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doi: 10.1046/j.1365-2133.1998.02164.xpmid: 9640359
Lichen planus of the vulva can occur as part of more widespread disease or in isolation. Its cause is unknown, but it can become chronic and has a potential for malignant change. It may present a difficult management problem and several treatments have been used with variable success. This review focuses on the problem of vulval lichen planus, and highlights some of the treatments and management strategies that have been used to date.
GRÄser, Y.; EL Fari, M.; Presber, W.; Sterry, W.; Tietz, H-J.
doi: 10.1046/j.1365-2133.1998.02165.xpmid: 9640360
Polymerase chain reaction (PCR) fingerprinting detected DNA polymorphisms among frequently isolated species and strains of the genera Trichophyton, Microsporum and Epidermophyton. The patterns generated by this DNA‐based method permitted species and strains to be identified. The conventional methods to identify dermatophytes rely on the expression of characteristic morphological features, as well as several physiological properties. Identification is often delayed or problematic because isolates may be slow to form conidia or produce atypical microscopic structures or colony appearances. Using non‐specific primers such as (AC)10, (GTG)5, M13 core sequence and AP3, characteristic PCR profiles were generated for 17 species. Intraspecies variables were also observed for four of six varieties of T. mentagrophytes, whereas no detectable DNA variability was found within the three varieties of T. tonsurans. Comparing species‐specific PCR fingerprints of clinical isolates with those of type strains, species could be identified by their PCR fingerprints, even if they could not be identified by the accepted phenotypic characteristics.
doi: 10.1046/j.1365-2133.1998.02166.xpmid: 9640361
Novel, functional skin staining with fluorescent, ultradeformable lipid vesicles (Transfersomes™, IDEA, Munich, Germany) was developed and combined with confocal laser scanning microscopy. This revealed the structural and barrier characteristics of intact skin to a resolution of ≥ 0.2 μm, that is, to the limit of light microscopy. Different routes of penetration into the stratum corneum were visualized and new details in the skin anatomy and barrier were unveiled. Most prominent was the lateral inhomogeneity of the stratum corneum, where three to 10 neighbouring corneocyte ‘columns’ were found to form a cluster. Corneocyte edges inside each cluster intercalated extensively, but adjacent clusters were separated by ‘gorges’ a few micrometres deep; lipid packing was also less regular and tight in the intercluster region. Two quantitatively different hydrophilic pathways were found in the horny layer: an intercluster route with low penetration resistance comprising ≤ 1% of the total or ≤ 20% of the pathway area in the skin, and an intercorneocyte pathway that resists penetration better and is more abundant (≥ 3% of the skin or ≥ 80% of the pathway area). This latter route is strongly tortuous, as it goes between all the corneocytes in a cluster. It traces the irregularities between the intercellular lipid lamellae and/or the adjacent corneocyte envelopes which may act as virtual channels in the skin. It was inferred that such channels coincide with the route of water evaporation through the skin and exhibit the permeability barrier maximum in the stratum corneum conjunctum.
Kazama, T.; Yamamoto, Y.; Hashimoto, T.; Komai, A.; Ito, M.
doi: 10.1046/j.1365-2133.1998.02167.xpmid: 9640362
We applied confocal laser scanning microscopy to fluorescence overlay antigen mapping (FOAM) for differential diagnosis of bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA). FOAM of tissue‐bound IgG and marker basement membrane components (BMCs) including integrin β4, laminin‐1, laminin‐5 and type IV collagen, showed that tissue‐bound IgG in perilesional skin samples from five patients with BP was localized on the epidermal side of type IV collagen, and colocalized with some of the other three BMCs, whereas IgG in a sample from a patient with EBA was on the dermal side of all the BMCs. FOAM of binding sites of autoantibodies in patients' sera and markers including integrin β4, laminin‐1, type IV collagen and type VII collagen, showed that the binding sites of autoantibodies from 16 patients with BP were localized on the epidermal side of type IV and type VII collagens, and localized above or codistributed with integrin β4 and laminin‐1, whereas those from five patients with EBA were codistributed with type IV and type VII collagens, and localized on the dermal side of integrin β4 and laminin‐1. These spatial relationships are compatible with their previously described ultrastructural locations. Thus, this method appears to be useful in the differential diagnosis of BP and EBA.
