Predicting neuropathy and reactions in leprosy at diagnosis and before incident events-results from the INFIR cohort study.

BACKGROUND: Leprosy is a disease of skin and peripheral nerves. The process of nerve injury occurs gradually through the course of the disease as well as acutely in association with reactions. The INFIR (ILEP Nerve Function Impairment and Reactions) Cohort was established to identify clinically relevant neurological and immunological predictors for nerve injury and reactions. METHODOLOGY/PRINCIPAL FINDINGS: The study, in two centres in India, recruited 188 new, previously untreated patients with multi-bacillary leprosy who had no recent nerve damage. These patients underwent a series of novel blood tests and nerve function testing including motor and sensory nerve conduction, warm and cold detection thresholds, vibrometry, dynamometry, monofilament sensory testing and voluntary muscle testing at diagnosis and at monthly follow up for the first year and every second month for the second year. During the 2 year follow up a total of 74 incident events were detected. Sub-clinical changes to nerve function at diagnosis and during follow-up predicted these new nerve events. Serological assays at baseline and immediately before an event were not predictive; however, change in TNF alpha before an event was a statistically significant predictor of that event. CONCLUSIONS/SIGNIFICANCE: These findings increase our understanding of the processes of nerve damage in leprosy showing that nerve function impairment is more widespread than previously appreciated. Any nerve involvement, including sub-clinical changes, is predictive of further nerve function impairment. These new factors could be used to identify patients at high risk of developing impairment and disability.

Evolution of vision reducing cataract in skin smear positive lepromatous patients: does it have an inflammatory basis?

AIM: To describe the incidence and risk factors of vision reducing cataract in skin smear positive lepromatous patients. METHODS: Prospective longitudinal cohort study: 212 newly diagnosed lepromatous patients were followed during the two years of treatment with multidrug therapy and for a further five years, with biannual ocular examinations. Incidence of vision reducing (< or =6/18) cataract was calculated as the number of patients with cataract per person year of cataract-free follow up among those who did not have cataract at baseline. RESULTS: Cataract was present in 27 (11%) of lepromatous patients at diagnosis. Forty nine patients (2.87%/person year (95% confidence interval (CI), 2.17% to 3.80%)) developed cataract during a total follow up period of 1704 person years; 45 of these were > or =41 years old and were followed for a total of 638 person years with an incident rate of 0.070 (95% CI, 0.0523 to 0.094). Stepwise multiple regression confirmed the association of age (per decade) (hazard ratio (HR) = 2.50 (95% CI, 1.82 to 2.78), p<0.001), clofazimine crystals on the cornea (HR = 49.92 (5.48 to 454.82), p = 0.001), grade 2 deformity in all limbs (HR = 3.17 (1.12 to 8.97), p = 0.029), and uveal inflammation (HR = 3.52 (1.42 to 8.67), p = 0.006). No significant association was found with oral steroids. CONCLUSIONS: Cataract develops at the rate of 7%/person year in lepromatous patients over 40 years of age. It is associated with increasing age, subclinical intraocular inflammation, and grade 2 deformity.

Iris atrophy in patients with newly diagnosed multibacillary leprosy: at diagnosis, during and after completion of multidrug treatment.

AIM: To describe the prevalence and incidence of iris atrophy in patients with multibacillary (MB) leprosy. METHODS AND PATIENTS: Prospective longitudinal cohort study. 301 newly diagnosed patients with MB leprosy were followed up during the 2 years of treatment with multidrug therapy (MDT) and for a further 5 years with biannual ocular examinations. Incidence of iris atrophy was calculated as the number of patients with iris atrophy per person-year (PY) of follow-up among those who did not have iris atrophy at baseline. Stepwise multiple regression confirmed the presence of specific associations of demographic and clinical characteristics (p<0.05) with iris atrophy, detected by univariate analysis. RESULTS: Iris atrophy was present in 6 (2%) patients at enrolment. During MDT, with 445 PYs of follow-up, 9 patients developed iris atrophy (IR 0.02, 95% CI 0.01 to 0.04) that was associated with cataract (HR 15.13, 95% CI 3.71 to 61.79, p<0.001) and corneal opacities (HR 6.83, 95% CI 1.62 to 28.8, p = 0.009). After MDT, with 2005 PYs of follow-up, 60 patients developed iris atrophy (IR 0.03, 95% CI 0.023 to 0.039) that was associated with age (per decade; HR 1.40, 95% CI 1.10 to 1.78, p = 0.006), skin smear positivity (HR 3.50, 95% CI 1.33 to 9.24, p = 0.011), cataract (HR 3.66, 95% CI 1.85 to 7.25, p<0.001), keratic precipitates (HR 2.76, 95% CI 1.02 to 7.47, p = 0.046) and corneal opacity (HR 3.95, 95% CI 1.86 to 8.38, p<0.001). CONCLUSIONS: Iris atrophy continues to develop in 3% of patients with MB leprosy every year after they complete a 2-year course of MDT, and is associated with age, increasing loads of mycobacteria, subclinical inflammation, cataract and corneal opacity.

Incidence of ocular morbidity among multibacillary leprosy patients during a 2 year course of multidrug therapy.

AIM: To evaluate the incidence of and risk factors for ocular complications in multibacillary (MB) leprosy patients during their 2 year, fixed duration, multidrug therapy (MDT). METHODS: Periodic eye examinations were conducted prospectively on a cohort of 301 consecutive newly diagnosed MB patients every 6 months during their 2 year course of MDT. Incidence of ocular pathology was calculated as the number of events per person year of event free follow up of patients who did not have the specific finding at baseline. RESULTS: 292 (97%) patients had one or more follow up visits. The incidence of lagophthalmos was 1.2%/patient year (95% CI 0.5% to 2.8%); corneal opacity was 7.4%/patient year (95% CI 5.1% to 10.6%); uveal involvement was 5.1%/patient year (95% CI 3.3% to 7.8%), and cataract that reduced vision to 6/18 or less was seen in 4.3%/patient year (95% CI 2.7% to 6.9%) of patients. Overall, 23 individuals (5.8%/patient year, 95% CI 3.9 to 8.8) developed leprosy related potentially blinding pathology during the 2 years of MDT. CONCLUSIONS: Approximately 20% of patients with MB leprosy can be expected to develop ocular complications of leprosy during a 2 year course of MDT, many (11%) of which are potentially vision threatening. Ophthalmological monitoring to detect and treat ocular complications at defined intervals during MDT is indicated.