LEPROSY (MUSCULOSKELETAL PBL) -2014Description:

o
disease affecting skin and peripheral nerves caused by infection with Mycobacterium
leprae(1, 2)
o
M. leprae originally described by Hansen
Also called:
o
Hansen's disease
Definitions:
o
indeterminate leprosy - initial stage of leprosy, lesions may heal spontaneously (about
75%) or patient will progress along spectrum of leprosy based on interaction between
organism and specific immune response mounted by host (2)
o
spectrum of leprosy in order of decreasing cell-mediated response(2)

tuberculoid leprosy - few skin lesions (< 6) and low bacterial load

borderline - unstable balance between cell-mediated immunity and bacterial

replication that can progress to either tuberculoid or lepromatous leprosy
o
borderline tuberculoid leprosy < 6 skin lesions that tend to be
asymmetrically distributed and well-circumscribed
o
borderline leprosy 6 skin lesions that are not clearly distinguishable as
tuberculoid or lepromatous by appearance
o
borderline lepromatous leprosy 6 skin lesions that tend to be widely and
symmetrically disseminated with only slight erythema or hypopigmentation

lepromatous leprosy - diffuse skin lesions and high bacterial loads

o
leprosy reactions - episodic immunologically mediated acute inflammatory response that
can occur in up to 1/3 of patients and may be associated with irreversible nerve damage and
limb deformity, can occur in treated or untreated patients (1, 2, 3)

Type 1 reaction (also called reversal reaction)

o
inflammatory process associated with nerve damage if treatment
inadequate or delayed
o
peak occurrence within first 2 months of treatment but may occur up to 12
months of treatment or after treatment
o
clinical manifestations include erythema, edema, and onset of new skin
lesions
o
peripheral nerves may be tender with potentially dramatic loss of nerve
function (nerve damage may progress silently for prolonged periods)
o
occurs in borderline disease and may indicate a shift toward tuberculoid
leprosy

Type 2 reaction (also called erythema nodosum leprosum [ENL])

o
systemic inflammatory response
o
occurs only in patients with borderline lepromatous and lepromatous
leprosy
o
clinical manifestations include fever with crops of small pink skin nodules
and potential for iritis, neuritis, lymphadenitis, orchitis, bone pain, dactylitis, arthritis,
and proteinuria
o
may start in first or second year of antimicrobial therapy with intermittent
relapse over several years
o
Lucio phenomenon(3, 4)

rare type of reaction restricted to Central and South America or patients with
Mexican ancestry

diffuse infiltration of skin

characterized by onset of symmetrical erythematous, black, stellate, necrotic

lesions (most common in lower extremities)

significant nasal mucosa involvement may occur which can lead to subsequent
nasal destruction

occurs with primary diffuse lepromatous leprosy (subtype of lepromatous leprosy)

may occur within 3-4 years after onset

Types:
o
World Health Organization (WHO) field classification when slit-skin smear not available

single lesion, paucibacillary (1 patch)

paucibacillary (2-5 patches)

multibacillary (> 5 patches)

Reference - World Health Organ Tech Rep Ser 1998;874:1 as referenced in(1, 2)
classification based on skin lesion count reported to result in misclassification of
multibacillary leprosy and risk of undertreatment
o
based on comparison with skin smear and Ridley-Jopling classification in
264 untreated patients with leprosy in the Philippines

Reference - Clin Infect Dis 2007 Apr 15;44(8):1096

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Text
Ridley-Jopling classification (in order of decreasing cell-mediated immune response to M.
tuberculosis) only used with biopsy with bacterial index (BI) to measure acid-fast bacilli in
dermis

polar tuberculoid (in patients with intact cellular immune response) - high degree of
cell-mediated immunity with low bacilli count and delayed hypersensitivity, present with
single lesion and BI value < 2 (equivalent to paucibacillary)

borderline tuberculoid - < 6 skin lesions, BI value < 2 (equivalent to paucibacillary)

mid-borderline - 6 skin lesions, BI value 2 (equivalent to multibacillary) similar

to borderline lepromatous but has potential to move to tuberculoid pole, may be
distinguished by appearance of skin lesion

borderline lepromatous - 6 skin lesions, BI value 2 (equivalent to

multibacillary)

polar lepromatous - patient has very low or no resistance with high bacilli and
numerous, poorly demarcated lesions throughout body, BI value 2 (equivalent to
multibacillary)

Reference - Int J Lepr Other Mycobact Dis 1966 Jul-Sep;34(3):255 as referenced in(3)

most patients have intermediate leprosy forms (borderline tuberculoid, midborderline, and borderline lepromatous)(1)

lepromatous leprosy occurs in patients with absence of specific cellular immunity

but intact immunity to M. tuberculosis(1)
pure neuritic leprosy (no skin involvement) reported in 4.6% of patients (179 of 3,853)
attending leprosy clinic in India (Indian J Lepr 1996 Apr-Jun;68(2):137)
multibacillary and borderline leprosy uncommon in childhood(2)
o

o
o

Who is most affected:

o
residents of or immigrants from Brazil, Nepal, Mozambique, Democratic Republic of the
Congo (Wkly Epidemiol Rec 2007 Jun 22;82(25):225
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males twice as often as females after puberty(1)

higher rate of deformity in women attributed to delay in presentation (Lepr Rev

2002 Sep;73(3):262)
Causes:
o
Mycobacterium leprae(1, 2, 3)

acid-fast gram-positive bacillus

very slow growing

o

Pathogenesis:
o
transmission(1, 3)

via aerosol spread of nasal secretions with uptake through nasal or respiratory
mucosa

spread in body only occurs in patients with genetic susceptibility (associated with
nramp1 gene)

M leprae has tropism for macrophages and Schwann cells particularly peripheral
nerve Schwann cells and shows preference for growth in cooler regions of the body

cannot pass via intact skin, not spread by touching

transmission can continue for decades (Lepr Rev 2002 Dec;73(4):326 as referenced
in(1))
o
nerve damage(1)

M leprae replicates in Schwann cells slowly over years

specific T cells eventually recognize mycobacterial antigens in nerve and initiate

chronic inflammatory reactions

swelling in inflexible perineurium of peripheral nerve leads to ischemia and

eventually fibrosis with axonal death
o
humans are primary reservoir, but 9-banded armadillo and mouse are susceptible to M.
leprae(1, 2, 3)

