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DOI: 10.1055/s-0039-1687884
Neurological Complications of Leprosy
Publikationsverlauf
Publikationsdatum:
18. September 2019 (online)
![](https://www.thieme-connect.de/media/sin/201904/lookinside/thumbnails/10-1055-s-0039-1687884_190013-1.jpg)
Abstract
Leprosy is a challenging international health concern. Despite tremendous efforts in reducing worldwide disease prevalence in the past decades, some countries remain endemic and are plagued by high levels of disability. The neurological complications of leprosy are varied and complex, with current research focused on evaluating tools for earlier diagnosis of neuropathy, especially in resource-limited countries. While treatment with multidrug therapy is highly effective, active research aims to simplify regimens to improve adherence, minimize adverse effects, and prevent antimicrobial resistance. Although promising progress has been made in the past decades, further efforts are needed to push the international community toward achieving worldwide elimination.
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References
- 1 Bhat RM, Prakash C. Leprosy: an overview of pathophysiology. Interdiscip Perspect Infect Dis 2012; 2012: 181089
- 2 Grzybowski A, Sak J, Pawlikowski J, Iwanowicz-Palus G. Gerhard Henrik Armauer Hansen (1841-1912)--the 100th anniversary of the death of the discoverer of Mycobacterium leprae. Clin Dermatol 2013; 31 (05) 653-655
- 3 Cassirer-Costa F, Medeiros NI, Chaves AT. , et al. Cytokines as biomarkers to monitoring the impact of multidrug therapy in immune response of leprosy patients. Cytokine 2017; 97: 42-48
- 4 Shibuya M, Bergheme G, Passos S. , et al. Evaluation of monocyte subsets and markers of activation in leprosy reactions. Microbes Infect 2018 ;S1286-4579(18)30165-5
- 5 WHO DoCoNTD. Global leprosy situation, 2010. Releve epidemiologique hebdomadaire 2010; 85 (35) 337-348
- 6 Smith CS, Aerts A, Kita E, Virmond M. Time to define leprosy elimination as zero leprosy transmission?. Lancet Infect Dis 2016; 16 (04) 398-399
- 7 Toh HS, Maharjan J, Thapa R. , et al. Diagnosis and impact of neuropathic pain in leprosy patients in Nepal after completion of multidrug therapy. PLoS Negl Trop Dis 2018; 12 (07) e0006610
- 8 Sarker UK, Uddin MJ, Chowdhury R, Roy N, Bhattacharjee M, Roy J. Clinical profile of peripheral neuropathy in leprosy. Mymensingh Med J 2015; 24 (04) 671-678
- 9 Ganesan DK, Muthunarayanan L. Is disability in leprosy still a burden? A cross-sectional study in a rural block in Tamil Nadu, India. Trans R Soc Trop Med Hyg 2018; 112 (01) 31-35
- 10 WHO. Global Leprosy Strategy 2016–2020; 2016
- 11 World Health Organization. WHO Expert Committee on Leprosy. World Health Organ Tech Rep Ser 2012; (968) 1-61 , 1, 61
- 12 Tabah EN, Nsagha DS, Bissek AZ. , et al. The burden of leprosy in Cameroon: fifteen years into the post-elimination era. PLoS Negl Trop Dis 2016; 10 (10) e0005012
- 13 Bernardes F, Paula NA, Leite MN. , et al. Evidence of hidden leprosy in a supposedly low endemic area of Brazil. Mem Inst Oswaldo Cruz 2017; 112 (12) 822-828
- 14 Al Awaidy ST. Progress towards a leprosy-free country: the experience of Oman. PLoS Negl Trop Dis 2017; 11 (11) e0006028
- 15 Lane JE, Walsh DS, Meyers WM, Klassen-Fischer MK, Kent DE, Cohen DJ. Borderline tuberculoid leprosy in a woman from the state of Georgia with armadillo exposure. J Am Acad Dermatol 2006; 55 (04) 714-716
- 16 Domozych R, Kim E, Hart S, Greenwald J. Increasing incidence of leprosy and transmission from armadillos in Central Florida: a case series. JAAD Case Rep 2016; 2 (03) 189-192
