Showing papers in "British Journal of Dermatology in 1996"

A review of skin ageing and its medical therapy

Abstract: Intrinsic (chronological) skin ageing is characterized by atrophy of the skin with loss of elasticity and slowed metabolic activity. The superposition of environmental damage, particularly exposure to ultraviolet radiation (photodamage), on the intrinsic ageing process results, at least initially, in a hypertrophic repair response, with a thickened epidermis and increased melanogenesis. Even more striking changes occur in the dermis: massive elastosis (deposition of abnormal elastic fibres), collagen degeneration, and twisted, dilated microvasculature. Regular use of a sunscreen alone appears to allow some repair as well as protection from further photodamage. Topical tretinoin has been shown to partially reverse the clinical and histological changes induced by the combination of sunlight exposure and chronological ageing. A formulation of tretinoin in an emollient cream (Retinova, Renova), developed specifically for the treatment of photodamaged skin, has been extensively investigated in multicentre, double-blind trials and has been shown to produce significant improvement within 4-6 months of daily use, compared with vehicle alone, as part of a regimen including sun protection and moisturizer use. Histological changes in the epidermis and dermis noted after 12 months suggest tretinoin repairs photodamage by reconstitution of the rete pegs, repair of keratinocyte ultrastructural damage, more even distribution of melanocytes and melanin pigment, deposition of new papillary dermal collagen, and improvements in vasculature. Alpha-hydroxy acids (AHAs) have also been widely used for therapy of photodamaged skin, and these compounds have been reported to normalize hyperkeratinization and increase viable epidermal thickness and dermal glycosaminoglycans content. The single randomized controlled study now available appears to substantiate AHA efficacy and safety. In summary, recent work has substantially elucidated the ageing processes that affect the skin and has demonstrated that many of the unwanted changes can be improved by topical therapy.

Apoptosis as a mechanism of keratinocyte death in toxic epidermal necrolysis

Abstract: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are life-threatening diseases characterized by extensive epidermal destruction. The aim of our study was to investigate apoptosis in keratinocytes of patients with TEN and TEN/SJS overlap syndrome. Keratinocytes from TEN patients were found to undergo extensive apoptosis. These results suggest that cell destruction in TEN occurs as a result of apoptosis. Our findings suggest that apoptosis inhibitory agents may play an important part in the therapeutic strategy of TEN.

Validation of the U.K. diagnostic criteria for atopic dermatitis in a population setting

Abstract: Summary One reason why so little is known about the epidemiology of atopic dermatitis (AD) is lack of suitable diagnostic criteria. A simple list of diagnostic criteria for AD for use in epidemiological studies has recently been developed by a U.K. working party. These have performed well in hospital validation studies of subjects with skin diseases. This study sought to validate the newly proposed criteria for AD in a population setting by conducting a cross-sectional survey of 695 schoolchildren aged 3–11 years in three randomly selected primary schools in West Lambeth, London. As a point prevalence measure, the U.K. criteria had a sensitivity of 70%, a specificity of 93%, and a positive predictive value of 47% when compared with a dermatologist's examination findings. Subsequent analysis suggested that most children classified as false positives had suffered from AD in the last year, but were inactive at the time of examination. When adjusted for these cases, the sensitivity and specificity increased to 80 and 97%, respectively, corresponding to positive and negative predictive values of 80 and 97%, respectively. The U.K. diagnostic criteria for AD appear to work well as a 1-year period prevalence measure in London schoolchildren. Further validation in adults and other countries are needed.

Psoriasis in the community: prevalence, severity and patients' beliefs and attitudes towards the disease

Abstract: The prevalence of psoriasis in a defined semi-urban general practice population of 5395 was estimated by means of a postal questionnaire, describing the features of psoriasis followed by physical examination of positive responders, and by a practice disease register, which directly identified psoriatic patients. A point prevalence of 1.48% was found based on examination at the time of study with an equal sex distribution. The mean age of development of the disease was 33 years. At the time of examination, the disease was mild in most patients (mean PASI 2.87). However, there was evidence of marked variability in severity within individuals with time. At some stage, 60% of individuals had required referral to a consultant dermatologist, and approximately 50% of these had received second-line, i.e. non-topical, treatments. Approximately 25% of patients had been in remission at some stage. Forty-one per cent of patients were aware that psoriasis was a genetically determined disease and 37% thought that stress was an exacerbating factor. Seventy per cent of patients were aware that the condition was not curable, but 63% thought that treatment was worthwhile. Fifty-three per cent described themselves as 'bothered' by the appearance of the condition. This concern was positively (and inversely) related to current age, and to stress as an exacerbating factor, but not to sex, PASI, duration of psoriasis, previous hospital referral, or the presence of pruritus. In this study of psoriasis in the community, the findings, particularly in relation to patients' attitude to the disease, disease severity, fluctuation in severity and referral requirements, are of potential interest in health care planning.

