Dermatologic Manifestations of Leprosy Treatment & Management
- Author: Felisa S Lewis, MD; Chief Editor: Dirk M Elston, MD more...
The management of leprosy includes early pharmacotherapy and physical, social, and psychological rehabilitation. The goals of pharmacotherapy are to stop the infection, reduce morbidity, prevent complications, and eradicate the disease. Since 1981, multidrug therapy (MDT) has been advocated by the World Health Organization (WHO) and the United States government. MDT prevents dapsone resistance, quickly reduces contagiousness, and reduces relapses, reactions, and disabilities. If a patient has been previously treated with dapsone monotherapy, re-treatment with a modified MDT regimen of rifampin, clofazimine, and dapsone can reduce or delay the risk of relapse.
The length of treatment ranges from 6 months to 2 years. Patients are considered noninfectious within 1-2 weeks of treatment (usually after the first dose). These drugs are conveniently packaged in monthly calendar blister packs. Monitor for drug resistance and adverse reactions to medications.
Paucibacillary disease can be treated with a combination of 2 drugs, whereas multibacillary disease requires triple-drug therapy. Single skin lesions (paucibacillary) can be treated with a single dose of 3 drugs. The length of treatment depends on the type of disease and on the access to drugs.
WHO and US treatment regimens for paucibacillary and multibacillary disease are listed below. Therapy for single skin lesions is not universal, because 80% of single skin lesions heal spontaneously. Therefore, only the WHO has a recommended treatment.
Current WHO recommendations for treatment of leprosy are as follows :
Paucibacillary disease - Dapsone at 100 mg/d plus rifampin at 600 mg once a month for 6 months; children aged 10-14 years – Dapsone at 50 mg/d plus rifampin at 450 mg once a month for 6 months
Multibacillary disease - Dapsone at 100 mg/d plus rifampin at 600 mg once a month plus clofazimine at 300 mg once a month and 50 mg/d for 1 year; children aged 10-14 years - Dapsone at 50 mg/d plus rifampin at 450 mg once a month plus clofazimine at 150 mg once a month and 50 mg/d for 1 year
Single skin lesion - A single dose of rifampin at 600 mg, ofloxacin at 400 mg, and minocycline at 100 mg; children aged 10-14 years - Single dose of rifampin at 300 mg, ofloxacin at 200 mg, and minocycline at 50 mg; treatment of single skin lesions not recommended for pregnant women and children younger than 5 years
Current US recommendations for the treatment of leprosy are as follows :
Paucibacillary disease - Dapsone at 100 mg/d plus rifampin at 600 mg/d for 1 year
Multibacillary disease - Dapsone at 100 mg/d plus rifampin at 600 mg/d plus clofazimine at 50 mg/d for 2 years
Resistance to rifampin and dapsone has been reported. WHO treatment recommendations are as follows :
Rifampin resistance: 24-month treatment broken down as 6 months of 50-mg/d clofazimine, 400-mg/d ofloxacin, and 100-mg/d minocycline, followed by 18 mo of 50-mg/d clofazimine plus 400-mg/d ofloxacin or 100-mg/d minocycline
Dapsone resistance in paucibacillary disease - Clofazimine is substituted for dapsone; clofazimine at 300 mg once a month and 50 mg/d plus rifampin at 600 mg once a month for 6 months
Dapsone resistance in multibacillary disease: Treat as described above with only clofazimine and rifampin, omitting the dapsone
Other drugs that have been proposed as alternatives include moxifloxacin and rifapentine, but no specific regimens have been validated as effective.
In patients taking dapsone, the CBC count should be checked frequently early during the therapy and then less frequently later during therapy.
A modified course of MDT using rifampin and clofazimine was used effectively in patients with dapsone hypersensitivity syndrome.
A small study also demonstrated the efficacy of a 4-week regimen of 600 mg of rifampin and 400 mg ofloxacin for paucibacillary disease.
Treatment of pure neural leprosy often follows that of multibacillary disease.
Skin lesions usually resolve within the first year of treatment, although some may persist for up to 5 years in multibacillary disease.
Lack of improvement despite MDT may be due to anergy. This may be proven by a negative Mantoux test prior to administering the BCG injection. When given with MDT, BCG stimulates the suppressed cell-mediated immunity to produce a delayed hypersensitivity reaction, and induces clearance of bacilli.
One promising avenue to measure treatment efficacy may be to follow immunoglobulin G levels of LID-1 fusion protein, and ML0405 and ML2331, both recombinant proteins. One study of Brazilian and Venezuelan patients demonstrated a decrease in reactivity across the clinical spectrum (highest levels in lepromatous leprosy → lowest levels in paucibacillary leprosy) and with MDT.