M leprae is dependent on host metabolic products which may explain long incubation
periods(1)

mean 4 years for tuberculoid leprosy

mean 10 years for lepromatous leprosy

can vary from months to 30 years

o
clinical form of leprosy determined by patient's immunologic response to M. leprae(1)

deficient cell-mediated immunity results in lepromatous leprosy

intact cell-mediated immunity results in tuberculoid leprosy, limiting scope of

disease

borderline form most common and can progress unpredictably toward either
tuberculoid or lepromatous leprosy(2)
Likely risk factors:
o
recent immigrants from endemic countries (2)
o
household contacts of persons with leprosy(1)
o
infants of untreated mothers(4)
o
independent risk factors observed in analysis of 21,870 contacts of 1,037 patients with
leprosy in Bangladesh

persons living under same roof and using same kitchen

age - increased risk in persons aged 10-19 years and 30 years old

blood relationship, especially first degree (genetic predisposition)

type of leprosy - contact with patient with multibacillary, or paucibacillary with 2-5
lesions associated with higher risk than single lesion paucibacillary
o

Reference - COLEP study (J Infect Dis 2006 Feb 1;193(3):346

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Text PDF)
novel M. leprae genotype associated with armadillo exposure in southern United States (N

Engl J Med 2011 Apr 28;364(17):1626

EBSCOhost Full Text)
Possible risk factors:
o
genetic factors associated with variable susceptibility to leprosy

variants of genes in NOD2-mediated signaling pathway associated with

susceptibility to infection with M. leprae in genomewide association study with 706
patients and 1,225 controls (N Engl J Med 2009 Dec 31;361(27):2609

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Text), editorial can be found in N Engl J Med 2009 Dec 31;361(27):2666

EBSCOhostFull Text, commentary can be found in N Engl J Med 2010 Apr

15;362(15):1446
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susceptibility loci on chromosome 10p13, based on genomes of 224 families from
South India (Nat Genet 2001 Apr;27(4):439
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PARK2 and PACRG genes associated with susceptibility to leprosy, based on 975
unrelated patients with leprosy cases and controls from Brazil (Nature 2004 Feb
12;427(6975):636
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HLA DR2 and DR3 alleles associated with tuberculoid leprosy and HLA DQ1
associated with lepromatous leprosy (Nat Rev Genet 2001 Dec;2(12):967
EBSCOhost Full Text as referenced in(1))
toll-like receptor 2 (TLR2) gene mutation more common in 45 patients with
lepromatous leprosy compared to 45 patients with tuberculoid leprosy and 45 controls
(FEMS Immunol Med Microbiol 2001 Jul;31(1):53)
polymorphisms in NRAMP1 gene associated with multibacillary leprosy in study of
273 patients with leprosy and 201 controls from Mali (Am J Trop Med Hyg 2001
Dec;65(6):733 PDF)
vitamin D receptor gene may be associated with tuberculoid and lepromatous

leprosy (J Infect Dis 1999 Jan;179(1):187

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leprosy as Immune reconstitution inflammatory syndrome (IRIS) has been reported in
patients receiving antiretroviral therapy for HIV infection in countries where leprosy is endemic

(BMJ 2007 Feb 3;334(7587):217

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infliximab -- development of borderline lepromatous leprosy following treatment
of rheumatoid arthritis with infliximab and subsequent type 1 (reversal) reaction after

discontinuation of infliximab noted in 2 case reports (Clin Infect Dis 2006 Jul 15;43(2):e19
EBSCOhost Full Text PDF)
Factors not associated with increased risk:

HIV infection does not appear to be associated with leprosy

based on 3 case-control studies before highly active antiretroviral therapy was
readily available
Complications:
o
leprosy reactions(1, 2, 3, 4)

spontaneous fluctuations in clinical state in addition to primary infection

due to changes in immune response to M. leprae

type 1 reaction (reversal reaction)

o
occurs in 1/3 of patients with borderline forms
o
inflammatory process associated with nerve damage and poor clinical
response
o
peak occurrence within first 2 months of treatment but may occur after
treatment
o
clinical manifestations include erythema and edema of skin lesions
o
peripheral nerves may be tender with potentially dramatic loss of nerve
function (nerve damage may progress silently for prolonged periods)
o
due to spontaneous increases in T-cell reactivity to mycobacterial antigens
o
infiltration of interferon gamma- and TNF-alpha-secreting CD4-positive
lymphocytes in skin lesions and nerves results in edema and painful inflammation
o
usually occurs in response to treatment initiation
o
often associated with shift from borderline leprosy toward tuberculoid form
o
MEDICAL EMERGENCY - rapid and sustained reversal of inflammatory
process in type 1 reactions essential to prevent continuing nerve damage
o
risk factors for reversal reactions (in 594 newly diagnosed patients in
Ethiopia followed for 6-11 years)

starting effective treatment

borderline classification

pregnancy or delivery within 6 months prior to diagnosis (later

pregnancies not associated with increased risk)

having reversal reaction in first year after diagnosis (risk factor for
later reactions)

HIV diagnosis as risk factor for recurrent reversal reactions (based

on 3 of 29 recurrent cases)

Reference - Lepr Rev 2000 Sep;71(3):309

type II reaction (erythema nodosum leprosum)

o
occurs only in patients with borderline lepromatous and polar lepromatous
leprosy
o
systemic inflammatory response
o
reactive syndrome with fever, painful small pink skin nodules, malaise,
wasting, vasculitis and potential for iritis, neuritis, lymphadenitis, orchitis, bone pain,
dactylitis, arthritis, and proteinuria
o
may start in first or second year of antimicrobial therapy with intermittent
relapse over several years
o
can be triggered by treatment, vaccination, tuberculin skin testing or other
immune system stimulation
o
associated with high circulating concentrations of TNF-alpha and systemic
toxicity
o
erythema nodosum leprosum develops in 10%-50% patients treated for
lepromatous leprosy (The Medical Letter 1996 Feb 16;38(968):15)

Lucio phenomenon(4)
o
occurs in primary diffuse lepromatous leprosy (subtype of lepromatous
leprosy)
o
characterized by necrotic lesions of extremities and occasionally on face
o
nasal mucosa significantly affected, often with nasal destruction
o
intermittent fever, lymphadenopathy and splenomegaly may occur
o
peripheral and ocular nerve involvement less frequent than with other
subtypes of lepromatous leprosy

clinical manifestations of leprosy reactions in patients with recent diagnosis in

o

case report (PLoS Negl Trop Dis 2009 Sep 29;3(9):e425

EBSCOhost Full Text full-text)
pregnancy associated with increased risk for leprosy reactions (level 3
[lacking direct] evidence)
o
based on review of retrospective case series and cohort studies

type 1 reactions more likely to occur during postpartum period, with both
overt and silent neuritis
o
type 2 (erythema nodosum leprosum) reactions may occur throughout
pregnancy and during lactation
o
no prospective, controlled studies found on complications of pregnancy in
women treated with multidrug therapy regimens
o
Reference - Int J Lepr Other Mycobact Dis 1999 Mar;67(1):6
leprosy reactions uncommon in childhood(2)
nerve damage can occur independent of reactions(3)
sensory loss may lead to(1, 2)
repeated trauma
pressure necrosis
pressure ulcer
secondary infections
ocular complications(1)
blindness from nerve damage and bacillary invasion
2.8% blindness and 11% potentially blinding pathology in newly diagnosed
lepromatous leprosy patients
o
based on case series with 691 patients in India, Philippines and Ethiopia
o
Reference - Lepr Rev 2002 Sep;73(3):225
lagophthalmos (inability to close eyelid)
o
may result from paresis of orbicularis oculi
o
may occur bilaterally in late lepromatous disease
o
can lead to exposure keratitis and resultant blindness
o
combination of patches over malar region or around eye plus Type I
reaction may be risk factor for lagophthalmos