Comparison of photodynamic therapy with cryotherapy in the treatment of Bowen's disease

Abstract: The efficacy and suitability of photodynamic therapy (PDT) was compared with that of cryotherapy in the treatment of 40 lesions of Bowen's disease. Lesions were randomized to receive either cryotherapy with liquid nitrogen, or PDT using a portable desktop lamp incorporating a 300 W xenon short arc discharge source. A porphyrin precursor, 5-aminolaevulinic acid (5-ALA), was applied topically 4 h before irradiation in the PDT group. Each lesion received 125 J/cm2 at a fluence rate of 70 mW/cm2. All patients were reviewed at 2-monthly intervals and treatments repeated if required. Cryotherapy produced clearance in 10 of 20 lesions after one treatment, the remaining 10 lesions requiring two or three treatment applications. PDT resulted in clearance of 15 of 20 lesions after one treatment and of the remaining five lesions after a second treatment. The probability that a lesion cleared after one treatment was greater with PDT than cryotherapy (P < 0.01). Cryotherapy was associated with ulceration (five of 20), infection (two of 20) and recurrent disease (two of 20); no such complications occurred following PDT. PDT using a non-laser light source and topical 5-ALA appears to be at least as effective as cryotherapy in the treatment of Bowen's disease with fewer adverse effects.

Cutaneous manifestations of systemic lupus erythematosus

Abstract: We have assessed the cutaneous signs in 73 patients with systemic lupus erythematosus (SLE), seen during a 5-year period in an English hospital. Most previous information about the cutaneous manifestations of SLE has been obtained from studies performed in the U.S.A. We classified lesions as specific cutaneous and mucosal LE (acute, subacute and chronic) or non-specific LE-related, e.g. photosensitivity, urticaria, erythema, Raynaud's phenomenon or vasculitis. Acute cutaneous LE lesions included a butterfly rash with erythematous macules, telangiectasia or papulosquamous lesions, seen in 37 patients (51%) and facial oedema seen in four patients (5%). Five patients (7%) had psoriasiform subacute cutaneous LE. Chronic cutaneous LE was common: 18 patients (25%) had chronic discoid lesions (DLE) and, in 12 (15%), these had preceded systemic disease. One patient had facial lupus profundus. Ten patients (14%) had scarring alopecia secondary to DLE. Fifteen patients (20.5%) had chronic chilblain lupus. Twenty-three patients (31.5%) had a history of mouth ulceration. Of these, 11 (15%) gave a history of ulcers at the onset of their disease. Three (4%) had erythema and superficial ulceration of the palate, not typical of aphthous ulcers, and three (4%) had chronic buccal plaques. Cheilitis due to DLE was seen in three (4%), episcleritis in three (4%), five (7%) had nasal disease, six (8%) bullous skin eruptions, one 'the bullous eruption of SLE', four bullae associated with cutaneous vasculitis, and one bullae associated with ultraviolet radiation. Forty-six (63%) observed photosensitivity. A non-scarring alopecia occurred in 29 (40%). Vascular phenomena were common: three patients (4%) had chronic palmar erythema, Raynaud's phenomenon occurred in 44 patients (60%), chronic urticaria, worsened by sun exposure, was noted by 32 (44%) (in whom the lesions often lasted more than 36 h), eight (11%) had cutaneous vasculitis and three (4%) livedo reticularis. Skin changes play a prominent part in SLE and may provide helpful diagnostic information. In this British population, chilblains and urticaria were particularly common. Lesions of subacute cutaneous LE were relatively unusual in this group of patients with SLE.

Patterns of matrix metalloproteinase and TIMP-1 expression in chronic and normally healing human cutaneous wounds.

Abstract: The present study was carried out to characterize the patterns of expression of matrix metalloproteinases or their tissue inhibitor (TIMP-1) in normally healing, acute vs. chronic, skin wounds. In situ hybridization was performed to localize collagenase, stromelysin-1, stromelysin-2, matrilysin, urokinase plasminogen activator (uPA) and TIMP-1 mRNAs in 14 chronic venous ulcers and 10 normally healing wounds, representing different time points after wounding. Surgical wounds, made in piglets harvested at several time points, were studied as controls. Collagenase, stromelysin-1 and -2, as well as uPa, were expressed in keratinocytes in both acute and chronic wounds, while epithelial TIMP-1 mRNA was not detected in any chronic wound biopsies studied. However, TIMP-1 was expressed at the epithelial edges of both acute human and pig wounds. Our results suggest that the balance between metalloenzymes and their inhibitor TIMP-1, is disturbed, in poorly healing wounds.

