Leprosy

Background

Leprosy is a chronic infection caused by the acid-fast, rod-shaped bacillus Mycobacterium leprae. Leprosy can be considered 2 connected diseases that primarily affect superficial tissues, especially the skin and peripheral nerves. Leprosy is suspected to be transmitted via droplets from the nose and mouth after prolonged close contact with someone.^[1] Initially, a mycobacterial infection causes a wide array of cellular immune responses. These immunologic events elicit the second part of the disease, peripheral neuropathy, with potentially long-term consequences.

The social and psychological effects of leprosy and its highly visible debilities and sequelae (as seen in the image below) have resulted in a historical stigma associated with leprosy. To minimize the prejudice against those with leprosy, the condition is also known as Hansen disease, named after G.A. Hansen, who is credited with the 1873 discovery of M leprae. This mycobacterium grows extremely slowly but has been successfully cultured in vitro using Dubos-Lowenstein-Jensen medium and thyroxine sodium.^[2]

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Hands with Z-thumbs, clawing, contractures, and shortening of fingers due to repetitive injury and healing. Ho Chi Minh City, Vietnam. Courtesy of D. ....

In the 1990s, the World Health Organization (WHO) launched a campaign to eliminate leprosy as a public health problem by 2000. Elimination, as defined by the WHO, meant a reduction of patients with leprosy requiring multidrug therapy to fewer than 1 per 10,000 population. This goal was achieved in terms of global prevalence by 2002 and, as of 2015, had been maintained. As of 2015, none of the 122 countries where leprosy was endemic in 1985 still have prevalence rates of greater than 1 per 10,000 population.^[3] However, in 2019, much of the disease burden of leprosy was concentrated in India, Brazil, and Indonesia, with India alone accounting for over 79% of cases worldwide as of 2018.^[1]

In April 2021, the WHO launched its 2021-2030 strategy, “Towards zero leprosy.” The goal of this strategy is the “elimination of leprosy.” Elimination is now defined as the interruption of transmission in a geographic zone. These goals are centered around four pillars: implement integrated, country-owned zero leprosy road maps in all endemic countries; scale up leprosy prevention alongside integrated active case detection; manage leprosy and its complications and prevent new disability; and combat stigma and ensure human rights are respected.^[1]  In 2019, the WHO reported 202,256 new leprosy cases, corresponding to a prevalence of 1.4 per million.^[1] The case prevalence of leprosy (registered number of people on treatment) at the end of 2020 was 129,192, with a case rate of 16.6 per million. This reduction in cases is likely due to underreporting as a result of the pandemic.^[4]

Although multidrug regimens had been used globally to cure nearly 18 million patients with leprosy since 1981,^[1]  the number of new leprosy cases remained relatively unchanged from 1980 to 2000, ranging from 500,000-700,000 worldwide per year.^[5] Between 2001 and 2006, the global incidence of leprosy declined suddenly, largely owing to new case reductions in India.

The goal of the WHO by the end of 2015 was to reduce the rate of new cases with grade-2 disabilities(G2D) worldwide by at least 35%. This was done by enforcing activities to decrease the delay in diagnosing the disease and actuate treatment with multidrug therapy. This also reduced transmission of the disease in the community.^[5]  Now, the goal for 2030 is to reduce the rate of new cases with G2D by 90%.^[1]  

Access and delivery of antibiotics continue to be a problem in most endemic nations. With the precise transmission mechanism of leprosy still unknown and the lack of an effective vaccine, leprosy will probably continue to pose an ongoing public health problem in the coming decades.

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Pathophysiology

Leprosy can manifest in different forms, depending on the host response to the organism.

Individuals who have a vigorous cellular immune response to M leprae have the tuberculoid form of the disease that usually involves the skin and peripheral nerves. The reaction types include type 1 reaction (T1R). The number of skin lesions is limited, and they tend to be dry and hypoesthetic. Nerve involvement is usually asymmetric. This form of the disease is also referred to as paucibacillary leprosy because of the low number of bacteria in the skin lesions (ie, < 5 skin lesions, with the absence of organisms on smear). Results of skin tests with antigen from killed organisms are positive in these individuals.