- 17 Marcos LA, Dobbs T, Walker S, Waller W, Stryjewska BM. Indigenous cases of leprosy (Hansen's disease) in Southern Mississippi. J Miss State Med Assoc 2015; 56 (07) 188-191
- 18 Rendini T, Levis W. Autochthonous leprosy without armadillo exposure, Eastern United States. Emerg Infect Dis 2017; 23 (11) 1928
- 19 Leon KE, Jacob JT, Franco-Paredes C, Kozarsky PE, Wu HM, Fairley JK. Delayed diagnosis, leprosy reactions, and nerve injury among individuals with Hansen's disease seen at a United States clinic. Open Forum Infect Dis 2016; 3 (02) ofw063
- 20 Tremblay F, Albert M. Arthritis, progressive maculopapular rash and severe peripheral neuropathy in a 60-year-old man. Diagnosis: leprosy. CMAJ 2014; 186 (03) 206-209
- 21 Maritati M, Contini C. A case of leprosy in Italy: a multifaceted disease which continues to challenge medical doctors. J Immigr Minor Health 2016; 18 (02) 490-493
- 22 Xavier MB, do Nascimento MGB, Batista KNM. , et al. Peripheral nerve abnormality in HIV leprosy patients. PLoS Negl Trop Dis 2018; 12 (07) e0006633
- 23 Truman RW, Ebenezer GJ, Pena MT. , et al. The armadillo as a model for peripheral neuropathy in leprosy. ILAR J 2014; 54 (03) 304-314
- 24 Sharma R, Lahiri R, Scollard DM. , et al. The armadillo: a model for the neuropathy of leprosy and potentially other neurodegenerative diseases. Dis Model Mech 2013; 6 (01) 19-24
- 25 Han XY, Seo YH, Sizer KC. , et al. A new Mycobacterium species causing diffuse lepromatous leprosy. Am J Clin Pathol 2008; 130 (06) 856-864
- 26 Pinheiro RO, de Souza Salles J, Sarno EN, Sampaio EP. Mycobacterium leprae-host-cell interactions and genetic determinants in leprosy: an overview. Future Microbiol 2011; 6 (02) 217-230
- 27 Britton WJ, Lockwood DN. Leprosy. Lancet 2004; 363 (9416): 1209-1219
- 28 Suzuki K, Udono T, Fujisawa M, Tanigawa K, Idani G, Ishii N. Infection during infancy and long incubation period of leprosy suggested in a case of a chimpanzee used for medical research. J Clin Microbiol 2010; 48 (09) 3432-3434
- 29 Ridley DS, Jopling WH. Classification of leprosy according to immunity. A five-group system. Int J Lepr Other Mycobact Dis 1966; 34 (03) 255-273
- 30 Gaschignard J, Grant AV, Thuc NV. , et al. Pauci- and multibacillary leprosy: two distinct, genetically neglected diseases. PLoS Negl Trop Dis 2016; 10 (05) e0004345
- 31 Salgado CG, Pinto P, Bouth RC. , et al. miRNome expression analysis reveals new players on leprosy immune physiopathology. Front Immunol 2018; 9: 463
- 32 Aarão TLS, de Sousa JR, Falcão ASC, Falcão LFM, Quaresma JAS. Nerve growth factor and pathogenesis of leprosy: review and update. Front Immunol 2018; 9: 939
- 33 Andrade PR, Jardim MR, da Silva AC. , et al. Inflammatory cytokines are involved in focal demyelination in leprosy neuritis. J Neuropathol Exp Neurol 2016; 75 (03) 272-283
- 34 Thapa M, Sendhil Kumaran M, Narang T, Saikia UN, Sawatkar GU, Dogra S. A prospective study to validate various clinical criteria used in classification of leprosy: a study from a tertiary care center in India. Int J Dermatol 2018; 57 (09) 1107-1113
- 35 Kulshreshtha D, Malhotra KP, Malhotra HS. , et al. Mandating nerve biopsy: a step towards personalizing therapy in pure neuritic leprosy. J Peripher Nerv Syst 2018; 23 (03) 190-196
- 36 Jardim MR, Antunes SL, Santos AR. , et al. Criteria for diagnosis of pure neural leprosy. J Neurol 2003; 250 (07) 806-809
- 37 Santos DFD, Mendonça MR, Antunes DE. , et al. Revisiting primary neural leprosy: clinical, serological, molecular, and neurophysiological aspects. PLoS Negl Trop Dis 2017; 11 (11) e0006086
- 38 Scollard DM. Infection with Mycobacterium lepromatosis. Am J Trop Med Hyg 2016; 95 (03) 500-501
