Impact of smoking on imiquimod response in patients with vulval intraepithelial neoplasia.

BACKGROUND: Vulval intraepithelial neoplasia (VIN) is a precancerous condition that may progress to invasive malignancy. VIN is associated with human papillomavirus (HPV) infection in most cases, and with inflammatory skin disorders in a smaller proportion of patients. Treatment of VIN has traditionally been surgical excision; however, topical treatments, including imiquimod cream, are becoming increasingly used. Patient factors influencing response to imiquimod therapy, in particular smoking, have not yet been published. AIM: To assess the impact of smoking and other patient characteristics that may influence the treatment response to topical imiquimod for VIN. METHODS: This was a retrospective cohort study of 46 women treated with topical imiquimod for VIN in a single centre dermatology unit from January 2011 to July 2017. RESULTS: Complete clinical resolution of VIN was observed in 28 of 46 patients (61%), but was significantly reduced in the smoking cohort. CONCLUSIONS: Smoking may impair response to imiquimod for VIN, and should be considered when discussing VIN treatment options with patients.

Segmental cherry angiomas associated with extragenital lichen sclerosus: a report of two cases.

Cherry angiomas (Campbell de Morgan spots) are common acquired red skin papules composed of dilated capillary loops, usually of unknown aetiology. Extragenital lichen sclerosus (LS) presents as porcelain-white scaly atrophic lesions with or without genital involvement. We report two cases of segmental multiple cherry angiomas in association with extragenital LS. Two unrelated women, aged 46 and 66 years, presented with extragenital LS affecting their axillae and lower abdomen. During the examination, both patients were noted to have several hundred red skin papules in a segmental distribution, affecting the left thigh and flank of one woman, and the right abdomen and back of the other. Clinically and histologically, the papules were consistent with cherry angiomas. The striking segmental distribution of multiple cherry angiomas may be due to genetic mosaicism; however, segmental Fabry disease was excluded by sequence analysis of the α-galactosidase A gene. Any causal link between cherry angiomas and LS remains uncertain.

Involution of infantile haemangiomas after imiquimod 5% cream.

Infantile haemangioma is a common childhood condition, which usually resolves spontaneously and is managed expectantly. In a small percentage of complex cases, haemangiomas may be associated with complications such as persistent bleeding, ulceration, feeding difficulties or visual impairment. Active treatment is often necessary in such cases. Current interventions include surgical, laser and immunomodulatory treatments. Imiquimod 5% cream is a novel alternative topical treatment that may have a potential role in management of these patients. We present our experience of imiquimod 5% cream in the treatment of five children with difficult haemangiomas. We discuss its efficacy and some of the side effects that may be encountered, which have not previously been reported.

Guidelines for the management of actinic keratoses.

These guidelines stemmed from a consensus meeting held by the British Photobiology Group (BPG) in 1999. Following this meeting one of the authors (J.M.M.) was invited to draw up guidelines for the management of actinic keratoses by the British Association of Dermatologists Therapy Guidelines and Audit Subcommittee. Relevant evidence was sought using the search terms 'solar keratosis' and 'actinic keratosis' in Medline from 1966 onwards. Additional and earlier literature was reviewed on the basis of references within post-1966 publications. All articles of apparent relevance were reviewed independently of the nature of the publication. The quality of the evidence elicited has been indicated. The National Ambulatory Medical Care Survey (U.S.A.) was used for further data on topical chemotherapy. Papers were reviewed and discussed by the contributors to the BPG Workshop (see Acknowledgments). Recommendations are evidence based where possible. Strength of recommendation is coupled with quality of evidence. Strength of recommendation includes consideration of apparent cost-benefit and practical considerations. Quality of evidence reflects the nature of the trial structure that provides data of efficacy.

Neonatal pneumococcal sepsis in association with fatal maternal pneumococcal sepsis.

