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SARKANY, R.P.E.; ANSTEY, A.; DIFFEY, B.L.; JOBLING, R.; LANGMACK, K.; MCGREGOR, J.M.; MOSELEY, H.; MURPHY, G.M.; RHODES, L.E.; NORRIS ON BEHALF OF THE BRITISH PHOTODERMATOLOGY GROUP, P.G.
doi: 10.1111/j.1365-2133.1999.02649.xpmid: 10733266
Phototherapy is a popular and effective treatment for many patients with skin diseases. However, repeated journeys to hospital for phototherapy can be inconvenient and expensive. If it were available, many patients might prefer home‐based phototherapy as long as it was safe and effective. Indeed, many psoriasis patients already self‐treat with ultraviolet A sunbeds at home. This report represents a consensus view from a British Photodermatology Group workshop held in December 1996, the purpose of which was to examine the potential role of home‐based phototherapy in dermatological practice. We conclude that home‐based therapy represents a suboptimal treatment with greater attendant risks than phototherapy in a hospital environment. The level of medical supervision of the home treatment is crucial to its safety and effectiveness. Until further studies are forthcoming, home phototherapy should be largely restricted to those with overwhelming difficulties in attending hospital.
RIZOVA, H.; CARAYON, P.; BARBIER, A.; LACHERETZ, F.; DUBERTRET, L.; MICHEL, L.
doi: 10.1111/j.1365-2133.1999.02650.xpmid: 10733267
Allergic contact dermatitis is a T‐cell‐mediated inflammation, induced by contact with sensitizers and occurring through the release of epidermal cytokines and the activation of epidermal Langerhans cells (LCs). The aim of this study was to analyse early events of LC activation induced either by contact allergens or by irritants devoid of any contact allergenic properties, in order to obtain an in vitro method to discriminate between these two groups of molecules. Various contact sensitizers and irritants were studied for their effects on the endocytosis of major histocompatibility complex class II (MHC‐II) molecules by freshly‐isolated human epidermal LCs. As observed by flow cytometry, a spontaneous decrease in the surface expression of MHC‐II (HLA‐DR) molecules, linked to spontaneous internalization of the MHC‐II molecules by LCs, was obtained by moving freshly‐isolated LCs from 4 °C to 37 °C. Pre‐incubation of LCs with either sensitizers or irritants increased the spontaneous internalization of HLA‐DR molecules with a similar magnitude, but no clear discrimination between sensitizer and irritant effects was obtained by flow cytometry analysis. In contrast, confocal microscopy enabled discrimination between the effects of sensitizers and irritants: sensitizer‐treated samples showed internalized HLA‐DR molecules aggregated in large vesicles with very bright fluorescence; irritant‐treated samples were not different from untreated controls and showed compact HLA‐DR molecules in small vesicles with diffuse fluorescence, and mostly localized in the submembranous zone. Electron microscopy demonstrated that sensitizer‐treated LCs internalized HLA‐DR molecules preferentially in lysosomes collected near the nucleus, whereas the irritant‐treated and non‐treated LCs internalized these molecules in the prelysosomes only near the cell membrane. We conclude that contact allergens and irritants induce distinct patterns of HLA‐DR endocytosis, which may be useful for the development of in vitro screening tests.
CHANG, Y.T.; WONG, C.K.; CHOW, K.C.; TSAI, C.H.
doi: 10.1111/j.1365-2133.1999.02651.xpmid: 10733268
Amyloid deposits in primary cutaneous amyloidosis (PCA) may be initially derived from cytokeratin, possibly after keratinocyte death. However, the mechanism of keratinocyte death remains obscure. To investigate the potential role of apoptosis in the pathogenesis of PCA, a retrospective study was conducted on the skin tissues from 20 Chinese patients with PCA. We used a terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labelling (TUNEL) method for detecting the apoptotic cells. Immunohistochemical staining was performed to examine the expression of the B‐cell leukaemia/lymphoma‐2 gene (bcl‐2) and Fas. Apoptotic cells were shown in 11 of 20 cases (55%) by TUNEL. Histological sections showed that dyskeratotic cells and vacuolar alteration of the basal cells were more commonly observed in the TUNEL‐positive group. In all cases of PCA, epidermal expression of bcl‐2 was minimal, while expression of Fas was observed on keratinocytes in the basal to granular layers; however, these findings were not different from those in normal skin. Our results suggest that the keratinocyte destruction in PCA may occur as an initial result of apoptosis, which in turn leads to the amyloid formation.
