshly isolated T cells was almost identical in the three groups. After culture with GAS, T cells from the psoriatic patients and control showed a significant increase in mean percentage CLA+ expression compared to medium (P < 0.002, P < 0.05, respectively). This induction was inhibited by the addition of anti-IL-12 antibody. However, in psoriatic patients, but not in controls, the GAS-induced increase was significantly greater than that of C. albicans (P < 0.002) and was accompanied by a decrease in T cells positive for the peripheral lymph node homing receptor, L-selectin (P < 0.05). The percentage of V beta 2+ T cells was markedly higher in the CLA+ than in the CLA- T-cell subset in psoriatic patients (P < 0.01) and controls; both subsets proliferated to GAS, in each group. These findings suggest a differential modulation of specific tissue homing receptors on T cells by GAS in psoriasis.

Cytokine expression in psoriatic skin lesions during PUVA therapy.

To determine whether an improvement in skin lesions as a result of PUVA therapy may be correlated with changes in cytokine patterns, RT-PCR amplification was used to compare the levels of IL-2, IL-6, IL-8, IL-10, TNF-alpha and IFN-gamma cytokine mRNA expression in serial biopsies from three chronic plaque psoriatic patients. In each case, 3-mm punch biopsies were taken from lesional skin before and during 2-28 days of treatment with PUVA. Total mRNA was extracted from each biopsy, cDNA synthesized, and then amplified by 35 cycles of PCR using cytokine-specific primers. The specificity of the PCR products was confirmed by the Southern blot technique. Substantial levels of specific mRNA for each of the cytokines studied was present in the lesions prior to treatment. In two of the three patients who responded well to PUVA, a reduction in all the cytokines including IL-10 was observed compared with baseline levels. In contrast, PUVA proved to be ineffective in clearing the psoriasis of the third patient whose skin lesions worsened during the course of treatment. This was accompanied by an increase in IFN-gamma but not of the other cytokines investigated, above the pretreatment level. This study showed an association between PUVA-induced resolution and decreases in the levels of various cytokines highly expressed in psoriatic lesions.

Acne in schoolchildren: no longer a concern for dermatologists.

OBJECTIVE: To determine the prevalence and severity of acne among schoolchildren in Glasgow. DESIGN: Secondary schools in Glasgow were divided by postcode into five socioeconomic cluster groups. Different numbers of schools were selected at random from the five groups to ensure proportional representation. One class from each registration year of the chosen schools was selected at random and the whole class recruited into the study. SETTING: 15 Secondary schools in Glasgow. SUBJECTS: 2014 Randomly selected schoolchildren aged 12-17 (5% of total secondary school roll). INTERVENTIONS: None. END POINT: Assessment of facial acne by two independent examiners by a recognised acne scoring system. MEASUREMENTS AND MAIN RESULTS: The prevalence of acne in boys increased from 40% (75/189) at age 12 to 95% (108/114) at age 16, and in girls it increased from 61% (114/187) at age 12 to 83% (136/164) at age 16. On a scale of 0 to 10 only 18 boys (1.8%) and three girls (0.3%) had grades of acne of 1.0 or greater; most of the pupils had grade 0.05-0.375 (minimal) acne. Nine per cent of boys (88/973) and 14% of girls (145/1041) had visited their general practitioner specifically for advice on and treatment for acne; only five pupils (0.3%) had been referred to a dermatologist. CONCLUSIONS: Both the prevalence and severity of acne have decreased over the past 20 years. This has probably been due to improvement of treatment for acne by primary care doctors and the greater availability and use of over the counter preparations for acne.

A comparison of narrowband (TL-01) UVB-induced erythemal response at different body sites.

