Jennifer Cohn
Vatinee Y. Bunya

BASICS

DESCRIPTION

• Chronic granulomatous disease caused by Mycobacterium leprae

• Also called Hansen’s disease

• Primarily affects peripheral nerves, upper respiratory tract mucosa, and skin

• Secondarily affects eyes, nose, ears, muscle, bone, and testes

• Considered one of the 13 neglected tropical diseases

• WHO classification: Paucibacillary (PB) or multibacillary (MB)

– PB form is also known as tuberculoid leprosy (TT) or borderline tuberculoid (BT) in the Ridley–Jopling classification system. It does not show intraocular manifestations.

– MB form is also known as lepromatous leprosy (LL), borderline lepromatous (BL), or borderline (BB).

• Ocular leprosy tends to be slow and progressive, can be blinding.

• Eye thought to be a source of re-infection in previously treated generalized disease

• Blindness is especially debilitating as patients may also have compromised mobility and sense of touch.

EPIDEMIOLOGY

Incidence

• WHO estimated ∼400,000 new cases in 2004.

• Worldwide incidence currently has a declining trend.

Prevalence

• ∼400,000 to 20 million cases have been estimated worldwide.

• 2–3 million suffer permanent disability from leprosy.

• ∼5–7% of infected individuals suffer from leprosy related blindness.

• Regions of highest prevalence include India, sub-Saharan Africa, Latin America, and Caribbean.

• Prevalence has dramatically decreased since the 1980s due to advent of multidrug therapy.

RISK FACTORS

• Poverty/squalor

• Impaired cell-mediated immunity

• Residence in endemic areas

• Close contact with infected persons, particularly those with MB disease

• Males affected more than females

• Host genetic susceptibility (see the “Genetics” section below)

Genetics

• Genes involved in innate immune response thought to increase host susceptibility to M. leprae and subsequent immune activation: HLA-DRB1, HLA-DRDQ, TNFSF15, RIPK2, NOD2, PARK2, LRRK2.

GENERAL PREVENTION

• Single-dose rifampin in close contacts of patients with newly diagnosed disease provides 57% reduction in subsequent 2-year incidence.

• BCG vaccination or dapsone prophylaxis is marginally effective and not recommended.

PATHOPHYSIOLOGY

• Granulomatous infiltration of peripheral nerves

• Predilection for “cooler” areas; hence ocular leprosy limited to anterior segment

• Infiltration of lids and globe related to tracking along CN VII, corneal nerves, ciliary (uveal) nerves

ETIOLOGY

• Infection with M. leprae

• Transmission thought to occur via respiratory route

COMMONLY ASSOCIATED CONDITIONS

• HIV/AIDS

• Intestinal helminth infections

DIAGNOSIS

HISTORY

• Recent close contact with an infected patient

• HIV status/impaired cell-mediated immunity

• Origin from or travel to endemic areas

• Photophobia, epiphora, decreased vision

• May not have pain due to corneal hypoesthesia

PHYSICAL EXAM

• Cornea: Leprous pannus superiorly, prominent corneal nerves (early ocular finding), hypoesthesia, exposure, corneal pearls (chalky white stromal avascular deposits), interstitial keratitis

• Conjunctiva: conjunctivitis, leproma (superficial granulomatous nodule)

• Lens: Cataract, PSC (often treatment induced)

• Uvea: iridocyclitis (can occur even after treatment), iris pearls (miliary leproma)

• External: CN VII palsy, lagophthalmos, cicatricial entropion/ectropion, brow and lash madarosis (loss of hair, late finding), dacryocystitis/fibrosis with resulting dry eye

• Rarely affects posterior segment; retinal pearls and/or uveal effusions have been reported

• Systemic: Thickening of facial skin (“leonine facies”), thickened peripheral nerves, decreased sensation to touch and temperature, variable skin lesions including erythema nodosum, hypopigmented or erythematous macules, papules or nodules, Lucio phenomenon (ulcerated erythematous lesions)

DIAGNOSTIC TESTS & INTERPRETATION

• Routine lab tests used primarily to rule out other disease or evaluate drug-related toxicities and/or contraindications:

– PPD and chest x-ray to rule out TB prior to systemic steroids

– T. pallidum agglutination/RPR for syphilis

– LFTs depending on treatment regimen

Diagnostic Procedures/Other

• Must establish a tissue diagnosis:

– Can accomplish via conjunctival or corneal scrapings, AC tap, or skin smears or biopsy

Pathological Findings

• Modified Fite’s stain to visualize acid-fast lepra bacilli

• Caseous granulomas causing axonal degeneration is pathognomonic.