Six Area, Six Sign Atopic Dermatitis (SASSAD) severity score: a simple system for monitoring disease activity in atopic dermatitis*

Abstract: The Six Area, Six Sign Atopic Dermatitis severity score has proved to be a simple and effective system for recording and monitoring disease activity in atopic dermatitis. The score is obtained by grading six signs (erythema, exudation, excoriation, dryness, cracking and lichenification), each on a scale of () (absent), 1 (mild), 2 (moderate), or 3 (severe), at each of six sites; arms, hands, legs, feet, head and neck, trunk. The maximum score is 108.

The cutaneous features of tuberous sclerosis: a population study

Abstract: We report the cross-sectional age-related prevalence of cutaneous features of the tuberous sclerosis complex in a defined population. Of 131 affected individuals, 126 (96%) exhibited skin signs. Although there is considerable variation in the age of expression of all the skin lesions, there is a trend towards the earlier expression of hypomelanic macules and forehead fibrous plaques compared with facial angiofibromas and ungual fibromas. Shagreen patches are usually present by puberty. Ungual fibromas appeared for the first time as late as the fifth decade and were the only clinical feature in three individuals. Gum fibromas were present in 36%. Ten individuals (8%) presented because of the skin manifestations and 21% received treatment for symptomatic skin lesions. Two individuals had large hamartomas at unusual sites (occiput and forearm).

Histopathological and epidemiological characteristics of patients with erythema exudativum multiforme major, Stevens-Johnson syndrome and toxic epidermal necrolysis

Abstract: The clinical and histopathological classification of erythema exudativum multiforme major (EEMM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are difficult, due to the lack of clear-cut criteria. Based on a new clinical classification, 149 of 219 (68%) histopathological specimens, from a total of 534 patients with EEMM, SJS and TEN, have been reviewed. A comparison was made with the clinical picture, and any past history of infection or drug intake. All patients had been included in the German Registry of Severe Skin Reactions between April 1990 and December 1993. No differences could be found between the biopsies examined and the total number of histopathological specimens, concerning clinical diagnosis, gender and age. Sections from 28 of 149 specimens were not diagnostic or were too old to be properly evaluated. In nine cases, other diagnoses were proposed. One hundred and eleven of the histological slides with the diagnosis of EEMM (n = 16), SJS (n = 34) and TEN (n = 61), were classified as epidermal type of erythema multiforme. In these 111 slides, necrotic keratinocytes could be found, ranging from individual cells to confluent epidermal necrosis. The epidermo-dermal junction showed changes ranging from vacuolar alteration up to subepidermal blisters. The dermal infiltrate was superficial and mostly perivascular. It was sparse in SJS and TEN, and more pronounced in EEMM. Oedema in the papillary dermis was evident occasionally in all clinical groups. In 59 of 111 cases (53%), at least one eosinophil was present in the dermis. In 11 of 111 (10%), more than 10 eosinophils per field could be seen. Eosinophils were less common in the patients with the most severe forms of TEN, in whom there was detachment of more than 30% of the skin surface area. No differences in the history for drug intake, or for infection with Mycoplasma pneumoniae, herpes simplex and other organisms, could be detected between patients with or without eosinophils in their skin sections. This dermatopathological study of patients with EEMM, SJS and TEN indicates that the epidermal type of erythema multiforme is the pathological correlate for these diseases.

Safety of long-term high-dose minocycline in the treatment of acne.

Abstract: Minocycline is widely used as a second-line antimicrobial for acne vulgaris. Some patients require doses of up to 200 mg daily to control their acne. To assess the long-term safety of minocycline when used at higher doses, 700 patients treated with minocycline at doses of 100 mg daily, 100/200 mg on alternate days and 200 mg daily, were recruited. The mean duration of treatment was 10.5 months. Side-effects were monitored and full blood count, blood urea, electrolytes and liver function tests were carried out on 200 of the 700 patients. Side-effects were recorded in 13.6%, and included vestibular disturbance, candida infection, gastrointestinal disturbance, cutaneous symptoms (pigmentation, pruritus, photosensitive rash and urticaria) and benign intracranial hypertension. Pigmentation was the only side-effect found to be significantly increased in patients taking higher doses of minocycline, as compared with lower doses (P < 0.01). All patients with pigmentation had taken a total cumulative dose of over 70 g. No significant abnormalities were found in any of the haematological and biochemical profiles. We conclude that minocycline, at doses of up to 200 mg/day, is safe, long-term, for acne, when such doses are clinically necessary.