In most dermatology centres where phototesting is performed, the starting dose is calculated as a proportion of the minimal erythema dose (MED). Previous studies have found significant differences in MED readings between forearm and back skin with both broadband and narrowband (NB) UVB. Our objective was to compare MEDs obtained from three body sites, the forearm, back and abdomen, to see if there was a significant difference in individuals. We recruited 20 healthy volunteers who were exposed to our standard dose series for phototesting with NB-UVB to three body sites: forearm, back and abdomen. MEDs were assessed 24 h post exposure. The median MED for the abdomen was 0.79 J/cm2, the back 0.95 J/cm2 and the arm 1.11 J/cm2. Friedman's analysis of variance by ranks showed that these differences were significant (P = 0.003). There was no correlation between skin type and MED for any of the three anatomical sites. Our results support phototesting for all patients prior to treatment with NB-UVB. Furthermore, we have shown that the abdomen is the anatomical site of choice for phototesting, as this will result in a reduced risk of burning episodes.

The relevance of elevated Borrelia burgdorferi titres in localized scleroderma.

A 46-year-old man with a 2-year history of localized scleroderma of his right upper arm and elevated Borrelia burgdorferi titres is described. The association of Borrelia burgdorferi infection and localized scleroderma is discussed.

Keratinocyte expression of intercellular adhesion molecule 1 (ICAM-1) correlated with infiltration of lymphocyte function associated antigen 1 (LFA-1) positive cells in evolving allergic contact dermatitis reactions.

Adhesion molecules are considered to have an important role in inflammatory reactions. We investigated the kinetics of ICAM-1 expression on keratinocytes and correlated this with the numbers of lymphocytes expressing LFA-1 in the dermis and epidermis of evolving allergic contact dermatitis reactions. In nickel-sensitive individuals, after application of a nickel patch, increased expression of ICAM-1 on keratinocytes was observed as early as 3 h and reached a maximum at 48 h. The number of lymphocytes expressing LFA-1 in the dermis and epidermis was greatest at 48 h. The LFA-1 cells were observed to be in close proximity to keratinocytes expressing ICAM-1, thus supporting the hypothesis that T-lymphocytes attach to keratinocytes via LFA-1/ICAM-1 molecules.

Thermographic assessment of patch-test responses.

Infra-red thermography was used to quantify, at patch test sites, the allergic responses to experimental preparations of nickel sulphate and primary irritant responses to sodium lauryl sulphate in small groups of volunteers. The technique was also used to assess the patch-test responses in a much larger group of patients who had undergone routine patch testing for contact allergy with a wide range of test substances and among which there were large numbers of allergic, irritant and equivocal reactions. Thermographically, when compared to the surrounding normal skin surface, the sites of allergic reactions appeared as hot areas, the temperature and area of which were apparently dependent on the severity of the response. For allergic responses, there was a good correlation between the clinical assessment and either of two thermographic parameters, temperature and area of involvement. Compared with an aqueous solution of nickel sulphate, 'poor' formulations of the allergen, such as a suspension in soft paraffin base, elicited smaller and cooler reactions. Irritant reaction sites were not 'hot' and the temperature at such sites was no different from that of the surrounding normal skin. Infra-red thermography is a convenient non-invasive technique which apparently can be used to discriminate between irritant and allergic responses and to quantify the latter type of response.

25 years' experience of a gluten-free diet in the treatment of dermatitis herpetiformis.

Gluten-free diets have been used in the treatment of patients with dermatitis herpetiformis in our department since 1967. Of the 212 patients with dermatitis herpetiformis attending between 1967 and 1992, 133 managed to take the diet, and 78 of these achieved complete control of their rash by diet alone. Of the remaining 55 patients taking a gluten-free diet, all but three were taking partial diets; over half of these patients managed to substantially reduce the dose of medication required. Of the 77 patients taking a normal diet, eight entered spontaneous remission, giving a remission rate of 10%; a further two patients who had been taking gluten-free diets were found to have remitted when they resumed normal diets. Loss of IgA from the skin was observed in 10 of 41 (24%) patients taking strict gluten-free diets. These patients had been taking their diets for an average of 13 years (range 5-24 years), and their rash had been controlled by diet alone for an average of 10 years (range 3-16 years). The advantages of a gluten-free diet in the management of patients with dermatitis herpetiformis are: (i) the need for medication is reduced or abolished; (ii) there is resolution of the enteropathy, and (iii) patients experience a feeling of well-being after commencing the diet. Thus, we propose that a gluten-free diet is the most appropriate treatment for patients with dermatitis herpetiformis.