based on chart review of 1,226 patients with leprosy treated

between 1982-1987 in India

26 patients (2.1%) had recent lagophthalmos

85% patients with lagophthalmos had combination of patches over

malar region or around eye plus Type I reaction

Reference - Lepr Rev 1991 Jun;62(2):143

other systemic complications
testicular atrophy(1)
o
due to diffuse infiltration and acute orchitis that can occur with type II
reactions
o
azoospermia and gynecomastia can result from loss of testosterone
renal involvement and amyloidosis rarely seen with effective treatment(1)
dry skin (due to autonomic disruption) that may fissure and ulcerate(2)
chronic neuropathic pain described in 16 patients with multibacillary leprosy (Lancet 2000
o

o
o

Sep 23;356(9235):1080
o

EBSCOhost Full Text), commentary can be found in Lancet 2001

Jan 27;357(9252):313
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progressive gangrene of bilateral toes in patients with tuberculoid leprosy, related to antiphospholipid antibodies in case report (BMC Infect Dis 2005 Sep 21;5:74
Text full-text)

History:

o
o
o

Chief concern (CC):

single or multiple skin lesions which may be (1, 2)

numb (not in majority with lepromatous disease)

dry with scaly appearance

hairless

smooth and shiny

diffuse (with lepromatous disease)

hypopigmented or reddish patches

Impaired sweating(2)
numbness, weakness in hands and feet or face(1, 2)
burn or ulcer in anesthetic hand or foot(1)

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o
o
o
o

borderline patients may present with(1, 4)

nerve pain
sudden palsy
new skin lesions
eye pain, redness, impaired visual acuity
systemic febrile illness
blindness(1)

History of present illness (HPI):

nerve damage can result in wrist drop, clawing of hand or foot drop (2)
pure neuritic leprosy presents with asymmetrical involvement of peripheral nerve trunks
and no visible skin lesions(1)
musculoskeletal manifestations may be common

based on 4 case series and 2 case reports

61% had rheumatic manifestations in series of 70 patients with leprosy in India

o
54% had arthritis
o
17% had soft tissue rheumatism
o
3% had enthesitis
o

Reference - Indian J Dermatol Venereol Leprol 2004 Mar-Apr;70(2):76

EBSCOhost Full Text, commentary can be found in Indian J Dermatol Venereol Leprol

2004 Jul-Aug;70(4):250
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symmetrical polyarthritis of wrists and fingers similar to rheumatoid arthritis
reported in 20 (42%) of series of 48 patients with joint symptoms admitted to leprosy
center in Pakistan (Br J Rheumatol 1994 Oct;33(10):963)
among 28 patients with leprosy in India
o
20 presented with rheumatologic complaints initially
o
5 patients with pure neuritic leprosy (no cutaneous features) presented
with inflammatory arthritis and/or tenosynovitis
Reference - Rheumatology (Oxford) 2007 Apr;46(4):653
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polyarthritis (resembling rheumatoid arthritis) and tenosynovitis reported in case
series of 30 patients with leprosy at rheumatology clinic in India (J Indian Med Assoc 2008
Mar;106(3):165)
rheumatoid-like polyarthropathy preceded neurological and cutaneous symptoms
of leprosy by 10 months in case report of 70-year-old immigrant from Hong Kong diagnosed
o

with borderline lepromatous leprosy (Clin Exp Dermatol 2007 Nov;32(6):784

EBSCOhost Full Text)
5-year history of intermittent inflammatory arthritis and fever before neurologic
manifestation and diagnosis of borderline leprosy in case report (Joint Bone Spine 2006
May;73(3):314)

Physical:

Skin:
thorough physical exam for lesions(1)

examine for hypoesthesia to light touch, pin-prick, and temperature and for
anhidrosis

51% of patients with positive skin smears did not have sensory loss in study of 594
new leprosy cases in Ethiopia (Lepr Rev 2000 Mar;71(1):34)
findings in lepromatous leprosy(1, 2, 4)

multiple macules, papules, plaques, and nodules

lesions have smooth, shiny surface and only slight hypopigmentation or erythema

impaired sweating, decreased hair growth, and loss of sensation in lesions usually
occur in later disease

decreased sensation begins over extensor surfaces of legs, feet, forearms, and
hands (in glove and stocking pattern)

palpable enlargement of peripheral nerves (more common in late stages of polar

lepromatous leprosy)
findings in tuberculoid leprosy

disease limited to well-defined skin patches or nerve trunks (1)

o
o

o
o
o
o

o
o

few hypopigmented macular skin lesions with anesthesia(1, 2)

lesions appear dry and scaly with impairment of sweating (2)
thickened superficial nerves(1, 2)
picture of rash associated with tuberculoid leprosy can be found in Am Fam
Physician 1999 Nov 1;60(7):2087
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borderline forms associated with(2)
abundant skin lesions
irregular anesthesia
impairment of nerves
skin fissures and ulcerations may occur(1)
picture of borderline lepromatous type can be found in N Engl J Med 2001 Apr

26;344(17):1293
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HEENT: (head eyes ears nose throat)
lepromatous leprosy may lead to leonine facies (thickened skin predominantly on forehead,
earlobes, eyebrows and cheeks)(2)
dry insensitive cornea and conjunctiva(1)
look for corneal trauma or ulcerations(1)
Neuro:
peripheral nerve trunk damage(1)

nerves become thickened, with or without tenderness, with peripheral patterns of

sensory and motor loss

most commonly posterior tibial nerve, followed by ulnar, median, lateral popliteal,
and facial nerves
small dermal nerve damage(1)

hypoesthesia and anhidrosis in borderline-tuberculoid and tuberculoid leprosy

stocking-glove sensory loss in lepromatous leprosy

muscle wasting and contractures may occur (1)
pure neuritic leprosy - no skin lesions with asymmetrical trunk involvement, most common
in India and Nepal(1)