Potential deformities can be prevented by educating patients about how to minimize existing nerve damage and by treating any sequelae of this damage. Close follow-up is important to ensure patient compliance (see Complications).
Further inpatient care
Patients with leprosy may need hospitalization for acute complications. Sanatoria, which were widely used in the past, are no longer necessary. Most patients can be treated in an outpatient setting.
Community-based rehabilitation programs are important to integrate and support people with leprosy and their families. A current list of Hansen disease clinics in the United States can be obtained from the National Hansen's Disease (Leprosy) Program.
Emergency surgery may be necessary if a patient with profound nerve inflammation presents with a nerve abscess or loss of nerve function secondary to compression. Prompt recognition and surgical drainage of the abscess can often restore nerve function.
Elective surgery may be required for correction of lagophthalmos (ie, inability to close the eye).
Reconstructive surgery can be used to repair nasal collapse in patients with lepromatous leprosy, but it is not recommended until the disease has been inactive for a minimum of 1 year.
Other surgery may be needed to improve function or for cosmesis.
Contractures can be surgically repaired.
Consultations with an ophthalmologist, a plastic surgeon, an orthopedic surgeon, an otolaryngologist, a neurosurgeon, and/or a neurologist may be necessary.
Reasons for a consultation with an ophthalmologist include the following:
Erythema nodosum leprosum (ENL)–induced iritis
Direct invasion of the anterior chamber of the eye by Mycobacterium leprae
Corneal and conjunctival insensitivity
Infection or scarring from involvement of CN V and CN VII
Specialists in rehabilitation medicine, including physical and occupational therapists, can help in reducing morbidity.
Consultation with a prosthetics specialist also may be appropriate.
Restrictions on activity depend on the extent of nerve damage.
In patients with bone or joint destruction, weight bearing should be minimized.
Patients with anesthesia of the limbs must be educated about their condition, and they should wear appropriate protection (especially footwear).
Plantar ulceration requires rest and avoidance of weight bearing.
Weakness or paralysis requires physical therapy to prevent contractures.
Reactional states occur in approximately 20-50% of patients and are acute inflammations of the disease. They may be induced by MDT, physical or mental stress, puberty, childbirth, trauma, pregnancy, or surgical procedures. A leprous reaction should be considered a medical emergency and mandates immediate care. These states can result in permanent neurologic sequelae and are the leading causes of grade 2 disability. Patients at the highest risk are those with multibacillary leprosy, those with preexisting/persistent nerve impairment, those with positive anti-PGL-I, and those with positive bacillary indexes in skin smears. MDT should be continued through the reactional episode.
Lepra type I (reversal) reactions usually affect patients with borderline disease. Reversal reactions are a shift toward the tuberculoid pole after the start of therapy, and they are type IV cell-mediated allergic hypersensitivities, with CD4+ lymphocytes infiltrate lesions with high levels of IFN-gamma and TNF-alpha, indicating an improvement in cell-mediated immunity. These reactions are characterized by increased inflammation of preexisting lesions and edema of the face and extremities, with edema and tenderness of peripheral nerves. New skin lesions are common, and the patient may have an acute febrile illness. The peak time for type I reactions is during the first 6 months of therapy and for up to 12 months. Corticosteroid treatment is aimed at controlling acute inflammation, relieving pain, and reversing nerve and eye damage. With treatment, approximately 60-70% of the patient's nerve function is recovered. If neuritis is absent, NSAIDs may be helpful. Skin lesions have been successfully treated with the addition of topical tacrolimus.
Lepra type II reactions, or erythema nodosum leprosum (ENL), occur in approximately 10% of patients with borderline lepromatous leprosy and in 20% of patients with lepromatous leprosy. These reactions are type III humoral (antibody-antigen) hypersensitivities, with a systemic inflammatory response to immune complex deposition. The most common presenting symptoms are crops of painful erythematous nodules of the skin and subcutaneous tissue. Sweet syndrome –like lesions have also occurred. Bullae, ulcers, and necrosis also may occur. Nerve damage is slower than in reversal reactions. The reaction usually manifests after a few years of therapy, and, although a single acute episode is possible, relapses occur intermittently over several years. Associated fever, malaise, arthralgias, neuralgia, iridocyclitis, dactylitis, orchitis, and proteinuria may be present. The use of clofazimine in MDT substantially reduces the incidence of ENL to 5%. Clofazimine has also been used to treat ENL. Mild cases can be treated with NSAIDs. Thalidomide is effective except in the case of neuritis or iritis, in which case corticosteroids should be used. Thromboembolic events are reported with thalidomide use. Other treatment therapies reported to be effective include colchicine, pentoxifylline, cyclosporine A, azathioprine, methotrexate, intravenous immunoglobulin, infliximab, and etanercept.
Lowering the dose of dapsone may decrease the severity of bullae and ulcers.
