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Infectious Disorders - Drug Targets

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ISSN (Print): 1871-5265
ISSN (Online): 2212-3989

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Leprosy Reactions: Clinical Pharmacologist Perspective with Repurposed Medications

Author(s): Pugazhenthan Thangaraju*, Aravind Kumar Balan, Hemasri Velmurugan, Sajitha Venkatesan and Sree Sudha Tanguturi Yella

Volume 23, Issue 2, 2023

Published on: 03 October, 2022

Article ID: e070922208607 Pages: 7

DOI: 10.2174/1871526522666220907125114

Price: $65

Abstract

The elimination of leprosy has been possible with the available anti-leprotic drugs. However, the lepra reactions usually occur months or years after multi-drug therapy completion, and continue to be a formidable challenge mainly owing to its role in causing nerve damage and disability. Corticosteroids are commonly used but they lead to systemic complications, and hence require dose reduction and adjunct therapy with a different target. Various drugs with different targets have been identified and are in practice to treat lepra reactions. The newer targets can include genetic and tissue targets in the skin and nerve. Thalidomide treatment reducing pentraxin-3, toll-like receptor antagonists, minocycline, apremilast, immunomodulators, and tenidap can be helpful in lepra reaction. Other modalities to manage lepra reactions include plasma exchange, intravenous immunoglobulins, and immunotherapy. Most of these treatments are based only on the pathological process of the reaction and tend to be incomplete leading to recurrence. Newer multimodal approaches are required based on various biomarkers (genetic, tissue, serological), which can be monitored to prevent the recurrence of reactions. Hence, there is a need for newer targets and drugs to be identified for the management of lepra reactions.

Keywords: Hypersensitivity reaction, leprosy neuritis, anti-leprosy drugs, newer drugs, biomarkers, plasma exchange.

