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Leprosy

para>Rare in infants <1 year of age é á

Pregnancy Considerations

Women with leprosy who become pregnant are more likely to develop types I and type II reactions and disease relapse postpartum, during the 3rd trimester and with lactation, respectively.

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ETIOLOGY AND PATHOPHYSIOLOGY

  • Widespread dissemination occurs (in susceptible individuals) once respiratory tract is infected.
  • Vigorous cellular immune response results in tuberculoid form (PB form).
  • Minimal cellular immune response results in lepromatous form (MB form).
  • M. leprae: Incubation period is 2 to 5 years for MB cases and 8 to 12 years for PB cases.
  • Spread via respiratory transmission and (likely) through broken skin

Genetics

  • Leprosy pathogenesis appears to be a three-step process: (i) One group of genes confers susceptibility to infection, (ii) different genes impact the clinical manifestation of disease, and (iii) a third set of genes influence leprosy reversal reaction (1).
  • 95% of humans are not susceptible to leprosy (2).
  • Vitamin D deficiency is correlated with genetic susceptibility to leprosy (3).

RISK FACTORS

  • Close family contacts of untreated leprosy patients (8-fold risk); higher risk if patient has MB leprosy
  • Impaired cell-mediated immunity/use of "biologic agents " Ł for autoimmune disease (tumor necrosis factor [TNF] antagonists)
  • Poor socioeconomic status
  • Contact with infected animals, in particular, armadillos (Texas and Louisiana)
  • Military service or travel in endemic areas

GENERAL PREVENTION

  • Early-case detection and treatment to control spread:Emphasize self-reporting.
  • Bacillus Calmette " ôGuerin (BCG) vaccination in certain locations worldwide may aid in disease prevention.

COMMONLY ASSOCIATED CONDITIONS

There is a somewhat higher incidence of leprosy in HIV patients but with concurrent infection: é á

  • HIV-positive patients with early or subclinical leprosy are somewhat more likely to develop overt disease.
  • Concurrent leprosy may accelerate HIV disease course; the interaction between leprosy and HIV is less clear than between HIV and TB (4).

DIAGNOSIS

HISTORY

  • Known or suspected contact with leprosy
  • Skin lesions and/or enlarged nerves accompanied by sensory loss
  • Ulcers in anesthetic feet are the most common cause of hospitalization.

PHYSICAL EXAM

  • Indeterminate leprosy (1): ≥1 small hypopigmented or hyperpigmented macules (which become anesthetic over time)
  • Tuberculoid (TT):Initial hypopigmented, hypesthetic macules with sharp demarcationsNerve involvement early: Ulnar, peroneal (foot drop), and greater auricular nerve(s) are palpable/visibly enlarged; neuritic pain; atrophy of small muscles of the hand; facial nerve involvement causes lagophthalmos, keratitis, and corneal ulceration.
  • Lepromatous (LL):More generalized, sometimes nondistinctive macules, and papules and nodulesNerve involvement occurs later; affects distal extremities initially

DIFFERENTIAL DIAGNOSIS

  • Systemic lupus erythematosus; sarcoidosis
  • Yaws; cutaneous leishmaniasis
  • Peripheral neuropathy
  • Syringomyelia

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

  • Acid-fast bacilli on skin smears by scraped incision; Quantify bacilli with bacterial index (BI) to guide treatment (5).
  • Histologic involvement of peripheral nerves is pathognomonic.
  • Mild anemia, elevated ESR, hyperglobulinemia
  • Serum assay: antibody to phenolic glycolipid 1 (PGL-1); sensitivity of >95% in LL and ~30% in TT
  • Detection of M. leprae in tissue by polymerase chain reaction (PCR) is the best method for PB cases and difficult-to-diagnose cases (6)[B].
  • Lymphocyte migration inhibition test: Cell-mediated immunity to M. leprae is absent in patients with LL but present in those with TT.

Diagnostic Procedures/Other

  • Skin biopsy
  • Fine-needle aspiration may be an alternative to skin biopsy.

Test Interpretation

  • TT: Noncaseating granulomas containing lymphocytes, epithelioid cells, and perhaps giant cells; bacilli difficult to demonstrate
  • LL: granulomas comprising macrophages, large foam cells, and many intracellular bacilli, frequently in spheroidal masses
  • Borderline leprosy: Granulomas change from epithelioid cell predominance in BT to a macrophage predominance as LL pole is approached.

TREATMENT

GENERAL MEASURES

  • Multidisciplinary approach, including orthopedic surgery, ophthalmology, and physical therapy in addition to specific drug therapy
  • Rigid-soled footwear, walking plaster casts or dressings to treat or prevent plantar ulcers
  • Physical therapy and casts prevent hand contractures.
  • Vocational retraining and rehabilitation along with psychological support
  • Immediate recognition and treatment of eye problems

MEDICATION

Pregnancy Considerations

Clofazimine and minocycline contraindicated; dapsone and rifampin (rifampicin) may be used (both are category C).