BATES, E.J.; PENNO, N.M.; HYND, P.I.
doi: 10.1111/j.1365-2133.1999.02652.xpmid: 10733269
Wool follicle matrix cell cultures were initiated as explants from Tukidale (carpet wool) sheep primary follicle bulbs after removal of the outer root sheath. Successful explantation required coculture on collagen with intact dermal papillae. Cells had a typical epidermal morphology (pavements of flattened, polyhedral cells). Extracellular matrix from dermal papillae, conditioned media, separation of dermal papilla from bulb matrices by tissue culture inserts and feeder layers were unable to support matrix cell explantation. Cultures could be maintained for up to 14 passages during which time the cells became larger with an increased cytoplasmic/nuclear ratio and irregular outline. Proliferation of matrix cells was greater on laminin than with either collagen type I or type IV. Proliferation was considerably reduced under serum‐free conditions. This was most apparent at low calcium (0.09 mmol/L). By Northern hybridization matrix cells were found to express keratin K18 at all stages of culture. Keratin K1.15 expression was evident by the tenth passage. The wool‐specific keratin K2.10 was not detected. The data demonstrate that successful wool matrix cell culture is achievable. Keratin gene expression occurs in these cells and varies with the stage of culture.
AHMED, N.U.; UEDA, M.; NIKAIDO, O.; OSAWA, T.; ICHIHASHI, M.
doi: 10.1111/j.1365-2133.1999.02653.xpmid: 10733270
Major photoproducts induced by carcinogenic ultraviolet (UV) radiation are the cylobutane pyrimidine dimers (CPDs) and pyrimidine–pyrimidone (6–4) photoproducts (6–4PPs). 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) is also a DNA base‐modified product generated by reactive oxygen species in conditions of ultraviolet stress. Although UVB‐induced CPDs and 6–4PPs have been investigated in animal and human skin, little is known about the role of 8‐OHdG in UVB‐induced human skin damage or carcinogenesis. Normal human skin from three volunteers was exposed to UV radiation, and the time course of induction and removal of 8‐OHdG was examined by immunohistochemical analysis with catalysed signal amplification on formalin‐fixed paraffin sections. Formation of CPDs and 6–4PPs was also examined by immunostaining on the same skin specimens. Control epidermis with no exposure to UV radiation showed little nuclear staining of 8‐OHdG, but an increased level of 8‐OHdG was clearly observed in epidermis biopsied after irradiation. Induced 8‐OHdG can rapidly be removed from nucleus during the first 24–48 h, as the staining intensity diminished gradually, almost reaching the control level by 72–96 h after irradiation. Staining for CPDs or 6–4PPs revealed induction of these photoproducts in human skin, although 6–4PP‐positive cells disappeared more rapidly than those that stained for CPDs or 8‐OHdG. Together with protective effect of antioxidants, our results indicate that not only CPDs and 6–4PPs but also 8‐OHdG may play a significant part in UV carcinogenesis.
GRABCZYNSKA, S.A.; MCGREGOR, J.M.; KONDEATIS, E.; VAUGHAN, R.W.; HAWK, J.L.M.
doi: 10.1046/j.1365-2133.1999.02654.xpmid: 10233214
Actinic prurigo (AP) and polymorphic light eruption (PLE) both belong to the group of idiopathic photodermatoses, but it remains controversial whether AP is a distinct photodermatosis or a variant of PLE. The aim of this study, by collecting data from 119 patients with features of these disorders, was to establish whether specific criteria could be used to distinguish AP from PLE prospectively. We found that presence of the eruption on both exposed and covered sites, its occurrence in winter, persistence of lesions beyond 4 weeks, mucosal and conjunctival involvement, excoriation and scarring of the skin were important features of AP which were not typical of PLE. On this basis, confident clinical diagnoses could be reached in 103 of 119 patients (87%), 57 with AP and 46 with PLE, supported by phototesting and negative lupus serology. HLA typing subsequently confirmed the strong association (90%) between AP and the DR4 allele, in particular with the rare subtype DRB1*0407 which was present in 60% of these patients. No HLA association was found in PLE. In the 16 remaining cases, however, clinical overlap meant that no definite diagnosis could be made; these patients were notionally described as having persistent PLE (PPLE). Demographic and HLA data in this group suggested that PPLE was perhaps most appropriately grouped with PLE. In addition to those patients who were difficult to classify, 35% of our typical AP patients also described clinical progression from PLE to AP, AP to PLE or coexistence of both AP and PLE. In conclusion, our study suggests that while AP and PLE are clinically distinct conditions in most cases, they may perhaps share a common pathophysiological basis. The AP phenotype may be determined by HLA and perhaps other factors in patients otherwise predisposed to PLE.