Lucio phenomenon is a cutaneous necrotizing vasculitis that is sometimes designated a type II reaction. It is common in Mexico and Central America and is characterized by erythematous, geometric, irregular-shaped macules that rapidly progress to ulceration and necrosis on acral areas or extremities of patients with diffuse lepromatous leprosy. Systemic symptoms such as hepatosplenomegaly, fever, arthritis, and nephritis are usually present. Thalidomide is ineffective in treating this type of reaction; however, no consensus on treatment had been determined. Most patients with Lucio phenomenon have not received MDT or were treated irregularly; therefore, MDT is recommended. Azathioprine or cyclophosphamide with corticosteroids with or without plasmapheresis has also been used.
The real challenge in managing leprosy is the treatment of reactional states.
If the course of MDT is not complete, continue taking those medications as directed.
Systemic steroids are effective in reducing inflammation and edema in reversal reactions; therefore, they are the most helpful medications in preventing nerve damage.
Prednisone at 1-2 mg/kg/d should be given until clinical improvement is seen, then tapered slowly over 3-6 months (and possibly longer). One study suggests a course of at least 8 months. This long course is necessary to decrease the severity of disabilities and deformities.
Clofazimine can also be used as a steroid-sparing agent for reversal reactions, alone or with corticosteroids.
Although the World Health Organization (WHO) does not support its use for ENL, thalidomide is highly effective with ENL. It is ineffective for the treatment of reversal reactions.
It is not unusual for an immunosuppressive therapy for a reactional state to cause a re-activation of a latent comorbid infection. Consider screening for chronic hepatitis B, chronic strongyloidiasis, latent tuberculosis, Chagas disease, and human immunodeficiency virus (HIV) infections before starting MDT, in patients who come from geographic areas where any of these conditions are endemic.
Neuropathy induced by leprosy can result in trauma, pressure necrosis, or secondary infection that goes unnoticed, leading to amputation of digits or limbs. Wrist and foot drop are also common. Silent neuropathy can occur in the absence of overt signs of nerve or skin inflammation. Even with corticosteroid treatment, only approximately 60% of nerve function is recovered. Cyclosporine A may be useful in controlling nerve impairment and pain. Intraneural corticosteroid injection in one case resulted in nerve regeneration and improved sensory and motor function. Tibialis posterior transfer by the interosseus route with early postoperative mobilization can correct foot drop in leprosy.[88, 89]
Injuries can result in ulcerations, cellulitis, scarring, and bony destruction. Foot ulcers discovered early should be treated with rest because they heal if they are not subject to weight bearing.
Osteoporosis and fractures can result from bony changes due to leprosy. Risedronate and other bisphosphates may help improve lumbar bone mineral density.
Contractures can develop and may result in fixation. Common sequelae include clawing of hands and feet.
Arthritis/arthralgias may occur in approximately 10% of patients with leprosy and joint symptoms, and in conjunction with reactional states. Most have polyarticular symmetric arthritis. The arthritis is generally not responsive to conventional therapy, but 50% become asymptomatic within 24 months of diagnosis.
Eye damage, especially in the anterior portion of the eye, can result in loss of the corneal reflex, lagophthalmos, ectropion, entropion, and blindness. One study found the risk of ocular complications in patients with multibacillary disease, after completion of MDT, to be 5.6%, with eye-threatening complications at 3.9%.
Skin drying and fissures can be caused by autonomic disruption.
Hypogonadism and testicular atrophy can lead to sterility and gynecomastia. Testosterone replacement is the treatment of choice.
Renal involvement in leprosy, particularly lepromatous leprosy and ENL, have been described. Findings may range from hematuria and proteinuria to acute and chronic glomerulonephritis, interstitial nephritis, and pyelonephritis.
No skin or serologic tests are available to identify a carrier of leprosy.
In the southern United States, close contact with armadillos should be avoided.
Household contacts of patients with lepromatous disease should be monitored annually for 5 years after diagnosis. There are no universal recommendations for chemoprophylaxis. Children especially should be observed for the development of disease. In endemic countries, chemoprophylaxis may be useful in controlling leprosy. The Prospective (sero-)Epidemiological Study on Contact Transmission and Chemoprophylaxis in Leprosy (COLEP) found that a single dose of rifampin was 57% effective in preventing leprosy in contacts for the first 2 years after diagnosis of a new index case. A 6-year follow-up reported sustained lack of additional prevention beyond 2 years. However, this remained statistically significant. It also found that the most effective groups affected were in the contact groups of female index cases and in those who were in the contact groups of 2 or more leprosy patients. In the United Kingdom, close contacts of lepromatous leprosy patients younger than 12 years are given rifampin at 15 mg/kg once a month for 6 months as prophylaxis.