- 39 Han XY, Sizer KC, Tan HH. Identification of the leprosy agent Mycobacterium lepromatosis in Singapore. J Drugs Dermatol 2012; 11 (02) 168-172
- 40 Jessamine PG, Desjardins M, Gillis T. , et al. Leprosy-like illness in a patient with Mycobacterium lepromatosis from Ontario, Canada. J Drugs Dermatol 2012; 11 (02) 229-233
- 41 Virk A, Pritt B, Patel R. , et al. Mycobacterium lepromatosis lepromatous leprosy in US citizen who traveled to disease-endemic areas. Emerg Infect Dis 2017; 23 (11) 1864-1866
- 42 Ahuja M, Lavania M, Singh I. , et al. Detection of Mycobacterium lepromatosis in patients with leprosy in India. Infect Drug Resist 2018; 11: 1677-1683
- 43 Lima PO, Cunha FM, Gonçalves HS, Aires MA, De Almeida RL, Kerr LR. Correlation between clinical tests and electroneuromyography for the diagnosis of leprosy neuropathy. Lepr Rev 2016; 87 (01) 60-70
- 44 Jardim MR, Chimelli L, Faria SC. , et al. Clinical, electroneuromyographic and morphological studies of pure neural leprosy in a Brazilian referral centre. Lepr Rev 2004; 75 (03) 242-253
- 45 Jaiswal N, Chakraborti S, Nayak K. , et al. Hansen's neuritis revisited - a clinicopathological study. J Neurosci Rural Pract 2018; 9 (01) 42-55
- 46 van Brakel WH, Nicholls PG, Das L. , et al. The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in North India. Lepr Rev 2005; 76 (01) 14-34
- 47 Nascimento OJ. Leprosy neuropathy: clinical presentations. Arq Neuropsiquiatr 2013; 71 (9B, 9b): 661-666
- 48 Subbarao NT, Jaiswal AK. A case of leprosy with multiple cranial neuropathy mimicking Melkerson Rosenthal syndrome. Indian J Lepr 2011; 83 (02) 101-102
- 49 Lalla R, Mulherkar RV, Misar PV. Incomplete peripheral facial nerve palsy and ulnar neuropathy due to leprosy mistaken as faciobrachial stroke. BMJ Case Rep 2015; 2015: 201
- 50 Lockwood DN, Saunderson PR. Nerve damage in leprosy: a continuing challenge to scientists, clinicians and service providers. Int Health 2012; 4 (02) 77-85
- 51 Naafs B, van Hees CL. Leprosy type 1 reaction (formerly reversal reaction). Clin Dermatol 2016; 34 (01) 37-50
- 52 Chiaratti FC, Daxbacher EL, Neumann AB, Jeunon T. Type 2 leprosy reaction with Sweet's syndrome-like presentation. An Bras Dermatol 2016; 91 (03) 345-349
- 53 Garbino JA, Heise CO, Marques Jr W. Assessing nerves in leprosy. Clin Dermatol 2016; 34 (01) 51-58
- 54 Raposo MT, Reis MC, Caminha AVQ. , et al. Grade 2 disabilities in leprosy patients from Brazil: need for follow-up after completion of multidrug therapy. PLoS Negl Trop Dis 2018; 12 (07) e0006645
- 55 Nascimento OJ, Freitas MR, Escada T. , et al. Leprosy late-onset neuropathy: an uncommon presentation of leprosy. Arq Neuropsiquiatr 2012; 70 (06) 404-406
- 56 Carod-Artal FJ. Infectious diseases causing autonomic dysfunction. Clin Auton Res 2018; 28 (01) 67-81
- 57 Anand V, Pradhan S, Kumar P. Autonomic neuropathy impairing quality of life after completion of MDT: are we managing enough?. Lepr Rev 2016; 87 (02) 239-242
- 58 Vital RT, Illarramendi X, Nascimento O, Hacker MA, Sarno EN, Jardim MR. Progression of leprosy neuropathy: a case series study. Brain Behav 2012; 2 (03) 249-255
- 59 de Freitas MR, Nascimento OJ, Quaglino EA, Oliveira A, Hahn MD. Small-fiber polyneuropathy in leprosy without skin changes: study of 17 cases. Arq Neuropsiquiatr 2003; 61 (3A, 3a): 542-546
- 60 Dash D, Saluja A, Singh RK, Bhatia R, Tripathi M. Guillain-Barre syndrome: a rare presentation of borderline tuberculoid leprosy with type 1 lepra reaction. J Neurosci Rural Pract 2018; 9 (03) 423-425
- 61 Raicher I, Stump PRNAG, Harnik SB. , et al. Neuropathic pain in leprosy: symptom profile characterization and comparison with neuropathic pain of other etiologies. Pain Rep 2018; 3 (02) e638