Making the diagnosis:

o
clinical diagnosis with at least 1 of 3 signs (World Health Organization [WHO] criteria)

hypopigmented or reddish patches with definite loss of sensation

thickened peripheral nerves

acid-fast bacilli on skin smears or biopsy material

Reference - World Health Organ Tech Rep Ser 1998;874:1 as referenced in(1)

use of these 3 criteria reported to have 97% sensitivity and 98% positive predictive
value for leprosy in Ethiopia (Int J Lepr Other Mycobact Dis 2002 Mar;70(1 Suppl):S1 as
referenced in(1))
o
skin smears have high specificity but low sensitivity (1)
o
histologic diagnosis considered gold standard for diagnosis (1), skin biopsy may be
necessary in paucibacillary disease or tuberculoid leprosy (2)
o
World Health Organization (WHO) field classification when slit-skin smear not available

single skin lesion (1 patch)

paucibacillary (2-5 patches)

multibacillary (> 5 patches)

Reference - World Health Organ Tech Rep Ser 1998;874:1 as referenced in(1, 2)

classification based on skin lesion count reported to result in misclassification of

multibacillary leprosy and risk of undertreatment
o
based on comparison with skin smear and Ridley-Jopling classification in
264 untreated patients with leprosy in the Philippines
Reference - Clin Infect Dis 2007 Apr 15;44(8):1096
EBSCOhost Full
Text
ML Flow test at point-of-care may predict results of slit skin smear for acid fast
bacilli (level 2 [mid-level] evidence)
o

Testing overview:
o
o

thorough physical exam for lesions(1)

full-thickness skin biopsy of lesion(2, 3)

o
2

sample obtained from advancing margin of active lesion, fixed in neutral buffered
formalin, embedded in paraffin, and examined by experienced pathologist
especially useful for patients with paucibacillary leprosy (with scant acid-fast
bacilli)
can be used to classify disease along clinical spectrum
slit-skin smears(1, 2)
obtained by making small slit in pinched skin and scraping with scalpel blade;
tissue fluid obtained is smeared on slide and stained for acid-fast bacilli by Fite method
detects intradermal acid-fast bacilli (AFB) (Z-N/Fite)
important (despite low sensitivity) for determining highly infectious patients and
those with greatest relapse risk
ML Flow test at point-of-care may predict results of slit skin smear for acid fast bacilli (level
[mid-level] evidence)

Blood tests:
o
o

serology not currently effective for diagnosis (1, 3)

phenolic glycolipid I (PGL-1) antibody testing(1, 4)

specific and sensitive for multibacillary leprosy

PGL-1 only present in 40%-50%with paucibacillary leprosy

not able to predict which contacts will develop leprosy

phenolic glycolipid I mycobacterial antigens in blood correlated with bacterial load

of leprosy and decrease after multidrug therapy in cohort of 100 new leprosy patients (Am
J Trop Med Hyg 1991 Jun;44(6):702, Clin Diagn Lab Immunol 2001 Jan;8(1):138 full-text)
ML Flow test at point-of-care may predict results of slit skin smear for acid fast
bacilli (level 2 [mid-level] evidence)

based on cohort study with partial blinding

2,137 patients in Brazil and Nepal with newly diagnosed leprosy classified
according to 3 methods
o
WHO classification

5 lesions = paucibacillary

6 lesions = multibacillary
o
ML Flow serology test for antibodies to M. leprae - positive or negative
o
slit skin smear for acid fast bacilli - positive or negative

20% of ML Flow test results in each country re-read by supervisors blinded to

lesion count

multibacillary leprosy (by WHO classification) reported in 39.5% of 1,071 patients

in Brazil and 35.6% of 1,066 patients in Nepal

among 411 patients with positive slit skin smear

o
ML Flow test was concordant (positive) in 95.5% in Brazil and 89% in Nepal
o
ML Flow test was discordant (negative) in 4.5% in Brazil and 11% in Nepal
o
WHO classification was concordant (multibacillary) in 85.5% in Brazil and
88% in Nepal
o
WHO classification was discordant (paucibacillary) in 14.5% in Brazil and
12% in Nepal

among 1,726 patients with negative slit skin smear

o
ML Flow test was concordant (negative) in 66% in Brazil and 75% in Nepal
o
ML Flow test was discordant (positive) in 34% in Brazil and 24.5% in Nepal
o
WHO classification was concordant (paucibacillary) in 78% in Brazil and
71% in Nepal
o
WHO classification was discordant (multibacillary) in 22% in Brazil and 29%
in Nepal

186 patients in Nigeria classified by WHO classification and ML Flow test (skin
smear unavailable) but incomplete data reported

Reference - Lepr Rev 2007 Mar;78(1):70

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DynaMed commentary -- authors claim ML Flow test of patients classified
paucibacillary by WHO system would detect majority of misclassified multibacillary
patients where skin smear unavailable

Imaging studies:
o

high-resolution sonography appears more accurate than clinical exam for

assessment of nerve enlargement in patients with leprosy (level 2 [mid-level]
evidence)

based on diagnostic case-control study

20 patients with leprosy reaction and 30 age-matched healthy control patients

evaluated
o
bilateral assessment of ulnar, lateral popliteal, medial and posterior tibial
nerves
o
grading of nerve thickness by palpation compared to observation of crosssectional area of major peripheral nerve trunks by ultrasound and color Doppler
nerves significantly thicker in patients with leprosy vs. healthy patients
poor agreement (kappa 0.3) between clinical palpation and sonography for all
examined nerves
o
nerve enlargement by ultrasound in 5 of 34 nerves found not thickened by
clinical exam
o
no nerve enlargement by ultrasound in 39 of 86 nerves found thickened on
clinical exam
o
sensory or motor loss observed by color Doppler in 12 of 23 nerves found
unimpaired by clinical exam
Reference - PLoS Negl Trop Dis 2009 Aug 11;3(8):e498
Text full-text

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Biopsy and pathology:

o

skin biopsy findings(2, 3)

lepromatous leprosy - many acid-fast bacilli, foamy histiocytes
tuberculoid leprosy - few acid-fast bacilli, granulomas, inflamed nerves

Other diagnostic testing:

o

lepromin skin test(3)

not diagnostic of leprosy or exposure to M. leprae
not available in United States
injection of reactive agent measures granulomatous response
o
Mitsuda lepromin most commonly used preparation though not approved
by FDA for use in United States
o
response measured as induration (in mm) 4 weeks after injection
o
response not leprosy specific
negative lepromin skin test with lepromatous leprosy
positive lepromin skin test with tuberculoid leprosy
positive lepromin skin test can occur in persons never exposed to M. leprae
Mycobacterium leprae polymerase chain reaction (PCR)(3)
PCR-based and reverse transcription-PCR-based techniques have
o
100% specificity
o
34-80% sensitivity in patients with tuberculoid leprosy
o
> 90% sensitivity in patients with lepromatous leprosy
for identification of acid-fast bacilli (either profuse or sparse) if tissue site, clinical
history, or other circumstances are questionable
not indicated for identification of acid-fast bacilli not identifiable by good-quality
Fite-stained section
specimens suitable if freshly acquired and processed immediately (specimens can
be frozen indefinitely)
specimens unsuitable from treated patients or if specimens have been refrigerated
or are unfixed/unfrozen
PCR analysis can detect M. leprae in nasal swabs from unaffected exposed persons,