A live male infant was born at 37 weeks' gestation after a normal pregnancy to a 34-year-old mother. The baby developed bacteraemia with Streptococcus pneumoniae and recovered completely following treatment with antibiotics. The mother simultaneously developed bacteraemia with the same organism and died from septic shock. Blood culture isolates from mother and child were both serogroup 23F, and were shown to be identical by DNA fingerprinting. The literature reports rare cases of vaginal carriage and/or endometritis with this organism resulting in neonatal sepsis. Transmission to the neonate may have been ascending or haematogenous. A postmortem examination was refused.

Teaching children about skin cancer: the draw-and-write technique as an evaluation tool.

Childhood exposure to sunlight is a risk factor for melanoma. To formulate a meaningful program to educate children about the ill effects of the sun, their extant knowledge base must be determined. We have used the "draw-and-write" technique to assess children's perceptions about the sun, suntans, and skin cancer. A total of 693 school children aged 4 to 13 years were asked to draw pictures and label them in response to a series of carefully worded questions. Awareness of the need to apply sunscreen increased from 44% in children aged 4 to 6 years to 95% in children aged 9 to 10 years. Ten percent of children aged 4 to 6 years already perceived a suntan as attractive. While almost all children were aware of the negative immediate effects of sun exposure, namely sunburn, just 30% of American children aged 11 to 13 were aware that sun exposure is a risk for skin cancer. No differences between boys and girls were seen. The "draw-and-write" technique allows assessment of the attitudes and perceptions of children regarding the sun and skin cancer. It also provides valuable information on which to base health education and evaluate its cost-effectiveness.

What do children aged 5 to 11 years old know about the sun and skin cancer? The practical difficulties of international collaborative research when analysis of language is involved.

The objective of this study was to determine the perceptions of primary school children about sun exposure and skin cancer, and the language they use about these issues, as a basis for the design of health promotional materials. In all, 2857 children in five European countries took part in the study and were compared with 641 Australian children participating in a similar study, since the latter have been exposed to more intensive health education about the sun. The 'draw and write' technique was used. In Europe the level of awareness about the risks of excessive sun exposure and the need to protect the skin was considerably lower than in Australia, although there was some variation within northern Europe. Amongst the European children acknowledging a need to protect the skin, the principal means of protection quoted was the use of suncreams, with inadequate awareness of the value of clothing, hats and shade. European children expressed greater approval of suntans than did the Australian children. Some methodological problems were encountered as a result of nuances in the languages involved, emphasizing difficulties in international research of this type.

Health education about sun and skin cancer: language, ideas and perceptions of young children.

Excessive sunlight in early childhood is thought to be a risk factor for skin cancer. We report the use of the 'draw and write' technique for determining changing perceptions, attitudes and knowledge of young children (aged 4-12 years) to the sun and skin cancer. Children were asked to draw pictures and label them in response to a series of carefully worded invitations and questions. The captions were then analysed to assess changing views and perceptions about particular issues in relation to behaviour in the sun. Four hundred and sixty children completed the exercise. An increasing spiral of knowledge with age about effects of the sun and appropriate behaviour was demonstrated. The study revealed a relatively high level of knowledge. Misconceptions and stereotypes were demonstrated. This technique is a simple and effective way of eliciting information from children about health issues. It provides baseline data for producing material for health education for children in relation to sun and skin. It is also a method of assessing the effectiveness in young children of health promotion initiatives.

Keratin expression in pilosebaceous epithelia in truncal skin of acne patients.

This study compared the pattern of keratin expression in pilosebaceous follicles in uninvolved trunk skin of acne patients, comedones, and normal control skin by immunohistochemistry, using both immunofluorescent (IF) and immunoperoxidase (IP) techniques. The shape, size and gross morphology of truncal follicles varied greatly. There was no difference in keratin expression between normal skin and uninvolved skin of patients with acne. The upper part of the pilosebaceous duct expressed keratins K1, K5, K10 and K14, whereas the lower duct expressed keratins K5, K6, K14, K16, K17 and K19. The sebaceous gland showed considerable heterogeneity in keratin expression, with some lobules expressing keratins K1, K5, K7, K10, K14 and K17. The comedone wall showed a pattern of keratin expression similar to that of the upper follicle, except that there was, in addition, expression of keratins K6 and K16 suprabasally, and panepithelial expression of K17 in the comedone wall. IF techniques were found to be less sensitive than the IP method in the detection of individual keratins, but the use of multiple antibodies and many different transverse and longitudinal sections of follicles permitted full conclusions to be made. The increased expression of keratins K6, K16 and K17 in the comedone wall is likely to represent a secondary effect of increased cell turnover due to the primary underlying mechanism of comedogenesis, which is as yet unknown.

