Vitiligo Skin Biomarkers Associated With Favorable Therapeutic Response.

Vitiligo is an acquired depigmentation skin disease caused by immune-mediated death of melanocytes. The most common treatment for vitiligo is narrow band ultraviolet B phototherapy, which often is combined with topical therapies such as tacrolimus. However, patients' responses to these treatments show large variations. To date, the mechanism for this heterogeneity is unknown, and there are no molecular indicators that can predict an individual patient's response to therapy. The goal of this study is to identify clinical parameters and gene expression biomarkers associated with vitiligo response to therapy. Six patients with segmental vitiligo and 30 patients with non-segmental vitiligo underwent transcriptome sequencing of lesional and nonlesional skin at baseline before receiving combined UBUVB and tacrolimus therapy for 6 month, and were separated into good response and bad response groups based on target lesion achieving > 10% repigmentation or not. Our study revealed that treatment-responsive vitiligo lesions had significantly shorter disease duration compared with non-responsive vitiligo lesions (2.5 years vs 11.5 years, p=0.046, t-Test), while showing no significant differences in the age, gender, ethnicity, vitiligo subtype, or disease severity. Transcriptomic analyses identified a panel of 68 genes separating the good response from bad response lesions including upregulation of immune active genes, such as CXCL10, FCRL3, and TCR, Further, compared with vitiligo lesions with long disease duration, the lesions with short duration also have much higher level of expression of immune-active genes, including some (such as FCRL3 and TCR genes) that are associated with favorable therapeutic response. In conclusion, our study has identified clinical parameters such as short disease duration and a panel of immune active and other gene expression biomarkers that are associated with favorable response to immune suppressive NBUVB + tacrolimus therapy. These markers may be useful clinically for individualized therapeutic management of vitiligo patients in the future.

Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

BACKGROUND: Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai. METHODOLOGY/PRINCIPAL FINDINGS: Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13%) and 0.35% (95% CI: 0.06-1.39%), respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients), fatigue (2 patients), cough (1 patient), sore throat (1 patient), diarrhea (1 patient) and erythematous rash (1 patient). The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05). Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia. CONCLUSIONS/SIGNIFICANCE: Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for patients in good physical condition after withdrawing anti-neurosyphilis regimen. We did not see an exacerbation of neutropenia in patients with the readministration of benzylpenicillin.