Tazarotene—first of a new generation of receptor-selective retinoids

Abstract: Tazarotene is a topically applied retinoid that targets the skin, the site of the fundamental defect(s) in psoriasis, modulating the major causes of the disease and achieving sustained efficacy. In vitro, binding of tazarotenic acid has been demonstrated to retinoic acid receptors (RARs), the probable molecular target of retinoid action in adult human skin, but not to retinoid X receptors (RXRs). In gene activation assays, tazarotene is selective for the RAR beta and RAR gamma subtypes. This selectivity could theoretically limit undesirable effects at the receptor level. In vitro, animal and clinical evidence reveals that topical tazarotene modulates all three pathogenic factors in psoriasis: abnormal keratinocyte differentiation, hyperproliferation, and increased expression of inflammatory markers. Tazarotene is minimally absorbed systemically after topical administration. Tazarotene is rapidly metabolized by esterase metabolism to its active free-acid form, tazarotenic acid, which has a relatively short elimination half-life (1-2 h). The pharmacokinetic profile of tazarotenic acid is predictable, with no significant accumulation. In preclinical toxicity studies, high topical doses produced only reversible topical irritation, and lower doses were well tolerated. Topical doses were neither carcinogenic nor teratogenic, had no effect on fertility or general reproduction, and were not phototoxic, sensitizing, or photoallergenic. The pharmacological selectivity of tazarotene and limited systemic exposure result in minimal systemic effects, while the lesser cytotoxic effects (relative to other retinoids) result in reduced local effects.

Effects of interleukins, colony-stimulating factor and tumour necrosis factor on human hair follicle growth in vitro : a possible role for interleukin-1 and tumour necrosis factor-α in alopecia areata

Abstract: The immune system may be involved in the regulation of normal hair follicle growth as well as in the pathogenesis of some hair diseases. Immunomodulatory cytokines not only act as mediators of immunity and inflammation but also regulate cell proliferation and differentiation and, as such, may play an important part in regulating hair growth. We have investigated the effects of a number of interleukins (IL), colony stimulating factors and tumour necrosis factors (TNF) on hair follicle growth in vitro. Dose-response studies showed that IL-1 alpha, IL-1 beta and TNF-alpha were potent inhibitors of hair follicle growth. The histology of hair follicles maintained with inhibitory doses of IL-1 alpha, IL-1 beta and TNF-alpha showed similar changes in hair follicle morphology, resulting in the formation of dystrophic anagen hair follicles. These changes in histology were characterized by the condensation and distortion of the dermal papilla, marked vacuolation of the hair follicle matrix, abnormal keratinization of the follicle bulb and inner root sheath, disruption of follicular melanocytes and the presence of melanin granules within the dermal papilla. Moreover, these changes in hair follicle morphology are similar to those reported in alopecia areata and suggest that IL-1 alpha, IL-1 beta and TNF-alpha may play an important part in the pathophysiology of inflammatory hair disease.

Validation of the U.K. diagnostic criteria for atopic dermatitis in a population setting. U.K. Diagnostic Criteria for Atopic Dermatitis Working Party.

Abstract: One reason why so little is known about the epidemiology of atopic dermatitis (AD) is lack of suitable diagnostic criteria. A simple list of diagnostic criteria for AD for use in epidemiological studies has recently been developed by a U.K. working party. These have performed well in hospital validation studies of subjects with skin diseases. This study sought to validate the newly proposed criteria for AD in a population setting by conducting a cross-sectional survey of 695 schoolchildren aged 3-11 years in three randomly selected primary schools in West Lambeth, London. As a point prevalence measure, the U.K. criteria had a sensitivity of 70%, a specificity of 93%, and a positive predictive value of 47% when compared with a dermatologist's examination findings. Subsequent analysis suggested that most children classified as false positives had suffered from AD in the last year, but were inactive at the time of examination. When adjusted for these cases, the sensitivity and specificity increased to 80 and 97%, respectively, corresponding to positive and negative predictive values of 80 and 97%, respectively. The U.K. diagnostic criteria for AD appear to work well as a 1-year period prevalence measure in London schoolchildren. Further validation in adults and other countries are needed.

Lichen planus and hepatitis C virus : prevalence and clinical presentation of patients with lichen planus and hepatitis C virus infection

Abstract: Although cases of lichen planus (LP) associated with hepatitis C virus (HCV) infection have been described, the association between the two diseases has not been established because the geographic origin of patients could be an important factor in HCV prevalence in patients with LP. The serum samples of 78 consecutive patients with cutaneous and/or mucous LP and 82 control patients were analysed for the presence of antibodies to HCV by enzyme-immunoassay and for the presence of antigens of HCV by two-stage polymerase chain reaction (PCR). The clinical features of patients with LP associated with HCV infection were compared with patients with LP without HCV infection. Sixteen of the 78 (20%) patients had anti-HCV antibodies. In 13 of these 16 cases (81%), HCV-RNA was detected by PCR in serum samples. In the 82 control patients, anti-HCV antibodies was observed in two (2.4%) patients. We have found a statistically significant association (P < 0.05) between erosive LP and HCV infection. We conclude that the high prevalence of HCV-RNA in patients with LP provides some evidence for the role of HCV in the pathogenesis of LP. Our results suggest an association between erosive LP and HCV infection.