Individuals with minimal cellular immune response have the lepromatous form of the disease, which is characterized by extensive skin involvement. Skin lesions are often described as infiltrated nodules and plaques, and nerve involvement tends to be symmetric in distribution. The organism grows best at 27-30°C; therefore, skin lesions tend to develop in the cooler areas of the body, with sparing of the groin, axilla, and scalp. This form of the disease is also referred to as multibacillary leprosy because of the large number of bacteria found in the lesions (ie, >6 lesions, with possible visualization of bacilli on smear). Results of skin tests with antigen from killed organisms are nonreactive.

Patients may also present with features of both categories (indeterminate or borderline leprosy); however, over time, they usually evolve to 1 or the other. Interestingly, most individuals who are exposed to leprosy never develop the disease, likely because over 95% of people have natural immunity to it.^[6]

Classification of leprosy

Leprosy has 2 classification schemas: the 5-category Ridley-Jopling system and the simpler and more commonly used WHO standard.^[7]

Ridley-Jopling: Depending on the host response to the organism, leprosy can manifest clinically along a spectrum bounded by the tuberculoid and lepromatous forms of the disease. Most patients fall into the intermediate classifications, which include borderline tuberculoid (BT) leprosy, midborderline (BB) leprosy, and borderline lepromatous (BL) leprosy. The classification of the disease typically changes as it evolves during its progression or management. The Ridley-Jopling system is used globally and forms the basis of clinical studies of leprosy. It also may be more useful in guiding treatment regimens and assessing risk for acute complications. Physical findings in each subtype are presented in the Clinical section.

​According to the WHO, in an endemic area, an individual is considered to have leprosy if they show either of the 2 following signs^[7] :

• A skin lesion consistent with leprosy and definite sensory loss, with or without thickened nerves
• Positive skin smears

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Epidemiology

Frequency

United States

In 2015, according to the Centers for Disease Control and Prevention (CDC), 178 new cases of leprosy were reported in the United States.^[8]

Eighty-five percent of leprosy cases in the United States are found in immigrants,^[9] although endemic foci exist in parts of Louisiana, Florida, and Texas along the Gulf of Mexico; in Mexican and Asian California populations; and in Spanish Americans in New York City.

Some cases among native US citizens can be accounted for by exposure to leprosy overseas. Some cases can be attributed to a contact with a known case of leprosy or exposure to infected armadillos, especially in the southern United States, where wild armadillos and many patients with leprosy in the United States are infected with the same strain of M leprae.^[8] Leprosy may be a zoonosis in the southern United States because armadillos are a large reservoir for this disease.

Nonetheless, history of exposure cannot be verified in many patients.^[10]

International

According to WHO figures based on reports from 159 countries, 208,619 new leprosy cases were reported globally in 2018. The worldwide prevalence reported at the end of 2018 was 184,212 cases (rate, 0.2/10,000). In 2018, Brazil, India, and Indonesia accounted for 79.6% of all new leprosy cases.^[11] In addition, 23 priority countries accounted for 96% of cases worldwide in 2018.

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WHO map showing new cases of new leprosy cases, 2020. Courtesy of the WHO.

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Mortality/Morbidity

Leprosy is rarely fatal, and the primary consequences of infection are nerve impairment and debilitating sequelae. According to one study, 33-56% of newly diagnosed patients already displayed signs of impaired nerve function.^[12]  According to estimates, 3 million people who have completed multidrug therapy for leprosy have sustained disability due to nerve damage. Although both lepromatous leprosy and tuberculoid leprosy involve the skin and peripheral nerves, tuberculoid leprosy has more severe manifestations. Nerve involvement results in sensory and motor function loss, which may lead to frequent trauma and amputation. The ulnar nerve most commonly is involved.

Damage in the following nerves is associated with characteristic impairments in leprosy:

• Ulnar and median - Clawed hand
• Posterior tibial - Plantar insensitivity and clawed toes
• Common peroneal - Foot drop
• Radial cutaneous, facial, and greater auricular nerves (may also be involved, as seen in the image below)
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Infiltration by bacteria may lead to destruction of nasal cartilage (lepromatous leprosy), ocular involvement, and diffuse thickening of the skin. Advanced cases of leprosy involve the loss of eyebrows and lashes, but these deformities are less common today.

