You are in: eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease LeprosyArticle Last Updated: Sep 21, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Benjamin Estrada, MD, Associate Professor, Department of Pediatrics and Adolescent Medicine, Division of Pediatric Infectious Diseases, University of South Alabama College of Medicine, University of South Alabama Children's and Women's Hospital Benjamin Estrada is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society Editors: Gary J Noel, MD, Department of Pediatrics, Clinical Associate Professor, Weill Medical College of Cornell University; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Larry I Lutwick, MD, Director, Division of Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Professor, Department of Internal Medicine, State University of New York at Downstate; Robert W Tolan Jr, MD, Chief of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine; Russell W Steele, MD, Professor and Vice Chairman, Department of Pediatrics, Head, Division of Infectious Diseases, Louisiana State University Health Sciences Center Author and Editor Disclosure Synonyms and related keywords: leprosy, Hansen's disease, Hansen disease, Mycobacterium leprae, M leprae, borderline leprosy, paucibacillary leprosy, tuberculoid leprosy, multibacillary leprosy, lepromatous leprosy, erythema nodosum leprosum, ENL, Lucio phenomenon, Lucio's phenomenon, lazarine leprosy, chronic granulomatous disease, Mycobacterium leprae, hypoesthesia, necrotizing erythema nodosum, leonine facies INTRODUCTIONSection 2 of 10
  BackgroundLeprosy is a chronic granulomatous disease caused by infection with Mycobacterium leprae. This disease, which was described almost 3000 years ago, is still associated with stigma. M 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 close to 12 million cases. PathophysiologyThe 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 pathophysiological 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. FrequencyUnited StatesMost observed infections are acquired abroad. In InternationalThe WHO has estimated the global prevalence of leprosy to be 10-12 million cases, with most reported in Africa and RaceLeprosy has no known racial predilection. Rather than race, lower socioeconomic status has traditionally been considered a risk factor for leprosy in endemic areas. SexThe male-to-female ratio is 2:1 to 3:1. AgeAlthough this infection is rarely reported in infancy, it can affect all ages. In areas of high prevalence, leprosy among children represents 7-10% of new cases. CLINICALSection 3 of 10
History
PhysicalThe 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. Hypoesthesia is the clinical manifestation of peripheral nerve involvement and is present in as many as 70% of children with this condition. Depending on the number of lesions and the number of bacillus observed on the lesion's smear, leprosy can be classified into the following 3 groups:
Erythema nodosum leprosum (ENL) is a condition observed in patients with borderline and lepromatous 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. The development of nonhealing ulcers in the lower extremities of patients with lepromatous 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 rate. CausesLeprosy is a chronic granulomatous disease caused by infection with M leprae. DIFFERENTIALSSection 4 of 10
Leishmaniasis Neurofibromatosis Pityriasis Rosea Sarcoidosis Tinea Versicolor
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| Drug Name | Rifampin (Rifadin, Rimactane) |
|---|---|
| Description | Also called rifampicin. Inhibits RNA synthesis in bacteria by binding to beta subunit of DNA-dependent RNA polymerase, which, in turn, blocks RNA transcription. |
| Adult Dose | Single-lesion paucibacillary disease: 600 mg PO as a single dose Paucibacillary leprosy: 600 mg PO as a single dose on day 1 of each 28-d cycle for 6 mo Multibacillary disease: 600 mg PO as a single dose on day 1 of each 28-d cycle for 12 mo |
| Pediatric Dose | Paucibacillary leprosy: 10 mg/kg/dose PO as a single dose on day 1 of each 28-d cycle for 6 mo; not to exceed 450 mg/dose Multibacillary leprosy: 10 mg/kg/dose PO as a single dose on day 1 of each 28-d cycle for 12 mo; not to exceed 450 mg/dose |
| Contraindications | Documented hypersensitivity |
| Interactions | Induces microsomal enzymes, which may decrease effects of acetaminophen, PO anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, PO contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur) |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Obtain CBC counts and baseline clinical chemistries before and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy is associated with thrombocytopenia, which is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur; nausea, vomiting, abdominal pain, and hepatotoxicity can occur |
| Drug Name | Dapsone (Avlosulfon) |
|---|---|
| Description | Competitive PABA antagonist. Prevents formation of folic acid, causing bacterial growth inhibition. |
| Adult Dose | Paucibacillary leprosy: 100 mg PO qd for 6 mo Multibacillary leprosy: 100 mg PO qd for 12 mo (Regimen recommended by WHO) |
| Pediatric Dose | Paucibacillary leprosy: 1 mg/kg PO qd for 6 mo Multibacillary leprosy: 1 mg/kg PO qd for 1 y Not to exceed 50 mg/d |
| Contraindications | Documented hypersensitivity; G-6-PD deficiency |
| Interactions | May inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists (eg, pyrimethamine), monitor for agranulocytosis during the second and third months of therapy; probenecid increases dapsone toxicity; trimethoprim with dapsone may increase toxicity of both drugs; because of increased in renal clearance, dapsone levels may decrease significantly when administered concurrently with rifampin |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Perform weekly blood counts (first mo); then perform WBC counts monthly (6 mo) and then semiannually; discontinue if significant reduction in platelets, leukocytes, or hematopoiesis is observed Caution in methemoglobin reductase deficiency, G-6-PD deficiency (patients receiving >200 mg/d), or hemoglobin M because of high risk for hemolysis and Heinz body formation; caution in patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis Peripheral neuropathy can occur (rare) Phototoxicity may occur when exposed to UV light |
| Drug Name | Clofazimine (Lamprene) |
|---|---|
| Description | Binds preferentially to mycobacterial DNA. |
| Adult Dose | Multibacillary leprosy: 300 mg PO once a month and 50 mg qd for 12 mo (Regimen recommended by WHO) |
| Pediatric Dose | Multibacillary leprosy: 150 mg PO once a month and 50 mg qod for 12 mo (Regimen recommended by WHO) |
| Contraindications | Documented hypersensitivity |
| Interactions | Dapsone may inhibit anti-inflammatory activity of clofazimine |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Severe abdominal symptoms may require exploratory laparotomies; caution in patients with GI problems (eg, abdominal pain, diarrhea); skin discoloration caused by drug may result in depression or suicide; apply oil to skin for dryness and ichthyosis |
| Drug Name | Ofloxacin (Floxin) |
|---|---|
| Description | A pyridine carboxylic acid derivative with broad-spectrum bactericidal effect. |
| Adult Dose | Single skin lesion paucibacillary leprosy: 400 mg PO as a single dose (Regimen recommended by the WHO) |
| Pediatric Dose | <18 years: Not recommended >18 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones May increase toxicity of theophylline and caffeine; may increase effects of anticoagulants (monitor PT) |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Abdominal pain, nausea, diarrhea, and headache |
| Drug Name | Minocycline (Dynacin, Minocin) |
|---|---|
| Description | Treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma species. |
| Adult Dose | Single skin lesion paucibacillary leprosy: 100 mg PO as a single dose (Regimen recommended by WHO) |
| Pediatric Dose | <8 years: Not recommended >8 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; severe hepatic dysfunction |
| Interactions | Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of gestation through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines |
| Drug Name | Clarithromycin (Biaxin) |
|---|---|
| Description | Treatment for 56 d has been demonstrated effective in elimination of more than 99.9% of M leprae present before treatment. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. |
| Adult Dose | 500 mg/d PO for 56 d |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; coadministration of pimozide, astemizole (recalled from US market), cisapride, or terfenadine (recalled from US market) |
| Interactions | Toxicity increases with coadministration of fluconazole, astemizole and pimozide; clarithromycin effects decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, HMG CoA-reductase inhibitors Serious cardiac arrhythmias may occur with coadministration of cisapride; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; give half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies |
| Drug Name | Thalidomide (Thalomid) |
|---|---|
| Description | Immunomodulatory agent that may suppress excessive production of tumor necrosis factor-a (TNF-a) and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration. Approved for the treatment of ENL. |
| Adult Dose | 300-400 mg/d PO hs for the first 2 d, then 100 mg/d |
| Pediatric Dose | <12 years: Not established |
| Contraindications | Documented hypersensitivity; women of childbearing age |
| Interactions | May increase sedation of alcohol, barbiturates, chlorpromazine, and reserpine |
| Pregnancy | X - Contraindicated; benefit does not outweigh risk |
| Precautions | Teratogenic in pregnancy (major human fetal abnormalities have been associated to the administration of thalidomide during pregnancy); mortality related to life-threatening human malformation caused by the use of this drug during pregnancy has been reported to be as high as 40%; because of teratogenic effects, women must use 2 additional methods of contraception or abstain from intercourse Has been associated with the development of peripheral neuropathy; sexually mature males treated with this drug must avoid sexual intercourse with women who have childbearing potential Bradycardia may occur; use protective measures (eg, sunscreens, protective clothing) against exposure to sunlight or UV light (eg, tanning beds); prescribing physician must enter STEPS program established by manufacturer |
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.
Article Last Updated: Sep 21, 2007