Hidradenitis suppurativa or acne inversa. A clinicopathological study of early lesions

Abstract: The pathogenesis of hidradenitis suppurativa (HS) has given rise to controversy about whether the central pathogenetic feature is an apocrine follicular occlusion (with subsequent bacterial infection) or it is a folliculitis with secondary involvement of both apocrine and eccrine sweat glands. Most previous concepts have focused on apocrine gland involvement. A prospective study of 27 consecutive patients (39 biopsies) was performed to investigate the immune-histological findings in early, newly formed lesions. Most of them were examined within 3 days of clinical onset. Histopathological findings showed that the initial lesion is an occluding spongiform infundibulofolliculitis. Furthermore, it was found that T cells predominated in the lymphocytic cell population. A high percentage of HLA-I)R positive lymphocytes was found in an inverse relationship with Leu-8 positive lymphocytes. Additionally, a sharp decline in the T-helper/suppressor ratio was observed after the initiation. These results reveal that the primary event in HS is an infundibulofolliculitis with secondary involvement of apocrine glands. Acne inversa would be a more appropriate name.

Safety and efficacy of oral calcitriol (1,25-dihydroxyvitamin D3) for the treatment of psoriasis.

Abstract: Summary plaque-type psoriasis has been successfully treated with oral calcitriol. but there has been no long-term follow-up on the safety and efficacy of this calciotropic hormone for psoriasis. In a single centre study, patients were enrolled in an open trial to evaluate the efficacy and safety of oral calcitriol for psoriasis. Of the 85 patients who received oral calcitriol, 88.0% had some improvement in their disease: 26.5, 36.2 and 25.3%. had complete, moderate and slight improvement in their disease. respectively. The mean baseline psoriasis area severity index score (PASI) of 18 4 ± 1.0 was reduced to 9.7 ±0.8 and 7.8±1.3 after 6 and 24 months on oral calcitriol therapy. Serum calcium concentrations and 24 h urinary calcium excretion increased by 3.9% and 148.2%, respectively. but were not outside the normal range. Bone mineral density remained unchanged. The clearance of creatinine decreased by 13 4% from baseline during the first 6 months of treatment, and thereafter. remained unchanged after 3 years of follow up. An evaluation of creatinine, inulin and para-aminohypurate (PAH) clearance was performed in eight patients. After 6 months on oral calcitriol. there was a 22.5% decline in creatinine clearance but no significant changes were observed in either inulin or PAH clearance, suggesting that calcitriol alters creatinine metabolism or secretion hut does not affect renal function. Oral calcitriol is effective and safe for the treatment of psoriasis.

Outdoor ultraviolet exposure of children and adolescents

Abstract: The weekday and weekend outdoor ultraviolet exposure of young people from primary and secondary schools in three geographically distinct regions of England was determined over a 3-month period in summer. Ultraviolet exposure was measured using personal film badges worn by each young person, and time spent outdoors, in hourly intervals, assessed using exposure records. In each area a class of 9-10-year-old children from a primary school and a class of 14-15-year-old adolescents from a secondary school took part, giving a total of 180 subjects. We found that primary school children received higher outdoor ultraviolet exposure than young people in secondary schools, and geographical differences in exposure could not be accounted for solely by differences in ambient ultraviolet. There was little difference between the exposure of males and females. Children and adolescents did not behave as homogeneous groups with regard to exposure.

Tinea capitis in south-east London--a new pattern of infection with public health implications.

Abstract: SUMMARY Recent observations on tinea capitis cases in London suggest that there has been a change in the pattern of infection with a recent and significant rise in the incidence of Infections due to anthropophilic fungi. The purpose of this study was to investigate the prevalence and Identity of tinea capitis in schools in south-east London and factors which might affect the spread of infection. This was achieved by carrying out a survey of all children, with parental consent for scalp examination, in 14 nursery, infant or junior schools in Lambeth. In addition, the accuracy of clinical diagnosis was compared with mycological findings. There were 1057 children from 4 to 14 years of age in the study. The infection rate in different schools ranged from 0 to 12% with a mean of 2.5%. A further 4.9% of children were scalp carriers of dermatophytes (range in classes 0–47%). A striking feature was that all infections were caused by anthropophilic fungi, mainly Trichophyton tonsurans or Microsporum rivalieri, and there was a correlation between the presence of two or more carriers within a class and the infection in the other children. There was a poor correlation between ability of trained observers to predict infection on clinical grounds and mycological results. This investigation shows variable but significant levels of scalp ringworm in schools and that the dominant organisms are anthropophilic. It provides support for the observation that there has been a shift in the pattern of tinea capitis in London and. possibly, other U.K. centres, with a trend towards more infections transmissible among children, with T. tonsurans being the commonest organism. The implications for control, which involve screening in schools, where appropriate, and guidance to general practitioners on treatment, are discussed.