Attempts have been made to develop a vaccine against leprosy. Although not widely used, antileprosy vaccination can be immunoprophylactic and therapeutic. Current vaccines with various degrees of use are the BCG vaccine; the Mycobacterium w vaccine; the Mycobacterium avium-intracellulare complex (Mycobacterium ICRC) vaccine; and the BCG plus heat-killed Mycobacterium leprae, Mycobacterium tufu, and Mycobacterium habana vaccine.
The BCG vaccine has variable results in protecting certain populations; therefore, it is not widely prescribed. However, repeat immunization with the BCG vaccine may result in further protection. In the United Kingdom, the BCG vaccine is given to household contacts younger than 12 years.
In India, the Mycobacterium w and Mycobacterium ICRC vaccines are given. Mycobacterium w has a synergistic effect with chemotherapy, with accelerated clearing of the infection and shortening of treatment.
Follow-up to monitor post-MDT reactions is no longer necessary because these reactions are rare. Nonetheless, prevention of disability and rehabilitation is important; therefore, suggested follow-up is 5-10 years after treatment is completed. Patients should be educated about the clinical signs of reoccurrence and should be instructed to return for an evaluation if they have any skin, eye, or nerve changes. Periodic assessments for neural impairment are recommended, and prompt treatment of reactions substantially reduces and prevents further damage and disability. Previous nerve involvement is predictive of further nerve function impairment.
Sensation and muscle strength in the hands, feet, and eyes should be checked on a regular basis. The eyes, nerves, and nose should be examined at follow-up to ensure timely recognition of reactivated disease.
Han XY, Sizer KC, Thompson EJ, Kabanja J, Li J, Hu P, et al. Comparative sequence analysis of Mycobacterium leprae and the new leprosy-causing Mycobacterium lepromatosis. J Bacteriol. 2009 Oct. 191(19):6067-74. [Medline]. [Full Text].
Truman RW, Singh P, Sharma R, et al. Probable zoonotic leprosy in the southern United States. N Engl J Med. 2011 Apr 28. 364(17):1626-33. [Medline].
Masaki T, Qu J, Cholewa-Waclaw J, Burr K, Raaum R, Rambukkana A. Reprogramming adult Schwann cells to stem cell-like cells by leprosy bacilli promotes dissemination of infection. Cell. 2013 Jan 17. 152(1-2):51-67. [Medline].
Polycarpou A, Walker SL, Lockwood DN. New findings in the pathogenesis of leprosy and implications for the management of leprosy. Curr Opin Infect Dis. 2013 Oct. 26(5):413-9. [Medline].
McInturff JE, Modlin RL, Kim J. The role of toll-like receptors in the pathogenesis and treatment of dermatological disease. J Invest Dermatol. 2005 Jul. 125(1):1-8. [Medline].
Tapinos N, Ohnishi M, Rambukkana A. ErbB2 receptor tyrosine kinase signaling mediates early demyelination induced by leprosy bacilli. Nat Med. 2006 Aug. 12(8):961-6. [Medline].
Makino M, Maeda Y, Mukai T, Kaufmann SH. Impaired maturation and function of dendritic cells by mycobacteria through IL-1beta. Eur J Immunol. 2006 Jun. 36(6):1443-52. [Medline].
Fulco TO, Lopes UG, Sarno EN, Sampaio EP, Saliba AM. The proteasome function is required for Mycobacterium leprae-induced apoptosis and cytokine secretion. Immunol Lett. 2007 May 15. 110(1):82-5. [Medline].
Teles RM, Graeber TG, Krutzik SR, Montoya D, Schenk M, Lee DJ, et al. Type I interferon suppresses type II interferon-triggered human anti-mycobacterial responses. Science. 2013 Mar 22. 339(6126):1448-53. [Medline]. [Full Text].
Liu PT, Wheelwright M, Teles R, Komisopoulou E, Edfeldt K, Ferguson B. MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy. Nat Med. 2012 Feb. 18(2):267-73. [Medline].
Goulart LR, Goulart IM. Leprosy pathogenetic background: a review and lessons from other mycobacterial diseases. Arch Dermatol Res. 2009 Feb. 301(2):123-37. [Medline].
Zhang FR, Huang W, Chen SM, et al. Genomewide association study of leprosy. N Engl J Med. 2009 Dec 31. 361(27):2609-18. [Medline].
Pesce C, Grattarola M, Menini S, Fiallo P. Cyclooxygenase 2 expression in vessels and nerves in reversal reaction leprosy. Am J Trop Med Hyg. 2006 Jun. 74(6):1076-7. [Medline].
Chaitanya VS, Lavania M, Nigam A, Turankar RP, Singh I, Horo I. Cortisol and proinflammatory cytokine profiles in type 1 (reversal) reactions of leprosy. Immunol Lett. 2013 Nov-Dec. 156(1-2):159-67. [Medline].