Graphical Abstract

[1]
Lastória JC, Abreu MAMM. Leprosy: Review of the epidemiological, clinical, and etiopathogenic aspects - Part 1. An Bras Dermatol 2014; 89(2): 205-18.
[http://dx.doi.org/10.1590/abd1806-4841.20142450] [PMID: 24770495]
[2]
Mendum TA, Schuenemann VJ, Roffey S, et al. Mycobacterium leprae genomes from a British medieval leprosy hospital: Towards understanding an ancient epidemic. BMC Genomics 2014; 15(1): 270.
[http://dx.doi.org/10.1186/1471-2164-15-270] [PMID: 24708363]
[3]
Walker SL, Lockwood DNJ. Leprosy Type 1 (reversal) reactions and their management. Lepr Rev 2008; 79(4): 372-86.
[http://dx.doi.org/10.47276/lr.79.4.372] [PMID: 19274984]
[4]
Rao PSSS, Sugamaran DST, Richard J, Smith WCS. Multi-centre, double blind, randomized trial of three steroid regimens in the treatment of type-1 reactions in leprosy. Lepr Rev 2006; 77(1): 25-33.
[http://dx.doi.org/10.47276/lr.77.1.25] [PMID: 16715687]
[5]
Van Veen NHJ, Nicholls PG, Smith WCS, Richardus JH. Corticosteroids for treating nerve damage in leprosy. A Cochrane review. Lepr Rev 2008; 79(4): 361-71.
[http://dx.doi.org/10.47276/lr.79.4.361] [PMID: 19274983]
[6]
De Sena CBC, Salgado CG, Tavares CMP, Da Cruz CAV, Xavier MB, Do Nascimento JLM. Cyclosporine A treatment of leprosy patients with chronic neuritis is associated with pain control and reduction in antibodies against nerve growth factor. Lepr Rev 2006; 77(2): 121-9.
[http://dx.doi.org/10.47276/lr.77.2.121] [PMID: 16895068]
[7]
Marlowe SNS, Leekassa R, Bizuneh E, et al. Response to ciclosporin treatment in Ethiopian and Nepali patients with severe leprosy type 1 reactions. Trans R Soc Trop Med Hyg 2007; 101(10): 1004-12.
[http://dx.doi.org/10.1016/j.trstmh.2006.11.010] [PMID: 17669450]
[8]
Scollard DM, Adams LB, Gillis TP, Krahenbuhl JL, Truman RW, Williams DL. The continuing challenges of leprosy. Clin Microbiol Rev 2006; 19(2): 338-81.
[http://dx.doi.org/10.1128/CMR.19.2.338-381.2006] [PMID: 16614253]
[9]
Polycarpou A, Walker SL, Lockwood DNJ. A systematic review of immunological studies of erythema nodosum leprosum. Front Immunol 2017; 8: 233.
[http://dx.doi.org/10.3389/fimmu.2017.00233] [PMID: 28348555]
[10]
Sahu S, Sharma K, Sharma M, et al. Neutrophil networking in ENL: Potential as a putative biomarker: Future insights. Front Med (Lausanne) 2021; 8: 697804.
[http://dx.doi.org/10.3389/fmed.2021.697804] [PMID: 34336901]
[11]
Prasad PV, Kaviarasan PK. Leprosy therapy, past and present: Can we hope to eliminate it? Indian J Dermatol 2010; 55(4): 316-24.
[http://dx.doi.org/10.4103/0019-5154.74528] [PMID: 21430881]
[12]
Thangaraju P, Varthya S, Venkatesan S. Target/therapies for chronic recurrent erythema nodosum leprosum. Indian J Pharmacol 2020; 52(3): 222-6.
[http://dx.doi.org/10.4103/ijp.IJP_788_19] [PMID: 32874007]
[13]
Thangaraju P, Venkatesan S, Showkath Ali MK. Leprosy case detection campaign (LCDC) for active surveillance. Trop Doct 2018; 48(1): 72-3.
[http://dx.doi.org/10.1177/0049475517702059] [PMID: 28403695]
[14]
Latheef AEN, Riyaz N. Hypnotherapy: A useful adjunctive therapeutic modality in hansen′s disease. Indian J Dermatol 2014; 59(2): 166-8.
[http://dx.doi.org/10.4103/0019-5154.127678] [PMID: 24700936]
[15]
Walker FR. A critical review of the mechanism of action for the selective serotonin reuptake inhibitors: Do these drugs possess anti-inflammatory properties and how relevant is this in the treatment of depression? Neuropharmacology 2013; 67: 304-17.
[http://dx.doi.org/10.1016/j.neuropharm.2012.10.002] [PMID: 23085335]
[16]
Narang T, Kaushik A, Dogra S. Apremilast in chronic recalcitrant erythema nodosum leprosum: A report of two cases. Br J Dermatol 2020; 182(4): 1034-7.
[http://dx.doi.org/10.1111/bjd.18233] [PMID: 31218666]
[17]
Marlowe SNS, Hawksworth RA, Butlin CR, Nicholls PG, Lockwood DNJ. Clinical outcomes in a randomized controlled study comparing azathioprine and prednisolone versus prednisolone alone in the treatment of severe leprosy type 1 reactions in Nepal. Trans R Soc Trop Med Hyg 2004; 98(10): 602-9.
[http://dx.doi.org/10.1016/j.trstmh.2003.12.013] [PMID: 15289097]
[18]
Durães MBS, de Abreu Neves Salles S, Leite RBV, Gazzeta OM. Azathioprine as a steroid sparing agent in leprosy Type 2 reactions: Report of nine cases. Lepr Rev 2011; 82(3): 304-9.
[http://dx.doi.org/10.47276/lr.82.3.304] [PMID: 22125939]
[19]
Breedveld F. Tenidap: A novel cytokine-modulating antirheumatic drug for the treatment of rheumatoid arthritis. Scand J Rheumatol 1994; 23: 31-44.
[http://dx.doi.org/10.3109/03009749409095199] [PMID: 7532319]
[20]
Hwang SH, Wecksler AT, Wagner K, Hammock BD. Rationally designed multitarget agents against inflammation and pain. Curr Med Chem 2013; 20(13): 1783-99.
[http://dx.doi.org/10.2174/0929867311320130013] [PMID: 23410172]
[21]
Texereau J, Chiche JD, Taylor W, Choukroun G, Comba B, Mira JP. The importance of Toll-like receptor 2 polymorphisms in severe infections. Clin Infect Dis 2005; 41 (Suppl. 7): S408-15.
[http://dx.doi.org/10.1086/431990] [PMID: 16237639]
[22]
Gupta SK, Kumari S. Chronic recalcitrant erythema nodosum leprosum: therapeutic dilemma and role of Mycobacterium indicus pranii vaccine. An Bras Dermatol 2022; 97(1): 49-53.
[http://dx.doi.org/10.1016/j.abd.2020.08.032] [PMID: 34848113]
[23]
Bhat R, Vaidya T. What is new in the pathogenesis and management of erythema nodosum leprosum. Indian Dermatol Online J 2020; 11(4): 482-92.
[http://dx.doi.org/10.4103/idoj.IDOJ_561_19] [PMID: 32832433]
[24]
Thangaraju P, Venkatesan S, Ali SMK. Final leprosy push: Out of society. Indian J Community Med 2018; 43(1): 58-9.
[http://dx.doi.org/10.4103/ijcm.IJCM_155_17] [PMID: 29531443]
[25]
Saraya MA, Al-Fadhli MA, Qasem JA. Diabetic status of patients with leprosy in Kuwait. J Infect Public Health 2012; 5(5): 360-5.
[http://dx.doi.org/10.1016/j.jiph.2012.08.001] [PMID: 23164565]
[26]
Silva GB, Daher EDF, Neto RDJP, et al. Leprosy nephropathy: A review of clinical and histopathological features. Rev Inst Med Trop Sao Paulo 2015; 57(1): 15-20.
[http://dx.doi.org/10.1590/S0036-46652015000100002] [PMID: 25651321]
[27]
Luo Y, Kiriya M, Tanigawa K, et al. Host-related laboratory parameters for leprosy reactions. Front Med 2021; 8: 694376.
[http://dx.doi.org/10.3389/fmed.2021.694376] [PMID: 34746168]
[28]
Vijay NR, Sarma S. Leprosy with erythema nodosumleprosum in pregnancy: A rare phenomenon! J South Asian FederObsGynae 2019; 11(5): 329-30.
[29]
Bandeira SS, Pires CA, Quaresma JAS. Leprosy reactions in childhood: A prospective cohort study in the Brazilian Amazon. Infect Drug Resist 2019; 12: 3249-57.
[http://dx.doi.org/10.2147/IDR.S217181]
[30]
WHO. Lepra reactions 2022. Available from: https://apps.who.int/iris/bitstream/handle/10665/332022/9789290227595-eng.pdf
[31]
Directorate general of health services. Ministry of health & family welfare. Government of India Lepra reactions 2022. Available from: https://dghs.gov.in/WriteReadData/userfiles/file/Leprosy/MO%20Training%20Manual.pdf

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