Immunohistochemical study of desmosomes in acne vulgaris.

Desmosomes contribute towards adhesion between adjacent keratinocytes. In acne vulgaris, increased intercellular adhesion is thought to contribute to the retention of keratinocytes within the follicular lumen during comedogenesis. Therefore, the distribution of different desmosomal components was investigated in normal and acne subjects. Biopsies were cryostat-sectioned (6 microns), and stained with antibodies to different desmosomal components: desmoplakin 1/2, desmoglein 1, desmocollin 3a/3b, and a late desmosomal antigen, G36-19. Desmoplakin 1/2, desmoglein 1 and desmocollin 3a/3b shared a similar distribution in follicles from control skin, from acne-affected skin, and in non-inflamed lesions. All three proteins were expressed around the periphery of keratinocytes of all the intrafollicular epidermis, except the basal lamina and the upper stratum corneum. In inflamed lesions, the expression of desmoglein 1 and desmocollin 3a/3b was diminished; in 12.5%, staining for these two proteins was completely abolished, and in 81.25% of the lesions investigated the staining was patchy. The antibody G36-19 bound to an antigen in the upper granular layer in the infundibular epidermis. No differences were noted in the staining pattern of the follicular epithelia of controls, non-inflamed, and inflamed lesions. This study, using monoclonal antibodies, did not identify any changes in the desmosomal components which might explain the increased adhesion between follicular keratinocytes during comedogenesis.

A prospective study of the effect of isotretinoin on the follicular reservoir and sustainable sebum excretion rate in patients with acne.

BACKGROUND AND DESIGN: A prospective study of 30 patients with moderate to severe acne was performed. The follicular reservoir and sustainable sebum excretion rates were measured before and after a 4-month course of isotretinoin at a dose of 1 mg/kg per day. RESULTS: The follicular reservoir and sustainable sebum excretion rates were profoundly reduced at the end of the course of isotretinoin (79% and 83%, respectively) and remained significantly suppressed at 1 year following therapy (43% and 36%, respectively). Those patients who relapsed clinically at 1 year after treatment had a significantly higher follicular reservoir rate. CONCLUSIONS: These data support the concept that up to 1 year after therapy, there is a reduction in the sebum secretion rate accompanying the remission of acne. This suppressed sebum secretion may modulate the microenvironment of the pilosebaceous canal through an effect on the follicular reservoir.

Melanoma and skin cancer: evaluation of a health education programme for secondary schools.

The effectiveness of an education package for secondary schools about the sun and skin cancer was assessed using questionnaires. A variety of teaching methods was used, including pamphlets, workbooks, and a video. The effect of this material was assessed by asking pupils to complete questionnaires immediately after receiving the package (July), and after the summer holiday (September). Five-hundred and forty-three children from seven schools were recruited into the study. Results of the questionnaire demonstrated a significant difference in knowledge (P < 0.001) and reported attitude (P < 0.001) compared with a control group. There was no significant difference in behaviour of the taught groups compared with the control group. The only significant activity associated with increased knowledge was wearing a sunscreen (P < 0.005). In contrast, in terms of attitude, those who covered up in the sun (P < 0.0001), wore a sunscreen (P < 0.004), and sat in the shade (P < 0.02), had significantly better attitudes than those who did not behave in this way. This project is a first attempt to assess health education in schools, and reports changes in knowledge, attitudes, and some aspects of behaviour. Adolescents are a group who are difficult to influence, but our study has produced some useful information about how these children respond to such teaching measures.

The relationship of psoriasis to malignancy: a clinical report.

