IGF-1 resist oxidative damage to HaCaT and depigmentation in mice treated with H2O2.

Vitiligo, an acquired pigmentary disorder of the skin, is characterized by a chronic and progressive loss of melanocyte from the epidermis and follicular reservoir. Growth factor of surrounding cells impacted on melanocytes survival. In this study, lower level of IGF-1 in the lesion was found than that in the donor area of vitiligo patients. IGF-1 improved activation of Nrf2, and inhibited ROS generation and endoplasmic reticulum dilation in HaCaT. C57BL/6 mice were treated with 5% H2O2, and combined with 50 µg/kg of IGF-1 pre-treatment or not once every day for 50 consecutive days. After 50 days, IGF-1 obviously ameliorated depigmentation of mice skin and reduced hair follicle length, skin thickness and Tyrosinase induced by H2O2. Moreover, IGF-1 significantly suppressed CD8+ T cells infiltration in mice skin, inhibited the production of IL-2 and IFN-γ, and decreased the expression of CXCL10 and CXCR3. Thus, the results indicated that IGF-1 could resist oxidative damage to HaCaT, suppress CD8+ T cells infiltration and pro-inflammatory cytokines secretion, and suppresses the thinning of epidermal layer in vivo. It suggests that IGF-1 inhibits oxidative damage to HaCaT and immunosuppressive effects on CD8+ T cells proliferation and activation to resist depigmentation induced by H2O2. This disclosed its multiple roles in the vitiligo, and shed a light on developing the application potential for IGF-1 in vitiligo.

Cutaneous tuberculosis in China - A multicentre retrospective study of cases diagnosed between 1957 and 2013.

BACKGROUND: China has one of the largest populations with tuberculosis worldwide. Cutaneous tuberculosis (CTB) is a rare manifestation of mycobacterial infection. Although CTB is well described, it is important to periodically revisit the prevailing clinical and epidemiological features in most populated countries such as China, India, and Indonesia, where tuberculosis is still a major health problem. OBJECTIVE: This retrospective study aimed to re-evaluate the CTB cases in China in the past 50 years to obtain a comprehensive insight into this multiplex entity. METHODS: Cases of diagnosed CTB with confirmed histology from four large medical centres in central China between 1957 and 2013 were collected and analysed, including demographic data, clinical manifestations and pathological findings. RESULTS: Of the 1194 cases enrolled, there were 666 (55.78%) and 528 cases (44.22%) of true CTB and tuberculids, respectively. Erythema induratum of Bazin (EIB) was the most common CTB (35.8%), followed by lupus vulgaris (LV, 32.7%), tuberculosis verrucosa cutis (18.9%), papulonecrotic tuberculid (8.0%), scrofuloderma (2.8%), tuberculosis cutis ulcerosa (1.3%), penile tuberculids (0.4%), and lichen scrofulosorum (0.1%). EIB was the predominant tuberculid (80.87%), while LV the predominant true CTB (58.7%). The number of diagnosed CTB showed a decreasing trend in the 1960s and 1970s, then increased again, and peaked in the 1990s. CONCLUSIONS: Cutaneous tuberculosis is still a common problem in China. Chronologic changes in CTB cases reported in China over the past 50 years may reflect the prevalence transition of overall tuberculosis. CTB has diverse clinical presentations, and each subtype is characterized by specific gender predilection, duration, age, clinic and pathological findings.

[Relationship between autophagy of melanocytes in patients with vitiligo and clinical types].

OBJECTIVE: To evaluate autophagy of melanocytes and its mechanism in patients with vitiligo and to analyze its correlation with clinical types of vitiligo. METHODS: Nine cases of segmental vitiligo (SV) and 11 cases of generalized vitiligo (GV) were recruited in Hangzhou Third Hospital between May 2014 and June 2015. Six people with healthy skin were recruited as controls. Epidermal melanocytes were obtained from the normal colour skin around the white spot area in SV and GV patients and from foreskin in controls for culture in vitro. Cultures for each group contained negative control and rapamycin (30 nmol/L) sub-groups. The autophagy was observed using transmission electron microscopy (TEM) and immunofluorescence laser scanning confocal microscope (LSCFM). Protein expressions of microtube-associated protein light chain 3 (LC3Ⅱ) and microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase related protein (TYRP)1, and TYRP2 were detected by Western blot. RESULTS: (1)Autophagy of melanocytes was observed under TEM and LSCFM in both SV and control groups before rapamycin treatment, but not in GV patients. The expressions of autophagosome and LC3Ⅱ protein were increased in melanocytes in SV, GV and control groups after autophagy induction(SV group 0.58±0.10 vs 0.37±0.06; GV group 0.57±0.16 vs 0.22±0.08; control group 0.67±0.09 vs 0.46±0.12), and the autophagy intensity was higher in the GV group compared to the SV group and the control group. (2)Before autophagy induction, the expressions of MITF, TYR, TYRP1, and TYRP2 protein were lower in the GV and SV patients compared with the control group; after autophagy induction, the expressions of MITF, TYR, and TYRP1 statistically significantly increased in melanocytes in all the three groups(all P<0.05), while TYRP2 protein expression was not significantly changed (all P>0.05). CONCLUSIONS: Autophagy of melanocytes may be present in vitiligo and affect the expression of functional molecules, and is related with clinical type of vitiligo.