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Pediatric Considerations

Minocycline contraindicated in children <5

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First Line

  • Multidrug therapy (MDT) is standard for treatment and is very effective. Resistance while low (<10%) is increasing, especially to rifampicin (7)[B].
  • In the United States (where patients are considered to have more active disease)SLPB or PB: Rifampicin 600 mg/day PO + dapsone 100 mg/day PO; treat for 1 year.MB: rifampicin 600 mg/day PO + dapsone 100 mg/day PO + clofazimine 50 mg/day PO; treat for 2 years.
  • Outside the United States (WHO regimen)SLPB: The "ROM " Ł regimen: Rifampicin 600 mg PO + ofloxacin 400 mg PO + minocycline 100 mg PO; treat with single dose of each given together.PB: Rifampicin 600 mg PO monthly (supervised) + dapsone 100 mg/d PO; treat for 6 months.MB: Rifampicin 600 mg PO monthly + clofazimine 300 mg PO monthly (both supervised) and dapsone 100 mg/d PO + clofazimine 50 mg/d PO; treat for 1 year.
  • Contraindications:Clofazimine and minocycline: pregnancyOfloxacin: relative contraindication in children and adolescentsMinocycline: in pregnancy, during lactation, and in children up to 5 years old
  • Precautions:Dapsone: GI upset, headaches, pruritus, exfoliative dermatitis, agranulocytosis, fever, rash, and photosensitivity. Hemolysis and methemoglobinemia are common reactions to dapsone, so screen for glucose-6-phosphate dehydrogenase (G6PD) deficiency to prevent drug-induced hemolysis.Clofazimine: GI upset and skin pigmentationRifampicin: reddish pigmentation of urine and other bodily fluids; increased cytochrome P450 3A4 isozyme (CYP3A4) activity, leading to significant decrease in blood levels of OCPs, steroids, and HIV protease inhibitorsMinocycline: Reduce dosage in renal damage.
  • Immune reactions to therapy are common and must be treated aggressively to reduce long-term disability.Type 1 ( "reversal " Ł) reaction: Worsening of skin lesions and nerve function with few systemic signs can be confused with drug failure " öoccurs mostly in borderline cases; it is an immunologic shift toward TT leprosy; prednisone (40 to 60 mg/day with taper over 3 to 5 months) is most common therapy. Recent study indicates 5 months is more beneficial than 3 months (8)[A].Type 2 ( "erythema nodosum leprosum " Ł) reaction: Acute onset of new tender nodules with fever " öoccurs mostly in BL or LL cases due to immune complex deposition; thalidomide (200 mg BID with slow taper over months) effective but very teratogenic; clofazimine is also effective.

Second Line

Weak evidence for shorter regimens, longer regimens, or newer drug combinations (9,10)[C]: é á

  • New MDT regimens have been suggested but need additional data to support them.Potentially effective agents may include clarithromycin, linezolid, gatifloxacin, and rifapentine.Clarithromycin, minocycline, and moxifloxacin may be effective in cases of MB treatment intolerance or drug-resistance.

ISSUES FOR REFERRAL

Surgical, ophthalmic, orthopedic, and occupational consultations as needed for complications é á

ADDITIONAL THERAPIES

  • Manage mild reversal reaction and erythema nodosum leprosum (ENL) with bed rest, analgesics, and sedatives " öobserve closely for worsening. Do not stop antileprosy drugs.
  • Neuropathic ulcers of the feet are most effectively treated with topical ketanserin and restricting weight bearing until the ulcer heals.

SURGERY/OTHER PROCEDURES

  • Reconstructive surgery: Nerve and tendon transplants, contracture release, and other cosmetic procedures may give more functional mobility and social acceptance.
  • Tarsorrhaphy or horizontal lid shortening for lagophthalmos with lid gap >5 mm or even lesser degree in patients with one eye; cataract surgery with posterior chamber intraocular lens implantation to avoid glasses in patients with nasal bridge collapse
  • Decompressive surgery to treat nerve damage in conjunction with steroid therapy; however, there may be no added benefit over steroid therapy alone.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

  • Frequent follow-up visits until therapy is stabilized, then monthly supervision.
  • Drug toxicity uncommon after 1st year of treatment
  • Periodic CBC, renal, and hepatic function tests
  • Yearly skin scrapings from most active sites

DIET

Nutritious, balanced diet é á

PATIENT EDUCATION

  • Educate about the indolent course of the disease and need to complete therapy.
  • Within 72 hours of beginning an appropriate drug regimen, patients are noninfectious and can lead a normal social life.
  • Patient education helps ease psychological distress and stigma; emphasize that a cure is possible with newer drug regime: I Can Do It Myself! is available from the WHO as an educational resource.
  • Encourage case reporting because early treatment may prevent/reduce tissue damage and deformities.

