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Notes: Summary Xeroderma pigmentosum (XP) is a rare autosomal recessive photosensitive disorder, which results in multiple face, neck and head basal cell carcinomas (BCCs), squamous cell carcinomas and melanomas. A 15-year-old boy with XP presented with multiple facial BCCs previously treated by surgical excision. Standard BCC treatments such as surgery are not ideal for patients with several facial BCCs because of the risk of scarring, and the patient refused further surgery. As an alternative, three times weekly application of imiquimod 5% cream in combination with oral acitretin (20 mg daily) was prescribed for 4–6 weeks. No adverse events were reported during treatment and all tumours had resolved at the 6-month follow up visit, highlighting the therapeutic potential of imiquimod 5% cream.

Notes: Background Clinical features of melanocytic naevi correlate poorly with the presence, histopathologically, of architectural disorder and cytological atypia, making the detection of histological atypia by means of macroscopic appearance unreliable.  Objectives The aim of this study was to investigate the diagnostic effectiveness of dermoscopy in the non-invasive detection of histological atypia in naevi.  Methods Observers blinded for histological diagnosis classified a series of 168 melanocytic naevi as common or atypical on the basis of their clinical features and on their dermoscopic profile. The diagnostic performance of both methods compared with the true (histopathological) diagnosis was assessed.  Results Dermoscopy using pattern analysis showed better results than clinical examination in the non-invasive detection of naevi with architectural disorder with or without cytological atypia (diagnostic accuracy 45% vs. 28%). A statistically significant difference in the frequency of dermoscopic parameters between atypical and common naevi was found for atypical pigment network (39% vs. 17%, P = 0·001) and dermoscopic regression structures (13% vs. 2%, P = 0·008). Dermoscopic features, which best predicted histological atypia in naevi, were regression structures (white scar-like areas or peppering), irregular vascular pattern and grey–blue areas (positive predictive values 83%, 83% and 73%, respectively). In contrast, no statistically significant difference in the mean values of the ABCD score between common and atypical naevi was found. The best diagnostic performance of dermoscopy by means of the ABCD rule (cut-off point of 4·0 of total dermoscopy score) was not dissimilar to that of clinical diagnosis (diagnostic accuracy 30%).  Conclusions Dermoscopy by means of pattern analysis enhances the diagnostic accuracy of dermatologists in the prediction of histological atypia in melanocytic naevi as compared with clinical examination alone.

Notes: The optimal use of topical corticosteroids (TC) in the treatment of inflammatory disorders of the skin is related to a number of factors concerning the drug on the one hand (potency, pharmacological properties, formulation), and the patient on the other hand (type and phase of the disease, characteristics of the lesion, site to be treated, age and general conditions). The careful balance between drug and disease/patient allows the establishment of a simple series of gold standard guidelines for TC treatment.

Notes: Background Epiluminescence microscopy (ELM) (dermoscopy, dermatoscopy) is a technique for non-invasive diagnosis of pigmented skin lesions that improves the diagnostic performance of dermatologists. Little is known about the possible influence of associated clinical features on the reliability of dermoscopic diagnosis during in vivo examination.Objective To compare diagnostic performance of in vivo dermoscopy (combined clinical and dermoscopic examination) with that of dermoscopy performed on photographic slides (pure dermoscopy).Design This case series comprised 256 pigmented skin lesions consecutively identified as suspicious or equivocal during examination in a general dermatological clinic. Clinical examination and in vivo dermoscopy were performed before excision by two trained dermatologists. The same observers carried out dermoscopy on photographic slides at a later time, and these three diagnostic classifications were reviewed together with the histological findings for the individual lesions. This was carried out in a university hospital.Results In vivo dermoscopy performed better than dermoscopy on photographic slides for classification of pigmented skin lesions compared with histological diagnosis, and both performed better than general clinical diagnosis. In vivo dermoscopic diagnosis of melanoma showed 98.1% sensitivity, 95.5% specificity and 96.1% diagnostic accuracy while dermoscopic diagnosis of melanoma on photographic slides was less reliable with 81.5% sensitivity, 86.7% specificity and 85.2% diagnostic accuracy. In particular, diagnosis of melanoma based on photographic slides led to nine false negative cases (three in situ , six invasive; thickness ranges 0.2–1.5 mm).Conclusions In vivo dermoscopy, i.e. combined clinical and dermoscopic examination, is more reliable than dermoscopy on photographic slides. In clinical practice, therefore, in vivo dermoscopy cannot be considered independent from associated clinical characteristics of the lesions, which help the trained observer to reach a more precise classification. This may have implications on the reliability of ELM diagnosis made by an observer not fully trained in the clinical diagnosis of pigmented skin lesions or by a remote observer during digital ELM teleconsultation.