Pandhi D, Chhabra N. New insights in the pathogenesis of type 1 and type 2 lepra reaction. Indian J Dermatol Venereol Leprol. 2013 Nov-Dec. 79(6):739-49. [Medline].
Global leprosy: update on the 2012 situation. Wkly Epidemiol Rec. 2013 Aug 30. 88(35):365-79. [Medline].
Drug resistance in leprosy: reports from selected endemic countries. Wkly Epidemiol Rec. 2009 Jun 26. 84(26):264-7. [Medline].
Ludwig RJ, Henke U, Wolter M, et al. Persistence of peri-neural granulomas after successful treatment of leprosy. J Eur Acad Dermatol Venereol. 2007 Nov. 21(10):1414-6. [Medline].
Khambati FA, Shetty VP, Ghate SD, Capadia GD. Sensitivity and specificity of nerve palpation, monofilament testing and voluntary muscle testing in detecting peripheral nerve abnormality, using nerve conduction studies as gold standard; a study in 357 patients. Lepr Rev. 2009 Mar. 80(1):34-50. [Medline].
Britton WJ, Lockwood DN. Leprosy. Lancet. 2004 Apr 10. 363(9416):1209-19. [Medline].
Gupta R, Kar HK, Bharadwaj M. Revalidation of various clinical criteria for the classification of leprosy--a clinic-pathological study. Lepr Rev. 2012 Dec. 83(4):354-62. [Medline].
Bhat R, Sharma VK, Deka RC. Otorhinolaryngologic manifestations of leprosy. Int J Dermatol. 2007 Jun. 46(6):600-6. [Medline].
Motta AC, Komesu MC, Silva CH, et al. Leprosy-specific oral lesions: a report of three cases. Med Oral Patol Oral Cir Bucal. 2008 Aug 1. 13(8):E479-82. [Medline].
Sehgal VN, Srivastava G, Singh N, Prasad PV. Histoid leprosy: the impact of the entity on the postglobal leprosy elimination era. Int J Dermatol. 2009 Jun. 48(6):603-10. [Medline].
Nascimento OJ. Leprosy neuropathy: clinical presentations. Arq Neuropsiquiatr. 2013 Sep. 71(9B):661-6. [Medline].
Rai D, Malhotra HS, Garg RK, Goel MM, Malhotra KP, Kumar V, et al. Nerve abscess in primary neuritic leprosy. Lepr Rev. 2013 Jun. 84(2):136-40. [Medline].
Garbino JA, Marques W Jr, Barreto JA, Heise CO, Rodrigues MM, Antunes SL, et al. Primary neural leprosy: systematic review. Arq Neuropsiquiatr. 2013 Jun. 71(6):397-404. [Medline].
Naves Mde M, Ribeiro FA, Patrocinio LG, Patrocinio JA, Fleury RN, Goulart IM. Bacterial load in the nose and its correlation to the immune response in leprosy patients. Lepr Rev. 2013 Mar. 84(1):85-91. [Medline].
Morgado de Abreu MA, Roselino AM, Enokihara M, Nonogaki S, Prestes-Carneiro LE, Weckx LL. Mycobacterium leprae is identified in the oral mucosa from paucibacillary and multibacillary leprosy patients. Clin Microbiol Infect. 2014 Jan. 20(1):59-64. [Medline].
Batista MD, Porro AM, Maeda SM, et al. Leprosy reversal reaction as immune reconstitution inflammatory syndrome in patients with AIDS. Clin Infect Dis. 2008 Mar 15. 46(6):e56-60. [Medline].
Menezes VM, Sales AM, Illarramendi X, et al. Leprosy reaction as a manifestation of immune reconstitution inflammatory syndrome: a case series of a Brazilian cohort. AIDS. 2009 Mar 13. 23(5):641-3. [Medline].
Scollard DM, Joyce MP, Gillis TP. Development of leprosy and type 1 leprosy reactions after treatment with infliximab: a report of 2 cases. Clin Infect Dis. 2006 Jul 15. 43(2):e19-22. [Medline].
Camacho ID, Valencia I, Rivas MP, Burdick AE. Type 1 leprosy reaction manifesting after discontinuation of adalimumab therapy. Arch Dermatol. 2009 Mar. 145(3):349-51. [Medline].
Ghorpade A. Ornamental tattoos and skin lesions. Tattoo inoculation borderline tuberculoid leprosy. Int J Dermatol. 2009 Jan. 48(1):11-3. [Medline].
Trindade MA, Palermo ML, Pagliari C, et al. Leprosy in transplant recipients: report of a case after liver transplantation and review of the literature. Transpl Infect Dis. 2011 Feb. 13(1):63-9. [Medline].