Worldwide, leprosy is considered a common cause of crippling of the hand, which is caused by ulnar nerve involvement.^[13] Peroneal nerve involvement can lead to foot drop, posterior tibial nerve involvement, and clawed toes.

Race

Leprosy was once endemic worldwide, and no racial predilection is known. In the late 1800s, the incidence of leprosy in northern Europe and North America dropped dramatically, and the disease now is reported primarily in tropical areas.

Sex

Leprosy generally is more common in males than in females, with a male-to-female ratio of 2:1. In some areas in Africa, the prevalence of leprosy among females is equal to or greater than that in males.^[14]

Age

Leprosy can occur at any age, but in developing countries, the age-specific incidence of leprosy peaks in children younger than 10 years, who account for 20% of leprosy cases. Leprosy is rare in infants; however, they are at a relatively high risk of acquiring leprosy from the mother, especially in cases of lepromatous leprosy or midborderline leprosy.

HIV coinfection

Unlike with tuberculosis, preliminary data suggest that coinfection with HIV does not seem to have an effect on leprosy. Furthermore, HIV coinfection does not seem to affect the ratio of lepromatous to tuberculoid leprosy.^[12]

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History

Symptoms

Symptoms are as follows:

• Painless skin patch. Chronic insensate patch is seen in the image below.

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  Chronic insensate patch due to leprosy infection. Ho Chi Minh City, Vietnam. Courtesy of D. Scott Smith, MD.

   

  

   
• Loss of sensation or paresthesias where the affected peripheral nerves are distributed
• Wasting and muscle weakness
• Foot drop or clawed hands (may result from neuritic pain and rapid peripheral nerve damage; as seen in the image below)
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• Ulcerations on hands or feet (ulcer at the metatarsal head is seen in the image below)
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Ridley-Jopling classification ^[15]

Signs and symptoms of tuberculoid leprosy include the following:

• Painless pale or red skin lesions with loss of sensation; lesions become raised as the disease progresses
• A few affected nerves with diminished sensation and burning or tingling sensations
• Significant sensory loss early in the disease course
• Milder disease and fewer bacteria

Signs and symptoms of lepromatous leprosy include the following:

• Painless pale or red skin lesions without loss of sensation; lesions become raised as the disease progresses
• Thickening of peripheral nerves with diminished sensation and burning or tingling sensations
• Extensive sensory loss over a longer period
• More severe disease and larger numbers of bacteria
• Facial deformities and paralysis
• Involvement of eyes, bones, and other tissues

WHO Classification

The WHO Classification of leprosy is as follows:

• Multibacillary: More skin lesions
• Paucibacillary: Fewer skin lesions
• Single-lesion paucibacillary: Single skin lesion

Symptoms in reactions

Symptoms in reactions are as follows:

• Type 1 (reversal) - Sudden onset of skin redness and new lesions
• Type 2 (erythema nodosum leprosum [ENL]; as seen in the image below) - Many skin nodules, fever, redness of eyes, muscle pain, and joint pain (seen in lepromatous leprosy only)^[15]
• Lucio phenomenon - Multiple ulcers

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Patient with erythema nodosum leprosum type 2 reaction several weeks after initiation of drug therapy. This photograph was taken after tendon release.....

Travel

Leprosy should be considered in anyone who has lived in the tropics or who has traveled for prolonged periods to endemic areas.

Exposure

The incubation period of leprosy is long, ranging from a few months to 20-50 years. The mean incubation time is estimated to be 10 years for lepromatous leprosy and 4 years for tuberculoid leprosy. The organism's slow dividing time (once every 2 wk) contributes to the challenge of epidemiologically linking exposures to the development of disease.

Because of immunologic reasons, only around 5-10% of the population is estimated to be susceptible to infection.

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Physical

The cardinal signs of leprosy include hypoesthesia, skin lesions, and peripheral neuropathy. The first physical signs of leprosy usually are cutaneous. The subtype of leprosy often determines the degree of skin involvement.