Setterfield, J.; Shirlaw, P.J.; Kerr‐Muir, M.; Neill, S.; Bhogal, B.S.; Morgan, P.; Tilling, K.; Challacombe, S.J.; Black, M.M.
doi: 10.1046/j.1365-2133.1998.02168.xpmid: 9640363
Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease frequently associated with scarring of involved clinical sites. At present, therapeutic intervention in the form of immunomodulating or immunosuppressive agents is often reserved until the onset of significant inflammation and/or early cicatrization. We have therefore studied the clinical and immunopathological findings in 67 patients with MMP in order to try to establish a reliable prognostic indicator by which patients at high risk may be identified early in the disease. Inclusion criteria were a predominantly mucosal disease and the detection of IgG and/or C3 anti‐basement membrane zone (BMZ) immunoreactants using immunofluorescence techniques. Patients were allocated to three disease subgroups on the basis of the modality and duration of therapeutic intervention required to achieve effective control of disease. In addition, at presentation and at each follow‐up visit, a clinical score for severity of involved clinical sites was awarded and serum collected for indirect immunofluorescence (IIF). A dual circulating anti‐basement membrane zone (anti‐BMZ) antibody response with IgG and IgA was significantly associated with a more severe and persistent disease profile (P< 0.001). The odds ratios for requiring systemic therapy were: 11.6 among patients in whom there was a clinical score ≥ 5 compared with a score < 5, and 31.3 and 66.9 among patients with IgG alone and both IgG and IgA, respectively, compared with negative IIF. The findings suggest that an assessment based upon a combination of site severity score and the presence of circulating IgG and IgA by IIF using 1 mol/L salt‐split human skin substrate may be considered a useful prognostic indicator.
Ameglio, F.; D'auria, L.; Bonifati, C.; Ferraro, C.; Mastroianni, A.; Giacalone, B.
doi: 10.1046/j.1365-2133.1998.02169.xpmid: 9640364
Few and contrasting data are available in the literature concerning the levels of various cytokines in blister fluid (BF) and in the serum of patients affected with bullous pemphigoid (BP). Using commercially available ELISA kits, this study reports the levels of 11 cytokines detected both in BF and sera of 15 BP patients and compares them with those of 15 control subjects' sera. Generally, no significant differences were observed in BP and control sera. In contrast, interleukin (IL) 1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, tumour necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ) showed increased BF levels as compared with BP sera. Two cytokines, IL‐11 and IL‐12 did not show significant differences between BP BF and sera, while an opposite behaviour was observed for transforming growth factor βl (TGF‐β1), whose serum levels were higher than the concentrations in BF. Using the number of lesions of the patients as a possible disease intensity marker, significant correlations were found with the BF levels of IL‐1β, IL‐8, TNF‐α and, most closely, IL‐5. These data may have pathogenetic relevance and suggest the possibility that these biological modulators may be used as a quantitative marker of disease intensity.
doi: 10.1046/j.1365-2133.1998.02171.xpmid: 9640365
The T‐cell activation antigen CD26 or dipeptidyl‐peptidase IV (DPP‐IV) belongs to a group of membrane‐bound proteases that are variably expressed by melanoma cell lines. In vitro studies have suggested that loss of CD26 is associated with tumour progression. To correlate its expression with the histological stage of tumour progression of malignant melanoma (MM), we studied the distribution of CD26/DPP‐IV in paraffin sections of a series of 110 benign and malignant pigment‐cell lesions of the skin using a cocktail of anti‐CD26 monoclonal antibodies and the three‐step ABC method. Only two of 44 benign lesions focally expressed CD26 in their junctional compartment. In MM, expression of CD26 was not related to any of the known histological prognostic factors, but was associated with the stage of tumour progression; thus, CD26 was expressed in the in situ or invasive radial growth phase in 34% of MM, whereas only 12% of MM expressed CD26 in the vertical growth phase. No CD26 expression occurred in metastatic melanomas. These data suggest that this proteinase plays a part in the early invasion of MM. Thus, CD26 may serve in the binding to, and enzymatic degradation, components of the extracellular matrix of the papillary dermis. Loss of CD26 in the vertical growth phase may contribute to the insufficient inactivation of regulatory peptides and unlimited action of growth factors.
