Predicting Neuropathy and Reactions in Leprosy at Diagnosis and Before Incident Events—Results from the INFIR Cohort Study

Abstract

BackgroundLeprosy 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 FindingsThe 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/SignificanceThese 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.

Clinical variables associated with leprosy reactions and persistence of physical impairment

“…The number of thickened nerves is signifi cantly associated with increased risk for physical impairments 2,18 . Furthermore, physical impairment at diagnosis has been associated with a worse prognosis for deformities 19,20 .…”

“…The proportion of patients evaluated using a neurological examination and diagnosed with physical impairment facilitates an indirect assessment of the effectiveness of programs to prevent impairment 18 .The Brazilian Ministry of Health has established that the physical impairment evaluation should be performed in at least 90% of the leprosy patients at diagnosis and 75% after treatment. In the present study, we demonstrate that leprosy reactions and physical impairment are frequent in this population.…”

“…Early identifi cation combined with the proper treatment of leprosy reactions can be an effective strategy to prevent physical impairment in leprosy 13,14 . Prednisone is the drug of choice not only for the treatment of leprosy reactions and silent neuritis events 21 but also to reduce swelling and prevent further physical impairment 18 .…”

Leprosy reactions after release from multidrug therapy in an endemic cluster in Brazil: patient awareness of symptoms and self-perceived changes in life

“…Neurological signs and symptoms are common in patients, but little known or ignored by health workers. A major international study in Indian emphasized the need for early recognition of neurological complications 23 . National leprosy control programmes should include this aspect of the symptomatology of leprosy and leprosy reactions in its training programme and IEC material.…”

Caracterização da dor, da sensibilidade discriminativa e dos achados neuropatológicos na biópsia cutânea em hanseníase em doentes após término do tratamento poliquimioterápico

“…Estudos prévios demonstraram a sua produção na pele e no nervo durante as reações hansênicas 139 . Também foi mensurada no sangue e estudos demonstraram a sua compartimentalização, ou seja, fica restrita à pele, ao nervo e nem sempre a mensuração sérica reflete sua real quantificação 140 . Além disso, o TNF-alfa pode causar desmielinização e morte de oligodendrócitos dose-dependente em estudos in vivo 141 .…”