but does not predict clinical disease or infectivity (Clin Infect Dis 2001 Mar 15;32(6):930
EBSCOhost Full Text)
qualitative sensory tests (sensory nerve conduction, warm perception tests) may
detect nerve function impairment earlier than commonly used monofilament test
and voluntary muscle test, but equipment costs may limit usefulness in leprosyendemic countries and unclear if any test has sufficient predictive value for early
detection (level 3 [lacking direct] evidence)

based on prospective cohort study (INFIR study) without clinical outcomes

188 newly diagnosed adults with multibacillary leprosy followed for 2 years

74 (39%) had reaction, neuritis or new nerve function impairment

73 cases with reaction or nerve function impairment were matched to 73 controls

sensory nerve conduction and warm perception tests often preceded deterioration
in monofilament testing and voluntary muscle testing by 12 weeks or more

all tests had low sensitivity, highest sensitivity (37%) reported for cold detection
threshold
all tests had high specificities, ranging from 90-95%, except 80% for warm
detection threshold
all tests had low positive predictive values, highest positive predictive value (14%)
reported for vibration perception threshold
Reference - INFIR Cohort Study (PLoS Negl Trop Dis 2008 Apr 2;2(4):e212 full-text)

Treatment overview:
o

recommended treatments of leprosy by World Health Organization (WHO)

for single skin lesion - single doses of rifampin 600 mg, ofloxacin 400 mg plus
minocycline 100 mg

for paucibacillary disease - 6 months treatment with rifampin 600 mg/month plus
dapsone 100 mg/day

for multibacillary disease - 12 months treatment with rifampin 600 mg/month plus
dapsone 100 mg/day plus clofazimine 300 mg/month plus clofazimine 50 mg/day
corticosteroids during initial treatment of leprosy may reduce short-term (but not longterm) incidence of new reactions (level 1 [likely reliable] evidence)
insufficient evidence to support any specific intervention for treatment or prevention of
ulcers in patients with leprosy
specialized footwear can reduce peak pressure during walking (level 3 [lacking direct]
evidence)

o
o
o

Treatment setting:
o

treatment with isolation no longer indicated (patient not infectious shortly after starting
drug therapy)

Counseling:
o

patient education important for effective management (1, 2)

reassurance that infectious transmission ceases within days of antibiotic treatment
clear explanation of leprosy and its outcomes may improve adherence to
treatments
emphasis on outcome not always leading to gross deformities
stress importance of care of limbs, and daily inspection for trauma

Medications:

Antibiotics:
o

recommended treatments of leprosy by World Health Organization (WHO)(1, 2)

treatment of paucibacillary disease - rifampin plus dapsone for 6 months
o
rifampin (Rifadin, rifampicin) 600 mg (supervised) once monthly
o
dapsone 100 mg/day (self-administered)
treatment of multibacillary disease - rifampin plus dapsone plus clofazimine for 12
months
o
rifampin 600 mg (supervised) once monthly
o
dapsone 100 mg/day (self-administered)
o
clofazimine (Lamprene) 300 mg once monthly (supervised) AND 50 mg/day
(self-administered)
paucibacillary leprosy with single skin-lesion may be treated with single doses of
rifampin 600 mg, ofloxacin (Floxin) 400 mg, and minocycline (Minocin) 100 mg
alternative suggested dosing for United States includes
United States experts recommend increased duration of treatment or use
alternative treatment due to concern for relapse
treatment of paucibacillary disease - rifampin 600 mg/day and dapsone 100
mg/day for 12 months

treatment of multibacillary disease - rifampin 600 mg/day, dapsone 100 mg,

clofazimine 50 mg/day for 2 years or standard WHO regimen for 2 years

Reference - Clin Infect Dis 2001 Mar 15;32(6):930

EBSCOhost Full Text fulltext
antibiotic selection recommendations from The Medical Letter (multi-drug regimen
necessary for successful treatment)

drugs of choice - dapsone plus rifampin with or without clofazimine

alternatives - minocycline, ofloxacin, clarithromycin

Reference - Treat Guidel Med Lett 2007 May;5(57):33 TOC(1)

clofazimine not commercially distributed in United States since 2004

clofazimine available for treatment of leprosy as investigational new drug

through National Hansen's Disease (Leprosy) Clinical Center

Reference - Manufacturer's Press Release 2005 Apr 25

rifampin most effective bactericidal drug against M. leprae

single dose kills 99.99% of organisms

patients with lepromatous leprosy not infectious within 2 days

o
to
o

Reference - Clin Infect Dis 2001 Mar 15;32(6):930

EBSCOhost Full Text fulltext
drug resistance observed with dapsone and rifampin, but frequency in population difficult
determine as M. leprae cannot be cultivated in vitro(3)
possible adverse effects of drug therapies
dapsone
o
rash, agranulocytosis, hemolysis (severe if patient is glucose-6-phosphate
dehydrogenase-deficient) and methemoglobinemia(2)
o
dapsone hypersensitivity syndrome in case report (J Occup Med Toxicol
2006 Jun 6;1:9 full-text)
o
HLA-B*13:01 allele associated with dapsone hypersensitivity syndrome in
case-control study with genetic analysis of 1,705 patients with leprosy (N Engl J Med
2013 Oct 24;369(17):1620)
clofazimine(1)
o
skin discoloration ranging from red to purple-black (most commonly
reported side-effect) fades slowly after withdrawal of clofazimine
o
characteristic ichthyosis on shins and forearms
pregnancy categories of antimicrobials
FDA Pregnancy Category C - rifampin, dapsone, clofazimine, clarithromycin,
ofloxacin, levofloxacin
FDA Pregnancy Category D - minocycline

Corticosteroids:
o

low dose prednisolone during first 4 months of multidrug treatment for

multibacillary leprosy reduces short-term incidence of new reactions and nerve
function impairment (level 1 [likely reliable] evidence)

based on randomized trial

636 patients aged 15-50 years with newly diagnosed multibacillary leprosy treated
with multidrug treatment for 1 year and randomized at onset to prednisolone (20 mg/day
for 3 months then tapered over 1 month) vs. placebo

90% follow-up rates and intention-to-treat analysis

comparing prednisolone vs. placebo

o
4% vs. 15% had skin or nerve reaction at 4 months (NNT 9)
o
effect not sustained at 1 year when 22% vs. 17% had skin or nerve reaction
(not statistically significant)

prednisolone only effective in patients without pre-existing nerve function

impairment

Reference - TRIPOD 1 trial (BMJ 2004 Jun 19;328(7454):1459

EBSCOhost Full

Text full-text), editorial can be found in BMJ 2004 Jun 19;328(7454):1447

EBSCOhost Full Text full-text

DynaMed commentary -- non-significant increased risk at 1 year suggests that

prednisolone may delay instead of prevent reactions
corticosteroids may not improve nerve function in patients with leprosy (level 2
[mid-level] evidence)

based on Cochrane review with inadequate statistical power for prespecified

outcomes

systematic review of 3 randomized and quasi-randomized trials evaluating

corticosteroids for treatment of nerve damage in 513 patients with leprosy

no significant difference in nerve function improvement comparing prednisolone to

placebo at 12 months in 2 trials
o
1 trial evaluated patients with mild sensory impairment for < 6 months
o
1 trial evaluated patients with nerve function impairment for 6-24 months
o
confidence intervals do not rule out clinically relevant differences

