British Journal of Dermatology

doi: 10.1111/j.1365-2133.2007.07823.xpmid: N/A

Kawasaki, K.; Kawakami, T.; Watabe, H.; Itoh, F.; Mizoguchi, M.; Soma, Y.

doi: 10.1111/j.1365-2133.2006.07678.xpmid: 17493064

SummaryBackground Matrilysin (MMP‐7), a member of the matrix metalloproteinase (MMP) family of proteins, is expressed in various types of malignant tumours. There have been no previous studies of the correlation between matrilysin expression and melanoma.Objectives Protein expression of matrilysin was evaluated in human cutaneous melanomas, metastatic melanomas, acquired common melanocytic naevi and Spitz naevi, and the data were corrected with the clinicopathological factors.Methods We retrospectively investigated 18 primary melanomas, 15 metastatic melanomas, 10 common melanocytic naevi and five Spitz naevi samples at our clinic using immunohistochemistry (IHC). Both promatrilysin and active matrilysin were found in the melanoma tissue extracts by Western immunoblotting. In situ hybridization demonstrated that melanoma cells selectively express matrilysin mRNA.Results Of the melanoma samples, 29 of 33 (87·9%) were positive for matrilysin, including 14 of 18 (77·8%) primary cutaneous melanomas and 15 of 15 (100%) metastatic melanomas. In contrast, matrilysin was not expressed in common naevi or Spitz naevi. The matrilysin IHC staining score in primary melanomas was associated with the presence of metastases, tumour thickness and TNM staging (P = 0·001, 0·025 and 0·021, respectively). The 5‐year overall survival was 26·3% for matrilysin‐positive cases and 100% for matrilysin‐negative cases among melanoma specimen.Conclusions We found matrilysin expression in primary melanomas and in metastatic melanomas. We further demonstrated that the matrilysin IHC staining score was associated with invasive depth of primary melanoma lesions and metastases. Our observations indicate that matrilysin may be associated with melanoma progression, and may enhance melanoma tumour cell invasion. Therefore, matrilysin may be potentially valuable as a prognostic indicator to predict the clinical behaviour of melanoma.

Matts, P.J.; Dykes, P.J.; Marks, R.

doi: 10.1111/j.1365-2133.2006.07706.xpmid: 17493065

SummaryBackground There continues to be a need for objective, noninvasive methods to measure melanin concentration in vivo in human skin, independent of the confounding chromophore, haemoglobin. Existing methods are limited by a lack of specificity and inability to resolve the spatial distribution of these chromophores.Objectives To validate and calibrate the measurement of eumelanin in vivo using SIAscopicTM techniques, relating this with histologically and analytically determined eumelanin concentrations in nonsun‐exposed skin from subjects of Fitzpatrick skin types I–VI.Methods Observations were made in five subjects from each of the Fitzpatrick skin types I–VI using chromophore mapping by contact and noncontact SIAscopy and other noninvasive spectrophotometric means. Measurements were performed on the inner aspect of both upper arms. Subsequently two 4 mm punch biopsies were taken from the inner upper arm, one per arm after injection of local anaesthesia. One biopsy was fixed in formalin and processed for histology; specifically, sections were stained for melanin using a silver staining technique and the amount of melanin was graded microscopically. The other biopsy was subjected to an analytical assay to yield precise quantitative measures of melanin. The correlation between the different methods of melanin measurement was determined.Results Clear, significant correlations were obtained between contact and noncontact SIAscope‐derived eumelanin values and actual eumelanin tissue content (determined both histologically and analytically), across the full range of Fitzpatrick skin types. There was no correlation between SIAscope‐derived eumelanin and haemoglobin values, indicating efficient separation of the two chromophores.Conclusions New contact and noncontact chromophore SIAscopic mapping techniques provide robust, rapid noninvasive measures of the concentration and spatial distribution of eumelanin in vivo, independent of haemoglobin, which correspond to true tissue values for this chromophore.

