Published on 18/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
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Anne E. Burdick and Ivan D. Camacho
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Leprosy or Hansen disease is an infection caused by Mycobacterium leprae (M. leprae), affecting the skin, respiratory mucosa, peripheral nerves, and other organs. The cardinal signs are anesthetic skin lesions, enlarged peripheral nerves, peripheral neuropathy with acid-fast bacilli in tissue biopsies or skin slit smears. A patient’s cell-mediated immunity against M. leprae determines his or her presentation of leprosy in the Ridley–Jopling spectrum: tuberculoid (TT), borderline tuberculoid (BT), mid-borderline (BB), borderline lepromatous (BL) and lepromatous (LL). A patient with TT leprosy has high cell-mediated immunity to M. leprae and few well-demarcated lesions located on cooler parts of the body. A patient with LL leprosy has low cell-mediated immunity to M. leprae and numerous disseminated infiltrated erythematous papules, plaques, and nodules, often presenting with peripheral neuropathy. BB leprosy patients have multiple annular ‘dimorphous’ plaques (see photo). On biopsy, TT lesions reveal rare acid-fast bacilli (AFB) and LL lesions have innumerable AFB. Indeterminate (I) leprosy presents as a single or few hypopigmented patches that tend to resolve spontaneously but may progress to leprosy anywhere on the spectrum. Pure neural leprosy is limited to peripheral nerve involvement without skin lesions.
Leprosy reactions occur in 25–50% of patients before, during or after treatment. BT, BB, and BL patients may develop a delayed hypersensitivity reaction, a type 1 ‘reversal’ reaction, with red edematous lesions and an acute peripheral neuritis. HIV patients may develop BT lesions and a type 1 reversal reaction as an immune reconstitution inflammatory syndrome within 6 months of starting highly active antiretroviral therapy if they also have a subclinical leprosy infection. Patients on infliximab and adalimumab may also manifest leprosy and a type 1 reversal reaction if they have concomitant subclinical leprosy.
Erythema nodosum leprosum, a type 2 reaction, is an immune complex reaction that develops in BL and LL cases. In a type 2 reaction, crops of new red indurated tender papules, plaques or nodules develop usually with fever and occasionally with iritis or orchitis. Lucio’s phenomenon, a rare vasculitis reaction, presents as tender purpuric and necrotic lesions.
Leprosy treatment consists of multidrug therapy with rifampin and dapsone, with or without clofazimine. For treatment purposes, the World Health Organization (WHO) classifies I, TT, and BT cases as paucibacillary and recommends monthly rifampin 600 mg and daily dapsone 100 mg for 6 months. WHO classifies BB, BL and LL cases as multibacillary and recommends monthly rifampin 600 mg, daily dapsone 100 mg and clofazimine 300 mg monthly and 50 mg daily for 12 months.
The US National Hansen’s Disease Program guidelines are different. For paucibacillary cases, daily rifampin 600 mg and daily dapsone 100 mg are recommended for 12 months. For multibacillary cases, daily rifampin 600 mg, daily dapsone 100 mg and daily clofazimine 50 mg are recommended for 24 months. In the US, clofazimine is only available through the National Hansen’s Disease Program as an investigational drug.
If clofazimine is not available or declined due to skin hyperpigmentation, or if a patient cannot take rifampin or dapsone, alternative antibiotics are minocycline 100 mg, ofloxacin 400 mg, levaquin 500 mg, clarithromycin 500 mg or moxifloxacin 400 mg. Rifampin is prescribed monthly for patients on prednisone, warfarin, oral contraceptives and other drugs with metabolism affected by rifampin. If multidrug therapy is interrupted for any reason, it should be resumed when possible for the remaining months required to complete the recommended duration of multidrug therapy.
Multidrug therapy should be continued during reactions. Mild type 1 reversal reactions and type 2 reactions are treated with non-steroidal anti-inflammatory drugs. For a severe type 1 reversal reaction with acute neuritis, particularly involving the face, aggressive therapy with systemic steroids are started to prevent potentially irreversible nerve damage. Prednisone 0.5–1 mg/kg daily should be started and tapered slowly, 5–10 mg every 2 to 4 weeks, for 3 to 6 months or longer depending on the patient’s response. Since high doses of steroids are often required to control a type 1 reversal reaction, the addition of a steroid sparing drug should be considered. Cyclosporine and methotrexate are effective for a type 1 reversal reaction, permitting a decreased dose or discontinuation of prednisone. In one case report, topical tacrolimus improved a severe type 1 reversal reaction.
A severe type 2 reaction also responds to prednisone 0.5–1 mg/kg daily and often requires a slower taper of 6 months or longer. Thalidomide, a known teratogen, is the drug of choice for men and women who are postmenopausal, surgically sterile, or are using appropriate contraceptives. The initial thalidomide dose ranges from 100 to 400 mg nightly depending on the type 2 reaction severity. The dose is decreased slowly over several months to a maintenance dose of 50–100 mg nightly to prevent recurrences. Other drugs for type 2 reaction include methotrexate, azathioprine, infliximab, and etanercept. Lucio phenomenon is treated with supportive care.
After completion of multidrug therapy, the National Hansen’s Disease Program advises paucibacillary patients to be screened annually for 5 years and multibacillary patients for 8 years. Household contacts who lived with a leprosy patient during the 3 years before multidrug therapy was started should have one screening exam according to WHO. The National Hansen’s Disease Program also recommends one screening for paucibacillary leprosy contacts and advises an annual screening for 5 years for multibacillary leprosy contacts.