3-month course of prednisolone associated with significantly greater need for

additional corticosteroids compared to 5-month course of high-dose or low-dose regimen in
1 trial comparing 3 corticosteroid regimens for severe type 1 reactions

Reference - Cochrane Database Syst Rev 2007 Apr 18;(2):CD005491 (review

updated 2011 Aug 10)
addition of IV methylprednisolone to oral prednisolone does not appear to
reduce type 1 reactions of leprosy but may reduce deterioration of sensory function
(level 2 [mid-level] evidence)

based on small randomized trial

42 patients aged 16-65 years with leprosy with type 1 reactions or nerve function
impairment were randomized to methylprednisolone IV plus prednisolone orally vs.
prednisolone orally alone for 16 weeks

no significant difference between groups in clinical improvement, sensory function,

need for additional prednisolone, or adverse events at 337 days follow-up

methylprednisolone associated with fewer patients with deterioration of sensory

function at end of treatment (p = 0.046)

Reference - PLoS Negl Trop Dis 2011 Apr 12;5(4):e1041

Text full-text

EBSCOhost Full

Other medications:
o

thalidomide appears highly effective for type II reactions (erythema nodosum leprosum)
but caution warranted due to teratogenic effects (Lancet 1994 Feb 19;343(8895):432
EBSCOhost Full Text, Indian J Lepr 1990 Jul-Sep;62(3):316, Microbes Infect 2002
Sep;4(11):1193)
limited evidence suggests thalidomide and clofazimine may prevent new skin
lesions caused by erythema nodosum leprosum (level 2 [mid-level] evidence)

based on Cochrane review of trials with methodologic limitations

systematic review of 13 randomized trials evaluating interventions for erythema

nodosum leprosum in 445 patients with leprosy

methodologic limitations included

o
randomization method not reported
o
allocation concealment not stated
o
lack of intention-to-treat analysis

meta-analysis not possible due to heterogeneity of interventions

comparing thalidomide vs. control in single trials

o
significant remission of skin lesions in 52% vs. 21.4% in aspirin group (risk
ratio [RR] 2.43, 95% CI 1.28-4.59)
o
adverse effects in 41.7% in thalidomide 100 mg group vs. 90% in
thalidomide 300 mg group (RR 0.46, 95% CI 0.23-0.93)

comparing clofazimine vs. control in single trials

o
absence of new lesions in 91.7% vs. 25% in prednisolone group (RR 3.67,
95% CI 1.36-9.91)
o
adverse effects in 100% vs. 50% in prednisolone group (RR 1.92, 95% CI
1.10-3.35)
o
recurrence in 2.8% vs. 36.1% in thalidomide group (RR 0.08, 95% CI 0.010.56)

no significant differences in any outcomes comparing

o
indomethacin vs. aspirin, chloroquine, or prednisolone in 2 small trials
o
levamisole vs. placebo in 1 small trial
o
pentoxifylline vs. thalidomide in 1 small trial

Reference - Cochrane Database Syst Rev 2009 Jul 8;(3):CD006949

infliximab reported to be effective for recurrent erythema nodosum leprosum (level 3
[lacking direct] evidence) in case report (N Engl J Med 2006 Aug 17;355(7):739
EBSCOhost Full Text)

o
o

cyclosporine has insufficient and conflicting evidence for use in treatment of type 2
reactions(3)
no controlled trials evaluating azathioprine or methotrexate(3)

Surgery and procedures:

o

surgery may be indicated for(1, 2)

debridement of foot ulcer, if not responding to medical treatment and reduction in

weight-bearing

contractures of hands and feet

foot drop

lagophthalmos

entropion (turning in of the edges of eyelid)

ectropion (turning out of the edges of eyelid)

addition of peripheral nerve decompressive surgery to prednisolone may not
improve sensory or motor nerve function in patients with leprosy and nerve damage
for < 6 months (level 2 [mid-level] evidence)

based on Cochrane review with limited evidence

systematic review of 2 randomized trials evaluating decompressive surgery for

nerve damage (< 6 months duration) in 88 patients with leprosy

both trials compared decompressive surgery plus prednisolone vs. prednisolone

alone, no significant differences in sensory or motor nerve function through 2 year followup

adverse effects related to decompressive surgery not adequately described

Reference - Cochrane Database Syst Rev 2012 Dec 12;(12):CD006983

Consultation and referral:

o
o
o

treatment and leprosy reactions best managed by tropical disease specialist or

dermatologist with specific expertise(2)
leprosy is reportable to federal agencies in United States and Canada (2)
consultation and laboratory services available from National Hansen's Disease (Leprosy)
Clinical Center

Other management:
o

insufficient evidence to support any specific intervention for treatment or

prevention of ulcers in patients with leprosy

based on Cochrane review

systematic review of 8 randomized trials evaluating measures designed to promote

healing of existing ulcers and prevent new ulcers in 557 patients with leprosy and
peripheral nerve damage

trials were small and had poor methodologic quality and interventions were
heterogeneous

zinc tape associated with nonsignificant trend toward benefit compared to more
traditional dressings in 3 trials

topical ketanserin associated with better effect on wound healing than clioquinol
cream or zinc paste in 1 trial with wide confidence intervals

topical phenytoin associated with statistically significant beneficial effects on ulcer

healing compared to saline dressing in 2 trials (results not combined for meta-analysis)

canvas shoes no more effective than PVC-boots in 1 trial

double rocker shoes did not promote healing more than below-knee plasters in 1
trial