PROGNOSIS

  • Generally indolent but may be interrupted by ENL and type 1 lepra reaction. Prognosis is good with early detection and therapy, especially with range of motion (< 1% relapse rate with completed regimen).
  • Recently, more cases of disease relapse and rifampicin resistance have been reported.
  • Gradual clearing of skin lesions within 1st year

COMPLICATIONS

  • Trauma and secondary infection leading to loss of digits and extremities; crippling of hands and feet
  • Corneal opacities may lead to blindness, cataracts.
  • Lucio phenomenon (arteritis)
  • Secondary amyloidosis

REFERENCES

11 George Priya Doss é áC, Nagasundaram é áN, Srajan é áJ, et al. LSHGD: a database for human leprosy susceptible genes. Genomics. 2012;100(3):162 " ô166.22 U.S. Department of Health and Human Services. National Hansen 's Disease (Leprosy) Program. http://www.hrsa.gov/hansensdisease/. Accessed July 30, 2015.33 Lu 'o 'ng é áKv, Nguy â ¬n é áLT. Role of the vitamin D in leprosy. Am J Med Sci. 2012;343(6):471 " ô482.44 Ustianowski é áAP, Lawn é áSD, Lockwood é áDN. Interactions between HIV infection and leprosy: a paradox. Lancet Infect Dis. 2006;6(6):350 " ô360.55 Pardillo é áFE, Fajardo é áTT, Abalos é áRM, et al. Methods for the classification of leprosy for treatment purposes. Clin Infect Dis. 2007;44(8):1096 " ô1099.66 Martinez é áAN, Talhari é áC, Moraes é áMO, et al. PCR-based techniques for leprosy diagnosis: from the laboratory to the clinic. PLoS Negl Trop Dis. 2014;8(4):e2655.77 Guerrero é áMI, Colorado é áCL, Torres é áJF, et al. Is drug-resistant Mycobacterium leprae a real cause for concern?: first approach to molecular monitoring of multibacillary Colombian patients with and without previous leprosy treatment. Biomedica. 2014;34(Suppl 1):137 " ô147.88 van Veen é áNH, Nicholls é áPG, Smith é áWC, et al. Corticosteroids for treating nerve damage in leprosy. A Cochrane review. Lepr Rev. 2008;79(4):361 " ô371.99 Ishii é áN, Barua é áS, Mori é áS, et al. Report of the tenth meeting of the WHO Technical Advisory Group on leprosy control. Nihon Hansenbyo Gakkai Zasshi. 2010;79(1):37 " ô42.1010 Worobec é áSM. Current approaches and future directions in the treatment of leprosy. Res Rep Trop Med. 2012;3:79 " ô91.

ADDITIONAL READING

  • Anderson é áH, Stryjewska é áB, Boyanton é áBL, et al. Hansen disease in the United States in the 21st century: a review of the literature. Arch Pathol Lab Med. 2007;131(6):982 " ô986.
  • Merle é áCS, Cunha é áSS, Rodrigues é áLC. BCG vaccination and leprosy protection: review of current evidence and status of BCG in leprosy control. Expert Rev Vaccines. 2010;9(2):209 " ô222.
  • U.S. Department of Health and Human Services. National Hansen 's Disease (Leprosy) Program. http://www.hrsa.gov/hansensdisease/.
  • World Health Organization. Leprosy. http://www.who.int/topics/leprosy/en/.
  • World Health Organization. Twelfth meeting of the WHO Technical Advisory Group on Leprosy Control: Brazzaville, Congo, April 2014. http://www.searo.who.int/entity/global_leprosy_programme/12th_tag/en/

CODES

ICD10

  • A30.9 Leprosy, unspecified
  • A30.0 Indeterminate leprosy
  • A30.1 Tuberculoid leprosy
  • A30.3 Borderline leprosy
  • A30.2 Borderline tuberculoid leprosy
  • A30.4 Borderline lepromatous leprosy
  • A30.5 Lepromatous leprosy
  • A30.8 Other forms of leprosy

ICD9

  • 030.9 Leprosy, unspecified
  • 030.2 Indeterminate leprosy [group I]
  • 030.1 Tuberculoid leprosy [type T]
  • 030.3 Borderline leprosy [group B]
  • 030.8 Other specified leprosy
  • 030.0 Lepromatous leprosy [type L]

SNOMED

  • leprosy (disorder)
  • Indeterminate leprosy
  • tuberculoid leprosy (disorder)
  • borderline leprosy (disorder)
  • Lepromatous leprosy (disorder)

CLINICAL PEARLS

  • Most humans are not susceptible to leprosy.
  • In suspected cases, take a careful exposure history and examine the skin for telltale lesions, sensory loss, and enlarged peripheral nerves to support the diagnosis.
  • MDT is the standard of care. Treatment should not be based solely on lesion count. For free consultation with the National Hansen 's Disease Program, call: (800) 642-2477.
  • Antileprosy prophylaxis is not currently recommended; close contacts should have annual skin examinations.