Pediatric Leprosy 

Updated: Aug 02, 2018
Author: Benjamin Estrada, MD; Chief Editor: Russell W Steele, MD 

Overview

Background

Leprosy was described almost 3000 years ago and is still associated with stigma. The causative pathogen, Mycobacterium leprae, was first described in 1873, when Gerhard Armauer Henrik Hansen discovered it while examining lymph nodes and other tissues obtained from patients with leprosy. Although significant progress was made during the 20th century in the treatment and eradication of this disease, the World Health Organization (WHO) estimates that the worldwide prevalence is still in the area of 10-12 million cases.

Neuromuscular symptoms associated with this disease are occasionally the first to be observed. Patients may also present with a history of chronic nasal discharge, which is frequently observed in individuals with lepromatous leprosy who have upper airway compromise. The hallmark clinical findings in leprosy are hypopigmented skin lesions with loss of sensation. These lesions are observed more frequently in the cooler areas of the body, such as the nose and earlobes. (See Clinical.)

Prolonged therapeutic regimens have traditionally been recommended in the treatment of leprosy; however, recent recommendations focus on regimens with shorter duration. The drugs that are more frequently used in the treatment of leprosy include rifampin, dapsone, clofazimine, ofloxacin, minocycline, and clarithromycin. Reconstructive surgery may be indicated in patients with soft tissue defects, particularly for plantar ulcerations in patients with leprosy. (See Treatment.)

Go to Leprosy for more information.

Pathophysiology and Etiology

Leprosy is a chronic granulomatous disease caused by infection with M leprae. The exact mechanism of M leprae transmission remains unknown; however, direct human-to-human contact, contact with respiratory secretions from infected individuals, and vertical transmission have been considered the most likely routes of transmission.

Most pathophysiologic changes observed in leprosy are caused by the ability of M leprae to survive in macrophage cells. Although the incubation period of M leprae can be several decades, it generally averages 5-7 years.[1]

Epidemiology

United States statistics

Most observed infections are acquired abroad. In California, cases of leprosy have been reported in persons who have emigrated from Mexico and Southeast Asia. Leprosy is also occasionally reported in Texas and Louisiana. In 2002, 133 cases of leprosy were reported in the United States. In 2006, approximately 6,500 persons with leprosy were living in the United States.[2]

International statistics

The WHO has estimated the global prevalence of leprosy to be 10-12 million cases, with most reported in Africa and Asia, particularly in the Indian subcontinent. The worldwide incidence rate is 2 cases per 10,000 population. In some areas, as many as 10% of cases develop in children younger than 15 years, among whom paucibacillary (PB) forms are more frequent.[3]

Age-, sex-, and race-related demographics

Although leprosy is rarely reported in infancy, it can affect all ages. In areas of high prevalence, leprosy among children represents 7-10% of new cases.[3, 4, 5, 6, 7] The male-to-female ratio is 2:1 to 3:1. Leprosy has no known racial predilection. Rather than race, lower socioeconomic status has traditionally been considered a risk factor for leprosy in endemic areas.

 

Presentation

History

Patients with leprosy are usually native to or have emigrated from endemic areas.[8] Leprosy should be considered as a diagnostic possibility among internationally adopted children who develop clinical findings suggestive of associated to this infection and who are originally from areas of the world where the disease is endemic.[9]

Neuromuscular symptoms associated with this disease are occasionally the first to be observed. Patients may also present with a history of chronic nasal discharge, which is frequently observed in individuals with lepromatous leprosy who have upper airway compromise.

Because of the prolonged incubation period, which averages 5 years, most cases are not diagnosed until several years after initial exposure.

Physical Examination

The hallmark clinical findings in leprosy are hypopigmented skin lesions with loss of sensation. These lesions are observed more frequently in the cooler areas of the body, such as the nose and earlobes (see the image below).

Infiltration of ear lobes in patient with lepromat Infiltration of ear lobes in patient with lepromatous leprosy.

Hypoesthesia is the clinical manifestation of peripheral nerve involvement and is present in as many as 70% of children with this condition.

Visible deformities in children with leprosy have been associated with increasing age at the time of diagnosis, multibacillary disease, lack of access to health care, and multiple nerve involvement.[10]

Depending on the number of lesions and the number of bacilli observed on the lesion’s smear, leprosy can be classified into the following 3 groups:

  • Paucibacillary (PB) or tuberculoid (TT) leprosy

  • Multibacillary (MB) or lepromatous (LL) leprosy

  • Borderline leprosy

Paucibacillary (tuberculoid) leprosy

TT leprosy presents with one or few (usually < 5) hypopigmented and hypoesthetic lesions. Sensory loss is frequently observed around the lesions. Patients with tuberculoid leprosy have a characteristic normal cell-mediated response to M leprae antigens.