Kavanagh, G.M.; Sabroe, R.A.; Greaves, M.W.; Archer, C.B.
doi: 10.1046/j.1365-2133.1998.02172.xpmid: 9640366
We have investigated the possible existence of the H3 histamine receptor in human skin with the highly selective ligands R α methylhistamine (RAMHA) (H3 agonist) and thioperamide (H3 antagonist). We compared the intradermal effects of RAMHA with histamine, and studied their potential modulation by the H1 antagonist terfenadine, and H2 antagonist cimetidine. The effects of RAMHA and thioperamide on codeine phosphate‐, substance P‐ and histamine‐induced weal and flare responses were also studied. RAMHA produced dose‐related weal and flare responses that were approximately 10‐ and fivefold less, respectively, than responses to histamine. Flare responses to RAMHA were significantly inhibited by oral terfenadine (P< 0.05). Weal and flare responses to histamine after oral cimetidine showed much intersubject variation, and cimetidine did not significantly alter either RAMHA‐ or histamine‐induced weal and flare responses. Codeine phosphate‐, substance P‐ and histamine‐induced responses were not significantly affected by concurrent administration of RAMHA. Thioperamide was not found to influence codeine phosphate‐, substance P‐, RAMHA‐ or histamine‐induced effects. RAMHA induces vascular (weal and flare) responses in human skin, and these responses are partially inhibited by terfenadine. There is a trend for RAMHA to have an additive effect to the weal induced by substance P and histamine, although our results largely do not reach statistical significance. Thioperamide does not affect the vascular responses to RAMHA, codeine phosphate, histamine or substance P. We cannot conclude that the effects of RAMHA are induced by H3 receptors on cutaneous endothelial or mast cells.
Long, C.C.; Darke, C.; Marks, R.
doi: 10.1046/j.1365-2133.1998.02173.xpmid: 9640367
Individuals of Celtic ancestry are claimed to be at greater risk of skin cancer than non‐Celts, and various positive and negative associations between certain human leucocyte antigen (HLA) phenotypes and the development of skin cancer have been described. The aims of this study were to determine whether any HLA phenotypes are associated either with Celtic or non‐Celtic ancestry, or skin type. One thousand and ten members of the Welsh Bone Marrow Donor Registry (WBMDR), whose HLA phenotypes are known, were asked to complete a questionnaire which enquired as to their family origins and their ‘Index of Celtic Ancestry’ scored out of 12. Three groups were identified; non‐Celts (score < 3), Celts (score > 9), and a subset of the Celts—‘high scoring’ Celts (score > 10). Details of hair and eye colour and skin type were also requested. Skin type and HLA‐A, ‐B, ‐DR and ‐DQ frequencies were compared between the three groups (Celts, non‐Celts and ‘high scoring’ Celts), and a random indigenous population of 9196 members of the WBMDR. Seven hundred and thirty‐six replies were received (279 male, 457 female, mean age 31 years). One hundred and forty‐four Celts, 51 ‘high scoring’ Celts and 170 non‐Celts were identified. Forty‐six (32%) Celts had skin type I or II compared with 36 (21%) non‐Celts (P= 0.039), and 37 (73%) ‘high scoring’ Celts had skin type I or II (P< 0.0001). However, there were no significant differences between the groups with regard to hair colour, eye colour or number of episodes of painful sunburn. The frequency of HLA‐DR4 was 32% in the non‐Celtic group, 44% in the Celtic group (not significant), and 53% in the ‘high scoring’ Celts (P= 0.008). However, the difference was not significant after correction. There were no significant associations between skin type and HLA phenotype. HLA‐DR4 is known to be associated with an increased risk of both basal cell carcinoma and malignant melanoma and its increased frequency in Celts may be an independent risk factor for skin cancer in addition to skin type.
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