Treatment of generalized vitiligo with anti-TNF-α Agents.
ABSTRACT Although the exact pathogenesis of vitiligo is not fully understood, it appears to be an autoimmune disease. It is hypothesized that tumor necrosis factor alpha (TNF-?) plays an important role in vitiligo. TNF-? can destroy melanocytes through the induction of various apoptotic pathways. In addition, TNF-? can inhibit melanocyte stem cell differentiation.
To evaluate the efficacy and safety of treating vitiligo patients with anti-TNF-? agents.
A total of 6 patients were recruited. All patients had widespread non-segmental vitiligo. Biologics, including infliximab, etanercept, and adalimumab, were given according to treatment regimens used for psoriasis. Photographs were taken at the initial visit, every two months during the therapy and then six months after therapy completion.
All patients completed the treatment; two patients were treated with infliximab, two with etanercept, and two with adalimumab. All of the biologics were well tolerated throughout the treatment period, and none of the patients reported any significant adverse events. Digital images were compared before, during and after treatment. Repigmentation of the vitiliginous areas was not observed in any of the patients. Vitiligo worsened in one patient who was treated with infliximab and developed a psoriasiform rash. However, the remaining patients did not develop any new depigmented patches during treatment or at the six-month follow-up; vitiligo was considered stable in these five patients.
Although the anti-TNF-? agents were well tolerated in all six vitiligo patients, efficacy was not observed. Further evaluation with larger studies may be required.
Article: Increased Tumor Necrosis Factor (TNF)-a and Its Promoter Polymorphisms Correlate with Disease Progression and Higher Susceptibility towards Vitiligo[show abstract] [hide abstract]
ABSTRACT: Abstract Tumor Necrosis Factor (TNF)-a, is a paracrine inhibitor of melanocytes, which plays a critical role in the pathogenesis of several autoimmune diseases including vitiligo, as abnormal immune responses have frequently been observed in vitiligo patients. Moreover, vitiligo patients show higher lesion levels of TNF-a. Genetic polymorphisms in the promoter region of TNF-a are involved in the regulation of its expression. The present study explores TNF-a promoter polymorphisms and correlates them with TNF-a transcript and protein levels in vitiligo patients and controls of Gujarat along with its effect on disease onset and progression. PCR-RFLP technique was used for genotyping of these polymorphisms in 977 vitiligo patients and 990 controls. TNF-a transcript and protein levels were measured by Real time PCR and ELISA respectively. The genotype and allele frequencies for the investigated polymorphisms were significantly associated with vitiligo patients. The study revealed significant increase in TNF-a transcript and protein levels in vitiligo patients compared to controls. In particular, haplotypes: AATCC, AACCT, AGTCT, GATCT, GATCC and AGCCT were found to increase the TNF-a levels in vitiligo patients. Analysis of TNF-a levels based on the gender and disease progression suggests that female patients and patients with active vitiligo had higher levels of TNF-a. Also, the TNF-a levels were high in patients with generalized vitiligo as compared to localized vitiligo. Age of onset analysis of the disease suggests that the haplotypes: AACAT, AACCT, AATCC and AATCT had a profound effect in the early onset of the disease. Moreover, the analysis suggests that female patients had an early onset of vitiligo. Overall, our results suggest that TNF-a promoter polymorphisms may be genetic risk factors for susceptibility and progression of the disease. The up-regulation of TNF-a transcript and protein levels in individuals with susceptible haplotypes advocates the crucial role of TNF-a in autoimmune pathogenesis of vitiligo.PLoS ONE 12/2012; 7(12):e52298. · 4.09 Impact Factor