Physical examination

Physical examination should include the following:

• Evaluation of skin lesions
• Careful sensory and motor examination
• Palpation of peripheral nerves for pain or enlargement, with particular attention paid to the following locations:

  • Elbows - Ulnar nerve
  • Wrist - Superficial radial cutaneous and median nerves
  • Popliteal fossa - Common peroneal nerve
  • Neck - Great auricular nerve

   

  

   

Physical findings in specific leprosy subtypes

​Tuberculoid leprosy

The initial lesion often is a sharply demarcated hypopigmented macule that is ovoid, circular, or serpiginous. The lesions may be somewhat elevated with a dry scaly center and erythematous borders.

Common lesion sites include the buttocks, face, and extensor surfaces of limbs. The perineum, scalp, and axilla are not normally involved because of the temperature differential in these zones, as predilection is toward cooler zones.

As the disease progresses, lesions tend to destroy the normal skin organs such as sweat glands and hair follicles.

Superficial nerves that lead from the lesions tend to enlarge and sometimes are palpable. The patient may experience severe neuropathic pain. Nerve involvement can lead to trauma and muscle atrophy.

Lepromatous leprosy

This form is characterized by extensive bilaterally symmetric cutaneous involvement, which can include macules, nodules, plaques, or papules. Multiple flat hypopigmented lesions are seen in the image below.

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Multiple flat hypopigmented lesions on shoulder and neck, suggestive of multibacillary leprosy. Note ulceration of hypothenar area of hand, indicative....

Unlike lesions in tuberculoid leprosy, those in lepromatous leprosy have poorly defined borders and raised and indurated centers. As in all forms of leprosy, lepromatous lesions are worse on cooler parts of the body. Common areas of involvement include the face, ears, wrists, elbows, buttocks, and knees.

Hoarseness, loss of eyebrows and eyelashes, and nasal collapse secondary to septal perforation may occur in advanced cases of disease. Involvement of the eye may include keratitis, glaucoma, or iridocyclitis as seen in the image below.

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Man with advanced deformities caused by unmanaged leprosy. Keratitis, loss of eyebrow, thickened skin, and typical hand impairments. Ho Chi Minh City,....

The leonine facies associated with leprosy develop as the disease progresses, and the facial skin becomes thickened and corrugated.

Axillary and inguinal adenopathy may develop, in addition to scarring of the testes and subsequent gynecomastia and sterility.

Nerve involvement in lepromatous leprosy is not as severe as in tuberculoid leprosy, since nerves, although visibly thickened and highly infected, still function reasonably well in early stages of the disease.

Borderline tuberculoid leprosy

The lesions are few or moderate and asymmetric with almost complete anesthesia. Peripheral nerves often are involved and thickened asymmetrically, and cutaneous nerves are sometimes enlarged.

Mid-borderline leprosy

The number of skin lesions is moderate, and they are asymmetrical and somewhat anesthetic. Peripheral nerves may be somewhat symmetrically enlarged, but cutaneous nerves are not.

Borderline lepromatous leprosy

Moderate to numerous slightly asymmetrical skin lesions appear with minor or no anesthesia. Peripheral nerves often are enlarged symmetrically, but cutaneous nerves are not.

Indeterminate leprosy

Skin lesions are typically either hypopigmented or hyperpigmented macules or plaques. Patients may note that these lesions are anesthetic or paresthetic.

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Causes

M leprae is the causative agent associated with leprosy, which has been recognized as an infectious disease for the last 2 millennia. M leprae was discovered as the causative agent in 1873. The acid fast, gram-positive bacillus is an obligate intracellular organism with a predilection for Schwann cells and macrophages.

The route of transmission has not been definitively established, although human-to-human aerosol spread of nasal secretions is thought to be the most likely mode of transmission in most cases. Leprosy is not spread by touch, since the mycobacteria are incapable of crossing intact skin. Living near people with leprosy is associated with increased transmission. Among household contacts, the relative risk for leprosy is increased 8- to 10-fold in multibacillary and 2- to 4-fold in paucibacillary forms. Animal reservoirs do exist (armadillos, certain nonhuman primates), and cases of suspected zoonotic transmission have been reported.