Ardalan M, Ghaffari A, Ghabili K, Shoja MM. Lepromatous leprosy in a kidney transplant recipient: a case report. Exp Clin Transplant. 2011 Jun. 9(3):203-6. [Medline].
Vanderborght PR, Pacheco AG, Moraes ME, et al. HLA-DRB1*04 and DRB1*10 are associated with resistance and susceptibility, respectively, in Brazilian and Vietnamese leprosy patients. Genes Immun. 2007 Jun. 8(4):320-4. [Medline].
Jarduli LR, Sell AM, Reis PG, Sippert EÂ, Ayo CM, Mazini PS. Role of HLA, KIR, MICA, and cytokines genes in leprosy. Biomed Res Int. 2013. 2013:989837. [Medline].
Alter A, Alcaïs A, Abel L, Schurr E. Leprosy as a genetic model for susceptibility to common infectious diseases. Hum Genet. 2008 Apr. 123(3):227-35. [Medline].
Schurr E, Alcaïs A, de Leseleuc L, Abel L. Genetic predisposition to leprosy: A major gene reveals novel pathways of immunity to Mycobacterium leprae. Semin Immunol. 2006 Dec. 18(6):404-10. [Medline].
Goulart LR, Ferreira FR, Goulart IM. Interaction of TaqI polymorphism at exon 9 of the vitamin D receptor gene with the negative lepromin response may favor the occurrence of leprosy. FEMS Immunol Med Microbiol. 2006 Oct. 48(1):91-8. [Medline].
Velayati AA, Farnia P, Khalizadeh S, Farahbod AM, Hasanzadh M, Sheikolslam MF. Interferon-gamma receptor-1 gene promoter polymorphisms and susceptibility to leprosy in children of a single family. Am J Trop Med Hyg. 2011 Apr. 84(4):627-9. [Medline]. [Full Text].
Fava V, Orlova M, Cobat A, Alcaïs A, Mira M, Schurr E. Genetics of leprosy reactions: an overview. Mem Inst Oswaldo Cruz. 2012 Dec. 107 Suppl 1:132-42. [Medline].
Bhushan P, Sardana K, Koranne RV, Choudhary M, Manjul P. Diagnosing multibacillary leprosy: a comparative evaluation of diagnostic accuracy of slit-skin smear, bacterial index of granuloma and WHO operational classification. Indian J Dermatol Venereol Leprol. 2008 Jul-Aug. 74(4):322-6. [Medline].
Silva EA, Iyer A, Ura S, et al. Utility of measuring serum levels of anti-PGL-I antibody, neopterin and C-reactive protein in monitoring leprosy patients during multi-drug treatment and reactions. Trop Med Int Health. 2007 Dec. 12(12):1450-8. [Medline].
Parkash O, Kumar A, Pandey R, Nigam A, Girdhar BK. Performance of a lateral flow test for the detection of leprosy patients in India. J Med Microbiol. 2008 Jan. 57:130-2. [Medline].
Parkash O, Kumar A, Pandey R, Franken KL, Ottenhoff TH. Detection of Mycobacterium leprae infection employing a combinatorial approach of anti-45 kDa and modified anti-PGL-I antibody detection assays. J Med Microbiol. 2007 Aug. 56:1129-30. [Medline].
Duthie MS, Balagon MF, Maghanoy A, Orcullo FM, Cang M, Dias RF. Rapid Quantitative Serological Test for Detection of Infection with Mycobacterium leprae, the Causative Agent of Leprosy. J Clin Microbiol. 2014 Feb. 52(2):613-9. [Medline].
Bang PD, Suzuki K, Phuong le T, Chu TM, Ishii N, Khang TH. Evaluation of polymerase chain reaction-based detection of Mycobacterium leprae for the diagnosis of leprosy. J Dermatol. 2009 May. 36(5):269-76. [Medline].
Natrajan M, Katoch K, Katoch VM, Das R, Sharma VD. Histological diagnosis of early and suspicious leprosy by in situ PCR. Indian J Lepr. 2012 Jul-Sep. 84(3):185-94. [Medline].
Phetsuksiri B, Rudeeaneksin J, Supapkul P, Wachapong S, Mahotarn K, Brennan PJ. A simplified reverse transcriptase PCR for rapid detection of Mycobacterium leprae in skin specimens. FEMS Immunol Med Microbiol. 2006 Dec. 48(3):319-28. [Medline].
Duthie MS, Orcullo FM, Abbelana J, Maghanoy A, Balagon MF. Comparative evaluation of antibody detection tests to facilitate the diagnosis of multibacillary leprosy. Appl Microbiol Biotechnol. 2016 Apr. 100 (7):3267-75. [Medline].
