Leprosy Treatment & Management

Updated: Jun 05, 2020
  • Author: Darvin Scott Smith, MD, MSc, DTM&H; Chief Editor: Michael Stuart Bronze, MD  more...
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Treatment

Medical Care

In response to the increased incidence of dapsone resistance, the WHO introduced a multidrug regimen in 1981 that includes rifampicin, dapsone, and clofazimine. Some clinical studies have also shown that certain quinolones, minocycline, and azithromycin have activity against M leprae. The WHO recommends the use of the long-term multidrug regimens for both paucibacillary and multibacillary leprosy. See Table 1.

Table 1. 2018 WHO Leprosy Treatment Guidelines. [18] (Open Table in a new window)

Age Group

Drug

Dosage and Frequency

Duration

Multibacillary Leprosy

Paucibacillary Leprosy

Adult

Rifampicin

600 mg once a month

12 months

6 months

Clofazimine

300 mg once a month and 50 mg daily

Dapsone

100 mg daily

Children (10-14 years)

Rifampicin

450 mg once a month

12 months

6 months

Clofazimine

150 mg once a month, 50 mg on alternate days

Dapsone

50 mg daily

Children < 10 years or < 40 kg

Rifampicin

10 mg/kg once a month

12 months

6 months

Clofazimine

100 mg once a month, 50 mg twice weekly

Dapsone

2 mg/kg daily

US regimens emphasize the use of rifampin, which is the most bactericidal drug used to treat leprosy. Corticosteroids have been used to treat nerve damage associated with leprosy, but a recent review of 3 randomized controlled trials shows no significant long-term effect. [19] Prednisolone is believed to minimize pain and acute inflammation. The recommended initial dose is prednisolone 40 mg daily.

Observations of increasing resistance in patients treated for leprosy have been reported in Southeast Asia, notably in Vietnam. [20] Although drug resistance is an ongoing concern, it is difficult to assess in this slow-growing organism. In a study of M leprae strains from South America, few of 230 strains subjected to molecular drug-susceptibility analysis were drug-resistant. Of the 230 strains, 3 were identified as clinically relapsing and were found to be resistant by genetic testing; 2 of the 3 were dapsone-resistant; and 1 was dapsone-resistant and rifampin-resistant using genetic testing for point mutation. [21] The map below shows distribution of rifampicin-resistant leprosy in 2015.

Map of countries reporting rifampicin resistance i Map of countries reporting rifampicin resistance in leprosy between 2009 and 2015. Courtesy of the WHO.

For rifampicin-resistant leprosy, the WHO recommends treatment with at least two of clarithromycin, minocycline, and quinolone, in addition to clofazimine daily for six months, followed by clofazimine and one of the above drugs for an additional 18 months. In cases of both rifampicin and ofloxacin resistance, the recommended treatment is clarithromycin, minocycline, and clofazimine for 6 months, followed by clarithromycin or minocycline and clofazimine for an additional 18 months. See Table 2.

Table 2. 2018 WHO Treatment Guidelines for Drug-Resistant Leprosy. [18] (Open Table in a new window)

Resistance Type

Treatment

First 6 months (daily)

Next 18 months (daily)

Rifampicin resistance

Ofloxacin 400 mg* plus

Minocycline 100 mg plus

Clofazimine 50 mg

Ofloxacin 400 mg* or

Minocycline 100 mg plus

Clofazimine 50 mg

Ofloxacin 400 mg* plus

Clarithromycin 500 mg plus

Clofazimine 50 mg

Ofloxacin 400 mg* plus

Clofazimine 50 mg

Rifampicin and ofloxacin resistance

Clarithromycin 500 mg plus

Minocycline 100 mg plus

Clofazimine 50 mg

Clarithromycin 500 mg or

Minocycline 100 mg plus

Clofazimine 50 mg

*Ofloxacin 400 mg can be replaced by levofloxacin 500 mg or moxifloxacin 400 mg

WHO guidelines (2018) for single-dose rifampicin are as follows: [18] For chemoprophylaxis, the WHO guidelines recommend the use of single-dose rifampicin for contacts of patients with leprosy.

  • Patients aged 15 years or older: Rifampicin 600 mg as a single dose
  • Patients aged 10-14 years: Rifampicin 450 mg as a single dose
  • Patients aged 6-9 years (≥20 kg): Rifampicin 300 mg as a single dose
  • Patients aged 2 years or older (< 20 kg): Rifampicin 10-15 mg/kg as a single dose
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Surgical Care

The goals of surgical treatment in patients with leprosy are to prevent further deterioration, to improve motor function, and, in some cases, to improve sensation.

Preoperative requirements

First, a full sensory and motor appraisal with functional and occupational assessment must be completed to determine the extent of damage. Additionally, patients must have completed the multidrug therapy and should have negative skin smear results. The patient should not use steroids a few months before surgery, and acute neuritis should not be evident. Stiffness of hands and feet should be minimized with preoperative therapy.