Prevalence of atopic eczema in the community : the Lothian atopic dermatitis study

Abstract: An epidemiological study of atopic eczema (AE), based on a semirural community in Scotland, using sound diagnostic criteria, has yielded prevalence data for all age groups including infants and adults. The overall 1-year period prevalence, age-standardized to the Scottish population, was 2.3%. The 1-year period prevalence was highest in the under 2s (9.8%), and showed a continuous reduction with increasing age. Over the age of 40, AE was found to be relatively rare, with a 1-year period prevalence of 0.2%. Adults over 16 years made up 38% of all patients with AE.

Chronic sun exposure alters both the content and distribution of dermal glycosaminoglycans

Abstract: Chronic sun exposure leads to structural and functional alterations in exposed skin. Photoageing is a process distinct from the changes taking place due to chronological ageing. Unique alterations in the dermal extracellular matrix occur as a result of photoageing and are responsible for many of these physiological changes taking place in sun-damaged skin. Accompanying the deposition of abnormal elastic tissue, or solar elastosis, are significant alterations in dermal glycosaminoglycans (GAGs). Accumulation of GAGs as a result of photoageing, as demonstrated in both humans and animal models of photoageing, seems almost paradoxical in view of the large amounts of GAGs present in the skin of newborns, making their skin well hydrated and supple, in sharp contrast to the weathered appearance of photoaged skin. We investigate the relative GAG content of photoaged skin using immunoperoxidase stains specific for hyaluronic acid and chondroitin sulphate, and determine the location of these GAGs using confocal laser scanning microscopy. Our results demonstrate significant increases in GAG staining in sun-damaged vs. sun-protected skin from the same individuals, as measured by computer-based image analysis. Furthermore, confocal laser scanning microscopy reveals that the increased dermal GAGs in sun-damaged skin are deposited on the elastotic material of the superficial dermis of photodamaged skin, and not between collagen and elastic fibres as in normal skin. The abnormal location of GAGs on these fibres may explain the apparent paradoxical weathered appearance of photodamaged skin despite increased GAGs.

Endocrine factors in pre‐ and postmenopausal women with hidradenitis suppurativa

Abstract: The relationship between hidradenitis suppurativa (HS) and hyperandrogenism is largely based on the finding of an increased free androgen index due to a low sex hormone binding globulin (SHBG). As SHBG is now believed to be regulated by factors that influence body weight, and previous studies were not controlled for body weight, we have re-evaluated the androgen status of female patients with HS. We have studied the endocrine status of 66 women with HS. Twenty-three had acne, and 23 were significantly obese (body mass index: BMI > 30). There was no relationship between obesity and disease duration. Nineteen of 56 women were hirsute. A premenstrual flare in disease activity was reported by 32 women, but this was not related to menstrual disturbances. No consistent relationship was reported with pregnancy. Eight women with HS were menopausal at presentation, and one developed her disease 6 years after the menopause. Plasma androgens in women with HS were compared with controls matched for BMI and hirsuties. There was no difference between HS and controls. Testosterone and dehydroepiandrosterone sulphate were normal in all subjects with HS. In obese subjects, SHBG was reduced, consistent with BMI-matched controls. We have found no supporting evidence for biochemical hyperandrogenism in women with HS when compared with age-, weight- and hirsuties-matched controls. We report the continuation and primary development of HS in postmenopausal women.

Laser treatment of port wine stains: therapeutic outcome in relation to morphological parameters.

Abstract: Thirty patients were treated with a flashlamp-pumped pulsed dye laser, with 0.45 ms pulse width and 585 nm wavelength. Punch biopsies were taken prior to treatment, and the biopsies were examined morphometrically. Three different test sites were exposed to laser light of fluence 5.25, 6.50 and 7.75 J/cm2. The degree of blanching was examined 6-8 weeks after treatment, and each site was retreated four times. Six patients (20%) achieved poor blanching, eight patients (27%) obtained moderate lightening and 16 patients (53%) showed good response. The vessels of the good responders were located significantly more superficially than the vessels of the moderate and poor responders (P < 0.05). The poor responders had significantly smaller vessels than the moderate and good responders (P < 0.01). The moderate responders had deeper, but larger vessels, than the poor responders. Hence, an increasing vessel diameter reduces the negative outcome of increasing vessel depth. The vessel diameter was correlated to the colour (P < 0.01), e.g. the mean vessel diameter was increasing from 16.5 microns in pink lesions to 51.2 microns in purple lesions. The vessel depth was partly reflected in the lesional colour, as the pink and purple lesions had significantly deeper vessels than the red ones (P = 0.02). These results indicate that pink lesions predict poor blanching due to deeply located small vessels, while red lesions predict a good therapeutic result because of more superficially located vessels.

