Impacts of exposure to topical calcineurin inhibitors on metabolism in vitiligo infants.

BACKGROUND: Tacrolimus ointment is a recently developed topical immunomodulator that has been approved for use in patients with vitiligo older than 2 years. Concern regarding potential systemic toxic effects has limited treatment options for children younger than 2 years. We wanted to determine whether topical tacrolimus therapy is safe and effective in patients with vitiligo younger than 2 years. METHODS: The present 6-month clinical trial was conducted to evaluate the efficacy and safety of 0.03% tacrolimus in the treatment of vitiligo in children under 2 years of age. Meanwhile, serum and urine samples were collected, and liquid chromatography-mass spectrometry was performed to generate the serum and urine metabolic profile data of patients and healthy controls. RESULTS: The overall response rate at the sixth month, which was defined by the degree of re-pigmentation, was 100%. As revealed by blood monitoring and metabolite detection 6 months later, there was no difference between the treatment group and the control group. There is no evidence that long-term topical application of 0.03% tacrolimus ointment will cause metabolite or other physical changes in the body. CONCLUSIONS: Tacrolimus ointment appears to be effective and safe in the treatment of vitiligo in children younger than 2 year. TRIAL REGISTRATION: http://www.chictr.org.cn identifier: ChiCTR 2100045920. IMPACT: We first reported the efficacy and safety of topical application of 0.03% tacrolimus ointment in infants with vitiligo characterized by the metabolites. There is no evidence that long-term topical application of 0.03% tacrolimus ointment will cause metabolite or other physical changes in the body. This study provide evidence for the TCI treatment of infants with vitiligo.

Altered circulating memory T cells in vitiligo cases followed NB-UVB therapy.

BACKGROUND: Vitiligo represents a commonly diagnosed autoimmune disease caused by the depletion of epidermal melanocytes. Many subsets of T cells contribute to vitiligo pathogenesis, including resident and circulating memory T cells. OBJECTIVES: To analyze the amounts of CD4+ and CD8+ memory T-cell subsets in peripheral blood specimens from vitiligo patients and alterations caused by narrowband ultraviolet B (NB-UVB) phototherapy. METHODS: Circulating CD4+ and CD8+ central memory T (TCM ) and effector memory T (TEM ) cell frequencies in 33 patients with non-segmental vitiligo and 16 healthy donors were evaluated by flow cytometry. Related chemokine levels were also detected. RESULTS: Peripheral blood CD4+ TCM and CD8+ TCM counts were markedly reduced in vitiligo cases while they were higher in active vitiligo compared with stable vitiligo cases. Circulating CD8+ TCM frequency in vitiligo was closely related to disease duration. Interestingly, CD4+ TCM and CD8+ TCM frequencies, alongside CXCL9 and CXCL10 amounts in peripheral blood of patients with vitiligo, were significantly decreased after NB-UVB phototherapy. CONCLUSIONS: Decreased frequencies of circulating CD4+ TCM and CD8+ TCM by NB-UVB suggest a possible immunosuppressive effect of phototherapy. The chemokines CXCL9 and CXCL10 are the bridge between circulating and skin resident memory T cells. NB-UVB blocks the homing of circulating memory T cells into vitiligo lesions by down-regulating CXCL9 and CXCL10. Targeting the above proteins could provide novel, durable treatment options to cure and prevent flares of this disease.

Repigmentation in two patients with vitiligo on AcEGCG 0.5% cream.

Per-acetylated epigallocatechin-3-gallate (AcEGCG), a fully acetylated derivative of EGCG, a more potent agent for protection of melanocytes from oxidative damage. We present two patients with vitiligo treated with AcEGCG 0.5% cream, who demonstrated skin repigmentation and control of depigmentation progression.

Topical epigallocatechin-3-gallate in the treatment of vitiligo.

OBJECTIVE: To preliminarily assess the efficacy and safety of the topical application of Epigallocatechin-3-gallate (EGCG) in treating vitiligo, a 6-month clinical trial was carried out. METHOD: Patients were randomly given topical application of EGCG on the assigned lesions, with pimecrolimus being used as the control for twice a day over a 6-month treatment period. Responses to treatment were assessed based on the changes in VASI score for percentage reduction in body surface area and the PGA scores. RESULTS: According to our results, both drugs were discovered to be markedly effective on repigmentation. The VASI of lesion had diminished from 1.19 ± 0.42 to 0.63 ± 0.38, in the EGCG-treated lesions, while from 1.18 ± 0.43 to 0.61 ± 0.36 in the pimecrolimus-treated lesions, and there was no statistically significant difference in VASI score between the EGCG-treated lesions and pimecrolimus-treated lesions (P = 0.755). Meanwhile, the mean PGA score on the EGCG applied side was 4.39 ± 2.23, while that was 4.43 ± 2.02 on the pimecrolimus applied side (P = 0.886). Furthermore, difference in the improvement degree between pimecrolimus side and EGCG side was not statistically significant (P = 0.845). Notably, no serious side effects were observed throughout the study. CONCLUSION: Findings of the study indicate that topical EGCG can be effective on treating vitiligo.

