Approach
Early diagnosis and treatment with multi-drug therapy (MDT) remains the single most important element in curing the disease, preventing disabilities, and possibly reducing transmission.
Multi-drug therapy: general principles
MDT was developed because of the widespread emergence of dapsone resistance, and the regimens were designed on the principle that they would effectively prevent development of resistance to any single drug used in the combination.[34][35]
The World Health Organization (WHO) recommends the same three-drug regimen for all patients with leprosy, regardless of whether they have multibacillary (MB) leprosy (≥6 lesions) or paucibacillary (PB) leprosy (1-5 lesions). MDT 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]
Patients who cannot take 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.[36] 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][38][39]
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. 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]
Rifampicin:
Standard monthly dose has proved relatively non-toxic.
Occasional cases of renal failure, thrombocytopenia, influenza-like syndrome, and hepatitis have been reported.
Highly bactericidal.
Drug resistance is low if combined with dapsone.
Clofazimine:
Virtually non-toxic in the dosage employed for MB leprosy.
Pigmentation of the skin, particularly within skin lesions, is common, but it clears completely within 6 to 12 months after treatment is discontinued.
In higher doses it may occasionally produce severe gastrointestinal adverse effects.
Dapsone:
Relatively non-toxic in the doses used.
Occasional cases of delayed hypersensitivity reactions, and less commonly, agranulocytosis.
Screening for HLA-B*13:01 before treatment may reduce incidence of dapsone hypersensitivity syndrome in high risk populations.[40]
Mild haemolytic anaemia is common following treatment with the drug.
Severe haemolytic anaemia is rare except in patients with glucose-6-phosphate dehydrogenase deficiency.
Drug resistance is low if combined with rifampicin.
WHO treatment guidelines have been followed here for the treatment of adult patients.
Treatment of immunological reactions
Two types of reactions affect 30% to 50% of patients with leprosy: type 1 reaction (reversal reaction) and type 2 reaction (erythema nodosum leprosum). These reactions are often incorrectly viewed as complications of multi-drug therapy. Reactions are medical emergencies that can increase leprosy-related morbidity and so it is important to specifically recognise and treat reactions, to reduce the burden of disability in leprosy.[41] A third reaction, known as Lucio's phenomenon, is relatively rare. Immunological reactions can occur any time, before, during, or after treatment.[5][35]
Type 1 reaction (reversal reaction):
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 during the next 3 months.[42]
Long-term corticosteroid use carries risk of adverse effects, prompting exploration of corticosteroid-sparing agents, such as methotrexate or ciclosporin.[43] Methotrexate or ciclosporin monotherapy may be an alternative option.[41]
Type 2 reaction (erythema nodosum leprosum):
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. Long-term corticosteroid use carries the risk of adverse effects, prompting exploration of corticosteroid-sparing agents, such as methotrexate.[43]
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. Higher doses of clofazimine can be as part of the multidrug regimen an option for those who cannot receive thalidomide, but its full effect is not observed until 4 to 6 weeks from initiation. [
]
Methotrexate monotherapy may be an alternative option.[41]
Lucio’s phenomenon
If not already on MDT, patients should be started on medications for lepromatous leprosy, including rifampicin, dapsone, and clofazimine. In addition, corticosteroids should be initiated and tapered over months.
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