Revisiting primary neural leprosy: Clinical, serological, molecular, and neurophysiological aspects

PLoS Negl Trop Dis. 2017 Nov 27;11(11):e0006086. doi: 10.1371/journal.pntd.0006086. eCollection 2017 Nov.

Abstract

Background: Leprosy neuropathy is considered the most common peripheral neuropathy of infectious etiology worldwide, representing a public health problem. Clinical diagnosis of primary neural leprosy (PNL) is challenging, since no skin lesions are found and the slit skin smear bacilloscopy is negative. However, there are still controversial concepts regarding the primary-neural versus pure-neural leprosy definition, which will be explored by using multiple clinical-laboratory analyses in this study.

Methodology/principal findings: Seventy patients diagnosed with primary neural leprosy from 2014 to 2016 underwent clinical, laboratorial and neurophysiological evaluation. All patients presented an asymmetric neural impairment, with nerve thickening in 58.6%. Electroneuromyography showed a pattern of mononeuropathy in 51.4%. Positivity for ELISA anti-PGL1 was 52.9%, while the qPCR of slit skin smear was 78.6%. The qPCR of nerve biopsies was positive in 60.8%. Patients with multiple mononeuropathy patterns showed lower levels of anti-PGL-1 (p = 0.0006), and higher frequency of neural thickening (p = 0.0008) and sensory symptoms (p = 0.01) than those with mononeuropathy.

Conclusions/significance: PNL is not a synonym of pure neural leprosy, as this condition may include a generalized immune response and also a skin involvement, documented by molecular findings. Immunological, molecular, and neurophysiological tools must be implemented for diagnosing primary neural leprosy to achieve effective treatment and reduction of its resultant disabilities that still represent a public health problem in several developing nations. Finally, we propose a algorithm and recommendations for the diagnosis of primary neural leprosy based on the combination of the three clinical-laboratorial tools.

MeSH terms

  • Adult
  • Algorithms
  • Brazil
  • Female
  • Humans
  • Leprosy, Tuberculoid / complications
  • Leprosy, Tuberculoid / diagnosis
  • Leprosy, Tuberculoid / pathology*
  • Male
  • Middle Aged
  • Mycobacterium leprae
  • Peripheral Nerves / pathology
  • Peripheral Nervous System Diseases / diagnosis
  • Peripheral Nervous System Diseases / etiology
  • Peripheral Nervous System Diseases / pathology*
  • Real-Time Polymerase Chain Reaction
  • Skin / pathology

Grants and funding

The authors thank the Brazilian funding agencies, Brazilian National Council for Scientific and Technological Development (CNPq) and Foundation for Research Support of the State of Minas Gerais (FAPEMIG), for providing financial support to the National Institute of Science and Technology in Theranostics and Nanobiotechnology – INCT-TeraNano – PhD to LRG (Grant numbers: CNPq-465669/2014-0 and FAPEMIG-CBB-APQ-03613-17). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.