Neural surgery

Attempts to restore autonomic function and sensation are rarely undertaken since little evidence shows that function is significantly regained. Draining of acute nerve abscesses and fascicular dissection can reduce the pressure on nerves and may improve sensation. In some cases, longitudinal epineurotomy may relieve some sensory loss. Considerable nerve function can be regained in the posterior tibial nerve with neurovascular decompression via release of the flexor retinaculum. Calcaneal bands can be slit to relieve distal compression of branches on the sole of the foot.

Nerve grafts may be of some benefit in patients with localized lesions. Neural surgery may also be indicated in patients with unremitting nerve pain.

Reconstruction and functional restoration  [15]

In leprosy management, the goal of most surgical procedures is to remedy motor paralysis due to primary nerve impairment. Claw fingers and Z-thumbs caused by ulnar nerve paralysis are among the most common deformities. Clawed hands are repaired with arthrodesis or with a tendon transfer to 1 of 4 insertion sites on the finger: interosseus tendons, proximal phalanx, dorsal extensor expansion, or flexor sheath annular pulleys. The palmaris longus, flexor digitorum superficialis, extensor carpi radialis longus, and extensor indices are tendons that can be used for transfer. Tendon transfers are also used to repair abduction and opposition of the thumb, dorsiflexion of the foot, and flexion and extension of the metacarpophalangeal and proximal interphalangeal joints, respectively.

Contractures of the hand, such as the thumb web contracture, can be repaired with Z-plasty, and joint stability can be improved with tenodesis.

The constrictions caused by repetitive injury and healing in patients with leprosy can be treated with several methods. Possible treatment options include removal of the carpal tunnel roof, ulnar nerve transposition anteriorly, and epicondylectomy.

Procedures that limit hyperextension of the metacarpophalangeal joint or keep it in flexion are not indicated in the insensate hands of patients with leprosy, who suffer from continued weakness.

Amputation is a last resort and is reserved for cases of extremely diseased tissue.

Eye procedures

Loss of eyelid function may be treated with passing a strip from the temporalis muscle through the eyelid and connecting it to the inner canthus. Tarsorrhaphy may help narrow the opening of the eyelid, and canthoplasty reduces sagging of the eyelids.

Cosmetic surgery

After the disease is controlled medically, the following cosmetic procedures may also be considered:

  • Nasal reconstruction
  • Removal of excess skin
  • Replacement of eyebrows using transplants of scalp hair
  • Removal of breast tissue formation due to gynecomastia
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Consultations

Consultations may include an orthopedic surgeon, dermatologist, neurologist, psychiatrist, and physical therapist, based on the needs of the individual patient.

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Complications

Careful attention to the development of reversal reactions during treatment and prompt and proper management will minimize long-term neurologic sequelae.

Type 1 reaction

Reversal reaction, or lepra type 1 reaction, is a delayed-type hypersensitivity reaction that arises when borderline leprosy shifts toward borderline lepromatous leprosy with treatment. These types of reactions reflect the development of an appropriate immune response and the local generation of tumor necrosis factor-alpha and interferon-gamma. The reaction is characterized by edema and erythema of existing skin lesions, formation of new skin lesions, neuritis, and additional sensory and motor loss.

The likelihood of a type 1 reaction in patients with borderline leprosy is 30%. [17]

Treatment includes nonsteroidal anti-inflammatory drugs (NSAIDs) and high-dose steroids. Prednisone is given at a dose of 40-60 mg/day with a decreasing taper of 5 mg every 2-4 weeks after improvement is demonstrated. For reactions not controlled by prednisone, ciclosporin is the second-line treatment. [22]

Type 2 reaction

Erythema nodosum leprosum (ENL), also known as lepra type 2 reaction, is a complication of lepromatous leprosy. It is characterized by the development of inflamed subcutaneous nodules accompanied at times by fever, lymphadenopathy, and arthralgias. High levels of tumor necrosis factor-alpha and immune complex deposition are associated with ENL. [17] Treatment includes prednisolone, clofazimine, or thalidomide. Erythema nodosum leprosum reaction is seen in the image below.

Patient with multibacillary leprosy showing subseq Patient with multibacillary leprosy showing subsequent erythema nodosum leprosum reaction. Santa Clara, California. Courtesy of D. Scott Smith, MD.

Mild ENL reactions are treated with aspirin 600-1200 mg/day in 4-6 doses per day.

Severe ENL reactions are treated with prednisone 60-80 mg/day with a slow taper, reducing by 5-10 mg every 2-4 weeks, depending on response and severity, to prevent residual deformity and nerve damage.

Alternatively, thalidomide 100 mg PO 4 times per day (if available and in the absence of contraindications) can be used in cases that involve large subcutaneous plaques, arthritis, and temperature that exceeds 38.8°C.

Lucio phenomenon

Lucio phenomenon is a severe complication of multibacillary leprosy that is marked by blue hemorrhagic plaques and necrotic ulcerations. The bacilli may extend to the endothelial cells along with the appearance of necrotic epidermis and vasculitis with thrombus formation and endothelial proliferation. Lucio phenomenon is treated aggressively using systemic steroids.

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