Multibacillary (lepromatous) leprosy

LL disease usually presents with multiple (> 5) poorly defined, hypopigmented or erythematous lesions associated with hypoesthesia. It is also associated with the presence of papules, macules, and nodular lesions. Necrotizing erythema nodosum has occasionally been reported in children.

Patients with advanced LL leprosy may present with loss of eyelashes or eyebrows (see the image below) and nasal septum perforation. The constellation of disfiguring facial features associated with this disease is named leonine facies.

Man with advanced deformities caused by unmanaged Man with advanced deformities caused by unmanaged leprosy: keratitis, loss of eyebrow, thickened skin, and typical hand impairments. Ho Chi Minh City, Vietnam. Image courtesy of D. Scott Smith, MD.

The peripheral neuropathy observed in LL leprosy causes muscle weakness and atrophy and has been associated with clawhands and foot drops. Other clinical manifestations of LL leprosy include corneal opacifications, keratitis, iritis, testicular atrophy, and kidney disease resulting in renal failure. Patients with LL leprosy present with characteristically abnormal cell-mediated responses to M leprae antigens.[11]

Erythema nodosum leprosum (ENL) is a condition observed in patients with borderline and LL leprosy. It is usually associated with neuritis, fever, and arthralgias. The development of ENL has been suggested to be caused by the presence of immune complexes.[12]

The development of nonhealing ulcers in the lower extremities of patients with LL leprosy secondary to arthritis is known as the Lucio phenomenon. These ulcerations are more common in individuals of Latin American descent and are associated with a high mortality.

Neuropathic pain is a potential sequela of MB leprosy that can present more than 10 years after completion of therapy.[13]

Leprosy immune reconstitution disease can develop among patients coinfected with HIV who undergo treatment with highly active antiretroviral therapy.[14]

Borderline leprosy

TT disease and LL disease represent the 2 ends of the leprosy spectrum. Between these 2 ends lies a broad disease group designated as borderline. Borderline epilepsy is characterized by the presence of single or multiple skin lesions with a raised central area. It is often subclassified as borderline tuberculoid (BT), midborderline (BB), and borderline lepromatous (BL).

 

DDx

Diagnostic Considerations

Other problems to be considered include the following:

  • Pian (yaws) (infection with Treponema pertenue)

  • Vitiligo

  • Erythema nodosum

  • Granuloma annulare

Differential Diagnoses

 

Workup

Laboratory Studies

While in contact with patients with leprosy, healthcare workers should employ standard precautions. It has been suggested that M leprae is sensitive to ultraviolet light, and this sensitivity may be useful in sterilization and disinfection practices.[15]

M leprae cannot be cultured in vivo; however, some laboratory studies are available that can be useful in the diagnosis of leprosy. Measurement of phenolic glycolipid-1 antibodies may be helpful in epidemiologic studies and follow-up treatment.

Detection of M leprae by polymerase chain reaction (PCR) is promising; however, PCR detection is not widely available and has not been standardized.[16] RNA gene probes have been used to assist in the diagnosis and response to treatment among patients with paucibacillary (PB) and multibacillary (MB) disease. The absence of M leprae rRNA in skin samples of previously diagnosed patients correlates with response to treatment. Probes targeting 16S rRNA and 16S rDNA have been used in the diagnosis of smear-negative MB disease.[17, 18, 19, 20]

Drug resistance can be tested in vivo by inoculation of mouse footpad. This type of test is not widely accessible, and results are not usually available until 6 months after inoculation.[21]

Lepromin testing is an intradermal skin test that contains heat-killed M leprae. Patients with PB leprosy and individuals who are asymptomatic but live in endemic areas usually present an area of induration after the antigen administration; however, patients with MB leprosy rarely react to the administration of this antigen. The use of this test has no practical diagnostic value and has recently been discouraged.

Tissue Analysis and Histologic Findings

Skin biopsies and smears are helpful not only in establishing the diagnosis of leprosy but also in the process of establishing the difference between PB and MB disease. Skin biopsy specimens obtained from patients with leprosy should always be stained with hematoxylin and eosin (H&E) and an acid-fast stain.