Increased expression of inducible nitric oxide synthase in psoriatic skin and cytokine-stimulated cultured keratinocytes

Abstract: Since nitric oxide (NO) has been implicated in the pathogenesis of various hyperproliferative and inflammatory diseases, the mRNA expression of constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) were investigated in psoriatic skin by reverse transcriptase coupled to the polymerase chain reaction (PCR). The study showed that the mRNA expression of brain nitric oxide synthase (bNOS), one of two isoforms of cNOS, was weak in both psoriatic plaques lesions and uninvolved skin, while mRNA transcripts for the second isoform, endothelial nitric oxide synthase (eNOS), were not detectable using the present method. In contrast, the mRNA expression of iNOS was markedly increased in lesional skin as compared to uninvolved skin. Cultured human keratinocytes exposed to a combination of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) for 4 h, showed strong gene expression of iNOS, while in 24 h, the expression had returned to baseline expression. In summary, the study demonstrates that mRNA for the inducible form of NOS is over-expressed in psoriatic lesions. The cause of this may be the local presence of inflammatory cytokines. These findings imply that iNOS may play an important part in local regulation of NO synthesis in psoriasis and other inflammatory dermatoses.

The cost of atopic eczema

Abstract: Atopic eczema affects 2.3% of the U.K. population. We have carried out a community study in a semi-rural area to assess its economic impact. One hundred and fifty-five patients with atopic eczema were identified and expenditure was assessed over a 2-month period. The mean personal cost to the patient was pounds 25.90, while the mean cost to the health service was pounds 16.20. There were 58 lost working days and 17 lost school days. A cohort of 10 severely affected patients attending the Royal Infirmary of Edinburgh were studied; each patient spent, on average, pounds 325 in 2 months, and lead to a mean health service expenditure per patient of pounds 415, in 2 months. If these results were extrapolated to the U.K. population, the annual personal cost to patients with atopic eczema would be pounds 297m, the cost to the health service would be pounds 125m, and the annual cost to society of lost working days would be pounds 43m, making the total expenditure on atopic eczema pounds 465m.

Protective effect of gluten-free diet against development of lymphoma in dermatitis herpetiformis.

Abstract: A retrospective study of 487 patients with dermatitis herpetiformis showed that lymphoma developed in eight patients, the expected incidence being 0.21 (standardized registration ratio 3810). All lymphomas occurred in patients whose dermatitis herpetiformis had been controlled without a gluten-free diet (GFD) or in those who had been treated with a GFD for less than 5 years. The results are suggestive of a protective role for a GFD against lymphoma in dermatitis herpetiformis and give further support for advising patients to adhere to a strict GFD for life.

An appraisal of acitretin therapy in children with inherited disorders of keratinization.

Abstract: Retinoid therapy represents the treatment of choice for severe inherited disorders of keratinization. This paper reviews our experience of acitretin, compares acitretin with etretinate and defines guidelines for treatment. Forty-six children have received acitretin since 1992 in our hospital: 29 children had either lamellar ichthyosis (nine), non-bullous ichthyosiform erythroderma (five), bullous ichthyosiform erythroderma (four), Sjogren-Larsson syndrome (three) or another rare condition (eight). The other 17 children who had psoriasis (16) and extensive viral warts (one), were excluded. Data on efficacy and tolerability of retinoid therapy were available for all but one patient. The cumulative follow-up was 472 months for acitretin. The mean (+/- standard deviation) optimal dosage for acitretin was 0.47 +/- 0.17 mg/kg per day, and this did not significantly differ between disorders. The overall improvement was considerable, with only three patients responding poorly. Mild to moderate mucocutaneous dryness was frequent. Minor abnormalities of liver function tests (four patients) and triglycerides (one patient) never led to changes of therapy. Irreversible side-effects did not occur. Acitretin therapy for children with inherited keratinization disorders is best started at 0.5 mg/kg per day. It represents a safe and effective treatment, provided that the minimal effective dose is maintained and that side-effects are carefully monitored. When switching from etretinate to acitretin, a 20% reduction is recommended if the etretinate dose is over 0.75 mg/kg per day or if side-effects are dose limiting. Otherwise the same dose can be used.