Reference - Cochrane Database Syst Rev 2008 Jul 16;(3):CD004833

specialized footwear for foot ulcers may be beneficial(1)

ulcers in leprosy heal if protected from weight-bearing (Lepr Rev 1999

Mar;70(1):63 as referenced in(1))

footwear can reduce peak pressure during walking (level 3 [lacking

direct] evidence)

based on trial of 6 types of footwear used in leprosy programs and patients'

prescribed footwear in 10 leprosy patients
o
all footwear (except extra depth shoe without insole) had significantly
lower peak pressure than barefoot walking
o
peak pressure during walking inversely correlated to insole thickness
o
Reference - Lepr Rev 1994 Sep;65(3):262

cheap canvas shoes with cushioned insoles protective, cost-effective, and preferred
to orthopedic shoes in randomized trial (Lepr Rev 1998 Jun;69(2):182 as referenced in(1))

review of plastic footwear for leprosy can be found in Lepr Rev 1990 Mar;61(1):73
early mobilization following surgical correction of foot drop may shorten
rehabilitation stay without increasing risk of tendon pullout in patients with
Hansen's disease (level 2 [mid-level] evidence)

based on small randomized trial

24 patients with Hansen's disease and surgically corrected foot drop deformity
were randomized to early mobilization (active motion at 5 days) vs. 4 weeks of
immobilization

mean rehabilitation stay was 43 days for early mobilization group vs. 59 days for
immobilized group (p < 0.001)

no tendon pullout in either group

no significant differences in active range of motion, ankle strength or 6-minute

walking distance in mean follow-up 19 months

Reference - Clin Orthop Relat Res 2010 Sep;468(9):2477 full-text

community-based socioeconomic rehabilitation may be helpful (Lepr Rev 2000
Dec;71(4):422 as referenced in(1))
o

Follow-up:
o
o
o

suggested follow-up for 5-10 years after treatment completion (2)

0.01%-0.14% annual relapse rate after multidrug therapy stopped (Clin Infect Dis 2001 Mar
15;32(6):930
EBSCOhost Full Text)
5%-10% expected to have type 1 reversal reaction within first year, follow-up every 3

months for first year is advised (Clin Infect Dis 2001 Mar 15;32(6):930
EBSCOhost Full
Text full-text) as referenced in(2)
Prognosis
o
clinical course may vary with classification of leprosy(1, 2)

course may have slow progression or sudden type I reactions with conversion to
other forms

borderline tuberculoid leprosy can be associated with rapid and severe nerve
damage

lepromatous disease associated with chronicity and long-term complications

including
o
nerve damage
o
hypoesthesia
o
muscle weakness
o
thickening of skin in forehead, earlobes, eyebrows, and cheeks

multibacillary leprosy (> 5 skin patches) associated with higher risk for reversal
reactions and impairment of nerve function
o
response to treatment generally good(2)

neurologic deficits often at least partially reduced with early treatment

skin lesions usually resolve within 1 year, but may persist for up to 5 years in
multibacillary disease

relapse or reaction may occur after cessation of multidrug therapy

o
risk of leprosy reaction appears highest in first year of multidrug therapy (level 2
[mid-level] evidence)

based on prospective study with high loss to follow-up

375 patients in Ethiopia with borderline lepromatous or lepromatous leprosy

monitored for reversal reactions during and after multidrug therapy

reactions included in study were limited to patients

o
not treated with dapsone before multidrug therapy
o
requiring prednisolone treatment

follow-up for 3.5 years - about 30-40% patients did not attend follow-up clinics after
treatment ended (based on patient registration records)

reversal reactions
o
43.6% with borderline lepromatous leprosy within 2 years

4.9% at diagnosis

26.3% in first year

12.4% in second year

o
19.2% with lepromatous leprosy within 2 years

0% at diagnosis

12.8% in first year

6.4% in second year

erythema nodosum leprosum reactions

o
2.7% with borderline lepromatous leprosy within 2 years

0.8% at diagnosis

1.1% in first year

0.8% in second year

o
11.1% with lepromatous leprosy within 2 years

2.8% at diagnosis

5.5% in first year

2.8% in second year

reactions gradually decline after first year, but can occur into fourth year after
treatment

Reference - Int J Lepr Other Mycobact Dis 1992 Jun;60(2):173

prediction rules may predict nerve function impairment

BANDS prediction rule may predict risk of nerve function impairment at 2

years (level 2 [mid-level] evidence)
o
based on prospective cohort derivation study without external validation
o
2,510 patients from Bangladesh Acute Nerve Damage Study (BANDS) with
new diagnosis of leprosy classified according to World Health Organization criteria
and followed for 2 years
o
166 patients (6.6%) developed nerve function impairment defined as

2 points in sensory score

based on ballpoint pen test - touch with pen in relevant

sensory area at standard test sites, score based on number of points with
absent sensation

nerves tested include ulnar (five sites), median (seven

sites), and posterior tibial nerves (11 sites)

2 point reduction in Medical Research Council grade of

movement tested for any of facial, ulnar, median and lateral popliteal nerves

clinical diagnosis of nerve function impairment

o
risk of nerve function impairment within 2 years was

1.3% (95% CI 0.8-1.8%) for 1,957 patients with paucibacillary

leprosy and no nerve-function loss at baseline

16% (95% CI 12-20%) for 407 patients with either paucibacillary

leprosy and nerve-function loss at baseline or multibacillary leprosy and no
nerve-function loss at baseline

65% (95% CI 56-73%) for 146 patients with multibacillary leprosy

and any nerve-function loss at baseline
o

Reference - Lancet 2000 May 6;355(9215):1603

EBSCOhost Full Text,

commentary can be found in Lancet 2000 Nov 18;356(9243):1767

EBSCOhost Full Text
multibacillary leprosy plus phenolic glycolipid I (PGL-I) antibodies may
predict high risk of nerve function impairment (level 2 [mid-level] evidence)
o
based on prospective cohort derivation study without external validation
o
864 patients in Bangladesh with newly diagnosed with leprosy were
followed for median 46 months
o
115 patients (13%) developed nerve function impairment defined as
decision to start corticosteroids due to any of

nerve function reduction by 2 points in sensory and/or motor

function tests

corneal anesthesia

nerve tenderness score of 2 (palpation of nerve causes patients to

jump or cry)

mixed mild symptoms of neuritis

rates of developing nerve function impairment based on WHO classification
and anti-PGL-I antibodies

3.5% (95% CI 2.2-5.4%) in 549 seronegative paucibacillary patients

13% (95% CI 8.5-19%) in 176 seropositive paucibacillary patients

and seronegative multibacillary patients

53% (95% CI 45-62%) in 139 seropositive multibacillary patients

Reference - PLoS Negl Trop Dis 2008 Aug 27;2(8):e283 full-text
DynaMed commentary

article reported to validate BANDS prediction rule but used "longstanding nerve function impairment" as part of rule where original article used
"any nerve function loss"

definition of nerve function impairment event and exclusion criteria

regarding nerve function impairment status at diagnosis not comparable

o
o

Prevention:
o

leprosy in close contacts rare(1)

last case in United Kingdom in 1923
examine household contacts for clinical signs of leprosy and advise them to report
any new skin lesions promptly
bacille Camille-Gurin (BCG) vaccine
BCG given to children < 12 years old in United Kingdom (1)
effectiveness rates vary from 20%-80%(3)
neonatal BCG appears effective against leprosy (level 2 [mid-level]
evidence)
o
based on cohort study
o
112,744 schoolchildren in Brazilian Amazon born between 1983-1991 with
no or 1 BCG scar entered into study
o
74% protection in neonatal BCG vaccination for all leprosy types
o
93% protection in persons with multibacillary leprosy
o
67% protection in persons with paucibacillary leprosy
o
Reference - Lepr Rev 2004 Dec;75(4):357
BCG appears modestly effective against leprosy (level 2 [mid-level]
evidence)
o
based on population-based case-control study in India
o
364 cases of leprosy (identified from survey of 2,175,514 persons) were
paired with matched controls and assessed for BCG vaccination
o
significant protective association between BCG and leprosy (odds ratio [OR]
0.46, 95% CI 0.34-0.6)
o
BCG effectiveness