Reja AH, De A, Biswas S, Chattopadhyay A, Chatterjee G, Bhattacharya B. Use of fine needle aspirate from peripheral nerves of pure-neural leprosy for cytology and PCR to confirm the diagnosis: a pilot study. Indian J Dermatol Venereol Leprol. 2013 Nov-Dec. 79(6):789-94. [Medline].
Ray R, Mondal RK, Pathak S. Diagnosis of erythema nodosum leprosum (type 2 reaction) by cytology. Acta Cytol. 2014. 58(1):29-32. [Medline].
Rothschild BM, Rothschild C. Skeletal manifestations of leprosy: analysis of 137 patients from different clinical settings in the pre- and post-modern treatment eras. J Clin Rheumatol. 2001 Aug. 7(4):228-37. [Medline].
Frade MA, Nogueira-Barbosa MH, Lugão HB, Furini RB, Marques Júnior W, Foss NT. New sonographic measures of peripheral nerves: a tool for the diagnosis of peripheral nerve involvement in leprosy. Mem Inst Oswaldo Cruz. 2013 May. 108(3):[Medline].
Garbino JA, Heise CO, Marques W Jr. Assessing nerves in leprosy. Clin Dermatol. 2016 Jan-Feb. 34 (1):51-8. [Medline].
Gupta SK, Nigam S, Mandal AK, Kumar V. S-100 as a useful auxiliary diagnostic aid in tuberculoid leprosy. J Cutan Pathol. 2006 Jul. 33(7):482-6. [Medline].
Reja AH, Biswas N, Biswas S, Dasgupta S, Chowdhury IH, Banerjee S. Fite-Faraco staining in combination with multiplex polymerase chain reaction: a new approach to leprosy diagnosis. Indian J Dermatol Venereol Leprol. 2013 Sep-Oct. 79(5):693-700. [Medline].
Reddy RR, Singh G, Sacchidanand S, et al. A comparative evaluation of skin and nerve histopathology in single skin lesion leprosy. Indian J Dermatol Venereol Leprol. 2005 Nov-Dec. 71(6):401-5. [Medline].
Nery JA, Bernardes Filho F, Quintanilha J, Machado AM, Oliveira Sde S, Sales AM. Understanding the type 1 reactional state for early diagnosis and treatment: a way to avoid disability in leprosy. An Bras Dermatol. 2013 Sep-Oct. 88(5):787-92. [Medline].
World Health Organization. WHO-recommended MDT regimens. World Health Organization. Available at http://www.who.int/lep/mdt/regimens/en/.
Jing Z, Zhang R, Zhou D, Chen J. Twenty five years follow up of MB leprosy patients retreated with a modified MDT regimen after a full course of dapsone mono-therapy. Lepr Rev. 2009 Jun. 80(2):170-6. [Medline].
World Health Organization. WHO Model Prescribing Information: Drugs Used in Leprosy, 1998. Available at http://apps.who.int/medicinedocs/en/d/Jh2988e/5.html. Accessed: January 31, 2014.
Bureau of Primary Health Care. Standard treatment regimens. US Department of Health and Human Services. Health Resources and Services Administration. Available at http://www.hrsa.gov/hansens/clinical/regimens.htm.
Sapkota BR, Shrestha K, Pandey B, Walker SL. A retrospective study of the effect of modified multi-drug therapy in Nepali leprosy patients following the development of adverse effects due to dapsone. Lepr Rev. 2008 Dec. 79(4):425-8. [Medline].
Balagon MF, Cellona RV, Abalos RM, Gelber RH, Saunderson PR. The efficacy of a four-week, ofloxacin-containing regimen compared with standard WHO-MDT in PB leprosy. Lepr Rev. 2010 Mar. 81(1):27-33. [Medline].
Lakshmi C, Srinivas CR. Lepromatous leprosy treated with combined chemotherapy and immunotherapy (injection BCG): three case reports. Int J Dermatol. 2014 Jan. 53(1):61-5. [Medline].
Duthie MS, Hay MN, Rada EM, et al. Specific IgG antibody responses may be used to monitor leprosy treatment efficacy and as recurrence prognostic markers. Eur J Clin Microbiol Infect Dis. 2011 May 5. [Medline].
Antunes DE, Araujo S, Ferreira GP, Cunha AC, Costa AV, Gonçalves MA. Identification of clinical, epidemiological and laboratory risk factors for leprosy reactions during and after multidrug therapy. Mem Inst Oswaldo Cruz. 2013 Nov. 108(7):901-8. [Medline].
Rao PS, Sugamaran DS, Richard J, Smith WC. Multi-centre, double blind, randomized trial of three steroid regimens in the treatment of type-1 reactions in leprosy. Lepr Rev. 2006 Mar. 77(1):25-33. [Medline].