Yosipovitch, G.; Duque, M.I.; Fast, K.; Dawn, A.G.; Coghill, R.C.

doi: 10.1111/j.1365-2133.2006.07711.xpmid: 17263822

SummaryBackground Patients who suffer from chronic itch employ creative techniques to alleviate their itch, often using painful thermal stimuli, such as hot and very cold showers, as well as mechanical stimuli, such as scratching.Objectives The present study examined whether the sensory perception of itch is attenuated by remote interactions between both thermal and mechanical stimuli and afferent information related to itch.Patients and methods Itch was induced with histamine iontophoresis in 21 healthy young subjects. Repetitive thermal stimuli including innocuous warmth, innocuous cool, noxious cold and noxious heat as well as scratching were applied 3‐cm distal to the area of histamine iontophoresis. Subjects rated their perceived intensity of histamine‐induced itch with a computerized visual analogue scale.Results Itch intensity ratings were significantly reduced during each period of scratching and repeated noxious heat and cold. Innocuous cooling and warming did not significantly alter itch intensity ratings. Inter‐individual differences in histamine‐induced itch sensitivity were unrelated to inter‐individual differences in pain sensitivity.Conclusions The present psychophysical study demonstrates that repetitive noxious thermal and scratching stimuli inhibit itch and do not require direct physical interaction with the area of the skin from which itch originates.

Mentink, L.F.; De Jong, M.C.J.M.; Kloosterhuis, G.J.; Zuiderveen, J.; Jonkman, M.F.; Pas, H.H.

doi: 10.1111/j.1365-2133.2006.07717.xpmid: 17263817

SummaryBackground Pemphigus is a bullous mucocutaneous autoimmune disease characterized by IgG autoantibodies to desmoglein (Dsg) 1 and/or Dsg3. Occasionally direct immunofluorescence of pemphigus skin reveals IgA depositions with an intraepidermal intercellular pattern in addition to the IgG deposition.Objectives To investigate if pemphigus patients, in addition to having IgG autoantibodies, also generate IgA antibodies to Dsg1 and/or Dsg3.Patients/methods Sera of 100 pemphigus patients and 36 bullous pemphigoid controls were tested by IgA enzyme‐linked immunosorbent assay (ELISA) to the recombinant extracellular domains of Dsg1 and Dsg3. The patients were selected on clinical grounds and positive IgG ELISA index values for Dsg1 and/or Dsg3. They were divided into four groups: patients having IgG to only Dsg1 (n = 34), patients having IgG to both Dsg1 and Dsg3 (n = 31), patients having IgG to only Dsg3 (n = 27) and patients who had paraneoplastic pemphigus (PNP) (n = 8).Results IgA antibodies to Dsg1 were found in 13 (38%) of the patients with IgG to Dsg1, in five (16%) of the patients with IgG to both Dsg1 and Dsg3, in four (15%) of the patients with IgG to Dsg3 and in none of the PNP patients. IgA antibodies to Dsg3 were found in one (3%) of the patients with IgG to Dsg1, in 18 (58%) of the patients with IgG to both Dsg1 and 3, in 18 (67%) of the patients with IgG to Dsg3, and in four (50%) of the PNP patients. Immunofluorescence analysis demonstrated intraepidermal intercellular staining IgA antibodies in serum and intercellular IgA deposits in skin of IgA ELISA‐positive patients, although to a lesser extent than by ELISA.Conclusions This study shows that in a considerable number of supposedly IgG‐mediated pemphigus patients IgA to Dsg1 and Dsg3 is also present. In most cases the antigen specificity of the IgA follows the antigen specificity of the IgG, although in a small number of cases IgA is present against the Dsg not recognized by IgG.