- 62 Ghia D, Gadkari R, Nayak C. Complex regional pain syndrome secondary to leprosy. Pain Med 2012; 13 (08) 1067-1071
- 63 Santana EMF, Brito KKG, Antas EMV. , et al. Factors associated with the development of physical disabilities in Hansen's disease. Rev Inst Med Trop São Paulo 2018; 60: e27
- 64 Aben-Athar CYUP, Lima SS, Ishak R, Vallinoto ACR. Assessment of the sensory and physical limitations imposed by leprosy in a Brazilian Amazon population. Rev Soc Bras Med Trop 2017; 50 (02) 223-228
- 65 Van Brakel WH, Nicholls PG, Das L. , et al. The INFIR Cohort Study: assessment of sensory and motor neuropathy in leprosy at baseline. Lepr Rev 2005; 76 (04) 277-295
- 66 Wagenaar I, Post E, Brandsma W. , et al. Early detection of neuropathy in leprosy: a comparison of five tests for field settings. Infect Dis Poverty 2017; 6 (01) 115
- 67 Garbino JA, Naafs B, Ura S, Salgado MH, Virmond M. Neurophysiological patterns of ulnar nerve neuropathy in leprosy reactions. Lepr Rev 2010; 81 (03) 206-215
- 68 Chen X, Zhang L, Huang M, Zhai X, Wen Y, Pan C. Coexistence of nerve enlargement and neuratrophy detected by ultrasonography in leprosy patients. Sci Rep 2018; 8 (01) 7812
- 69 Lugão HB, Nogueira-Barbosa MH, Marques Jr W, Foss NT, Frade MA. Asymmetric nerve enlargement: a characteristic of leprosy neuropathy demonstrated by ultrasonography. PLoS Negl Trop Dis 2015; 9 (12) e0004276
- 70 Gupta S, Bhatt S, Bhargava SK, Singal A, Bhargava S. High resolution sonographic examination: a newer technique to study ulnar nerve neuropathy in leprosy. Lepr Rev 2016; 87 (04) 464-475
- 71 Bathala L. , N Krishnam V, Kumar HK. , et al. Extensive sonographic ulnar nerve enlargement above the medial epicondyle is a characteristic sign in Hansen's neuropathy. PLoS Negl Trop Dis 2017; 11 (07) e0005766
- 72 Jain S, Visser LH, Suneetha S. Imaging techniques in leprosy clinics. Clin Dermatol 2016; 34 (01) 70-78
- 73 Pottecher P, Flageul B, Sibileau E, Laredo JD, Bousson V. Peripheral hypertrophic neuropathy due to leprosy: ultrasound and MR imaging findings. Diagn Interv Imaging 2016; 97 (04) 471-473
- 74 Lugão HB, Frade MA, Mazzer N, Foss NT, Nogueira-Barbosa MH. Leprosy with ulnar nerve abscess: ultrasound findings in a child. Skeletal Radiol 2017; 46 (01) 137-140
- 75 Tiwari V, Malhotra K, Khan K. , et al. Evaluation of polymerase chain reaction in nerve biopsy specimens of patients with Hansen's disease. J Neurol Sci 2017; 380: 187-190
- 76 Patnaik N, Agarwal S, Sharma S, Sharma S, Pandhi D. Evaluation of key histologic variables in skin biopsies of patients of borderline leprosy with type 1 lepra reaction. Indian J Dermatol Venereol Leprol 2014; 80 (05) 402-408
- 77 Cabalar M, Yayla V, Ulutas S, Senadim S, Oktar AC. The clinical & neurophysiological study of leprosy. Pak J Med Sci 2014; 30 (03) 501-506
- 78 Cavalheiro AL, Costa DT, Menezes AL, Pereira JM, Carvalho EM. Thermographic analysis and autonomic response in the hands of patients with leprosy. An Bras Dermatol 2016; 91 (03) 274-283
- 79 Opinion PoL. Memorandum on Leprosy 2012. Public Health Eng; 2013
- 80 Liu J, Wen Y, Xing Y, Wang S. Borderline tuberculoid leprosy mimicking sarcoidosis: a case report. Medicine (Baltimore) 2018; 97 (32) e11616
- 81 Smith CS, Aerts A, Saunderson P, Kawuma J, Kita E, Virmond M. Multidrug therapy for leprosy: a game changer on the path to elimination. Lancet Infect Dis 2017; 17 (09) e293-e297
- 82 Rao PN, Dogra S, Suneetha S. Global leprosy program: does it need uniform-multi-drug therapy now?. Indian Dermatol Online J 2015; 6 (06) 425-427
