Marie Antoinette F. Cabahug M.D.

, FPDS
Dr. Gerhard Henrick Armauer Hansen
 EPIDEMIOLOGY
 10 to 15 million people in the world
 Studies determining susceptibility & expression of disease:
1. Environmental factors
 endemic in many areas of Asia :
 Indian subcontinent X Philippines
 Sub-SaharanAfrica X Pacific Island
 South & CentralAmerica
 Tropical, developing countries
 Low economic status with inadequate housing
 unsuitable sanitation; poor nutrition & lack of education

2. Genetic factors
 Immunologic evidence of exposure in 50% or more of potentially
exposed persons

 Adults 2-3 fold ↑ in men than women

 Children gender ratio 1:1
ETIOLOGY
 Mycobacterium Leprae
 Slender, straight (cigar-shaped) or slightly curved
gram (+) acid-fast rod about 3.0X0.5 µm
 Grows best at temp. below human core body

temperature (32° to 35°C)

 Viable for 9-16 days and in moist soil for 46 days
 Direct sunlight for 2 hours
 UV light for 30 minutes

 Cultivated in mouse foot pads & armadillos but

humans are main reservoirs of M. Leprae
Mycobacterium leprae
Acid fast stain
ETIOLOGY
 2 recognized modes of transmission:
1. Infectious droplets via respiratory route
2. Ulcerated skin lesions
 both mechanism, close contact
associated with acquiring infection

 Predisposing factors:
1. residence in an endemic area
2. having a blood relative with leprosy
3. poverty (malnutrition)
4. close contact with affected armadillos
PATHOGENESIS
 Clinical spectrum depends on variable limitation
of host to develop effective CMI to M. leprae

 Organism → invade & multiply peripheral nerves

→ infect surviving endothelial & phagocytic cells
in organs

 Sub-clinical infection common in residents of

endemic areas & handed by host CMI response

 Clinical expression develop “Granuloma” &

patients develops “Reactional state”
PATHOGENESIS
 Granulomatous spectrum of leprosy consist of:
 Highly resistance tuberculoid response (TT)
 Low or (-) resistance lepromatous pole (LL)
 Dimorphic or borderline region (BB)
 2 intermediary regions:
1. Borderline lepromatous (BL)
2. Borderline tuberculoid (BT)
 In order of decreasing resistance:
TT BT BB BL LL
DIAGNOSIS
 Begins with suspicion of Leprosy

 Considered in patients with neurologic or

cutaneous lesions

 Suspicious if several risk factors are (+):

1. Birth or residence in endemic areas
2. Blood relative with disease reflecting genetic
make-up or environmental exposure
3. Armadillo exposure

 Firm diagnosis requires (+) of a consistent

peripheral nerve abnormality or demonstration
of organism in tissues
 DIAGNOSIS
 Nerve changes:
 Several kinds of peripheral nerve abnormalities:
1. Nerve enlargement (asymmetrical) especially nerves close
to the skin:
*Great auricular *Superficial peroneal
*Ulnar *Sural
*Median *Posterior tibial
2. Sensory loss in skin lesions
3. Acral distal symmetrical anesthesia = withering away of type
C fibers involving loss of heat & cold discrimination before
loss of perception of pinprick or light touch starting on acral
areas then, extends centrally but spares the palms
 Anhidrosis = common manifestation of sympathetic
nerve involvement
DIAGNOSIS

Sural
 DIAGNOSIS

Palpation of the median nerve Palpation of the peroneal

Cord-like enlargement of the
(lateral popliteal) nerve
greater auricular nerve

Palpation of the ulnar nerve

DIAGNOSIS

Palpation of the sural nerve

Palpation of the posterior tibial nerve

DIAGNOSIS

Test for sensory loss in skin lesions

 LABORATORIES
 Identifying organism in affected tissue
important, organism cannot be cultured
 2 ways in identifying organism:
1. Skin biopsies = skin & nerve lesions
 Fite-faraco stain
 Epitheloid cell granulomas = organism around dermal nerves
 Lepra cells or Virchow cells = macrophages filled with M.
leprae cells

 H & E stain
 Grenz zone = (lepromatous leprosy)
extensive cellular infiltrate separate from epidermis
Histopathology
Lepromatous leprosy
 Histopathology

Lepra cells or Virchow cells - macrophages filled with M.