Chang, Y‐C.; Wu, W‐M.; Chen, C‐H.; Lee, S‐H.; Hong, H‐S.; Hsu, L‐A.

doi: 10.1111/j.1365-2133.2006.07716.xpmid: 17263818

SummaryBackground Genetic factors play an important role in susceptibility for psoriasis. The angiotensin I‐converting enzyme (ACE) is expressed by keratinocytes. Administration of ACE inhibitors may induce or exacerbate psoriasis in clinical practice. Thus, ACE gene variants may contribute to the genetic background of psoriasis.Objectives To assess the role of the ACE insertion/deletion (I/D) polymorphism in psoriasis among ethnically Chinese Taiwanese subjects.Methods In total, 312 patients with psoriasis and 615 control subjects were analysed for the ACE I/D polymorphism by polymerase chain reaction.Results A marginally significant difference (P = 0·035) was found in the distribution of ACE I/D genotype frequencies between patients with psoriasis and controls. The frequency of the II genotype in patients with psoriasis was significantly higher than that in the control group (55·1% vs. 46·7%, respectively, P = 0·015). Although the I allele frequency in patients with psoriasis (72·4%) was higher than that in the control group (68·2%), the difference was not significantly different (P = 0·062). After adjusting for age and gender, carriers of the II genotype were 1·45 (95% confidence interval 1·09–1·92) times more likely than noncarriers to have psoriasis (P = 0·010).Conclusions Our results suggest that the presence of the I allele may confer susceptibility to development of psoriasis among ethnically Chinese Taiwanese individuals.

Kingo, K.; Mössner, R.; Kõks, S.; Rätsep, R.; Krüger, U.; Vasar, E.; Reich, K.; Silm, H.

doi: 10.1111/j.1365-2133.2006.07731.xpmid: 17263806

SummaryBackground Interleukin (IL) 19, IL‐20 and IL‐24 belong to the IL‐10 cytokine family and have been identified to play a role in the regulation of epidermal functions and in inflammation. The genes encoding IL‐19, IL‐20 and IL‐24 are located within a gene cluster on chromosome 1q31–32 and carry frequent genetic variations.Objectives This study investigated whether variations in the IL19, IL20 and IL24 genes that have previously been associated with plaque‐type psoriasis may also play a role in palmoplantar pustulosis (PPP).Patients Fifteen polymorphisms were analysed in 43 patients with PPP and in 149 healthy control subjects.Results The rare allele of IL20 1380 A→G (rs2981573) was less frequent in patients with PPP compared with healthy controls (OR 1·95, 95% CI 1·00–3·79). Haplotype analyses of IL19 and IL20 suggested an increased risk for PPP associated with IL20 haplotype GAA (OR 2·39, 95% CI 1·17–4·86) and a reduced risk for PPP associated both with IL19 haplotype GATGATA (OR 0·41, 95% CI 0·16–1·05) and IL20 haplotype GGG (OR 0·48, 95% CI 0·23–0·98). Extended haplotype analysis revealed an association of IL19/IL20 haplotype GACACCGGAA with a higher risk for PPP (OR 2·31, 95% CI 1·05–5·10) and of IL20/IL24 haplotype CAAAC with a reduced risk for PPP (OR 0·12, 95% CI 0·02–0·82).Conclusions This exploratory study supports the hypothesis that variations of genes of the IL‐19 subfamily of cytokines influence susceptibility to PPP. However, due to the limited size of the study samples, this current concept should be considered as preliminary and the results need to be confirmed in future independent studies.

Kurschat, P.; Eming, S.; Nashan, D.; Krieg, T.; Mauch, C.

doi: 10.1111/j.1365-2133.2006.07724.xpmid: 17263813

SummaryBackground Increased serum levels of angiogenesis‐related factors such as endostatin, vascular endothelial cell growth factor (VEGF) or basic fibroblast growth factor (bFGF) have been demonstrated for a variety of solid and nonsolid tumours. Therefore, these factors have been suggested as diagnostic and in some studies as prognostic tumour markers.Objectives The purpose of the present study was to investigate a possible correlation of endostatin, VEGF or bFGF serum levels with disease progression in melanoma. Especially, we compared these factors to the established melanoma marker S‐100 B, which increases in advanced disease but often fails to indicate early metastatic spread to regional lymph nodes.Patients and methods Sera from 197 melanoma patients and 35 healthy controls were measured by enzyme‐linked immunosorbent assay; 72 patients had primary tumours (American Joint Committee on Cancer stages I and II), 55 had regional lymph node metastasis (stage III) and 70 patients had distant organ metastasis (stage IV).Results Endostatin, VEGF and bFGF serum levels were significantly elevated in stage IV disease, compared with the control group. In stage III, endostatin and bFGF, but not VEGF or S‐100 B, were significantly increased. However, follow‐up of this patient group did not show a correlation with the future clinical course including time until progression or overall survival, arguing against a role of endostatin, VEGF or bFGF as prognostic markers.Conclusions These data indicate that endostatin or bFGF might be useful as diagnostic markers for the early detection of locoregional metastasis.