- 83 Manickam P, Mehendale SM, Nagaraju B. , et al. International open trial of uniform multidrug therapy regimen for leprosy patients: findings & implications for national leprosy programmes. Indian J Med Res 2016; 144 (04) 525-535
- 84 Cruz RCDS, Bührer-Sékula S, Penna GO. , et al. Clinical trial for uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): adverse effects approach. An Bras Dermatol 2018; 93 (03) 377-384
- 85 Cambau E, Saunderson P, Matsuoka M. , et al; WHO Surveillance Network of Antimicrobial Resistance in Leprosy. Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009-15. Clin Microbiol Infect 2018; 24 (12) 1305-1310
- 86 Dacso MM, Jacobson RR, Scollard DM, Stryjewska BM, Prestigiacomo JF. Evaluation of multi-drug therapy for leprosy in the United States using daily rifampin. South Med J 2011; 104 (10) 689-694
- 87 Williams DL, Lewis C, Sandoval FG. , et al. Drug resistance in patients with leprosy in the United States. Clin Infect Dis 2014; 58 (01) 72-73
- 88 Lugão HB, Frade MA, Marques Jr W, Foss NT, Nogueira-Barbosa MH. Ultrasonography of leprosy neuropathy: a longitudinal prospective study. PLoS Negl Trop Dis 2016; 10 (11) e0005111
- 89 Van Veen NH, Nicholls PG, Smith WC, Richardus JH. Corticosteroids for treating nerve damage in leprosy. Cochrane Database Syst Rev 2016; (05) CD005491
- 90 Wagenaar I, Post E, Brandsma W. , et al; TENLEP study group. Effectiveness of 32 versus 20 weeks of prednisolone in leprosy patients with recent nerve function impairment: a randomized controlled trial. PLoS Negl Trop Dis 2017; 11 (10) e0005952
- 91 Capadia GD, Shetty VP, Khambati FA, Ghate SD. Effect of corticosteroid usage combined with multidrug therapy on nerve damage assessed using nerve conduction studies: a prospective cohort study of 365 untreated multibacillary leprosy patients. J Clin Neurophysiol 2010; 27 (01) 38-47
- 92 Walker SL, Waters MF, Lockwood DN. The role of thalidomide in the management of erythema nodosum leprosum. Lepr Rev 2007; 78 (03) 197-215
- 93 Nashed SG, Rageh TA, Attallah-Wasif ES, Abd-Elsayed AA. Intraneural injection of corticosteroids to treat nerve damage in leprosy: a case report and review of literature. J Med Case Reports 2008; 2: 381
- 94 Dellon AL. Multiple crush concept applied to multiple nerves in leprous neuropathy. Clin Podiatr Med Surg 2016; 33 (02) 203-217
- 95 Wan EL, Rivadeneira AF, Jouvin RM, Dellon AL. Treatment of peripheral neuropathy in leprosy: the case for nerve decompression. Plast Reconstr Surg Glob Open 2016; 4 (03) e637
- 96 Duthie MS, Balagon MF. Combination chemoprophylaxis and immunoprophylaxis in reducing the incidence of leprosy. Risk Manag Healthc Policy 2016; 9: 43-53
- 97 Moet FJ, Pahan D, Oskam L, Richardus JH. ; COLEP Study Group. Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial. BMJ 2008; 336 (7647): 761-764
- 98 Costa JEF, Morais VMS, Gonçales JP, Silva DM, Coêlho MRCD. Prevalence and risk factors for hepatitis B and C viruses in patients with leprosy. Acta Trop 2017; 172: 160-163
- 99 Machado PR, Machado LM, Shibuya M, Rego J, Johnson WD, Glesby MJ. Viral co-infection and leprosy outcomes: a cohort study. PLoS Negl Trop Dis 2015; 9 (08) e0003865
- 100 Pires CA, Jucá Neto FO, de Albuquerque NC, Macedo GM, Batista KN, Xavier MB. Leprosy reactions in patients coinfected with HIV: clinical aspects and outcomes in two comparative cohorts in the Amazon Region, Brazil. PLoS Negl Trop Dis 2015; 9 (06) e0003818
- 101 Galtrey CM, Modarres H, Jaunmuktane Z. , et al. Leprosy in a patient infected with HIV. Pract Neurol 2017; 17 (02) 135-139
- 102 Pavie J, De Castro N, Molina JM, Flageul B. Severe peripheral neuropathy following HAART initiation in an HIV-infected patient with leprosy. J Int Assoc Physicians AIDS Care (Chic) 2010; 9 (04) 232-235