A large variety of cutaneous reactions to malignancy have been described but to our knowledge none include psoriasis. Two cases of psoriasiform reactions in association with malignancy were first documented by Braverman, and Bazex's syndrome is now well documented in the literature. Both conditions, although clinically psoriasiform, are said to demonstrate an eczematous histology. A number of patients with psoriasis and malignancy have presented to us in the Dermatology Department. The appearance or behaviour of their psoriasis appeared to be linked to their malignancy. We have collected them together to report on this phenomenon which appears infrequently in the literature.

Construction of affinity sorbents utilizing glutathione analogs.

Solution-phase N-fluorenylmethoxycarbonyl (Fmoc) mediated peptide synthesis has been adapted to the synthesis of glutathione (gamma-glutamyl-cysteinyl-glycine) analogs. A protecting group strategy has been devised in which all of the masking groups are removed with mild base. This allows for the synthesis of acid-sensitive materials and lessens concerns about the alkylation at sulfur by carbocations known to be present in the trifluoroacetic acid mixtures usually employed for deprotection of peptides made by the Fmoc methodology. A series of structurally varied glutathione analogs were prepared by modifying the peptide in two ways. The first involved C-terminal substitution for glycine by one of several different amino acids. The second involved substitution of one of five alkyl or aryl groups onto the cysteine sulfhydryl. The complete set of all combinations would yield 48 reagents, of which 25 have actually been synthesized. Following confirmation of the structures by FAB mass spectrometry, the peptides were immobilize by conjugation to epoxyfunctionalized Sepharose at pH 11-12. The amount and identity of immobilized peptide was assayed by amino acid analysis of acid-hydrolyzed resin. One of the tripeptides was purified by ion-exchange and preparative HPLC.

A double-blind evaluation of topical isotretinoin 0.05%, benzoyl peroxide gel 5% and placebo in patients with acne.

A double-blind, randomized study comparing isotretinoin gel (Isotrex), its vehicle base, and benzoyl peroxide was performed on 77 patients with mild to moderate acne vulgaris. The effect of treatment was assessed by acne grade and lesion count. The vehicle base had no effect, but both active groups produced significant improvements. Benzoyl peroxide and isotretinoin significantly reduced non-inflamed lesions at 4 (P < 0.05), 8 (P < 0.01), 12 (P < 0.01) weeks. Benzoyl peroxide had a more rapid effect on inflamed lesions, their being significant reductions at 4, 8 and 12 weeks (P < 0.01), whereas with isotretinoin there was a significant improvement at 12 weeks (P < 0.01). In addition, compared to placebo, both active treatments significantly reduced inflamed and non-inflamed lesions. Acne grade had improved significantly in the benzoyl peroxide group by 4 weeks (P < 0.01) and in the isotretinoin group by 8 weeks (P < 0.05). No significant change in haematological or biochemical parameters occurred. An irritant dermatitis occurred equally with both treatments but was well tolerated by the patients. This data confirms the clinical benefit of benzoyl peroxide in acne. The initial effect of isotretinoin on non-inflamed lesions in this study suggests that the prime mode of action is on comedone formation or separation whereas benzoyl peroxide has an effect on both comedones and inflammation.

Seborrhoea--an indicator for poor clinical response in acne patients treated with antibiotics.

The relationship between sebum excretion rate (SER) and clinical improvement was investigated in 255 acne patients treated for 6 months with either oral erythromycin (1 g/day), minocycline (100 mg/day), oxytetracycline (1 g/day) or cotrimoxazole (400 mg/day); topical therapy was 5% benzoyl peroxide. In all but the cotrimoxazole treated group, there was a significant correlation between a high SER and reduced clinical response. This was particularly evident in those patients with an SER of greater than 2.5 micrograms/cm2/min. These patients showed only 17% improvement compared with 100% improvement in those subjects with an SER of 1.0 micrograms/cm2/min or less. The presence of obvious seborrhoea in a patient who has failed to respond to an adequate 6-month course of antimicrobial therapy, should indicate the earlier rather than later use of isotretinoin for their acne.