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Laboratory Studies

The WHO case definition of leprosy is M leprae infection in an individual who has not completed a course of treatment and has 1 or more of the following:

• Hypopigmented or reddish skin lesions with loss of sensation
• Involvement of the peripheral nerves as demonstrated by their thickening and associated loss of sensation
• Skin smear positive for acid-fast bacilli

This definition does not include patients who have completed an entire round of treatment but still have residual disabilities. The WHO recommendation as of 2018 is to continue to base diagnosis on the above clinical presentation combined with a confirmatory laboratory test, such a slit-skin smear or biopsy.

Laboratory studies include the following:

• Skin biopsy, nasal smears, or both are used to assess for acid-fast bacilli using Fite stain. Biopsies should be full dermal thickness taken from an edge of the lesion that appears most active.^[16]
• Serologic assays can be used to detect phenolic glycolipid-1 (specific for M leprae) and lipoarabinomannan (commonly seen in mycobacteria).^[16] However, serological tests show low sensitivity for paucibacillary leprosy.
• Molecular probes detect 40-50% of cases missed on prior histologic evaluation. Since probes require a minimum amount of genetic material (ie, 104 DNA copies), they can fail to identify paucibacillary leprosy.

Although the necessity of point-of-care and rapid diagnostic tests is recognized, these types of tests have yet to be developed.

Laboratory tests related to drug treatment follow-up include the following:

• CBC count
• Creatinine level
• Liver function tests

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Other Tests

Immunologic tests include the following:

• Polymerase chain reaction (PCR): PCR and recombinant DNA technology have allowed for the development of gene probes with M leprae–specific sequences. This technology can be used to identify the mycobacterium in biopsy samples, skin and nasal smears, and blood and tissue sections.^[17]
• Phenolic glycolipid-1: This is a specific serologic test based on the detection of antibodies to phenolic glycolipid-1. This test yields a sensitivity of 95% for the detection of lepromatous leprosy but only 30% for tuberculoid leprosy.
• Lymphocyte migration inhibition test (LMIT): As determined by a lymphocyte transformation and LMIT, cell-mediated immunity to M leprae is absent in patients with lepromatous leprosy but present in those with tuberculoid leprosy.
• Lepromin skin test (not available in the United States): Although not diagnostic of exposure to or infection with M leprae, this test assesses a patient's ability to mount a granulomatous response against a skin injection of killed M leprae. Patients with tuberculoid leprosy or borderline lepromatous leprosy typically have a positive response (>5 mm). Patients with lepromatous leprosy typically have no response.
• Contact or family screening for history of leprosy

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Procedures

Skin biopsy samples stained with hematoxylin-eosin and Fite-Faraco or Ziehl-Neelsen are the primary basis for laboratory diagnosis and categorization. A full-thickness skin biopsy sample should be taken from an advancing border of an active lesion and should include dermis and epidermis. Skin smears that demonstrate acid-fast bacilli strongly suggest a diagnosis of leprosy, but the bacilli may not be demonstrable in tuberculoid (paucibacillary) leprosy.

A nerve biopsy can be beneficial in ruling out diseases such as hereditary neuropathies or polyarteritis nodosa. Nerve biopsies also may help identify abnormalities in patients with subclinical leprosy and may be the only way to definitively diagnose completely neuropathic forms of leprosy. If a nerve biopsy is needed to confirm diagnosis, a purely sensory nerve (eg, sural or radial cutaneous nerve) should be used. This procedure is rarely necessary.^[18]

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Histologic Findings

Findings vary but can include dermatitis, giant cells, infiltration of nerve bundles with mononuclear cells, and granulomas. Lepromatous lesions generally contain numerous acid-fast bacilli and fat-laden macrophages with a paucity of lymphocytes. Histopathology of leprosy is seen in the image below.

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Histopathology of leprosy: Large numbers of acid-fast bacilli (in clusters) in histiocytes and within nerves. Fite-Faraco stain 500 X. Courtesy of Tar....

In contrast, tuberculoid lesions contain few-to-no acid-fast bacilli but manifest granulomatous changes with epithelial cells and lymphocytes. The immunopathologic spectrum of leprosy has been delineated in the Neurologic Manifestations of Leprosy topic in Medscape Reference's Neurology volume.

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Staging

Leprosy is staged or graded based on microscopy findings to classify cases as paucibacillary or multibacillary so that duration and type of drug therapy can be determined.

