Leprosy

WHO recommends the same three-drug regimen for all leprosy patients, regardless of whether they have MB leprosy (≥6 lesions) or PB leprosy (1-5 lesions). Multi-drug therapy blister calendar packs contain rifampicin, dapsone, and clofazimine. The only difference is that patients with PB leprosy are treated for at least 6 months, while patients with MB leprosy are treated for at least 12 months.[34]World Health Organization. Guidelines for the diagnosis, treatment and prevention of leprosy. Oct 2018 [internet publication]. https://www.who.int/publications/i/item/9789290226383

Infectiousness becomes negligible after starting therapy containing rifampicin.[30]Levy L, Shepard CC, Fasal P. The bactericidal effect of rifampicin on M. leprae in man: a) single doses of 600, 900 and 1200 mg; and b) daily doses of 300 mg. Int J Lepr Other Mycobact Dis. 1976 Jan-Jun;44(1-2):183-7. http://www.ncbi.nlm.nih.gov/pubmed/776856?tool=bestpractice.com

If toxic effects or resistance occur, an alternative regimen should be used. Dapsone should be stopped if severe toxic effects occur; no further modification required.

Patients who cannot one of the first-line drugs because of adverse effects, contraindications, or intercurrent diseases can replace them with a fluoroquinolone (e.g., ofloxacin, levofloxacin, moxifloxacin), or minocycline, or clarithromycin as part of the multi-drug regimen.[34]World Health Organization. Guidelines for the diagnosis, treatment and prevention of leprosy. Oct 2018 [internet publication]. https://www.who.int/publications/i/item/9789290226383 [44]WHO Expert Committee on Leprosy. 7th report. World Health Organ Tech Rep Ser. 1998;874:20. http://www.who.int/lep/resources/Expert.pdf http://www.ncbi.nlm.nih.gov/pubmed/9627517?tool=bestpractice.com [45]Manickam P, Nagaraju B, Selvaraj V, et al; Team of Study Investigators. Efficacy of single-dose chemotherapy (rifampicin, oflaxacin and minocycline-ROM) in PB leprosy patients with 2 to 5 skin lesions, India: randomised double-blind trial. Indian J Lepr. 2012;84:195-207. http://www.ncbi.nlm.nih.gov/pubmed/23484334?tool=bestpractice.com [46]Cunha Mda G, Virmond M, Schettini AP, et al. OFLOXACIN multicentre trial in MB leprosy FUAM-Manaus and ILSL-Bauru, Brazil. Lepr Rev. 2012;83:261-268. http://www.ncbi.nlm.nih.gov/pubmed/23356027?tool=bestpractice.com

Fluoroquinolones have been associated with adverse effects including tendonitis, tendon rupture, arthralgia, neuropathies, other musculoskeletal or nervous system effects, aortic dissection, significant hypoglycaemia, and mental health adverse effects.[37]European Medicines Agency. Quinolone- and fluoroquinolone-containing medicinal products. Mar 2019 [internet publication]. https://www.ema.europa.eu/en/medicines/human/referrals/quinolone-fluoroquinolone-containing-medicinal-products [38]US Food and Drug Administration. FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients. Dec 2018 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-increased-risk-ruptures-or-tears-aorta-blood-vessel-fluoroquinolone-antibiotics [39]US Food and Drug Administration. FDA reinforces safety information about serious low blood sugar levels and mental health side effects with fluoroquinolone antibiotics; requires label changes. Oct 2018 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-reinforces-safety-information-about-serious-low-blood-sugar-levels-and-mental-health-side

In the case of rifampicin-resistant leprosy, the WHO recommends the use of two second-line drugs - a fluoroquinolone (e.g., ofloxacin, levofloxacin, moxifloxacin), or minocycline, or clarithromycin - for 6 months, followed by one second-line drug for an additional 18 months. This should be given in addition to clofazimine for the whole duration of treatment.[34]World Health Organization. Guidelines for the diagnosis, treatment and prevention of leprosy. Oct 2018 [internet publication]. https://www.who.int/publications/i/item/9789290226383

In the case of resistance to both rifampicin and a fluoroquinolone, patients may be treated with clarithromycin and minocycline for 6 months, followed by either clarithromycin or minocycline for an additional 18 months, in addition to clofazimine for the whole duration of treatment.[34]World Health Organization. Guidelines for the diagnosis, treatment and prevention of leprosy. Oct 2018 [internet publication]. https://www.who.int/publications/i/item/9789290226383

Fluoroquinolones have been associated with adverse effects including tendonitis, tendon rupture, arthralgia, neuropathies, other musculoskeletal or nervous system effects, aortic dissection, significant hypoglycaemia, and mental health adverse effects.[37]European Medicines Agency. Quinolone- and fluoroquinolone-containing medicinal products. Mar 2019 [internet publication]. https://www.ema.europa.eu/en/medicines/human/referrals/quinolone-fluoroquinolone-containing-medicinal-products [38]US Food and Drug Administration. FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients. Dec 2018 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-increased-risk-ruptures-or-tears-aorta-blood-vessel-fluoroquinolone-antibiotics [39]US Food and Drug Administration. FDA reinforces safety information about serious low blood sugar levels and mental health side effects with fluoroquinolone antibiotics; requires label changes. Oct 2018 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-reinforces-safety-information-about-serious-low-blood-sugar-levels-and-mental-health-side