Michaëlsson, G.; Kristjánsson, G.; Pihl Lundin, I.; Hagforsen, E.

doi: 10.1111/j.1365-2133.2006.07725.xpmid: 17263812

SummaryBackground Palmoplantar pustulosis (PPP) is a chronic inflammatory disease affecting mainly smoking women. Some patients also have psoriasis. A subgroup of patients with psoriasis has been shown to have silent gluten sensitivity with relevance for their psoriasis. Nothing is known about gluten sensitivity in PPP.Objectives To find out whether any patients with PPP are gluten‐sensitive and whether this might be relevant for the PPP activity.Patients and methods One hundred and twenty‐three patients (113 women) with PPP participated. Screening for IgA antibodies against gliadin and tissue transglutaminase (tTG) was performed, the duodenal mucosa in patients with and without these antibodies was studied and the effect of a gluten‐free diet (GFD) was followed up.Results Twenty‐two patients (18%) had IgA antibodies against gliadin and nine of 94 (10%) against tTG. Twelve patients with antibodies and 11 without underwent gastro‐duodenoscopy. Four displayed villous atrophy, whereas all other specimens were judged as essentially normal at routine staining. However, with immunohistochemistry, the numbers of CD3+ and CD8+ lymphocytes in the epithelium were found to be increased in patients with any type of antibody, although they were most numerous in those with both types of antibodies. Seven of 123 patients (6%) had coeliac disease (three previously diagnosed). Patients with antibodies who adhered to the GFD displayed total or nearly total clearance of the skin lesions and normalization of the antibody levels.Conclusions Patients with PPP should be screened for antibodies against gliadin and tTG. Those with antibodies can be much improved on a GFD regardless of the degree of mucosal abnormalities.

Majeski, C.J.; Johnson, J.A.; Davison, S.N.; Lauzon, G.J.

doi: 10.1111/j.1365-2133.2006.07736.xpmid: 17263803

SummaryBackground Assessing pruritus severity is difficult because of its subjective nature. A questionnaire that takes into account how the symptom is perceived by the patient may provide a more accurate representation of the pruritus. However, recently developed questionnaires do not specifically quantify severity of the symptom.Objectives To develop a self‐report questionnaire to measure pruritus severity and to provide initial evidence of its validity and reliability.Methods We modified a previously developed interview for the characterization and evaluation of pruritus, which was completed along with the RAND‐36 Health Status Inventory and Dermatology Life Quality Index by patients with psoriasis‐associated pruritus. Exploratory factor analysis, studies of internal consistency, and correlation analyses with health‐related quality of life scores were used to help determine which components of the modified pruritus interview to include in the new questionnaire, the Itch Severity Scale (ISS). The ISS was then assessed for construct validity, internal consistency reliability and test–retest reliability.Results Seven of the initial 11 components of the modified pruritus interview were included in the ISS. ISS scores correlated moderately with physical (r = −0·483) and mental (r = −0·492) health composite scores of the RAND‐36 and strongly with Dermatology Life Quality Index scores (r = 0·628), evidence of construct validity. It had an internal consistency reliability of 0·80 and a test–retest reliability of 0·95.Conclusions Based on this preliminary evidence of validity and reliability, this new seven‐item ISS may be useful in comparing pruritus severity among different disease populations or in assessing pruritus treatment effectiveness.