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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^[19]

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See Table

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.^[20] 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.^[21] 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.^[22] The map below shows distribution of rifampicin-resistant leprosy in 2015.

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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 6 months, followed by clofazimine and 1 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^[19]

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See Table

WHO guidelines (2018) for single-dose rifampicin are as follows18: 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 ^[16]

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 also may 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%.^[18]

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.^[23]

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.^[18] Treatment includes prednisolone, clofazimine, or thalidomide. Erythema nodosum leprosum reaction is seen in the image below.

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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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Guidelines Summary

The WHO treatment guidelines recommend treatment of both paucibacillary and multibacillary leprosy with a combination of 3 drugs. For rifampicin-resistant leprosy, the WHO guidelines indicate treatment with a multidrug regimen for the first 6 months, followed by second line treatments for the next 18 months.^[19]

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Medication Summary

The goals of pharmacotherapy are to eliminate the infection, to prevent complications, to halt its further transmission and spread, and to reduce morbidity.

The multidrug therapy (MDT) plan recommended by the WHO can be used to plan therapy based on the type of leprosy (paucibacillary or multibacillary) and whether it is supervised monthly or self-administered daily (see Medical Care).

Clofazimine is no longer commercially available in the United States. It is available only by obtaining an investigational new drug (IND) permit from the National Hansen’s Disease Program (NHDP) from the US Department of Health and Human Services. For more information, visit www.hrsa.gov/hansensdisease/ or call 1-800-642-2477.

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Dapsone

• Dosing, Interactions, etc.

Clinical Context:  Bactericidal and bacteriostatic against mycobacteria; mechanism of action is similar to that of sulfonamides, in which competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth. Part of a 3-drug regimen for treatment of both paucibacillary (6 months) and multibacillary (12 months) leprosy.

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Rifampin (Rifadin)

• Dosing, Interactions, etc.

Clinical Context:  For use in combination with at least 1 other antituberculous drug; inhibits DNA-dependent bacterial but not mammalian RNA polymerase. Most bactericidal drug used against M leprae. Cross-resistance may occur.

Treat for 6-9 mo or until 6 mo have elapsed from conversion to sputum-culture negativity.

Part of a 2-drug regimen for treatment of paucibacillary leprosy; part of a 3-drug regimen for treatment of both paucibacillary (6 months) and multibacillary (12 months) leprosy.

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Clofazimine (Lamprene)

• Dosing, Interactions, etc.

Clinical Context:  Inhibits mycobacterial growth, binds preferentially to mycobacterial DNA. Has antimicrobial properties, but mechanism of action is unknown. Part of a 2-drug regimen for treatment of paucibacillary leprosy; part of a 3-drug regimen for treatment of both paucibacillary (6 months) and multibacillary (12 months) leprosy. No longer commercially available in the United States; available only by obtaining an investigational new drug (IND) permit from the National Hansen's Disease (Leprosy) Program (NHDP).

• References

Minocycline (Minocin, Solodyn)

• Dosing, Interactions, etc.

Clinical Context:  Minocycline is a semisynthetic tetracycline. Has bacteriostatic activity. Inhibits protein synthesis, and is selectively concentrated in susceptible organisms. It is used in single-lesion paucibacillary leprosy in patients who cannot tolerate clofazimine. Also used as a second-line treatment in combination with clarithromycin, ofloxacin, and clofazimine in patients with rifampin-resistant leprosy.

• References

Ofloxacin (Floxin)

• Dosing, Interactions, etc.

Clinical Context:  Ofloxacin is a pyridine carboxylic acid derivative with broad-spectrum bactericidal effect. It is used in single-lesion paucibacillary leprosy. Also used as a second-line treatment in combination with clarithromycin, minocycline, and clofazimine in patients with rifampin-resistant leprosy.

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Class Summary

These agents have bactericidal and bacteriostatic activity against mycobacteria.

• References

Clarithromycin (Biaxin (DSC))

• Dosing, Interactions, etc.

Clinical Context:  Clarithromycin is a macrolide antibiotic used to treat various bacterial infections. Used as a second-line treatment in combination with minocycline, ofloxacin, and clofazimine in patients with rifampin-resistant leprosy.