Notes: Langerhans cells can originate in vitro from immature precursors stimulated with granulocyte macrophage-colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF)-α and stem cell factor (SCF). We asked whether these cytokines also control the differentiation state of Langerhans cells within the epidermis and upon leaving this tissue. We harvested sheets of human epidermis by controlled dispase hydrolysis of keratomes, cultured them in RPMI and 10% fetal calf serum for 48 h and analysed the sheets and the cells migrated spontaneously into the medium, most of which were Langerhans cells containing Birbeck granules.1 By flow cytometry, the intensity of CD1a expression was reduced quite evenly among Langerhans cells migrated from sheets within 48 h. The cells in the sheets underwent loss of dendrites, with a significant reduction in the cell perimeter that was prevented by GM-CSF and TNF-α together. Either of these cytokines induced expression of CD18 by cells in the sheets and those in the medium. Moreover, TNF-α induced expression of CD54 by cells in the medium, but not by those retained in the sheets, whereas human SCF induced, dose dependently, expression of CD54 by cells in the sheets, but not from those in the medium.2 The proliferation of allogeneic lymphocytes was much higher when stimulating Langerhans cells were harvested from cultures with any cytokine, rather than from cultures without cytokines. We conclude the following: (i) GM-CSF and TNF-α help to maintain full differentiation of Langerhans cells within the epidermis; (ii) cytokine influence on Langerhans cells adhesiveness is in part context dependent; and (iii) pretreatment with cytokines influences positively the number or accessory activity of Langerhans cells on lymphocytes during subsequent mixed leucocyte reaction.

Notes: In view of the critical role of dendritic cells in immune mediated skin diseases, we have investigated the membrane antigen patterns and ultrastructure of cutaneous dendritic cells in eight patients with chronic discoid lupus erythematosus and five with subacute cutaneous lupus erythematosus. In the lesional epidermis, the expression of HLA-DR antigens by epidermal dendritic cells was reduced, as compared with perilesional, clinically normal skin. In addition, only few CD1a+ dendritic cells (Langerhans' cells), along with some CD11c+ and CD14+ cells (presumable precursors of Langerhans' cells), were found in atrophic areas of lesional epidermis. In contrast, the number of Langerhans' cells in non-atrophic areas of lesional epidermis was similar to that in perilesional skin. On electronmicroscopy, epidermal Langerhans' cells appeared depleted of organelles and dendrites and contained tubuloreticular inclusions. In the lesional dermis, both CD1a+ and CD36+ dendritic cells were found, associated with CD4+ and CD8+ T-cells, respectively. Moreover, CD11c+ and CD14+ cells were found around capillaries in the papillary dermis on electronmicroscopy. Indeterminate cells (dendritic cells with features of Langerhans' cell lineage, but apparently without Birbeck granules) and dendritic macrophages were found, associated with lymphocytes and mast cells. No cells with intermediate/transitional features between these two dendritic cell types were found. Conversely, peculiar dendritic cells—with short and blunt dendrites and cytoplasm containing many flat, rough cisternae, moderately well developed Golgi apparatus and no lysosomes—were found in the same location as the CD11c+ and CD14+ cells identified by light microscopy. These findings might be interpreted as follows: 1 the alterations in cytological differentiation and expression of functionally meaningful molecules by epidermal Langerhans' cells in cutaneous lupus erythematosus lesions suggest an impairment of their immunological efficiency; 2 in the lesional dermis of cutaneous lupus erythematosus, a CD4+ T-cell/CD1a+ dendritic cell-based, delayed-type immune response is possibly modulated by a suppressor T-cell circuit in which CD36+ dendritic cells may act as accessory cells; 3 CD11c+ and CD14+ cells with peculiar ultrastructure are possible precursors of both CD1a+ indeterminate cells and CD36+ dermal dendrocytes in the dermis.

Notes: The dermal infiltrates of four patients with the Sézary syndrome were studied by electron microscopy and the data were evaluated quantitatively. The nuclear contour index of lymphocytes was calculated, and many tumour cells had an index greater than 6.5. Dendritic cells were found in all cases. The dendritic cells contained smooth and rough endoplasmic reticulum, moderately well-developed Golgi apparatus, scanty lysosomes and many thin and intermediate filaments; their surface was scalloped with numerous vesicles. Birbeck granules were not found in the cytoplasm of dendritic cells. Dendritic cells comprised 24% of infiltrating cells and were interspersed with lymphocytes; 75% of the lymphocytes were in contact with dendritic cells; 35% of the lymphocytes in contact with dendritic cells had a nuclear contour index higher than 6.5 and 76% had a nuclear contour index higher than 5. The data strongly suggest a functional relationship between lymphocytes and dendritic cells in the dermal infiltrate of Sézary syndrome. They are discussed in relation to the hypothesis that the disease is a consequence of chronic immune stimulation.

Notes: In four bullous pemphigoid patients electron microscopic and direct immunofluorescence examinations were carried out on sections of the border of a blister, apparently normal skin surrounding the blister, apparently normal skin distant from the blister, and apparently normal skin subjected to the stimulus of a xenon lamp. The bullous pemphigoid blister was formed by cleavage of the basal cells away from the basal lamina which remained intact. The intercellular spaces were widened and the half-desmosomes reduced in number in the skin surrounding the blister. Xenon lamp irradiation produced a pattern similar to that of the skin surrounding the blister, but without immunoglobulins and complement fixed in vivo.