Type 1 reaction (reversal reaction) is a medical emergency that can increase leprosy-related morbidity. It is important that it is recognised and treated to reduce the burden of disability in leprosy. It is seen most frequently in patients with borderline tuberculoid (BT), mid-borderline leprosy (BB), borderline lepromatous (BL), and lepromatous leprosy (LL). Existing skin lesions become erythematous and oedematous. Spontaneous nerve pain, tenderness, paraesthesias, and/or loss of nerve function (claw hand, foot drop, facial palsy) are commonly associated with it. Systemic symptoms are unusual. It is often incorrectly viewed as a complication of multi-drug therapy.

Prednisolone provides rapid symptomatic relief and helps reverse nerve function impairment. The regimen must be tailored individually based on whether nerve tenderness and motor or sensory deficits are present. Symptoms should be reassessed every 2 weeks. If nerve function improves, the dose can be reduced slowly over the next 3 months.[42]Van Veen NH, Nicholls PG, Smith WC, et al. Corticosteroids for treating nerve damage in leprosy. Cochrane Database Syst Rev. 2016 May 23;(5):CD005491. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005491.pub3/full http://www.ncbi.nlm.nih.gov/pubmed/27210895?tool=bestpractice.com

Additional treatment recommended for SOME patients in selected patient group

Long-term corticosteroid use carries the risk of adverse effects, prompting the use of corticosteroid-sparing agents, such as methotrexate or ciclosporin.[43]Perez-Molina JA, Arce-Garcia O, Chamorro-Tojeiro S, et al. Use of methotrexate for leprosy reactions. Experience of a referral center and systematic review of the literature. Travel Med Infect Dis. 2020 Sep - Oct;37:101670. http://www.ncbi.nlm.nih.gov/pubmed/32302727?tool=bestpractice.com Methotrexate or ciclosporin monotherapy may be an alternative option.[41]World Health Organization. Leprosy/Hansen disease: management of reactions and prevention of disabilities. 2020 [internet publication]. https://www.who.int/publications/i/item/9789290227595

Type 2 reaction (erythema nodosum leprosum) is a medical emergency that can increase leprosy-related morbidity. It is important that it is recognised and treated to reduce the burden of disability in leprosy. It is seen most frequently in patients with BL and LL. It is characterised by the rapid appearance of crops of painful, erythematous subcutaneous nodules, which can ulcerate. Neuritis may develop. Systemic features are common (fever, malaise, anorexia) as are arthralgias, orchitis, epididymitis, and iritis. It is often incorrectly viewed as a complication of multi-drug therapy.

The current treatment of choice, thalidomide, is extremely effective at improving symptoms. However given its teratogenicity, thalidomide is avoided in women of childbearing potential. Treatment of this particular population remains a challenge. Prednisolone can be used instead. Long-term corticosteroid use carries the risk of adverse effects, prompting the use of corticosteroid-sparing agents, such as methotrexate.[43]Perez-Molina JA, Arce-Garcia O, Chamorro-Tojeiro S, et al. Use of methotrexate for leprosy reactions. Experience of a referral center and systematic review of the literature. Travel Med Infect Dis. 2020 Sep - Oct;37:101670. http://www.ncbi.nlm.nih.gov/pubmed/32302727?tool=bestpractice.com While the combination of thalidomide and prednisolone is approved for the treatment of erythema nodosum leprosum plus neuritis, it should be avoided because of the increased risk of deep vein thrombosis. 

Increased doses of clofazimine as part of the multi-drug regimen can be an option for those who cannot receive thalidomide, but its full effect is not observed until 4 to 6 weeks from initiation. [ ] How do systemic corticosteroids and non-steroidal immunomodulatory therapies compare for the treatment of erythema nodosum leprosum?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.814/fullShow me the answer

Methotrexate monotherapy may be an alternative option.[41]World Health Organization. Leprosy/Hansen disease: management of reactions and prevention of disabilities. 2020 [internet publication]. https://www.who.int/publications/i/item/9789290227595

Lucio's phenomenon is a relatively rare immunological reaction. It occurs in diffuse non-nodular lepromatous leprosy (lepra bonita). It has been associated with a different species, Mycobacterium lepromatosis.[4]Han XY, Jessurun J. Severe leprosy reactions due to Mycobacterium lepromatosis. Am J Med Sci. 2013;345:65-9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3529828 http://www.ncbi.nlm.nih.gov/pubmed/23111393?tool=bestpractice.com It is characterised by crops of haemorrhagic skin infarcts and plaques that become necrotic and ulcerated, leaving behind atrophic scars. Systemic symptoms are unusual.

If not already on multi-drug therapy, patients should be started on medications for lepromatous leprosy. In addition, corticosteroids should be initiated and tapered over months.