Analysis of POFUT1 gene mutation in a Chinese family with Dowling-Degos disease.

Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis characterized by reticular pigmented anomaly mainly affecting flexures. Though KRT5 has been identified to be the causal gene of DDD, the heterogeneity of this disease was displayed: for example, POFUT1 and POGLUT1 were recently identified and confirmed to be additional pathogenic genes of DDD. To identify other DDD causative genes, we performed genome-wide linkage and exome sequencing analyses in a multiplex Chinese DDD family, in which the KRT5 mutation was absent. Only a novel 1-bp deletion (c.246+5delG) in POFUT1 was found. No other novel mutation or this deletion was detected in POFUT1 in a second DDD family and a sporadic DDD case by Sanger Sequencing. The result shows the genetic-heterogeneity and complexity of DDD and will contribute to the further understanding of DDD genotype/phenotype correlations and to the pathogenesis of this disease.

Evaluation of the combination of BP180-NC16a enzyme-linked immunosorbent assay and BP230 enzyme-linked immunosorbent assay in the diagnosis of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is an acquired autoimmune subepidermal blistering disease characterized by circulating IgG autoantibodies directed against BP180 and BP230 hemidesmosomal proteins. Previous studies have demonstrated that antibodies against the NC16a domain of BP180 mediate BP pathogenesis, while antibodies against BP230 enhance the inflammatory response. Recently, commercial BP180-NC16a enzyme-linked immunosorbent assay (ELISA) and BP230 ELISA kits were developed to detect anti-BP180 and anti-BP230 autoantibodies in human BP sera. AIMS: To evaluate the efficacy of BP180-NC16a ELISA and BP230 ELISA in the initial diagnosis of BP. METHODS: Sera from 62 BP patients and 62 control subjects were tested by BP180-NC16a ELISA and BP230 ELISA and compared with findings from indirect immunofluorescence (IIF) and immunoblotting (IB) to determine the sensitivity and specificity of these assays. RESULTS: The sensitivities of BP180-NC16a ELISA and BP230 ELISA were 87.1% (54/62) and 56.5% (35/62), respectively, and the specificities of both were 100% (62/62). Using both ELISAs for diagnosis increased the sensitivity to 95.2% (59/62) and was statistically comparable with IB sensitivity. CONCLUSIONS: ELISA is a convenient, effective, and reliable method for serodiagnosis of BP, and combined use of BP180-NC16a ELISA and BP230 ELISA can increase the sensitivity of this diagnostic approach.

Accuracy of indirect immunofluorescence on sodium chloride-split skin in the differential diagnosis of bullous pemphigoid and epidermolysis bullosa acquisita.

BACKGROUND: Previous reports have shown that indirect immunofluorescence (IIF) performed on sodium chloride-split skin (SSS) is helpful to differentiate epidermolysis bullosa acquisita (EBA) from bullous pemphigoid (BP). Antibodies of BP may bind to the epidermal side of SSS, while antibodies of EBA bind to the dermal side. AIMS: To determine the accuracy of IIF-SSS in the differential diagnosis of EBA and BP utilizing immunoblotting (IB) analysis. METHODS: Sera from 78 patients, diagnosed with BP by clinical features, histopathology, and direct immunofluorescence (DIF), were assayed using IIF-SSS and IB. RESULTS: Of the 43 serum samples with an epidermal reaction to IIF-SSS assay, 42 were recognized with BP antigens (180 kDa or 230 kDa). Of the 11 serum samples with a dermal reaction pattern, 7 were recognized with the 290 kDa antigen of EBA and 3 with sera bound BP antigens. Seven serum samples with epidermal and dermal combined staining, of which 5 of them reacted with BP antigens, 1 reacted with both BP and EBA antigens. One serum sample from each group showed a negative result by IB. Approximately 9.0% (7/78) of patients diagnosed with BP using regular methods were actually EBA. CONCLUSIONS: Epidermal reaction using the IIF-SSS assay highly correlated with the diagnosis of BP. However, dermal reactions correlated poorly with EBA, with some serum samples from BP patients binding to dermal-side antigens. In both epidermal and dermal stained sera using IIF-SSS, there was a possibility of BP and EBA. Differential diagnosis should be confirmed using IB, especially in cases of dermal and double staining patterns assayed using IIF-SSS.

Histological classification of melasma with reflectance confocal microscopy: a pilot study in Chinese patients.

OBJECTIVE: To investigate the histological classification of melasma with reflectance confocal microscopy (RCM) in vivo. METHODS: Two hundred and ten cases with facial melasma lesions were enrolled. After informed consent, the target melasma lesion of 10 patients were imaged with RCM and then biopsied as well. Under the RCM scanning, the distribution of the melanin determined the histological types, and then, the results of RCM images were compared with those of the histopathology. The other 200 cases were tested only with RCM. RESULTS: For the 10 cases imaged and biopsied, compared with that of the perilesional normal skin, the amount of melanin was significantly increased in the epidermis in all lesions under RCM, while three cases also found melanin in the dermis. Thus, seven of the 10 patients were categorized as the epidermal type while the other three as mixed ones, and the results were well correlated with those of the histopathology. Of the other 200 patients, 143 cases 71.5%) were categorized as the epidermal type while the other 57 (28.5%) cases as mixed ones. LIMITATIONS: If more melasma cases are biopsied, the data will be more convincing. CONCLUSION: RCM in vivo analysis shows complete coherence with histopathology results, which could be an alternative for the classification of melasma, and based on the results of RCM imaging, melasma is classified into two major types: the epidermal type and mixed type.

Seborrheic keratosis or verruca plana? A pilot study with confocal laser scanning microscopy.

BACKGROUND: Differentiation of some seborrheic keratosis (SK) and verruca plana (VP) lesions is a challenge. Confocal laser scanning microscopy (CLSM) has been proved to be useful in the diagnosis of skin diseases; however, to date, there is no report on the differential study of the two diseases with CLSM. OBJECTIVES: To obtain the CLSM image characteristics of SK and VP, and then test the differential ability of CLSM imaging. METHODS: We recruited 10 patients with typical lesions of SK under CLSM images to validate the features reported. Another 10 patients with typical VP lesions were also recruited, imaged with CLSM and biopsied to obtain the features under CLSM images based on histology analysis. Then, we attempt to summarize and refine those characteristics collected to obtain the most significant ones. All the cases with lesions suggestive of SK or VP were advised to undergo imaging with CLSM, and if CLSM imaging reflected discordantly with the clinical diagnosis, a biopsy was suggested for the exact lesion imaged. Those cases with CLSM and histology results were collected. Finally, two clinical dermatologists, who had no previous experience with CLSM, were tested with the simplified features of CLSM images to differentiate the suspected lesions of SK and VP among the cases collected. RESULTS: In total, there were 58 cases with CLSM images and histology results collected, in which, 40 cases were diagnosed as SK and 18 cases as VP by histology. The two blinded dermatologists' judgments were identical to histology analysis. CONCLUSION: CLSM proved to be valuable in the differential diagnosis of SK and VP. The simplified characteristics were easily understood and acceptable to those with no previous experience of CLSM.