Notes: Summary Background  Langerhans cells (LCs) play essential roles in the initiation and regulation of cutaneous immune responses mediated through their successful migration from the epidermis to draining lymph nodes while carrying antigen. Tumour necrosis factor (TNF)-α, a keratinocyte-derived cytokine, has recently been shown to play an important role in the mobilization of LCs from human epidermis. Although it is known that with age the immune system changes, the influence of increasing age on the function of human LCs has not been defined clearly.Objectives  To examine the influence of age on the ability of TNF-α to induce LC migration.Methods  Ten elderly (six men, four women; mean age 76 years, range 72–79) and 10 young (six men, four women; mean age 23 years, range 18–35) volunteers received intradermal injections of 200 U of human recombinant TNF-α diluted in sterile saline, and control injections of sterile saline alone, at each of two paired sites identified on photoprotected buttock skin. Two hours later, paired injection sites were excised by punch biopsy. One set of paired biopsies was processed for assessment of the frequency and morphology of epidermal LCs, following preparation of epidermal sheets and immunofluorescence staining for the LC marker CD1a. The remaining paired biopsies were processed in formalin and the inflammatory response to TNF-α was assessed by standard histological examination.Results  Mean ± SEM baseline values for LC frequency within epidermal sheets were significantly different between young (1156·3 ± 38·5 cells mm−2) and elderly subjects (835·7 ± 48·2 cells mm−2; P 〈 0·01). Intradermal injections of 200 U of TNF-α caused a significant reduction in the frequency of LCs in both elderly and young subjects (P 〈 0·01). However, the extent of TNF-α-induced LC migration was substantially different between the two groups, with a mean 9% reduction in LC frequency in elderly volunteers compared with a mean 23% decrease in young subjects. Exposure to TNF-α was associated with a perivascular polymorphonuclear infiltrate at 2 h in all young subjects; in contrast, only 50% of the elderly individuals showed evidence of such a response.Conclusions  There are significant differences between young and old skin with respect to both resting LC numbers and their response to TNF-α. These age-related changes in LC frequency and function may contribute to the altered cutaneous immune function observed in the elderly.

Notes: Background There is a lack of good data about patient satisfaction with teledermatology and about its potential interaction with quality-of-life factors. Objectives To assess the association between perceived skin-related quality of life and patient satisfaction with a nurse-led teledermatology service. Methods In a mobile nurse-led teledermatology clinic located in four inner city general practices in Manchester, the teledermatology service used digital cameras to capture and store images of skin conditions for remote diagnosis by dermatologists. One hundred and twenty-three adult patients, non-urgent dermatology referrals from primary care, completed the Dermatology Life Quality Index (DLQI) and a 15-item patient satisfaction questionnaire. Results In common with other studies of patient satisfaction, subjects reported highly favourable views of ‘hotel’ aspects of the service (93%) and found it ‘convenient’ (86%). However, 40% of patients would have preferred to have had a conventional face-to-face consultation with a dermatologist, and 17% felt unable to speak freely about their condition. Patient satisfaction with the service was related to quality of life. Patients reporting lower quality of life as measured by the DLQI were more likely to prefer a face-to-face encounter with a dermatologist (r = 0·216, P 〈 0·05), and to evince anxiety about being photographed (r = 0·223, P 〈 0·05). Conclusions Patient acceptance and satisfaction with telemedicine services is complicated by patients' subjective health status. Telehealthcare providers need to recognize that patients with poor quality of life may want and benefit from face-to-face interaction with expert clinicians.

Notes: Background Lactoferrin (LF), an iron-binding protein found in exocrine secretions, is known to possess antibacterial properties. It has recently been proposed that LF may also influence inflammatory reactions. Objectives To characterize in humans the ability of recombinant homologous LF to inhibit the induced migration of epidermal Langerhans cells (LCs) from the skin, a process known to be dependent upon the proinflammatory cytokines tumour necrosis factor (TNF)-α and interleukin 1β and to influence cutaneous inflammatory reactions. Methods We investigated the anti-inflammatory properties of LF in human volunteers. Results Topical exposure to LF 2 h prior to sensitization caused a significant reduction in contact allergen (diphenylcyclopropenone, DPC)-induced LC migration from the epidermis as judged by the altered frequency of cells expressing either HLA-DR or CD1a determinants. That this reduction was secondary to an inhibition of TNF-α production was indicated by the fact that LF failed to influence LC migration induced by intradermal injection of this cytokine. In approximately 50% of those volunteers who displayed local inflammation in response to DPC, LF was found to cause a discernible reduction in the clinical severity of the reaction, associated with reduced infiltration of inflammatory cells. Conclusions These data demonstrate that LF is able to influence cutaneous immune and inflammatory responses, possibly because of an impaired production of local proinflammatory cytokines.