54% (95% CI 39-66%) overall

68% (95% CI 26-86%) against multibacillary leprosy

57% (95% CI 29-74%) against paucibacillary leprosy

48% (95% CI 22-65%) against single skin lesion leprosy

o
Reference - Public Health 2005 Mar;119(3):209
efficacy of repeat BCG vaccination inconsistent in 2 randomized trials
o
repeat BCG vaccine may further increase protection against
leprosy but not against tuberculosis (level 2 [mid-level] evidence)

based on randomized trial with low follow-up rates

121,020 persons in rural area of northern Malawi (virtually the

entire population 1986-1989)

previously unvaccinated persons randomized to BCG alone

vs. BCG plus killed M. leprae

previously vaccinated persons randomized to second BCG

vs. BCG plus killed M. leprae vs. placebo

66,155 persons without BCG scar were randomized to 1 of 2 groups

BCG vaccine alone

BCG plus killed M. leprae (dose of killed M. leprae vaccine

increased from 5 x 107 to 6 x 108 bacilli during the trial)

54,865 persons with positive or doubtful BCG scar were

randomized to 1 of 3 groups

placebo
BCG alone
BCG plus killed M. leprae (6 x 108 bacilli)
follow-up at 5-9 years achieved for 63% previously unvaccinated
and 66% previously vaccinated participants
139 new cases of leprosy occurred during follow-up (107
considered as definitely post-vaccination cases)
comparing BCG alone vs. placebo in scar-positive patients

certain or probable leprosy found after vaccination in

0.068% vs. 0.124% (p = 0.05, NNT 1,786)

certain or probable, definitively postvaccination, leprosy in

0.06% vs. 0.112% (p barely > 0.05, NNT 1,923)
addition of killed M. leprae did not significantly improve protection
over primary BCG vaccination or secondary BCG vaccination
no evidence that any of the trial vaccines contributed to protection
against pulmonary tuberculosis

Reference - Lancet 1996 Jul 6;348(9019):17

EBSCOhost Full

Text
o

repeat vaccination with BCG does not appear to protect against

leprosy (level 2 [mid-level] evidence)

based on subgroup analysis of open-label, cluster randomized trial

in Brazil

152,438 children aged 7-14 years randomized by school to

intradermal injection with BCG, Moreau strain (n = 72,980) vs. no-treatment
control (n = 79,458)

children followed for up to 6 years, 8 months

subgroup analysis reported for 92,770 children with 1 BCG scar at

baseline

leprosy reported in 56 cases in revaccinated group vs. 61 cases in

control group in this subgroup analysis (incidence rate ratio 0.99, 95% CI 0.681.45)

Reference - BCG-REVAC trial (PLoS Negl Trop Dis 2008 Feb

13;2(2):e167 full-text)

review of BCG can be found in Scand J Infect Dis 2001;33(4):243

EBSCOhost Full Text
addition of killed M. leprae appeared to increase effectiveness of BCG in 1
randomized trial (Indian J Lepr 1998 Oct-Dec;70(4):369) but not in another randomized

trial (Lancet 1996 Jul 6;348(9019):17

EBSCOhost Full Text), both limited by low
follow-up rates
dapsone chemoprophylaxis may reduce rate of leprosy in household contacts in
endemic countries (level 2 [mid-level] evidence)

based on systematic review of trials of varied quality

systematic review of 6 randomized trials, 6 controlled trials and 2 uncontrolled

trials evaluating chemoprophylaxis for prevention of leprosy in endemic countries and in
household contacts

most studies evaluated chemoprophylaxis in children or young people

all randomized trials were conducted in India

trials not evaluated for quality criteria

most trials evaluated dapsone

o
oral dapsone evaluated in 4 randomized and 6 controlled trials
o
intramuscular acedapsone evaluated in 2 randomized trials and 1
uncontrolled mass intervention trial
o
1 uncontrolled mass intervention trial evaluated rifampicin

all randomized trials had statistically significant results supporting efficacy

o
NNT rates to prevent 1 case of leprosy for dapsone ranged from 15 to 27 in
household contacts in 3 trials
o
NNT 393 for dapsone in 1 trial with cluster randomization of villages
o
NNT for acedapsone 17 and 25 in 2 trials

controlled trials of dapsone had results similar to randomized trials

Reference - J Infect 2000 Sep;41(2):137

single dose rifampicin given to contacts of patients with newly diagnosed

leprosy appears effective for prevention of leprosy for 2 years (level 2 [mid-level]
evidence)

based on cluster randomized trial with low follow-up rates and without intention-totreat analysis

28,092 close contacts of 1,037 patients with newly diagnosed leprosy in

Bangladesh were randomized by index-patient cluster to single dose rifampicin vs. placebo
orally in second month of index patients treatment
o
600 mg for adults 35 kg
o
450 mg for adults < 35 kg and children > 9 years old
o
300 mg for children aged 5-9 years

index patients classified according to World Health Organization criteria

o
paucibacillary leprosy with single lesion in 389 patients
o
paucibacillary leprosy with 2-5 lesions in 353 patients
o
multibacillary leprosy in 295 patients

21,711 (77%) contacts completed study requirements, of which 18,869 (87%)

available for 4-year follow-up

leprosy cases in contacts with rifampicin vs. placebo

o
59 (0.59%) vs. 91 (0.91%) over 4 years (p < 0.05)
o
29 (0.29%) vs. 67 (0.67%) during years 1-2 (p = 0.0002)
o
30 (0.32%) vs. 24 (0.26%) during years 3-4 (not significant)

to prevent 1 case of leprosy among contacts

o
NNT 265 (95% CI 176-537) after 2 years
o
NNT 297 (95% CI 170-1,206) after 4 years

Reference - BMJ 2008 Apr 5;336(7647):761

EBSCOhost Full Text full-text,

editorial can be found in BMJ 2008 Apr 5;336(7647):730

EBSCOhost Full Text,

commentary can be found in BMJ 2008 Apr 19;336(7649):847

EBSCOhost Full Text

Screening:
o

delayed diagnosis of leprosy associated with increased nerve damage and disability consider leprosy diagnosis in patients with peripheral neuropathy or persistent skin lesions
even if not from leprosy-endemic country(1)