doi: 10.1046/j.1365-2133.1999.02655.xpmid: 10233215
This nationwide follow‐up study concerns the pattern of malignant tumours in a cohort of patients with psoriasis, at an average of 9.3 years after discharge from hospital. The study confirms that the significantly increased risk of cancer in these patients, amounting to 1.4 times that in the general population, is mainly due to cancer of the skin and lung in both sexes and cancer of the pharynx and larynx in men. Non‐melanoma skin cancer is the most common malignancy, occurring in 196 of 795 patients with cancer: standardized incidence ratio (SIR, the ratio of observed to expected cancers) 2.4 for men and 2.6 for women. This means an overall lifetime risk (up to the age of 75 years) of 14.1%. In particular, squamous cell carcinoma (SCC) by itself (n = 45, SIR 3.9 for men and 4.7 for women), cancer in multiple sites (SIR 5.9 for basal cell carcinoma (BCC) and 11.7 for (SCC) and SCC on the lower extremities (SIR 18.0) are frequent. Women run the highest risk of BCC in the age range 20–40 years, while men in the age range 30–60 years run a particularly high risk of SCC. When monitoring patients extensively treated for psoriasis, this aberrant pattern of cancer should be taken into account.
BATAILLE, V.; SASIENI, P.; CURLEY, R.K.; COOK, M.G.; MARSDEN, R.A.
doi: 10.1046/j.1365-2133.1999.02656.xpmid: 10233216
The demand for pigmented lesion clinics (PLCs) is increasing in view of improved skin cancer awareness following public health education campaigns. These clinics offer an effective way of screening a large number of patients. However, there is no evidence, as yet, that they have an impact on mortality due to malignant melanoma. With the lack of follow‐up inherent to these busy screening clinics, there is some concern that melanomas may be missed. This study reports on 7874 patient visits to a PLC in a teaching hospital between 1985 and 1994. In total, 1705 biopsies were performed over the 9‐year period. Lesions were more likely to be biopsied in men compared with women. The yield for picking melanomas was one in 36 patient visits. The mean age of patients attending the PLC was 10 years less than the mean age for population‐based melanomas. Melanoma thickness did not significantly change over the 9‐year period. Only 0.2% of patients (14 cases) re‐presented to the PLC for a second or third visit with a final diagnosis of melanoma, but for five of these patients, the interval between the two visits was over 2 years. Most of these ‘re‐attending’ melanomas were early lesions. PLCs offer a fast, safe and efficient service for the screening of pigmented lesions but their role in reducing mortality due to malignant melanoma remains to be established. It is likely that these clinics have an important role in terms of public health education regarding sun avoidance and early recognition of skin cancer.
DICKER, T.J.; KAVANAGH, G.M.; HERD, R.M.; AHMAD, T.; MCLAREN, K.M.; CHETTY, U.; HUNTER, J.A.A.; ,
doi: 10.1046/j.1365-2133.1999.02657.xpmid: 10233217
From the Scottish Melanoma Group database for south‐east Scotland we evaluated 5‐year follow‐up in patients with cutaneous malignant melanoma excised between 1979 and 1994 and devised an ‘evidence‐based’ review protocol. Of the 1568 with stage I melanoma, 293 (19%) developed a recurrence, 32 had a second primary melanoma and 97 had an in‐situ melanoma.The disease‐free interval shortened progressively with increasing tumour thickness. Overall, 80% of recurrences were within the first 3 years, but a few patients (< 8%) had recurrences 5 or 10 years after the initial surgery. In‐situ melanomas did not recur. Almost half (47%) the recurrences were noted first by the patient, and only 26% were detected first at a follow‐up clinic. One hundred and thirty‐nine patients (89%) were still under review when their recurrences were detected, and 102 (65%) had been seen within the previous 3 months. Questionnaires were completed by 120 patients: sun protection and avoidance, and mole examination were more likely after melanoma excision. We recommend 3‐monthly review of patients with invasive lesions for the first 3 years. Thereafter, those with lesions ≥ 1.0 mm need two further annual reviews. Patients with in‐situ lesions should be reviewed once, to confirm adequate excision (0.5 cm margins) and to give appropriate education. Surveillance beyond 5 years is only justified if there are special risk factors.
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