Four views of Riehl's melanosis: clinical appearance, dermoscopy, confocal microscopy and histopathology.

BACKGROUND: Riehl's melanosis often poses a diagnostic challenge because of the variability in clinical morphology. Reflectance confocal microscopy (RCM), similar to dermoscopy, images lesions in an en face plane, thus enabling direct correlations with dermoscopic images. No published data are currently available regarding dermoscopic and RCM findings in Riehl's melanosis. OBJECTIVES: The aim of our study was to correlate the features of Riehl's melanosis across various imaging modalities including dermoscopy, confocal microscopy and histopathological examination to give a more precise description of this disease to improve the accuracy of diagnosis. METHODS: Fifteen patients with a previously established diagnosis of Riehl's melanosis were recruited. All lesions were imaged using dermoscope and in vivo RCM, followed by complete excision for histopathological analysis. RESULTS: A series of dermoscopic and RCM features of Riehl's melanosis were identified and shown to correlate well with histopathological examination. Pseudonetworks, grey dots/granules, liquefaction of basal cells, incontinence of pigment were the most distinctive characteristic. CONCLUSIONS: This study highlights the clinical, dermoscopic, confocal microscopic and histopathological features of Riehl's melanosis. It is necessary to further define the diagnostic features of clinically difficult lesions with these modalities, but clinical evaluation should not be neglected.

Mobile connected dermatoscope and confocal laser scanning microscope: a useful combination applied in facial simple sensitive skin.

Little is known as the effects of mobile connected dermatoscope services on diagnostic accuracy for sensitive skin. Confocal laser scanning microscope (CLSM) can non-invasively measure the thickness of epidermis. Combination of the two devices to observe sensitive skin may receive unexpected effects. To evaluate the application effect on sensitive skin with the combination of Handyscope and confocal laser scanning microscope. Twenty simple sensitive-skinned patients and 20 volunteers participated in the study. Cheek, typically, dermoscopic images were obtained from patients, and the changes in the skin texture were observed. Their epidermis thicknesses as well as the volunteers' were measured so that the thicknesses of the two groups were compared. Dermoscopic pictures of the skin texture obviously showed that dilated capillaries looked like earthworms with pigmented patches more or less floating above, and skin roughness as well as deepened dermatoglyph were also conspicuously present in some patients. The mean epidermal thickness of the patients was 79.01 µm and the volunteers' was 85.78 µm. The difference between the two groups reached 6.77 µm. There was a statistical significance (P = 0.001). Mobile connected dermatoscope and confocal laser scanning microscope might be the choice for simple sensitive skin investigation.

Ratio of size of recipient and donor areas in treatment of vitiligo by autologous cultured melanocyte transplantation.

BACKGROUND: Autologous melanocytes can be expanded in vitro, allowing the treatment of large lesions of vitiligo in one session. Theoretically, this procedure could provide a higher donor/recipient size ratio (DR ratio) compared with that in noncultured cell transplantation (with a DR ratio < 1 : 10). However, the exact DR ratio obtained from this procedure has not been reported. OBJECTIVES: To study whether transplantation of cultured pure melanocytes at a high DR ratio is as efficient as that at a low DR ratio. METHODS: One hundred and two patients with vitiligo were treated by transplantation of cultured pure melanocytes and were divided into two groups: a low DR ratio group, including patients with DR ratio ≤ 1 : 10 (mean 1 : 8, 35 cases) and a high DR ratio group with DR ratio > 1 : 10 (mean 1 : 27, 67 cases). The extent of repigmentation between these two groups was compared. RESULTS: There was no significant difference in repigmentation between the low DR ratio group (mean ± SD 77·4 ± 22·5%) and the high DR ratio group (77·6 ± 24·8%). Multiple regression analysis showed that even after adjustment for age, sex, type of vitiligo and transplanted cell density, there was no significant correlation between the extent of repigmentation and the DR ratio, indicating that patients treated with high DR ratio obtained a satisfactory result and showed no difference from the low DR ratio group. CONCLUSIONS: Various surgical procedures for the treatment of vitiligo which involve melanocyte transplantation or skin grafts have different inherent DR ratios. Transplantation of cultured pure melanocytes is an expensive and complicated procedure; however, it provides the highest DR ratio (> 1 : 10 and up to 1 : 60). Surgeons can select one of these methods for the treatment of vitiligo based on their experience and skill, on the size of lesions, and the availability of laboratory support.

