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 demarcations
- Nerve 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 nodules
- Nerve 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: pregnancy
- Ofloxacin: relative contraindication in children and adolescents
- Minocycline: 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 pigmentation
- Rifampicin: 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 inhibitors
- Minocycline: 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.