Safa G, Darrieux L, Coic A, Tisseau L. Type 1 leprosy reversal reaction treated with topical tacrolimus along with systemic corticosteroids. Indian J Med Sci. 2009 Aug. 63(8):359-62. [Medline].
Aires NB, Refkalefsky Loureiro W, Villela MA, Sakai Valente NY, Trindade MA. Sweet's syndrome type leprosy reaction. J Eur Acad Dermatol Venereol. 2009 Apr. 23(4):467-9. [Medline].
Chauhan S, D'Cruz S, Mohan H, Singh R, Ram J, Sachdev A. Type II lepra reaction: an unusual presentation. Dermatol Online J. 2006 Jan 27. 12(1):18. [Medline].
Fabi SG, Hill C, Witherspoon JN, Boone SL, West DP. Frequency of thromboembolic events associated with thalidomide in the non-cancer setting: a case report and review of the literature. J Drugs Dermatol. 2009 Aug. 8(8):765-9. [Medline].
Verma KK, Srivastava P, Minz A, Verma K. Role of azathioprine in preventing recurrences in a patient of recurrent erythema nodosum leprosum. Lepr Rev. 2006 Sep. 77(3):225-9. [Medline].
Kar BR, Babu R. Methotrexate in resistant ENL. Int J Lepr Other Mycobact Dis. 2004 Dec. 72(4):480-2. [Medline].
Faber WR, Jensema AJ, Goldschmidt WF. Treatment of recurrent erythema nodosum leprosum with infliximab. N Engl J Med. 2006 Aug 17. 355(7):739. [Medline].
Ramien ML, Wong A, Keystone JS. Severe refractory erythema nodosum leprosum successfully treated with the tumor necrosis factor inhibitor etanercept. Clin Infect Dis. 2011 Mar 1. 52(5):e133-5. [Medline].
Costa IM, Kawano LB, Pereira CP, Nogueira LS. Lucio's phenomenon: a case report and review of the literature. Int J Dermatol. 2005 Jul. 44(7):566-71. [Medline].
Crawford CL. No role for thalidomide in the treatment of leprosy. J Infect Dis. 2006 Jun 15. 193(12):1743-4; author reply 1744-5. [Medline].
Sahay G, Kar HK, Gupta R. Effect of Steroid Prophylaxis on Nerve Function Impairment in Multi-bacillary Leprosy Patients on MDT-MB. Indian J Lepr. 2015 Jul-Sep. 87 (3):133-43. [Medline].
Bilodeau M, Burns S, Gawoski J, Moschella S, Ooi W. Co-morbid infections in Hansen's disease patients in the United States: considerations for treatment. Am J Trop Med Hyg. 2013 Oct. 89(4):781-3. [Medline].
Sena CB, Salgado CG, Tavares CM, Da Cruz CA, Xavier MB, Do Nascimento JL. 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 Jun. 77(2):121-9. [Medline].
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 Dec 9. 2:381. [Medline]. [Full Text].
Rath S, Schreuders TA, Selles RW. Early postoperative active mobilisation versus immobilisation following tibialis posterior tendon transfer for foot-drop correction in patients with Hansen's disease. J Plast Reconstr Aesthet Surg. 2009 Feb 19. [Medline].
Shah RK. Tibialis posterior transfer by interosseous route for the correction of foot drop in leprosy. Int Orthop. 2009 Dec. 33(6):1637-40. [Medline].
Kanaji A, Higashi M, Namisato M, Nishio M, Ando K, Yamada H. Effects of risedronate on lumbar bone mineral density, bone resorption, and incidence of vertebral fracture in elderly male patients with leprosy. Lepr Rev. 2006 Jun. 77(2):147-53. [Medline].
Pereira HL, Ribeiro SL, Pennini SN, Sato EI. Leprosy-related joint involvement. Clin Rheumatol. 2009 Jan. 28(1):79-84. [Medline].
Silva Junior GB, Daher Ede F, Pires Neto Rda J, Pereira ED, Meneses GC, Araújo SM, et al. Leprosy nephropathy: a review of clinical and histopathological features. Rev Inst Med Trop Sao Paulo. 2015 Jan-Feb. 57 (1):15-20. [Medline].
Moet FJ, Pahan D, Oskam L, Richardus JH. Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial. BMJ. 2008 Apr 5. 336(7647):761-4. [Medline]. [Full Text].
Feenstra SG, Pahan D, Moet FJ, Oskam L, Richardus JH. Patient-related factors predicting the effectiveness of rifampicin chemoprophylaxis in contacts: 6 year follow up of the COLEP cohort in Bangladesh. Lepr Rev. 2012 Sep. 83(3):292-304. [Medline].
Smith WC. Chemoprophylaxis in the prevention of leprosy. BMJ. 2008 Apr 5. 336(7647):730-1. [Medline].