Age is an important risk factor for onset and sequelae of reversal reactions in Vietnamese patients with leprosy.

BACKGROUND: Reversal, or type 1, leprosy reactions (T1Rs) are acute immune episodes that occur in skin and/or nerves and are the leading cause of neurological impairment in patients with leprosy. T1Rs occur mainly in patients with borderline or multibacillary leprosy, but little is known about additional risk factors. METHODS: We enrolled 337 Vietnamese patients with leprosy in our study, including 169 subjects who presented with T1Rs and 168 subjects with no history of T1Rs. A multivariate analysis was used to determine risk factors for T1R occurrence, time to T1R onset after leprosy diagnosis, and T1R sequelae after treatment. RESULTS: Prevalence of T1Rs was estimated to be 29.1%. Multivariate analysis identified 3 clinical features of leprosy associated with T1R occurrence. Borderline leprosy subtype (odds ratio, 6.3 [95% confidence interval, 2.9-13.7] vs. polar subtypes) was the major risk factor; 2 other risk factors were positive bacillary index and presence of > 5 skin lesions. In addition, age at leprosy diagnosis was a strong independent risk factor for T1Rs (odds ratio, 2.4 [95% confidence interval, 1.3-4.4] for patients aged > or = 15 years old vs. < 15 years old). We observed that T1Rs with neuritis occurred significantly earlier than pure skin-related T1Rs. Sequelae were present in 45.1% of patients who experienced T1Rs after treatment. The presence of a motor or sensory deficit at T1R onset was an independent risk factor for sequelae, as was the age at diagnosis of leprosy (odds ratio, 4.4 [95% confidence interval, 1.7-11.6] for patients > or = 20 years old vs. < 20 years old). CONCLUSION: In addition to specific clinical features of leprosy, age is an important risk factor for both T1R occurrence and sequelae after treatment for T1Rs.

Susceptibility to leprosy is associated with PARK2 and PACRG.

Leprosy is caused by Mycobacterium leprae and affects about 700,000 individuals each year. It has long been thought that leprosy has a strong genetic component, and recently we mapped a leprosy susceptibility locus to chromosome 6 region q25-q26 (ref. 3). Here we investigate this region further by using a systematic association scan of the chromosomal interval most likely to harbour this leprosy susceptibility locus. In 197 Vietnamese families we found a significant association between leprosy and 17 markers located in a block of approx. 80 kilobases overlapping the 5' regulatory region shared by the Parkinson's disease gene PARK2 and the co-regulated gene PACRG. Possession of as few as two of the 17 risk alleles was highly predictive of leprosy. This was confirmed in a sample of 975 unrelated leprosy cases and controls from Brazil in whom the same alleles were strongly associated with leprosy. Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy.