Leprosy

History

• Of note, some patients may not be forthright about presenting manifestations or deny knowledge of prior diagnosis secondary to negative stigmata associated with diagnosis ^r2
• Focal skin numbness ^r11c1
  • Often 1 of the earliest complaints
• Skin lesions ^c2
  • May become apparent from months to years after focal cutaneous numbness occurs
  • Patients may note well-defined macules of varying size and nodules or areas of diffuse skin thickening ^c3c4c5
• Other cutaneous and noncutaneous symptoms follow over months and years
  • Eye-related manifestations ^r18
    • Severe ocular symptoms are not uncommon; symptoms may include dry eyes, reduced vision, or blindness ^c6c7
    • May be caused by lagophthalmos (due to cranial nerve involvement), lacrimal dysfunction, corneal hypoesthesia, keratitis, iridocyclitis, and cataract formation ^{c8c9c10c11c12}
  • Infection of nasal mucosa ^c13
    • Common; may present with rhinorrhea and foul-smelling discharge ^c14c15
  • Manifestations related to loss of sensation
    • Usually occur in patients with advanced disease
    • May include difficulty picking up or holding objects and gait disturbance ^c16c17c18
    • Can involve ataxia and paresthesia ^r19c19c20

Physical examination

• Typical skin and peripheral nerve findings vary along the leprosy spectrum
  • Of note, skin examination is best performed in natural sunlight; skin lesions are less likely to be noticed in artificial light ^r2
  • Skin lesions tend to occur less frequently in warmer regions of the body such as scalp, axillae, or perineum ^r2c21c22c23
  • 4 types of lesions are characteristic: macules, plaques, diffuse infiltrative lesions, and subcutaneous nodules; annular shape is typical of borderline subtype lesions ^{r2c24c25c26c27c28}
  • Tuberculoid skin lesions are typically hypoesthetic or anesthetic; lesions in patients with lepromatous disease are more variable but may exhibit intact sensation ^r2c29c30c31
    • Reduction or loss of sensation in lesions distinguishes them from many other, more common skin lesions
  • Marked peripheral nerve thickening is most characteristic of borderline and lepromatous disease ^c32
    • Commonly affected nerves are superficial and include greater auricular, radial cutaneous, median, ulnar, common peroneal, and posterior tibial
  • Scars from cuts or burns may be noted; if questioned, patient may report not having experienced pain with injury ^c33c34
  • Tuberculoid leprosy ^r10
    • Characteristics of typical skin lesions
      • Dry, bald, scaly, well-circumscribed lesions with elevated margins; lesions are associated with marked hypopigmentation and reduced or absent sensation ^c35c36c37
      • Usually occur in an asymmetric distribution; most commonly found on the face, trunk, or extremities ^{r11c38c39c40c41}
      • Lesions may be large but few in number ^r11
    • Peripheral nerve involvement
      • A single thickened, tender nerve may be palpable in a nearby superficial nerve sheath ^c42c43
  • Borderline tuberculoid leprosy ^r10r20
    • Hypopigmented and/or erythematous macules with well-defined irregular margins associated with reduced sensation ^c44c45c46
    • Lesions are more numerous than in tuberculoid leprosy
    • Cutaneous nerves in the vicinity of skin lesions may be tender, thickened, or both ^c47c48
  • Borderline leprosy (also known as middle-borderline or borderline borderline leprosy) ^r10r20
    • Clinical features of both borderline tuberculoid and borderline lepromatous disease are present, with mixed macules, papules, and plaques; lesion borders may be indistinct ^c49c50
    • Lesions are more numerous (usually more than 25) than typically noted in patients with borderline tuberculoid subtype ^r2
    • Skin lesions show partial or variable loss of sensation ^c51
    • Nerves are affected bilaterally and asymmetrically; they are thickened and tender ^c52c53
  • Borderline lepromatous leprosy ^r10r20
    • Skin macules, papules, and plaques with poorly defined margins and variable sensory loss; lesions may become thickened, infiltrated, and nodular ^{c54c55c56c57c58}
    • Skin lesions are often symmetrical and bilaterally distributed; range in number from countable to innumerable ^c59
    • Nerves are symmetrically involved and show thickening or tenderness, as well as sensory loss ^c60c61
  • Lepromatous leprosy ^r10r20
    • Characteristics of typical skin lesions
      • Poorly defined plaques, nodules, and papules with associated thickening and infiltration; sensation is variable but often intact ^c62c63c64
      • Lesions are numerous, widespread, and often symmetrical ^c65
      • Symmetrical nonscaling infiltrative dermopathy may develop, primarily in cooler areas of the body (eg, earlobes, central face, extensor surface of thighs and forearms) ^c66
    • Peripheral nerve involvement
      • Nerve trunks are bilaterally and symmetrically thickened and tender ^c67c68
      • Reduced sensation occurs symmetrically over extensor surface of the legs, feet, forearms, and hands (stocking-glove distribution), regardless of cutaneous lesion distribution ^c69
      • Autonomic involvement may lead to anhidrosis and impaired vasomotor function ^c70c71
• Head and facial manifestations may include:
  • Moon or leonine (thickening of facial skin with accentuation of facial creases) facies may be noted in some patients with late-stage lepromatous leprosy ^c72c73
  • Loss of eyebrow (particularly lateral portion of the brow) or eyelashes may be a late finding, usually in patients with lepromatous leprosy; findings may be asymmetrical ^c74c75
  • Lagophthalmos (inability to close the eye) occurs in advanced cases ^c76
  • Ocular findings may include dryness, conjunctival injection, and corneal opacity ^c77c78c79
  • Ear helices and lobes may be thickened or nodular; lobes may be pendulous ^c80c81c82
  • Saddle nose deformity may result from collapse of the nasal septal cartilage in patients with untreated late-stage disease ^c83
• Musculoskeletal findings associated with neuropathy are variable and may include:
  • Ulcerations; usually at sites of constant pressure (eg, plantar surfaces, hands) ^c84
  • Muscle atrophy of hands and feet resulting in contractures (eg, claw hand secondary to ulnar nerve damage^r12) ^c85c86
  • Motor dysfunction of hands and feet (eg, wrist drop secondary to radial nerve damage, foot drop secondary to lateral peroneal nerve damage^r12) ^c87c88c89
  • Shortening of digits and autoamputation secondary to bone resorption may occur in patients with lepromatous leprosy ^c90c91
• Sensory findings associated with neuropathy are variable
  • May involve abnormal temperature, touch, or pinprick (or monofilament) sensation ^c92c93c94
  • May be found in area of skin lesions and/or in distal extremities
• Other variable findings, primarily in lepromatous leprosy, may include:
  • Hoarseness due to laryngeal infection ^c95
  • Testicular tenderness in males with testicular involvement ^c96
  • Edema of hands and feet ^c97c98

Causes

• Infection caused by Mycobacterium leprae bacillus; genetic predisposition plays a role in both host susceptibility for disease and polar form (paucibacillary or multibacillary)^r21c99
  • Recently identified Mycobacterium lepromatosis has been associated with a small number of cases ^r22c100
  • An individual patient's adaptive, innate, cellular immune response contributes to control of infection; chronic granulomatous inflammation develops in certain patients in response to organism ^r6
  • Peripheral nerve damage (eg, demyelination, degeneration) affecting both motor and sensory function may result from 1 or both of the following: ^r2r23
    • Direct targeting, invasion, and destruction of Schwann cells (glial cells of peripheral nervous system) by Mycobacterium leprae (most commonly in multibacillary form)
    • Immune-mediated response to Mycobacterium leprae affecting peripheral nerves (especially in paucibacillary disease or reversal reactions)
  • Some patients infected with organism do not develop clinical disease;^r6fewer than 5% of patients appear genetically susceptible to disease^r17
• Reservoir
  • Humans are primary reservoir
  • Armadillos appear to be a natural reservoir in the Western hemisphere; chimpanzees and monkeys are possible sources of transmission ^r2
• Mode of transmission
  • Predominant mode of transmission is thought to be through respiratory droplets or nasal secretions ^r2
  • Transmission may occur through skin contact, transplacentally, and via breast milk
  • Some evidence exists for zoonotic transmission from armadillos^r20 and African green monkeys^r9
• Communicability
  • Mycobacterium is a slow-growing, intracellular organism; most patients with leprosy are noninfectious ^r6
    • However, multibacillary/lepromatous leprosy is most infectious among subtypes because organism is actively excreted from nasal mucosa and through skin
  • Prolonged close contact is thought to be required for human-to-human transmission
  • Infectivity ceases within a few days after initiating standard multidrug treatment ^r17
• Incubation
  • Average incubation period to clinical disease is thought to be between 3 and 10 years ^r23
  • Minimum incubation period may be as short as a few weeks; maximum incubation period may be up to 30 years or more ^r23

Risk factors and/or associations

Primary diagnostic tools

• Leprosy diagnosis is based on clinical examination and (where available) either histopathologic evaluation of biopsy specimens or demonstration of acid-fast organisms in slit skin smears; the organism cannot be cultivated in vitro. Clinical examination is necessary, but does not provide definitive diagnosis ^r11c128
  • Consider diagnosis in any patient with risk factors for disease (eg, residence in endemic area, contact with armadillos) presenting with either: ^r17
    • Hypoesthetic or anesthetic skin rash, particularly if rash is recalcitrant to ordinary therapies, or
    • A thickened or enlarged peripheral nerve, with loss of sensation and/or weakness of the innervated muscles ^r16
  • Histopathologic evaluation of skin or nerve biopsy specimen ^c129c130
    • Gold standard test for diagnosis and classification of the disease subtype, where available and cost effective (ie, developed countries) ^r2
  • Slit skin smear ^c131
    • Most common test to aid in diagnosis and classification in endemic countries ^r2
    • Provides estimation of bacillary load ^r2r7
  • Classify disease according to either Ripley-Jordan or WHO criteria ^r9
• Polymerase chain reaction ^c132
  • Not well standardized or widely available for leprosy, but may be helpful in difficult cases (eg, pure neural or atypical skin presentations) or to distinguish Mycobacterium leprae from Mycobacterium lepromatosis^r24
    • In the United States, testing can be done by the National Hansen's Disease Program ^r25
• Perform baseline studies before initiating multidrug therapy
  • Obtain CBC, urinalysis, and ALT, AST, serum calcium, BUN, creatinine, and bilirubin levels for serial monitoring of possible drug treatment adverse effects ^{r26c133c134c135c136}
  • Screen for glucose-6-phosphate dehydrogenase deficiency before initiating dapsone as part of a multidrug treatment regimen ^r11c137d1
• Additional special diagnostic concerns at time of disease confirmation
  • Ophthalmology examination ^c138
    • Required to assess for ocular involvement at time of diagnosis ^r17
    • Patients with an absent or nonintact corneal reflex require precautions to avoid corneal drying and trauma (eg, ocular lubricant, natural tears, eye patch) and expedited evaluation by an ophthalmologist for further diagnostic and treatment recommendations ^r2
  • Consider evaluation for evidence of tuberculosis to avoid inadvertent monotherapy for active tuberculosis infection with rifampin while treating leprosy, particularly in patients with HIV ^r17c139
  • Consider screening male patients with multibacillary disease for hypogonadism (ie, elevated follicle-stimulating hormone and luteinizing hormone with decreased testosterone) ^r2c140c141

Laboratory

• Polymerase chain reaction ^c142
  • Useful specimens for test include slit skin preparations, skin and nerve biopsies, and oral or nasal swabs ^r24
  • Diagnostic test characteristics
    • Sensitivity varies based on subtype of disease; up to 90% sensitivity is reported in patients with multibacillary disease and 34% to 80% in paucibacillary disease ^r24
    • Specificity approaches 100% in both multibacillary and paucibacillary forms of disease ^r24

Procedures

Other diagnostic tools

• Diagnostic biomarkers
  • Skin samples can be positive for transcription-associated biomarkers ^r28
  • Biomarkers can be detected in blood samples ^r29

Most common

• Differential diagnosis varies with the Ridley-Jopling classification of leprosy
• On the tuberculoid end of the spectrum, conditions in the differential can often be distinguished by more infiltrative changes than those seen in patients with other inflammatory disorders, and loss of sensation is nearly pathognomonic of tuberculoid lesions ^r2
  • Vitiligo ^c146d2
    • Pigmentary disorder of skin and mucous membranes characterized by depigmented patches
    • Hypopigmented lesions of leprosy could be confused with white patches seen in vitiligo
    • Vitiligo is characterized by complete loss of pigment whereas only partial pigment loss is seen in leprosy
    • Diagnosis is confirmed by biopsy demonstrating complete absence of melanocytes resulting in total loss of pigmentation
  • Tinea versicolor ^c147d2
    • Fungal skin infection that results in small, scaly lesions or patches that commonly affect the chest and shoulders
    • In tinea versicolor, macules are hypo- or hyperpigmented and distribution is symmetrical; in leprosy, macules are asymmetrical, hypopigmented, and may exhibit anesthesia
    • Symmetrical coalescing hypopigmented patches and macules on the upper chest are presentations of both diseases
    • Diagnosis is made by yellow-green fluorescence on Wood lamp examination and/or appearance of fungal elements in potassium hydroxide preparation of skin scrapings
  • Cutaneous tuberculosis ^c148d2
    • Rare extrapulmonary manifestation of tuberculosis caused by infection with Mycobacterium tuberculosis
    • May present with skin lesions similar to tuberculoid leprosy; granulomas are a common histologic finding
    • Often associated with lymphadenopathy
    • Differentiate histologically by proliferation of the epidermis, ulceration, absence of nerve destruction, increase in reticulin, and fibrosis
  • Sarcoidosis ^c149d2
    • Inflammatory disease of unknown cause, characterized histologically by noncaseating granulomas
    • Skin lesions may appear in many forms, including macules, plaques, papules, and nodules
    • Unlike leprosy, sarcoidosis is often characterized by multiorgan involvement (typically pulmonary)
    • Diagnosis is based on clinical presentation and suggestive histopathologic findings, including asteroid bodies and Schaumann (conchoidal) bodies (concentrically lamellated calcified nodules within the cytoplasm of multinucleated cells)
  • Diffuse cutaneous leishmaniasis ^c150d3
    • Disseminated disease caused by Leishmania species spread through bite from sandfly
    • Geographic occurrence overlaps with that of leprosy
    • May present with similar broad-spectrum symptoms as leprosy; cutaneous lesions are characteristic
    • Diagnosed by detection of Leishmania parasite by microscopic examination of skin lesion smears
  • Subacute cutaneous lupus ^c151
    • Autoimmune condition characterized by annular lesions with raised erythematous borders and central clearing
    • May be associated with features of systemic lupus erythematosus, such as joint pain
    • Presence of anti-SSA/Ro antibodies supports diagnosis and distinguishes it from leprosy
• On the lepromatous end of the spectrum, clinical differentiation from other diagnoses can be challenging; biopsy and slit skin analysis may be necessary to differentiate^r2
  • Post–kala-azar dermal leishmaniasis ^c152d3
    • Cutaneous leishmaniasis that follows treatment of visceral leishmaniasis; occurs most commonly in India and Sudan
    • Characterized by skin lesions including macules, papules, nodules, and patches; lesions may occur on face, trunk, or extremities, and may be hypopigmented, similar to leprosy
    • Diagnosed by detection of Leishmania parasite by microscopic examination of skin lesion smears
  • Secondary syphilis ^c153d4
    • Spirochetal disease occurring in 3 phases; second phase is characterized by diffuse macular rash, mucus patches in the mouth and genital area, diffuse lymphadenopathy, fever, and generalized illness
    • Involvement of palms and soles is characteristic, unlike in leprosy; history of a preceding chancre may also help to distinguish syphilis from leprosy
    • Diagnosis is based on clinical picture and positive serologic test result for syphilis. Darkfield examination of skin scraping or mucus patch will reveal spirochetes; however, darkfield microscopy is rarely performed and poses infectious risk
  • Neurofibromatosis ^c154
    • Genetic condition characterized by light brown (cafe-au-lait) macules and nodular cutaneous lesions; thickened nerves may be palpable on examination
    • In areas endemic for leprosy, clinical distinction may be difficult, but if available, imaging may detect characteristic optic and acoustic lesions; histopathologic appearance of biopsied lesions and genetic testing confirms clinical diagnosis

Admission criteria

Most patients require only outpatient therapy

Hospital admission may be necessary for management of severe type 1 or 2 reactions (erythema nodosum leprosum) or Lucio phenomenon

• No special isolation precautions or other infection control procedures are necessary

Recommendations for specialist referral

• If diagnosis is uncertain, refer to dermatologist for further diagnostic considerations (eg, skin biopsy)
• In the United States, refer patients with leprosy to the National Hansen's Disease Program; treatment is conducted in consultation with an expert in leprosy ^r17
• Consult ophthalmologist to optimize management of lagophthalmos, diminished corneal sensation, and other significant ocular complications
• Refer to physiatrist/rehabilitation medicine specialist for management of existing physical deformities and disability and to implement strategies to prevent further deformity and disability
• Consult reconstructive/plastic surgeon to assess feasibility and approach to correcting physical deformities (eg, nonhealing wounds, contractures, facial deformities)

Drug therapy

• Antimycobacterials
  • Rifampin ^c155
    • Rifampin is a cytochrome P-450, 3A4, 2C8, and 2C9 inducer and may diminish serum concentration of certain drugs (eg, corticosteroids, oral contraceptives) ^r2
    • Multibacillary leprosy
      • WHO regimen
        • Rifampin Oral capsule; Infants, Children, and Adolescents: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once daily with dapsone and clofazimine for 24 months.
        • Rifampin Oral capsule; Adults: 600 mg PO once daily with dapsone and clofazimine for 24 months.
      • US (National Hansen's Disease [Leprosy] Program) regimen ^r26
        • Rifampin Oral capsule; Children: 10 to 20 mg/kg (Max: 600 mg/dose) PO once daily with clofazimine and dapsone for 24 months.
        • Rifampin Oral capsule; Adults and Adolescents: 600 mg PO daily with clofazimine and dapsone for 24 months.
    • Paucibacillary leprosy
      • WHO regimen
        • Rifampin Oral capsule; Infants and Children 1 to 9 years or weighing less than 20 kg: 10 mg/kg/dose PO once monthly with dapsone for 12 months or dapsone and clofazimine for 6 months.
        • Rifampin Oral capsule; Children and Adolescents 10 to 14 years weighing 20 to 40 kg: 10 to 20 mg/kg/dose (Max: 600 mg/dose) PO once monthly with dapsone for 12 months or 300 mg PO once monthly with dapsone and clofazimine for 6 months.
        • Rifampin Oral capsule; Adolescents 15 to 17 years: 600 mg PO once monthly with dapsone for 12 months or dapsone and clofazimine for 6 months.
        • Rifampin Oral capsule; Adults: 600 mg PO once monthly with dapsone for 12 months or dapsone and clofazimine for 6 months.
      • US (National Hansen's Disease [Leprosy] Program) regimen ^r26
        • Rifampin Oral capsule; Children: 10 to 20 mg/kg (Max: 600 mg/dose) PO once daily with dapsone for 12 months.
        • Rifampin Oral capsule; Adults and Adolescents: 600 mg PO daily with dapsone for 12 months.
  • Dapsone ^r2c156
    • Multibacillary leprosy
      • WHO regimen
        • Dapsone Oral tablet; Children younger than 10 years: 2 mg/kg PO once daily with clofazimine and rifampin for at least 12 months.
        • Dapsone Oral tablet; Children 10 to 14 years: 50 mg PO once daily with clofazimine and rifampin for at least 12 months.
        • Dapsone Oral tablet; Adults and Adolescents >= 15 years: 100 mg PO once daily with clofazimine and rifampin for at least 12 months.
      • US (National Hansen's Disease [Leprosy] Program) regimen ^r26
        • Dapsone Oral tablet; Children: 1 mg/kg PO daily with clofazimine and rifampin for 24 months.
        • Dapsone Oral tablet; Adults and Adolescents: 100 mg PO daily with clofazimine and rifampin for 24 months.
    • Paucibacillary leprosy
      • WHO regimen
        • Dapsone Oral tablet; Children younger than 10 years: 2 mg/kg PO once daily with rifampin for at least 6 months.
        • Dapsone Oral tablet; Children 10 to 14 years: 50 mg PO once daily with rifampin for at least 6 months.
        • Dapsone Oral tablet; Adults and Adolescents aged 15 years and older: 100 mg PO once daily with rifampin for at least 6 months.
      • US (National Hansen's Disease [Leprosy] Program) regimen ^r26
        • Dapsone Oral tablet; Children: 1 mg/kg PO daily with rifampin for 12 months.
        • Dapsone Oral tablet; Adults and Adolescents: 100 mg PO daily with rifampin for 12 months.
  • Clofazimine ^r2c157
    • Multibacillary leprosy
      • WHO regimen
        • Clofazimine Oral capsule; Infants and Children 1 to 9 years weighing less than 40 kg: 50 mg PO twice weekly plus 100 mg PO once monthly with rifampin and dapsone for 12 months.
        • Clofazimine Oral capsule; Children 10 to 14 years and weighing less than 40 kg: 50 mg PO twice weekly plus 100 mg PO once monthly with rifampin and dapsone for 12 months.
        • Clofazimine Oral capsule; Children and Adolescents 10 to 14 years and weighing 40 kg or more: 50 mg PO every other day plus 150 mg PO once monthly with rifampin and dapsone for 12 months.
        • Clofazimine Oral capsule; Adolescents 15 to 17 years: 50 mg PO once daily plus 300 mg PO once monthly with rifampin and dapsone for 12 months.
        • Clofazimine Oral capsule; Adults: 50 mg PO once daily plus 300 mg PO once monthly with rifampin and dapsone for 12 months.
      • US (National Hansen's Disease [Leprosy] Program) regimen ^r26
        • Clofazimine Oral capsule; Children: 1 mg/kg PO daily with dapsone and rifampin for 24 months.
          • NOTE: The smallest capsule size is 50 mg and the capsule should never be cut open. Every other day dosing may be used at 2 mg/kg.
        • Clofazimine Oral capsule; Adults and Adolescents: 50 mg PO daily with dapsone and rifampin for 24 months.
    • Paucibacillary leprosy
      • WHO regimen ^r31
        • Clofazimine Oral capsule; Infants and Children 1 to 9 years weighing less than 40 kg: 50 mg PO twice weekly plus 100 mg PO once monthly with rifampin and dapsone for 6 months.
        • Clofazimine Oral capsule; Children and Adolescents 10 to 14 years and weighing less than 40 kg: 50 mg PO twice weekly plus 100 mg PO once monthly with rifampin and dapsone for 6 months.
        • Clofazimine Oral capsule; Children and Adolescents 10 to 14 years and weighing 40 kg or more: 50 mg PO every other day plus 150 mg PO once monthly with rifampin and dapsone for 6 months.
        • Clofazimine Oral capsule; Adolescents 15 to 17 years: 50 mg PO once daily plus 300 mg PO once monthly with rifampin and dapsone for 6 months.
        • Clofazimine Oral capsule; Adults: 50 mg PO once daily plus 300 mg PO once monthly with rifampin and dapsone for 6 months.
      • US (National Hansen's Disease [Leprosy] Program) regimen ^r26
        • Does not recommend clofazimine for treatment of paucibacillary leprosy
    • Clofazimine is manufactured as a 50-mg capsule that should not be broken; for children whose weight-based dose is less than 50 mg, a whole capsule may be administered at an extended interval ^r26
    • Clofazimine appears to provide some protection against type 2 leprosy reactions ^r35
    • Skin discoloration is a challenge to adherence; reverses within several years of discontinuation
    • In the United States, clofazimine is available only through the National Hansen's Disease (Leprosy) Program^r26
      • To request investigator status to use clofazimine, call the National Hansen's Disease (Leprosy) Program^r25 at +1-800-642-2477
• Corticosteroids ^c158
  • Prednisone ^c159
    • National Hansen's Disease (Leprosy) Program recommends: ^r35
      • Prednisone Oral solution; Infants, Children, and Adolescents: 1 mg/kg PO daily. Individualize dosage based on the nature and severity of the disease and patient response.
      • Prednisone Oral tablet; Adults: 40 to 60 mg PO daily. Individualize dosage based on the nature and severity of the disease and patient response.
    • For type 1 reactions with neuritis, treatment may be required for several months
    • For type 2 reactions, prednisone is continued until the reaction has been well controlled for several days, followed by a taper of 2 to 4 weeks or longer
• Immunomodulatory agents
  • Thalidomide ^r11c160
    • Thalidomide is approved for marketing only through a special restricted distribution program.^r37Information is available at www.celgeneriskmanagement.com^r38
    • Acute treatment of cutaneous manifestations of moderate to severe erythema nodosum leprosum
      • Thalidomide Oral capsule; Children 12 years of age, Adolescents, and Adults: 100 to 300 mg PO once daily at bedtime. Start patients weighing less than 50 kg at the low end of the dose range. Patients who have previously required higher doses or those with a severe cutaneous ENL reaction may start at 400 mg/day at bedtime or in divided doses. Reduce daily dose by 50 mg PO every 2 to 4 weeks once symptoms have subsided. Consider therapy interruption, a dose reduction, or therapy discontinuation in patients who develop grade 3 or 4 adverse reactions.
    • Maintenance therapy for prevention and suppression of cutaneous manifestations of recurrent erythema nodosum leprosum
      • Thalidomide Oral capsule; Children 12 years of age, Adolescents, and Adults: Maintain patients on the minimum dose required to control the reaction. Attempt to taper thalidomide every 3 to 6 months by decreasing the daily dose by 50 mg/day every 2 to 4 weeks. Consider therapy interruption, a dose reduction, or therapy discontinuation in patients who develop grade 3 or 4 adverse reactions.

• Treatment for adults (US regimen).

  Abbreviations: BB, mid-borderline; BL, borderline lepromatous; BT, borderline tuberculoid; LL, lepromatous; MB, multibacillary; PB, paucibacillary; TT, tuberculoid. *For lepromatous/multibacillary disease, the recommended durations of treatment are sufficient, even though large numbers of dead bacilli may remain in the tissues for several years before they are eliminated by physiological processes. There is no evidence that additional, prolonged treatment hastens the elimination of these dead organisms. †Clofazimine, used for decades to treat Hansen disease (leprosy) around the world, is no longer available on the open market. Because it is no longer on distributed commercially, the only way to obtain the drug in the United States is to once again treat it as an investigational new drug. The National Hansen's Disease Program holds this investigational new drug for its use in treating Hansen disease (leprosy) in the United States.

  From Health Resources & Services Administration: Recommended Treatment Regimens. HRSA website. Reviewed April 2018. Accessed May 29, 2021. http://www.hrsa.gov/hansensdisease/diagnosis/recommendedtreatment.html

  Agent	Dose	Duration*
  Tuberculoid (TT & BT) (WHO classification: paucibacillary, "PB")
  Dapsone	100 mg daily	12 months, then therapy discontinued
  + Rifampin	600 mg daily	12 months, then therapy discontinued
  Lepromatous (LL, BL, BB) (WHO classification: multibacillary, "MB")
  Dapsone	100 mg daily	24 months, then therapy discontinued
  + Rifampin	600 mg daily	24 months, then therapy discontinued
  + Clofazimine†	50 mg daily	24 months, then therapy discontinued

• Treatment for children (US regimen).

  Abbreviations: BB, mid-borderline; BL, borderline lepromatous; BT, borderline tuberculoid; LL, lepromatous; MB, multibacillary; PB, paucibacillary; TT, tuberculoid. *As there is no formulation less than 50 mg, and the capsule should never be cut open, alternate day dosing may be used at 2 mg/kg.

  From Health Resources & Services Administration: Recommended Treatment Regimens. HRSA website. Reviewed April 2018. Accessed May 29, 2021. http://www.hrsa.gov/hansensdisease/diagnosis/recommendedtreatment.html

  Agent	Dose	Duration
  Tuberculoid (TT, BT) (WHO classification: paucibacillary, "PB")
  Dapsone	1 mg/kg daily	12 months, then therapy discontinued
  + Rifampin	10 to 20 mg/kg daily (not exceeding 600 mg)	12 months, then therapy discontinued
  Lepromatous (LL, BL, BB) (WHO classification: multibacillary, "MB")
  Dapsone	1 mg/kg daily	24 months, then therapy discontinued
  + Rifampin	10 to 20 mg/kg daily (not exceeding 600 mg)	24 months, then therapy discontinued
  + Clofazimine	1 mg/kg daily*	24 months, then therapy discontinued

• Treatment for adults (WHO regimen).

  Abbreviations: BB, mid-borderline; BL, borderline lepromatous; BT, borderline tuberculoid; LL, lepromatous; MB, multibacillary; PB, paucibacillary; TT, tuberculoid.

  Data from WHO: Guidelines for the Diagnosis, Treatment and Prevention of Leprosy. WHO website. Published 2018. Accessed May 29, 2021. http://apps.who.int/iris/handle/10665/274127

  Agent	Dose	Duration
  Paucibacillary leprosy (2 to 5 skin lesions) (TT, BT subtypes)
  Dapsone	100 mg daily	6 months
  + Rifampin	600 mg monthly	6 months
  + Clofazimine	300 mg monthly and 50 mg daily	6 months
  Multibacillary leprosy (more than 5 skin lesions) (LL, BL, BB subtypes)
  Dapsone	100 mg daily	12 months
  + Rifampin	600 mg monthly	12 months
  + Clofazimine	300 mg monthly and 50 mg daily	12 months

• Treatment for children younger than 10 years or less than 40 kg (WHO regimen).

  Abbreviations: BB, mid-borderline; BL, borderline lepromatous; BT, borderline tuberculoid; LL, lepromatous; MB, multibacillary; PB, paucibacillary; TT, tuberculoid.

  Data from WHO: Guidelines for the Diagnosis, Treatment and Prevention of Leprosy. WHO website. Published 2018. Accessed May 29, 2021. http://apps.who.int/iris/handle/10665/274127

  Agent	Dose	Duration
  Paucibacillary leprosy (2 to 5 skin lesions) (TT, BT subtypes)
  Dapsone	2 mg/kg daily	6 months
  + Rifampin	10 mg/kg monthly	6 months
  + Clofazimine	100 mg monthly and 50 mg twice weekly	6 months
  Multibacillary leprosy (more than 5 skin lesions) (LL, BL, BB subtypes)
  Dapsone	2 mg/kg daily	12 months
  + Rifampin	10 mg/kg monthly	12 months
  + Clofazimine	100 mg monthly and 50 mg twice weekly	12 months

• Treatment for children aged 10 to 14 years (WHO regimen).

  Abbreviations: BB, mid-borderline; BL, borderline lepromatous; BT, borderline tuberculoid; LL, lepromatous; MB, multibacillary; PB, paucibacillary; TT, tuberculoid.