Notes: We present a brief account of the life and times of Dr Henry Grundy Brooke, a Manchester dermatologist and key figure in British dermatology in the nineteenth century. Our report highlights the achievements of a man whose contributions to dermatology continue to be of relevance in the new millennium.

Notes: Langerhans cells (LC) are members of the wider family of dendritic cells. LC reside in the epidermis where they serve as sentinels of the immune system, their responsibilities being to sample the external environment for changes and challenges and to deliver information (antigen) to responsive T lymphocytes within skin draining lymph nodes. The ability of LC to migrate from the epidermis to regional lymph nodes is therefore of pivotal importance to the induction of cutaneous immune responses. The journey that LC have to make from the skin has a number of requirements. Initially it is necessary that LC disassociate themselves from surrounding keratinocytes and are liberated from other influences that encourage their retention in the epidermis. Subsequently, migrating LC must successfully traverse the basement membrane of the dermal–epidermal junction and make their way, via afferent lymphatics, to draining lymph nodes. Effective entry into lymph nodes is necessary, as is correct positioning of cells within the paracortex. There is increasing evidence that both cytokines and chemokines, and their interaction with appropriate receptors expressed by LC, orchestrate the mobilization and movement of these cells. We here consider the parts played by these molecules, and how collectively they induce and direct LC migration.

Notes: Background Skin integrity is essential for the normal usage of a stoma appliance. However, there is little published on the prevalence, nature or management of stoma-related skin disorders. Objectives To document stoma-related skin disorders in a large cohort of patients. Methods We sent a postal questionnaire to all surviving patients who had had abdominal stoma surgery at Hope Hospital, Salford, U.K. in the 10 years from 1 January 1989. Those reporting skin disease were invited to attend a clinic run by a dermatologist and a stoma-care specialist nurse. All lesions were categorized and swabs taken for microbiological examination. Results Of 525 surviving patients, 325 (62%) replied to the questionnaire. Of these, 73% reported a skin problem that had affected normal stoma bag use. Dermatoses included irritant reactions, particularly from leakage of urine or faeces (42%); pre-existing skin diseases, principally psoriasis, seborrhoeic dermatitis and eczema (20%); infections (6%); allergic contact dermatitis (0·7%) and pyoderma gangrenosum (0·6% annual incidence). A further 15% of patients with skin problems had persistent or recurrent dermatitis not explained by allergy, frank infection or faecal irritation. This responded to short-term treatment with topical corticosteroids. Further investigation is under way into its pathogenesis. Conclusions Skin disorders are common in stoma patients, and various patterns can be recognized and effectively treated.

Notes: Neovascularization appears to play an early and important part in the evolution of psoriatic plaques. We studied the distribution and production of two known angiogenesis factors, endothelial cell stimulating angiogenesis factor (ESAF) and vascular endothelial growth factor (VEGF), in the skin of patients with chronic plaque psoriasis and normal control subjects. Our results showed that tissue levels of ESAF and VEGF were significantly elevated in involved as compared with normal control skin (P = 0·006 and P 〈 0·0001, respectively). Tissue levels of ESAF and VEGF were also raised in involved skin as compared with uninvolved skin in patients with psoriasis (P = 0·001 and P 〈 0·0001, respectively). Tissue levels of ESAF and VEGF in plaques of psoriasis correlated closely with the clinical severity of psoriasis (r = 0·6 and r = 0·9, respectively). Serum levels of ESAF and VEGF were significantly raised in patients with psoriasis as compared with control subjects (P = 0·001 and P = 0·02, respectively). In vitro culture studies revealed that ESAF is produced by both keratinocytes and fibroblasts in approximately equal quantities in normal skin, whereas VEGF is secreted predominately by keratinocytes. A similar pattern is seen in both involved and uninvolved skin of patients with psoriasis. However, there is increased secretion of both factors in keratinocytes and fibroblasts from involved and uninvolved skin as compared with normal control skin (P 〈 0·001). The increased levels and secretion in plaques of psoriasis of two molecules, ESAF and VEGF, known to promote new blood vessel formation, suggest a pathogenetic role for them in this disease.