Oxygen accelerated scalable synthesis of highly fluorescent sulfur quantum dots.

Here, we report a facile and efficient approach for the large-scale synthesis of highly fluorescent sulfur quantum dots (SQDs) from inexpensive elemental sulfur under a pure oxygen (O2) atmosphere. The important finding of this work is that the polysulfide (S x 2-) ions could be oxidized to zero-valent sulfur (S[0]) by O2, which is the accelerator of the reaction. The SQDs prepared by this method possess nearly monodisperse size (1.5-4 nm), high fluorescence quantum yield (21.5%), tunable emission, and stable fluorescence against pH change, ionic strength variation and long-term storage. Moreover, the reaction yield of SQDs reached as high as 5.08% based on the content of S element in SQDs, which is much higher than other reported approaches (generally <1%). The prepared SQDs could be easily processed for widespread applications thanks to their low toxicity and superior dispersibility both in water and common organic solvents. These high-quality SQDs may find applications similar to or beyond those of carbon QDs and silicon QDs.

Efficacy of the Topical Calcineurin Inhibitors Tacrolimus and Pimecrolimus in the Treatment of Vitiligo in Infants Under 2 Years of Age: A Randomized, Open-Label Pilot Study.

BACKGROUND: The efficacy of topical calcineurin inhibitors (TCIs) for the treatment of infants with vitiligo aged less than 2 years remains to be fully determined. OBJECTIVE: This aim of this pilot study was to assess the efficacy and tolerability of the TCIs tacrolimus and pimecrolimus in infants with vitiligo aged under 2 years. METHODS: Infants with vitiligo aged < 2 years were randomly assigned to receive either tacrolimus ointment 0.03% or pimecrolimus cream 1% for a period of 6 months. During this period, topical treatment was applied twice daily. The proportion of body surface area of the treated lesions, locations, and possible adverse effects were recorded. In addition, the overall satisfaction scores of the patients' parents was evaluated by virtue of the visual analog scale (VAS). RESULTS: Forty-six infants with vitiligo were enrolled in this study. The overall response rate (> 0% repigmentation) was 100%, while the effective rate (> 50% repigmentation) of the tacrolimus and pimecrolimus groups was 69.6% and 65.2%, respectively. Meanwhile, the effective rates for vitiligo located on the head and neck, trunk, and extremities were 70%, 64.3% and 50%, respectively, while the response rates for non-segmental and segmental vitiligo were 74.4% and 28.6%, respectively. Only a low incidence of local adverse reactions (including mild redness and skin picking) was reported during the treatment process. CONCLUSIONS: Topical tacrolimus ointment 0.03% or pimecrolimus cream 1% have efficacy for vitiligo in infants, which serves to achieve an appropriate level of safety and tolerability during the 6-month period of applications. Thus, TCIs proved to be a therapeutic option for vitiligo in infants under 2 years of age.

Role of chemokines and the corresponding receptors in vitiligo: A pilot study.

To determine the levels and sources of chemokines in the serum and epidermis of vitiligo patients, we examined 80 active patients, 80 stable patients and 40 healthy controls. First, the serum levels of candidate chemokines were measured by Luminex assay, and levels of CCR5, CXCR1 and CXCR3 were measured in peripheral mononuclear cells (PMBC) by flow cytometry. Then, the local epidermis levels of elevated chemokines in vitiligo were tested by Luminex. Finally, the mRNA and protein expression levels of elevated chemokines in HaCaT cells stimulated with interferon (IFN)-γ or tumor necrosis factor (TNF)-α were tested by quantitative real-time polymerase chain reaction and Luminex. The serum levels of CCL5, CXCL8 and CXCL10 in active vitiligo were significantly elevated compared with those in stable vitiligo patients. Furthermore, the levels of CCL3 and CCL4 had weak and positive correlations with the Vitiligo Area Scoring Index. In the peripheral blood of active vitiligo patients, the percentages of CD3+ CD8+ CCR5+ and CD3+ CD8+ CXCR3+ T cells were significantly increased compared with those in stable vitiligo and healthy controls. In the epidermis of lesions, the expression levels of CCL5 and CXCL10 in active vitiligo were significantly increased. In addition, the mRNA and protein levels of CCL5, CXCL8 and CXCL10 were significantly elevated in HaCaT cells after stimulation with TNF-α or IFN-γ. The CCR5/CCL5 and CXCR3/CXCL10 axes may play an important role in the progression and maintenance of vitiligo. Moreover, keratinocytes stimulated with TNF-α and IFN-γ may be a primary source of CCL5 and CXCL10.