• References

Further Outpatient Care

The WHO recommends that the monthly doses of rifampin be administered under direct observation during the visit.^[24]

Monthly outpatient follow-up is recommended during treatment, although weekly visits may be necessary if the patient experiences a leprosy reaction.

Follow-up laboratory studies during treatment include the following:

• Urinalyses
• CBC count
• Creatinine
• Liver function tests

Yearly skin scrapings taken from the 3 or 4 most active lesions are recommended.

Response to treatment

Successful treatment can result in flattening and elimination of nodules, papules, and plaques, as well as improved nerve function. Bacillary load rarely is a convenient method of assessing response to treatment. Noncompliance or drug resistance should be suspected if intact organisms are present after several months of treatment.

Once treatment is completed, the patient should be monitored for the next 5-10 years to evaluate for signs of relapse. The WHO defines relapse as marked increase in the bacillary index at any single site, usually accompanied by clinical deterioration.^[25] To date, the relapse rate following completion of multidrug therapy has been around 1% for both types of leprosy. In such cases, new bacillus-positive lesions may develop and should be treated with a thorough US regimen that incorporates once-daily rifampin (see Treatment).

Patients who have been successfully treated occasionally develop reversal reactions and further neuropathy. If skin biopsy samples are bacillus-negative, these patients are deemed to have a reversal reaction (see Complications).

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Deterrence/Prevention

Information campaigns about leprosy in high-risk areas are essential so that patients and their families, who were historically shunned from their communities, are encouraged to come forward and receive treatment.

Early diagnosis and treatment with multidrug therapy is the most effective way of preventing disabilities from leprosy, as well as preventing further transmission of the disease.^[26] However, vaccination with bacille Calmette-Guérin (BCG) is partially protective for leprosy.^[27]  For contacts of leprosy patients, the WHO GDG also recommends single-dose rifampicin as a preventative measure for adults and children older than 2 years old, who do not have contraindications such as pre-existing leprosy and tuberculosis.^[28]

• References

Prognosis

Without treatment, leprosy can lead to permanent muscle weakness, nerve damage, and disfiguration. Even with treatment, recovery from neurologic impairment is limited, but skin lesions generally clear within the first year of therapy. Discoloration and skin damage typically persist.

Physical therapy, reconstructive surgery, nerve and tendon transplants, and surgical release of contractures all have contributed to increasing the functional ability in patients with leprosy. A common residual deformity is insensitive feet or hands, as seen in persons with diabetes.

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Patient Education

Regional ambulatory clinics: The National Hansen's Disease Programs (NHDP) provide outpatient services and medical care to patients with leprosy in the United States and Puerto Rico. With the goals of prevention and early detection, the program supports delivery of services in areas with considerable populations of patients with leprosy. For additional information about these free services, contact the NHDP directly at 1-800-642-2477. The NHDP Center in Baton Rouge, La, provides free histopathologic services to facilitate diagnosis. Eleven outpatient HD clinics are located at hospitals, universities, and public health departments in Arizona, California, Florida, Georgia, Illinois, Massachusetts, New York, Puerto Rico, Texas, and Washington. These clinics provide the following services:

• Skin biopsy diagnostic confirmation
• Additional medical care
• Hospitalization for treatment complications
• Consultations
• Materials for professional and patient education

Patients with leprosy should be advised about the importance of continuing long-term therapy until the course of antibiotics is completed. The WHO recommends that the monthly administration of rifampin be directly observed.

In patients with leprosy who have advanced nerve damage, self-care techniques are of utmost importance in maintaining function and preventing further disability. The use of visual input to regulate activity, self-inspection, hygiene, and proper footwear can help prevent ulcer formation and tissue damage.

The WHO recommends examination of all household contacts of patients with leprosy, with careful instructions to seek medical care if signs and symptoms of leprosy appear.

Pregnancy in patients with leprosy can result in hormonal changes that lead to suppression of cell-mediated immunity, which may exacerbate symptoms of leprosy. Furthermore, pregnant women with leprosy are at greater risk of developing reactions and relapses. Type 1 reactions are more likely during the first few months following childbirth, whereas type 2 reactions typically occur during the third trimester of pregnancy and during lactation.^[20]

For a printer-friendly version of this information, go to: https://www.hrsa.gov/hansens-disease/leap/education

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