  Data from WHO: Guidelines for the Diagnosis, Treatment and Prevention of Leprosy. WHO website. Published 2018. Accessed May 29, 2021. http://apps.who.int/iris/handle/10665/274127

  Agent	Dose	Duration
  Paucibacillary leprosy (2 to 5 skin lesions) (TT, BT subtypes)
  Dapsone	50 mg daily	6 months
  + Rifampin	450 mg monthly	6 months
  + Clofazimine	150 mg monthly, 50 mg every other day	6 months
  Multibacillary leprosy (more than 5 skin lesions) (LL, BL, BB subtypes)
  Dapsone	50 mg daily	12 months
  + Rifampin	450 mg monthly	12 months
  + Clofazimine	150 mg monthly, 50 mg every other day	12 months

Nondrug and supportive care

• Preventing complications from peripheral neuropathy is 1 of the important aspects of leprosy management ^r2
• Patient education is critical in routine management, rehabilitation, and complication prevention ^r39c161
  • Teach patients how to recognize a leprosy reaction and the importance of seeking immediate medical care when concern exists for development of leprosy reaction
  • Highlight importance of frequent eye examinations that could help detect early damage in patients with anesthetic corneas
  • Stress importance of self-examination of hands and feet to prevent neurotrophic ulcers
  • Provide education about appropriate footwear and tips on how to care for feet ^c162
    • Advise against walking barefoot ^c163
    • Footwear
      • Neurotrophic ulcers can be prevented by using special protective footwear with molded inserts ^c164
      • In areas where specialty footwear is not available or affordable or is stigmatizing, focus on appropriate fit and smooth interior surfaces of locally available and socially acceptable shoes ^r39c165
        • Shoe size should ensure a one-half inch space between the longest toe and the interior of the shoe, adequate width to accommodate without pinching, and a roomy toe box
        • Leather uppers and soft rubber soles are recommended; shoes that can be tied or otherwise secured in place are recommended over slip-on styles
    • Moisturize skin with a lotion that does not contain alcohol ^c166
    • Consult podiatrist or other professional for management of calluses ^c167
    • Avoid heating pads, hot water bottles, or hot foot baths ^c168c169
  • Provide education about appropriate hand care ^c170
    • Keep skin of hands well hydrated ^c171
    • Use gloves for work that might injure hands ^c172
    • Exercise hands to maintain function ^c173
• Rehabilitation therapy ^c174
  • May be required for management of chronic neuropathy and secondary loss of function ^r2
  • Management of insensate foot is similar to the management of diabetic foot ^r2
• Reconstructive surgery ^c175
  • May be required for:
    • Facial deformity caused by facial nerve palsies and skin infiltration ^r2
    • Nonhealing wounds, contractures, and extremity deformities
• Counseling
  • Consider counseling to address potential negative social and psychological implications of diagnosis ^r17c176
• Isolation measures
  • Standard precautions are indicated; no additional isolation measures are required ^r17

Comorbidities

• Tuberculosis ^r40c177
  • Major guidelines do not address tuberculosis testing before initiating therapy for leprosy
  • Reasonable approach is for clinician to maintain a low threshold to assess for concomitant tuberculosis in an effort to avoid inadvertent single-drug therapy (rifampin) for tuberculosis; drug resistance and poor efficacy of subsequent antituberculosis treatment are possible pitfalls in this scenario
• HIV ^c178
  • Presence of HIV coinfection does not alter natural progression of leprosy or change diagnosis or treatment ^r41
  • Conventional antiretroviral therapy (HAART) is suggested in conjunction with multidrug treatment of leprosy, with attention to potential drug interactions ^r41
• Solid organ and hematopoietic stem cell transplant recipients ^r2
  • Care must be taken to avoid medication interactions, especially between rifampin and cyclosporine; alternate medications may be required for treatment in place of rifampin (eg, clarithromycin)
  • Optimum duration of drug treatment for leprosy is not definitively established

Special populations

• Pregnancy, postpartum status, and lactation increase risk of leprosy reactions ^r14
• Avoid thalidomide in women with childbearing potential and in children younger than 12 years ^r14

At-risk populations

• Household contacts, especially genetic relatives, of diagnosed patient ^r47

Screening tests

• Screening includes history of neurologic symptoms (eg, numbness, tingling, paresthesia) and complete skin and peripheral nervous system examination including palpation of superficial nerves ^{r47c239c240c241}
• Such examinations are recommended annually for 5 years, with further evaluation in the event of a suspicious rash or neurologic development ^r47
• At this time, there are no validated blood tests for diagnosis