All-trans retinoic acid compromises desmosome expression in human epidermis.

An undesirable side-effect of retinoid treatment is skin fragility. As desmosomes are important in maintaining the cohesion of epidermal keratinocytes, we investigated whether all-trans-retinoic acid (RA) compromises desmosome expression in human epidermis, thereby predisposing skin to fragility. Solutions containing 0.025% RA, 5% sodium dodecyl sulphate (SDS) as an irritant control, or vehicle alone were applied to three sites on the buttocks of normal volunteers (n = 9). Treated sites were occluded for 4 days, and biopsies taken under local anaesthesia. Cryostat sections were stained with a panel of antibodies to desmosomal proteins and visualized by immunofluorescence microscopy. Stained sections were randomized and assessed for intensity of staining. The epidermal thickness of each treated site was quantified by image analysis. Western blots of epidermal desmocollins were quantified by densitometry. RA and SDS treatments significantly, but equivalently, increased epidermal thickness compared with vehicle. Immunohistochemically, both RA and SDS were shown to reduce epidermal staining for desmoplakin, desmoglein 1, plakophilin 1 and desmocollin 3 equally compared with vehicle-treated skin (P < 0.001). RA produced a greater reduction in desmocollin 1 staining compared with SDS (P < 0.001). Similar reductions in desmocollins were found by Western blot analysis. Reduced desmocollin expression may indicate compromised desmosomal adhesion, leading to the skin fragility that results from retinoid treatment.

A simple clinical scoring system to improve the sensitivity and standardization of the diagnosis of mycosis fungoides type cutaneous T-cell lymphoma: logistic regression of clinical and laboratory data.

BACKGROUND: The diagnosis of mycosis fungoides (MF) is notoriously difficult to establish because in the early stages, histological features may be nonspecific or merely suggestive. OBJECTIVES: To standardize the diagnosis of MF. METHODS: We studied 138 patients with suspected MF referred over a 7-year period to a university department of a dermatology-based cutaneous lymphoma clinic. Six diagnostic criteria were evaluated: clinical morphology, clinical distribution, skin biopsy T-cell receptor gene rearrangement (TCR-GR), skin biopsy pan T-cell marker loss > or = 2, skin biopsy CD4/CD8 ratio > or = 6, and skin biopsy diffuse epidermal HLA-DR expression. These six clinical and laboratory criteria were compared by logistic regression analysis in patients with histologically diagnosed MF and those with benign disease. RESULTS: Of the 138 patients, 74 had histology of MF, 47 of benign dermatoses and 17 were indeterminate. Close associations were found between a histological diagnosis of MF and TCR-GR (odds ratio 14.4), classical morphology (7.5), classical distribution (2.5) and diffuse epidermal HLA-DR expression (2.8). Logistic regression models were developed depending on the availability of data (either TCR-GR or HLA-DR). Probabilities for correctly diagnosing MF compared with histology as the 'gold standard' were derived from these logistic regression models. A scoring system assigning point values based on these probabilities was then created in order to assist the clinician in making the diagnosis. If using TCR-GR data, a positive TCR-GR = 2.5 points, the presence of classical morphology = 2.0 points, and the presence of classical distribution = 1.5 points. A total score of > or = 3.5 points assigns a high probability (> 85%) of having MF. If using HLA-DR expression, then the presence of classical morphology = 2.5 points, a positive diffuse epidermal HLA-DR expression = 2.0 points, and the presence of classical distribution = 1.5 points. In this case, a total score of > or = 4.0 points assigns a high probability (> 85%) of MF. CONCLUSIONS: The logistic regression models and scoring systems integrate clinical and laboratory assessments, allow rapid probability estimation, and provide a threshold for the diagnosis of MF in an objective, standardized manner.

Fibrillin microfibrils are reduced in skin exhibiting striae distensae.

Striae distensae (striae: stretch marks) are a common disfiguring condition associated with continuous and progressive stretching of the skin--as occurs during pregnancy. The pathogenesis of striae is unknown but probably relates to changes in those structures that provide skin with its tensile strength and elasticity. Such structures are components of the extracellular matrix, including fibrillin, elastin and collagens. Using a variety of histological techniques, we assessed the distribution of these extracellular matrix components in skin affected by striae. Pregnant women were assessed for the presence of striae, and punch biopsies were obtained from lesional striae and adjacent normal skin. Biopsies were processed for electron microscopy, light microscopy and immunohistochemistry. For histological examination, 7 microns frozen sections were stained so as to identify the elastic fibre network and glycosaminoglycans. Biopsies were also examined with a panel of polyclonal antibodies against collagens I and III, and fibrillin and elastin. Ultrastructural analysis revealed alterations in the appearance of skin affected by striae compared with that of normal skin in that the dermal matrix of striae was looser and more floccular. Light microscopy revealed an increase in glycosaminoglycan content in striae. Furthermore, the number of vertical fibrillin fibres subjacent to the dermal-epidermal junction (DEJ) and elastin fibres in the papillary dermis was significantly reduced in striae compared with normal skin. The orientation of elastin and fibrillin fibres in the deep dermis showed realignment in that the fibres ran parallel to the DEJ. However, no significant alterations were observed in any other extracellular matrix components. This study identifies a reorganization and diminution of the elastic fibre network of skin affected by striae. Continuous strain on the dermal extracellular matrix, as occurs during pregnancy, may remodel the elastic fibre network in susceptible individuals and manifest clinically as striae distensae.

Comparison of teleconsultations and face-to-face consultations: preliminary results of a United Kingdom multicentre teledermatology study.

The objective of this multicentre study was to undertake a systematic comparison of face-to-face consultations and teleconsultations performed using low-cost videoconferencing equipment. One hundred and twenty-six patients were enrolled by their general practitioners across three sites. Each patient underwent a teleconsultation with a distant dermatologist followed by a traditional face-to-face consultation with a dermatologist. The main outcome measures were diagnostic concordance rates, management plans and patient and doctor satisfaction. One hundred and fifty-five diagnoses were identified by the face-to-face consultations from the sample of 126 patients. Identical diagnoses were recorded from both types of consultation in 59% of cases. Teledermatology consultations missed a secondary diagnosis in 6% of cases and were unable to make a useful diagnosis in 11% of cases. Wrong diagnoses were made by the teledermatologist in 4% of cases. Dermatologists were able to make a definitive diagnosis by face-to-face consultations in significantly more cases than by teleconsultations (P = 0.001). Where both types of consultation resulted in a single diagnosis there was a high level of agreement (kappa = 0.96, lower 95% confidence limit 0.91-1.00). Overall follow-up rates from both types of consultation were almost identical. Fifty per cent of patients seen could have been managed using a single videoconferenced teleconsultation without any requirement for further specialist intervention. Patients reported high levels of satisfaction with the teleconsultations. General practitioners reported that 75% of the teleconsultations were of educational benefit. This study illustrates the potential of telemedicine to diagnose and manage dermatology cases referred from primary care. Once the problem of image quality has been addressed, further studies will be required to investigate the cost-effectiveness of a teledermatology service and the potential consequences for the provision of dermatological services in the U.K.