In PB leprosy, giant cells in skin and nerves may accompany accumulation of epithelioid-lymphocyte granulomas. Bacilli are rare in this type of leprosy, and they are not present in nerves. In LL leprosy, bacilli are abundant; they can be observed in the areas surrounding blood vessels and are also present in nerves.

 

Treatment

Pharmacologic Therapy

Prolonged therapeutic regimens have traditionally been recommended in the treatment of leprosy; however, recommendations by the World Health Organization (WHO) now focus on regimens with shorter duration both for tuberculoid (TT) or paucibacillary (PB) leprosy and for lepromatous (LL) or multibacillary (MB) leprosy.

The drugs that are more frequently used in the treatment of leprosy include rifampin, dapsone, clofazimine, ofloxacin, minocycline, and clarithromycin. Multidrug therapy is required in all cases to prevent antimicrobial resistance.[22, 23, 24] Any regimen must contain multiple drugs to which Mycobacteriumtuberculosis is susceptible. Guidelines for preventing the transmission of Mtuberculosis are available.[25] In addition, the therapy must be taken regularly and continued for a sufficient period.

For MB leprosy, the standard regimen should include rifampin, dapsone, and clofazimine. For PB leprosy, rifampin is usually prescribed in combination with dapsone. For single-lesion PB leprosy, a single dose of rifampin combined with single doses of ofloxacin and minocycline is recommended. Dosages and duration of treatment for different presentations of leprosy are described elsewhere (see Medication).[22]

An issue of medicolegal importance in the management of leprosy is related to the use of thalidomide for the treatment of erythema nodosum leprosum (ENL). Patients, male or female, who receive therapy with this drug should be made aware of its significant teratogenic complications. Thalidomide should not be prescribed to women with childbearing potential. In addition, males undergoing treatment with thalidomide must avoid sexual intercourse with women who can become pregnant.

Other Therapeutic Measures

Because of the lack of sensation associated with leprosy, patients are usually at risk for significant injury associated with trauma or burns in hypoesthetic areas. Patients should be advised to protect areas at risk of injury.

Reconstructive surgery may be indicated in patients with soft tissue defects, particularly for plantar ulcerations in patients with leprosy.[26]

Long-Term Monitoring

The WHO has recommended that patients undergoing treatment for leprosy should be evaluated monthly.

In addition, patients should be informed about the potential signs and symptoms of recurrences and be advised to seek medical care if any of them are observed after treatment or after the initial episode has been completed.

 

Medication

Medication Summary

Prolonged therapeutic regimens have traditionally been recommended in the treatment of leprosy; however, recommendations by the World Health Organization (WHO) now focus on regimens with shorter duration both for tuberculoid (TT) or paucibacillary (PB) leprosy and for lepromatous (LL) or multibacillary (MB) leprosy.

The drugs that are more frequently used in the treatment of leprosy include rifampin, dapsone, clofazimine, ofloxacin, minocycline, and clarithromycin. Multidrug therapy is required in all cases to prevent antimicrobial resistance.

Antitubercular Agents

Class Summary

Any regimen must contain multiple drugs to which Mycobacteriumtuberculosis is susceptible. Guidelines for preventing the transmission of Mtuberculosis are available. In addition, the therapy must be taken regularly and continued for a sufficient period.

Rifampin (Rifadin)

Rifampin, also called rifampicin, inhibits RNA synthesis in bacteria by binding to the beta subunit of DNA-dependent RNA polymerase, which, in turn, blocks RNA transcription.

Dapsone

Dapsone is a competitive para-aminobenzoic acid (PABA) antagonist. It prevents formation of folic acid, causing bacterial growth inhibition.

Clofazimine (Lamprene)

Clofazimine binds preferentially to mycobacterial DNA. It was discontinued from the US market in 2005 but is now available as an orphan product.

Antibiotics

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Antibiotics with efficacy against mycobacteria are used.

Ofloxacin

Ofloxacin is a pyridine carboxylic acid derivative with broad-spectrum bactericidal effect.

Minocycline (Dynacin, Minocin, Solodyn)

Minocycline treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma species.

Clarithromycin (Biaxin)

Clarithromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Treatment with clarithromycin for 56 days has been demonstrated to be effective in eliminating more than 99.9% of M leprae present before treatment.

Immunomodulators

Class Summary

These agents modulate immune reactions resulting from diverse stimuli.

Thalidomide (Thalomid)

Thalidomide is an immunomodulatory agent that may suppress excessive production of tumor necrosis factor alpha (TNF-α) and may downregulate selected cell-surface adhesion molecules involved in leukocyte migration. It is approved for the treatment of erythema nodosum leprosum (ENL).