DIFFERENTIAL DIAGNOSIS

• Onchocerciasis

• Trachoma

• Syphilis

• Neurofibromatosis

• Leishmaniasis

• Sarcoidosis

• Autoimmune granulomatous uveitides

TREATMENT

MEDICATION

First Line

Systemic therapy

• Provided free of charge by WHO to all leprosy

patients worldwide

• WHO recommendations for multidrug therapy:

– PB form: 6-month duration of therapy

– Adults: rifampicin 600 mg once monthly, dapsone 100 mg daily

– Pediatric: rifampicin 450 mg once monthly, dapsone 50 mg daily

– MB form: 12-month duration of therapy

Adults: rifampicin 600 mg once monthly, clofazimine 300 mg once monthly, dapsone 100 mg once monthly; then clofazimine 50 mg daily and dapsone 100 mg daily

Pediatric: rifampicin 450 mg once monthly, clofazimine 150 mg once monthly, dapsone 50 mg once monthly; then clofazimine 50 mg daily and dapsone 50 mg daily

Pediatric Considerations

Multidrug therapy recommended for children older than 10 years of age. Weight-based dose adjustment necessary for younger children.

Pregnancy Considerations

Leprosy is exacerbated in pregnancy. There are no current contraindications to the above multidrug therapy regimens in pregnancy.

Second Line

Ophthalmic therapy

• Must be concurrent with multidrug therapy

• Many sources suggest escalation and prolongation of multidrug therapy with ocular disease; however, no official guidelines exist

• Artificial tears and other topical lubricants for corneal and lid pathology

• Topical and/or systemic steroids for keratitis and iridocyclitis

• Topical fluoroquinolones if necessary for corneal ulceration or dacryocystitis (ofloxacin shown to be effective against M. leprae)

• Often requires definitive surgical therapy for globe protection and visual rehabilitation (see the “Surgery/Other Procedures” section)

ADDITIONAL TREATMENT

Issues for Referral

• Management of multidrug therapy and systemic disease with infectious disease specialist or leprologist, and dermatologist

• Referral of close contacts to infectious disease specialist for prophylaxis (see the “Prevention” section)

• Consider referral for psychological/social support given long history of social stigma

SURGERY/OTHER PROCEDURES

• Conjunctiva: Pterygium excision, if applicable, may considerably reduce bacillary load

• Cornea: Penetrating keratoplasty for corneal scarring

• Uvea/glaucoma: Sector iridectomy for iris bombe, consider enucleation in blind, painful, glaucomatous eye

• Trichiasis: Epilation or electrolysis

• Lagophthalmos: Should be corrected if >5 mm, decreased corneal sensation, monocular, or for cosmesis. Tarsal shortening procedures, tarsorrhaphy, or frontalis muscle transfer.

• Entropion/ectropion: Should be corrected by clinically appropriate procedure

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Regular follow-up with ophthalmologist given possibility of recurrent uveitis despite multidrug therapy

PATIENT EDUCATION

International Federation of Anti-Leprosy Associations (ILEP) (http://www.ilep.org.uk/)

PROGNOSIS

• May have recurrent uveitis despite multidrug therapy

• Poor visual morbidity if MB form is untreated for prolonged period of time

• May be confounded by poverty

COMPLICATIONS

• Decreased vision

• Blindness

• Disfiguration

• Death

• Social stigma

ADDITIONAL READING

• Citirik M, et al. Lepromatous iridiocylcitis. Ocul Immunol Inflamm 2005;13:95–99.

• Hotz PJ, et al. Control of neglected tropical diseases. N Engl J Med 2007;357:1018–1027.

• Johnson GJ. Update on ocular leprosy. Community Eye Health 2001;14(38):25–26.

• Moet FJ, et al. for the COLEP Study Group: Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: Cluster randomised controlled trial. BMJ 2008;336(7647):761–764.

• Mondal K, Biswas S. Review of ocular leprosy. J Indian Med Assoc 2006;104(7):401–403, 407.

• WHO Multi-Drug Therapy: Elimination of Leprosy. http://www.who.int/lep/mdt/en/ (accessed March 15, 2010).

• Zhang FR, et al. Genomewide association study of leprosy. N Engl J Med 2009;361(27):2609–2618.

See Also (Topic, Algorithm, Electronic Media Element)

• WHO – Leprosy Elimination (http://www.who.int/lep/en/)

CODES

ICD9

• 030.0 Lepromatous leprosy (type l)

• 030.9 Leprosy, unspecified

• 364.3 Unspecified iridocyclitis

CLINICAL PEARLS

• Iris and corneal pearls are pathognomonic for ocular leprosy.

• Bilateral iridocyclitis is the primary cause of blindness in leprosy.

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