T lymphocytes in lesional skin of patients with dermatitis herpetiformis.

Ten patients with dermatitis herpetiformis had biopsies taken from involved and uninvolved skin. Monoclonal antibodies and the avidin-biotin peroxidase staining technique were used to stain for T cells and Langerhans cells in skin sections. A significant increase in the number of CD3-positive T cells was observed in the upper dermis of involved compared with uninvolved skin (P < 0.0005). Most of the T cells in involved skin were CD45RO-positive memory cells; CD4-positive T cells exceeded the number of CD8-positive T cells by a ratio of 4:1. In addition, CD1a-positive dendritic cells were observed within the clumps of T cells in involved dermis in nine of the 10 patients, but were absent from the dermis of uninvolved skin. Double immunofluorescent staining demonstrated that approximately 20-40% of the CD3-positive T cells were activated, and expressed the HLA-DR antigen. These findings suggest that activated T cells are involved in the pathogenesis of dermatitis herpetiformis skin lesions.

Dermatoses in five related female carriers of X-linked chronic granulomatous disease.

Eight female members of a family with X-linked chronic granulomatous disease were identified. Five were shown to be carriers of the disease gene. Each of these female carriers of the gene had a history of skin eruptions. The identification of the carrier state is important as genetic counselling should be offered and the prenatal diagnosis of this disorder is possible.

Differential T-cell reactivity to the round and oval forms of Pityrosporum in the skin of patients with psoriasis.

Pityrosporum yeasts have been implicated as a trigger for the initiation of scalp lesions in psoriasis. To determine whether Pityrosporum-reactive T cells are present in lesional psoriatic skin. T-cell lines (TCL) were cultured from the scalps of nine patients with psoriasis and seven with alopecia areata (disease controls), and from non-scalp lesions from six of the psoriatic patients. The psoriatic skin TCL were stained for CD3, CD4, CD8 and TCR alpha beta expression and tested in a proliferation assay with Candida albicans and purified protein derivative (PPD), and cytoplasmic and cell-wall extracts of P. ovale (oval) and P. orbiculare (round). The proliferative responses of corresponding peripheral blood mononuclear cells (PBMC) were also determined. All the PBMC samples responded to the Pityrosporum extracts to variable extents, but no significant difference in the response of the group to the two different forms of yeast was observed. The response was mediated by CD4+ T cells and inhibited by the addition of anti-HLA-DR antibody. In addition, all nine psoriatic scalp TCL, which were predominantly CD3+, CD4+ TCR alpha beta(+), responded to the cytoplasmic, and five of nine TCL to the cell-wall extract of P. orbiculare. In contrast, only three of the nine TCL proliferated to either extract of P. ovale. This difference was significant for both the cytoplasmic (P < 0.01) and cell wall (P = 0.01) extracts. Similarly, the TCL cultured from non-scalp psoriatic lesions also showed a more marked response to the P. orbiculare extracts (P = 0.05). Furthermore, four of seven and two of seven scalp TCL from lesions of alopecia areata responded to the P. orbiculare and P. ovale extracts, respectively; these responses did not differ significantly from those of the psoriatic scalp TCL. None of the skin TCL responded to either Candida albicans or PPD. These findings demonstrate that T cells with differential reactivity to the round and oval forms of Pityrosporum are present in, but are not specific for, psoriatic skin lesions. A role for these cells in the pathogenesis of psoriasis remains speculative.