Skin biopsy (4 mm, from periphery of lesion) for diagnosis and annually
Slit skin smears
Neurosensory testing
Chemistry panel, complete blood count
Glucose-6-phosphate dehydrogenase level prior to dapsone
Urinalysis (type 2 reaction)
Rifampin and dapsone (paucibacillary and multibacillary)
Clofazimine (multibacillary)
Britton WJ, Lockwood DN. Lancet 2004; 363: 1209–19.
Review of clinical features, diagnostic criteria and treatment of leprosy and reactions.
Worobec SM. Dermatol Ther 2009; 22: 518–37.
Review of leprosy and reactions.
Dinubile MJ, Keystone JS. Int J Dermatol 2011; 50: 1024–6.
Comparison of type 1 reversal reaction and type 2 reaction features.
Lockwood DN, Lambert SM. Dermatol Clin 2011; 29: 125–8.
Massone C, Talhari C, Ribeiro-Rodrigues R, Sindeaux RH, Mira MT, Talhari S, et al. Expert Rev Anti Infect Ther 2011; 9: 701–10.
Walker SL, Waters MF, Lockwood DN. Lepr Rev 2007; 78: 197–215.
Teixeira FM, Vasconcelos LM, Rola Cde A, Prata de Almeida TL, Valença JT Jr, Nagao-Dias AT. J Clin Rheumatol 2011; 17: 269–71.
A psoriatic man on infliximab for 2 years developed BL lesions and neuropathy.
Camacho ID, Valencia I, Rivas MP, Burdick AE. Arch Dermatol 2009; 145: 349–51.
An undiagnosed BT patient presented with a type 1 reversal reaction after discontinuing adalimumab 5 weeks prior for presumed seronegative arthritis.
Marlowe SN, Leekassa R, Bizuneh E, Knuutilla J, Ale P, Bhattarai B, et al. Trans R Soc Trop Med Hyg 2007; 101: 1004–12.
Forty-one patients with type 1 reversal reaction treated with cyclosporine 5–7.5 mg/kg/day for 12 weeks had 67–100% improvement after 24 weeks. Neuritis reoccurred when discontinued.
Sena CB, Salgado CG, Tavares CM, Da Cruz CA, Xavier MG, Do Nascimento JL. Lepr Rev 2006; 77: 121–9.
Twenty patients with neuritis unresponsive to 40 mg/day prednisone had improved sensation, strength and pain after cyclosporine 5 mg/kg/day with a 12-month taper.
Biosca G, Casallo S, López-Vélez R. Clin Infect Dis 2007; 45: e7–9.
A BL patient with type 1 reversal reaction and poor tolerance to corticosteroids responded to methotrexate 7.5 mg weekly. Prednisone was stopped in 2 months and lesions resolved in 6 months.
Kar BR, Babu R. Int J Lepr Other Mycobact Dis 2004; 72: 480–2.
A patient with a type 2 reaction unresponsive to prednisolone 50 mg daily improved with methotrexate 15 mg weekly for 2 weeks. Prednisolone was tapered to 20 mg daily with continued improvement on methotrexate 7.5 mg weekly.
Duraes SM, Salles SA, Leite VR, Gazzeta MO. Lepr Rev 2011; 82: 304–9.
Review of nine reports of type 2 reaction cases refractory to prednisone and clofazamine responded to azathioprine 2–3 mg/kg/day. The prednisone dose was decreased in 4 weeks and halved after 12 weeks with fewer type 2 reactions.
Marlowe SN, Hawksworth RA, Butlin CR, Nicholls PG, Lockwood DN. Trans R Soc Trop Med Hyg 2004; 98: 602–9.
Forty patients with RR randomized to prednisolone 40 mg daily vs prednisolone 40 mg daily with azathioprine 3 mg/kg daily for 12 weeks had no difference in outcome.
Safa G, Darrieux L, Coic A, Tisseau L. Indian J Med Sci 2009; 63: 359–62.
A pediatric BL case with a severe type 1 reversal reaction without neuritis who was unresponsive to prednisolone 1 mg/kg/day for 4 weeks had dramatic improvement after 7 days of tacrolimus 0.1% ointment applied twice daily and nearly cleared in 2 weeks. Prednisolone was tapered and discontinued after 12 weeks.
Ramien ML, Wong A, Keystone JS. Clin Infect Dis 2011; 52: e133–5.
An LL patient had type 2 reactions for 6 years, despite daily thalidomide 100 mg and multiple courses of 40–60 mg/day of prednisone, improved on etanercept 50 mg subcutaneously weekly for 6 weeks. Prednisone and thalidomide were stopped in 6 months.
Faber WR, Jensema AJ, Goldschmidt WF. N Eng/J Med 2006; 355: 739.
A BL patient with type 2 reaction multidrug therapy refractory to daily prednisolone 40 mg and thalidomide 300 mg, responded promptly to three doses of infliximab 5 mg/kg every other week with no recurrence for 1 year after the last dose.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Non-steroidal anti-inflammatory drugs (type 1 reversal reaction and type 2 reaction)
Prednisone (type 1 reversal reaction and type 2 reaction)
Thalidomide (type 2 reaction)
Minocycline, ofloxacin, levaquin, moxifloxocin, clarithyromycin
Cyclosporine (type 1 reversal reaction)
Methotrexate (type 1 reversal reaction and type 2 reaction)
Azathioprine (type 2 reaction)
Infliximab (type 2 reaction)
Etanercept (type 2 reaction)
Tacrolimus ointment (type 1 reversal reaction)