Acquired perforating dermatosis in a British dialysis population

Abstract: A perforating disorder of the skin developing in association with chronic renal failure and often also diabetes, acquired perforating dermatosis (APD), affects up to 10% of patients receiving maintenance haemodialysis in North America. The prevalence of this condition in British dialysis patients has not yet been ascertained. We have undertaken a skin survey of our dialysis population (n=80) to determine the prevalence and clinical presentation of APD, with subsequent assessment of disease management and outcome. Of 72 patients who participated in the survey, eight were found to have APD, seven of whom were also diabetic. Skin lesions had developed pre-dialysis in two patients, on commencement of dialysis in one, and after 1-3 years on dialysis in the remaining five. Patients typically presented with pruritic dome-shaped papules with central crusts arising on the trunk and extensor limb surfaces. Histological examination of biopsy specimens revealed two types of lesion, typified by either narrow or broad ulcer craters, each showing perforation of both collagen and elastic fibres. Topical/intradermal steroid or topical retinoid were effective therapies in certain of our patients. Clinical clearance was achieved after 3-12 months of treatment in five patients with improvement in the remaining two patients who received treatment. Of the four patients who were alive at 2-year review, three remained clear, while one patient continued to develop new lesions. We report an 11% prevalence of APD in our dialysis population, suggesting the disorder to be as prevalent in patients with chronic renal failure in Britain as in North America. An association of the disorder with long-standing diabetes was confirmed.

Assessment of dermal water by high-frequency ultrasound: comparative studies with nuclear magnetic resonance

Abstract: Summary Although a principal constituent of human skin, cutaneous water is difficull to sttidy. and litlle is known about water behaviour in physiological and pathological conditions of Ihe skin. It has heen proposed recently that changes in dermal echogenicity measured hy high-frequency ultrasonography reflect changes in dermal water content. To validate skin ultrasonography for assessment of dermal water changes we have studied the relationship hetween dermal echogenicity and skin water content determined hy nuclear magnetic resonance technique. Twenty MHz ultrasovmd scanning of the dorsal and ventral forearm skin was performed in 59 healthy volunteers (age 18–65) and dermal echogenicity was determined by counting low echogenic pixels (LEPs) in skin images, 1H magnetic resonance spectra were obtained from the same regions and the ratio of areas under the water- and fat-specific peaks (W/F) were calculated to measure a relative water content. Acute dermal oedemn (histamine weal) was studied in the same way in 40 individuals. Baseline dermal echogenicily correlated significantly with W/F. both in the ventral (r=0.47l and dorsal (r = O.57) forearm, lntradennal application of histamine caused a development of intradermal oedema which could be visualized by nuclear magnetic resonance imaging. In a corresponding ultrasound image oedema was seen as a low-echogenic area. The proportional increases in LBPs and W/F after histamine application were correlated, but the elevation in LEPs was 25–48% (95% contidence intervals) higher than that for W/F. These results suggest that high-frequency ultrasonography is a sensitive method for assessment of changes in dermal hydration. This technique may find important applications in comparative and non-invasive evaluations of dermal water in physiological conditions and in skin pathologies associated with oedema formation.

The effects of acne treatment with a combination of benzoyl peroxide and erythromycin on skin carriage of erythromycin resistant propionibacteria

Abstract: Summary Concomitant application of 5% w/w benzoyl peroxide and 3% w/w erythromycin has previously been shown to prevent the overgrowth, on the skin of acne patients, of crythromycin-resistant coagulase-negative staphylococci, which occurs when the antibiotic is used alone. Two in vivo studies were carried out to assess the ability of the same therapeutic combination to inhibit the growth of pre-existing erythromycin-resistant propionibacteria and to prevent the selection of resistant strains during treatment. A double-blind clinical trial in 37 patients with mild to moderate acne vulgaris showed that the combination brought about a > 3 log10 c.f.u. reduction in total propionibacterial numbers/cm2 after 6 weeks therapy (P 103 c.f.u. erythromycin-resistant propionibacteria/cm2 skin pretreatment, the combination of erythromycin and benzoyl peroxide reduced the total propionibacterial count by > 2.5 log10 and the number of erythromycin-resistant strains by a similar amount (P < 0.001, Wilcoxon). This was accompanied by highly significant reductions in acne grade and lesion counts (P < 0.001). These data suggest that the combination of 5% w/w benzoyl peroxide and 3% w/w erythromycin has greater in vivo antipropionibacterial activity than 3% w/w erythromycin alone, and brings about significant clinical improvement in acne patients with high numbers of erythromycin-resistant propionibacterial strains pretreatment.