leprae cells
Epitheloid cell granulomas – organisms
forming around dermal nerves
LABORATORIES
2. Slit smears of the skin
 small skin incision → scrapings obtain tissue fluid
→ smear & examine using Ziehl-Neelsen staining
Mycobacterium leprae
Ziehl-Neelsen staining
LABORATORIES
 Smears taken from cooler areas: earlobes, elbows & knees
 Organism/s is/are (+) – MULTIBACILLARY

 Organism/s is/are(-) – PAUCIBACILLARY

 Organisms counted per HPF = Bacillary index (BI) - bacterial

load of the infection

 Morphologic index (MI) - staining characteristic of organism

 MI changes sooner than BI “early indicator of efficacy of

treatment & detect medicine resistance especially Dapsone
 BACTERIAL INDEX (BI)
RIDLEY LOGARITHMIC SCALE

0 ------ No bacteria in 100 fields (oil immersion)

1+ ------ 1-10 bacteria in 100 fields
2+ ------ 1-10 bacteria in 10 fields
3+ ------ 1-10 bacteria in an average field
4+ ------ 10-100 bacteria in an average field
5+ ------ 100-1000 bacteria in an average field
6+ ------ many clumps of bacteria (>1000) in an
average field
 LEPROMIN SKIN TEST
MITSUDA TEST
 Lepromin skin test reagent - from armadillo-cultivated organism
 Not a useful test in the Diagnosis
 Determine immunologic status of patients in relation to bacillus
= helpful classifying a case
 Test for CMI
 Early reading 24-48 hrs known as Fernandez reaction
 4 wks known as Late Reaction of Mitsuda

 (+) in tuberculoid leprosy but (-) in lepromatous leprosy

 TT & BT are (+) (≥3 mm induration in 21 days)

 BB to LLp are (-) (<3 mm)

Lepromin skin test
Mitsuda test
 OTHER LABORATORIES
1. POLYMERASE CHAIN REACTION (PCR)
• PCR and recombinant DNA technology
allows development of gene probes with M.
Leprae-specific sequences
• Identifies the bacteria in biopsy samples,
skin and nasal smears, blood and tissue
sections
2. LYMPHOCYTE MIGRATION INHIBITION TEST
(LMIT)
• Determines cell-mediated immunity to M.
Leprae which is absent to Lepromatous
leprosy but present in tuberculoid leprosy
•

3. CONTACT OR FAMILY SCREENING FOR HISTORY OF LEPROSY

CLASSIFICATION OF LEPROSY
TT←BT↔BB↔BL↔LLs LLp

*TT = Tuberculoid
*BT = Borderline tuberculoid
*BB = Borderline
*BL = Borderline lepromatous
*LLs = Subpolar lepromatous
*LLp = Polar lepromatous
 CLASSIFICATION OF LEPROSY

 Clinical manifestations correlate with level of host

CMI to pathogen

 Ridley system TT←BT↔BB↔BL↔LLs LLp

 6 membered granulomatous spectrum range from
high to low resistance
 Detailed spectral classification of patients combining
clinical & histologic criteria = represents outcome of
host response to M. Leprae
 TT & LLp clinically stable but between poles, host
granulomatous posture may change
 CLASSIFICATION OF LEPROSY
TT←BT↔BB↔BL↔LLs LLp
 BB is highly unstable midsection or midpoint of infection
 BT patients may upgrade to TT so unstable

 LLs patients do not downgrade to LLp nor LLp patients

upgrade
 All TT patients are paucibacillary & almost all BT cases
 BB, BL, LLs & LLp are all multibacillary
 Tuberculoid corresponds to TT & BT
 Borderline or dimorphic to BB & BL
 Lepromatous to LLs & LLp
CLINICAL FEATURES
 Strong immunity, spontaneous manifestations &
absence of downgrading to a status of less host
resistance

 Skin lesions are solitary to few, well-defined

hypopigmented macules with raised edges & varying
in size involving the entire trunk

 Lesions asymmetrical & annular with a red or purple

border and central hypopigmentation

 Surface of lesion is dry, scaly, anesthetic & does not

sweat
 Sites of predilection = cool peripheral areas:
* Buttocks
* Extensor surface of the limbs
* Face
* Elbows & knees

 Peripheral nerves involve:

* Ulnar (most frequent)
* Peroneal
* Great auricular
Tuberculoid leprosy (TT)
Tuberculoid leprosy (TT)
Hypopigmented anesthetic macule
 Tuberculoid leprosy (TT)
Multiple hypopigmented anesthetic macules
 Tuberculoid leprosy (TT)
Dry, annular, edematous anesthetic plaque
 Strong Immunologic resistant to restrain infection