Notes: Summary The purpose of this study was: (i) to examine the impact of the clinical severity, anatomical location and treatment of psoriasis on patients' quality of life, and (ii) to investigate the effects of perceptions of psoriasis-related stress on patients' physical and mental health and on areas of disability in everyday life. All patients (n= 204) attending a psoriasis speciality clinic were invited to complete a multidimensional quality of life assessment comprising the Psoriasis Disability Index (PDI), the SF-36 Health Survey and the Psoriasis Life Stress Inventory (PLSI). Results(n= 150) indicated that overall clinical severity of psoriasis as assessed by the Psoriasis Area and Severity Index, and duration of psoriasis, were unrelated to impairment in any areas of quality of life. Anatomical location (social visibility) of psoriasis was associated with self-report of poor physical health (P = 0–01), and there was a modest association with patients' mental health (P = 0.04); however, anatomical location of psoriasis was not significantly associated with self-reported disability in everyday life, or stress scores.Patients who were classified as more reactive to the stress associated with psoriasis (78% of the sample) were functioning less well in terms of their mental health (P = 0.001) and also experienced significantly more disability in all areas of everyday life (P = 0.001). Differences in method of treatment for psoriasis did not significantly affect scores on the psoriasis-specific (PDI; PLSI) or generic (SF-36) quality of life measures. A multiple regression analysis demonstrated that stress resulting from anticipating other people's reactions to their psoriasis contributed more to the variance in patients' disability in everyday life than any other medical or health status variable.The results support the importance of assessing the effects of stress in patients' adjustment to their condition and may indicate a role for adjunctive psychological stress management training for a significant number of patients with psoriasis.

Notes: Changes in the microvasculature are considered to play an important part in the pathogenesis of psoriasis and its associated arthritis. The novel method of nailfold video capillaroscopy is an extension of the technique of widefield nailfold microscopy which has been of diagnostic and predictive use in the in vivo study of the microcirculation in systemic sclerosis and other connective tissue disorders. However, similar studies in patients with psoriasis and psoriatic arthritis and/or nail changes have produced conflicting results. We tested the hypothesis that any abnormalities in nailfold capillaries of either a quantitative or qualitative nature might be observed more readily in subjects with pathology adjacent to the nailfold, i.e. distal interphalangeal (DIP) joint changes and/or nail dystrophy, when using this technique. Forty-four patients with psoriasis were recruited (21 males, 23 females). Twelve patients had psoriasis alone, 13 had psoriasis and nail changes, six had DIP joint involvement with changes of psoriasis elsewhere, and 13 had psoriasis, DIP arthritis and nail changes. Capillary density and standard capillary dimensions were studied and compared with those of 44 age- and sex-matched control subjects. There was a significant (P 〈 0·05) decrease in capillary loop density in patients with either psoriasis plus nail disease (14·5 ± 5·7 capillaries per 3 mm field) or psoriasis plus nail and DIP joint disease (14·3 ± 5·0) when compared with controls (19·2 ± 3·8). In patients with psoriatic arthritis affecting the DIP joints, there was a statistically significant (P 〈 0·05) decrease in arterial and venous capillary limb diameters, and this was also seen in those with arthritis associated with nail changes. However, there was no difference in capillary dimensions between patients with psoriasis and/or nail changes when compared with normal controls. Morphological abnormalities previously described in the literature were not noted in any of our four patient groups. Our findings of diminution in both nailfold capillary bed density and dimensions of the arterial and venous capillary limbs suggest that vascular injury, previously noted in ultrastructural studies, may play a part in the pathogenesis of psoriatic arthritis. However, in contrast to previous studies, we found no specific pattern of a morphological nature of nailfold capillaries in patients with psoriasis with or without nail changes, when compared with normal controls.

Notes: Chronically sun-exposed or photodamaged human skin is characterized by a number of clinical features, including wrinkles. However, little is known about the molecular mechanisms that underlie these features. We investigated the hypothesis that the mechanism of wrinkle formation may involve loss of anchoring fibrils, composed mainly of collagen VII, which are important in maintaining dermal-epidermal junction integrity. Ten volunteers with moderate to severe photodamage of dorsal forearm skin were recruited to the study. Using immunohistochemistry, transmission electron microscopy and in situ hybridization, we compared collagen VII protein and mRNA content of photodamaged forearm skin with that of sun-protected hip and upper inner arm skin from the same subjects. Numbers of anchoring fibrils per linear μm of basement membrane (mean ± SEM) were significantly lower in photodamaged skin (1·79±0·10) as compared with sun-protected hip (2·28±0·11) and upper inner arm skin (2·21±0·10) (P〈0·01), and similarly keratinocyte expression of collagen VII mRNA, quantitated as number of positively stained keratinocytes per high power field, was significantly reduced in photodamaged skin (6·3±2·5) as compared with sunprotected hip (20·0±5·6) and upper inner arm skin (17·7±4·9) (P〈0·001). Semiquantitative assessment of immunohistochemical staining for collagen VII showed a non-significant reduction in photodamaged skin as compared with sun-protected skin. We propose that reduced content of collagen VII in photodamaged skin contributes to wrinkle formation by weakening the bond between the dermis and epidermis.