Treatment of vitiligo in children and adolescents by autologous cultured pure melanocytes transplantation with comparison of efficacy to results in adults.

BACKGROUND: Transplantation of autologous cultured pure melanocytes is a well-established procedure for the treatment of refractory and stabilized vitiligo. However, there was no report specifically comparing the efficacy with the regard to defined age groups (children-adolescence-adult). OBJECTIVE: We analysed the efficacy of this procedure in the treatment of vitiligo in children and adolescents and compare it with the results in adults treated during the same period and using identical procedures. METHODS: Melanocytes were isolated from the roof of suction blister, cultured and expanded with Hu16 medium in vitro, and transplanted to laser-denuded receipt area. A total of 12 children (8-12 years), 20 adolescents (13-17 years) and 70 adults with vitiligo were treated using this procedure. RESULTS: The patients obtained satisfactory results (repigmentation of 50% or more) results in children, adolescents and adults were 83.3%, 95.0% and 84.0% respectively. The mean extent of repigmentation in children, adolescents and adults was 80.7%, 78.9% and 76.6% respectively. There was no statistical difference in repigmentation among these three groups. After adjusting for all factors (gender, type of vitiligo, period of stability, location of the lesion or transplanted cell density) individually or totally using multiple regression analysis, age still did not correlate to the extent of repigmentation. CONCLUSIONS: The satisfactory results obtained in the treatment of vitiligo in children and adolescents by transplantation of cultured autologous pure melanocytes are comparable with the results in adults. Therefore, this procedure can be considered in refractory and stable vitiligo in children and adolescents, especially in patients with large vitiliginous lesions.

Clinical, histopathological and ultrastructural characteristics of naevus depigmentosus.

BACKGROUND: Naevus depigmentosus (ND) is a congenital, nonfamilial, well-circumscribed, uniformly hypopigmented macule, the relative size and distribution of which is stable throughout life. The aetiopathogenesis of ND is not yet fully understood, and reports about the clinical and histopathological characteristics of ND are few. OBJECTIVE: To investigate the clinical and histopathological characteristics of ND, and to make it easier to diagnose ND clinically. METHODS: A clinical survey on 38 patients with ND was performed according to the diagnostic criteria proposed by Coupe. Wood's lamp examination was used to distinguish the different appearance of ND and vitiligo. Skin-biopsy specimens were stained with haematoxylin and eosin, silver, antibodies to S-100 protein, tyrosinase-related protein-1 and tyrosinase, then used for ultrastructural study. Melanocytes were also cultured. RESULTS: Leucoderma was present at birth in 13 patients (34.2%), and appeared during the first 3 years of life in 15 patients. The trunk was the most commonly affected site, and the lesions usually had serrated, irregular borders. Under Wood's lamp, lesions had an off-white accentuation without fluorescence. Immunohistochemistry showed that the melanin content of ND lesions was decreased compared with perilesional normal skin, but there was no change in the number of melanocytes. Ultrastructural study showed that some aggregated melanosomes were present in the affected keratinocytes. CONCLUSION: As a result of the above findings, we suggest changes to Coupe's criteria for ND.

The double-RNA-specific adenosine deaminase (DSRAD) gene in dyschromatosis symmetrica hereditaria patients: two novel mutations and one previously described.

BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH, MIM 127400) is an autosomal dominant pigmentary genodermatosis. Pathogenic mutations in the double-RNA-specific adenosine deaminase (DSRAD) gene encoding an RNA editing enzyme have recently been identified. OBJECTIVES: To identify gene mutations of DSRAD in Chinese patients with DSH. METHODS: Three unrelated Chinese patients with DSH were subjected to mutation detection in DSRAD. Two had family histories of DSH. All the coding exons and their flanking sequences were amplified and sequenced. RESULTS: All three patients had heterozygous mutations including one non-sense, one frameshift and one missense mutation in DSRAD. CONCLUSIONS: Two novel mutations, c.3169delC (p.L1057fs) and c.3247C-->T (p.R1083C), and one recurrent mutation c.1420C-->T (p.R474X), were found in this series of Chinese patients with DSH.

A homozygous nonsense mutation in the EVER2 gene leads to epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is a genodermatosis with mainly autosomal recessive inheritance. Pathogenic mutations in two adjacent genes, EVER1 and EVER2, have recently been identified. In this study, we performed mutation detection for the EVER1 and EVER2 genes on samples from a Chinese patient with EV, who had consanguineous parents. A homozygous C-->T transition at nucleotide position 568 within exon 6 of the EVER2 gene was detected. The mutation led to a premature translation termination (R190X) and the predicted protein lacked 537 amino acids. This novel nonsense mutation is, to our knowledge, the first mutation reported in Chinese patients with EV.