 Limited so bacillary growth partially inhibited but host response

insufficient to self cure

 Lesions similar to TT, but smaller, more numerous (usually

3-10) & satellite lesions around large macule or plaque
characteristic

 Little or (-) scaling, less erythema, induration, & elevation

but can be larger(>10 cm in diameter) & single lesion may
involve entire extremity
 Loss of sensation is the rule, Nerve trunk involvement,
enlargement or palsies less than 2 & asymmetrical
Borderline tuberculoid (BT)
 Immunologic midpoint or midzone of granulomatous
spectra & most unstable area

 Numerous but countable & consist of red, irregular

shaped plaques surrounded by small satellite lesions &
islands of clinically normal skin with in plaque having
Swiss-cheese appearance or classic dimorphic
lesions

 Generalized but asymmetrical & edges not well defined

 Thickened & tender nerves but anesthesia moderate

Borderline leprosy (BB)
Borderline leprosy (BB)
 Low resistance to restrain bacillary proliferation but
sufficient to tissue destruction or inflammation in nerves

 Symmetrical, numerous from macules, papules, plaque

& nodules

 Number of small lepromatous lesions outnumber large

borderline type

 Nerve involvement appears later & enlarged, tender or

both & symmetrical

 Hyperesthetic or anesthetic
 Sensations & sweating normal but does not show
features of full blown lepromatous leprosy

 Classic dimorphic lesion in 1/3 of patients

 Lepromatous-like = numerous poorly defined papules &

nodules but accompanied by some sharply marginated
lesions elsewhere

 Lesions range from solitary to numerous to widespread

 Nerve trunk palsies range from none to 6 or > &

involvement of median & ulnar nerves are characteristic
Borderline lepromatous leprosy (BL)
Borderline lepromatous leprosy (BL)
 Divided into 2:
 Polar form (LLp)
 Subpolar (LLs) = clinical clue sharply marginated region in lesion
maybe residual of BL that downgraded to LLs

 Lack CMI against bacteria permits unrestricted bacillary

replication & widely disseminated multi-organ disease

 Lesions with numerous bacteria lesions & (-) reaction to

lepromin test

 Poorly defined skin colored nodules up to 2cm &

symmetrically distributed = LEPROMAS

 Diffuse dermal infiltration manifested by widening of nasal

root & fusion swelling of fingers mimics rheumatic dse.
 Progressive bacillary proliferation → thickening of dermis
→ thrown into folds = Leonine facies

 Hair loss on the eyebrows = Madarosis

 Severe acral distal symmetric anesthesia lead to debilitating

trophic changes on hands and feet

 Nerve trunk palsies but less common than BL

 Untreated LL cause disease to progress but can be altered

by reactional states
Lepromatous leprosy (LL)
Lepromas - ears
Lepromatous leprosy (LL)
Lepromatous leprosy (LL)

LOSS OF EYEBROWS/EYELASHES
Lepromatous leprosy (LL)

LEONINE FACIES
 Lepromatous leprosy (LL)

WIDENING OF THE NASAL ROOT SADDLE-NOSE DEFORMITY

 Lepromatous leprosy (LL)

ACTIVE, NEGLECTED NODULOUS LEPROMATOUS LEPROSY LESIONS

Lepromatous leprosy (LL)

DISFIGURED HANDS & FEET

REACTIONAL STATES
 Distinctive, tissue-destructive & inflammatory process
 Immunologically driven - increases morbidity of the disease

1. Delayed-type Hypersensitivity Reaction

 Jopling’s type 1 reaction
 Upgrading or Downgrading or Reversal reaction
 Common in BL but can occur in LLs or BT
 May upgrade to resistant granulomatous
presentation , remain unchanged, or downgrade
 Enhanced CMI response to M. leprae
 During antibiotic chemotherapy = reversal reaction
 When borderline disease shifts towards lepromatous pole
= downgrading reaction
 Not associated with systemic signs & symptoms
 Abrupt conversion of previously torpid plaques to tumid
lesions & appearance of new lesions in clinically normal
skin with or without an abrupt onset of neuritis
 Characteristic Purplish color
 Iritis , lymphedema (Elephantiasis graecorum), neuritis
 Can occur up to 3 yrs. after starting treatment & even after
treatment has stopped
 Reactional states
Delayed hypersensitivity reaction
2. Erythema Nodosum Leprosum (ENL)
 Jopling’s type 2 reaction
 In LL & BL patients
 Features common with Erythema nodosum
 Before, during, or after chemotherapy
 Crops of widely distributed painful & tender bright
pink dermal & subcutaneous nodules from normal skin
associated with fever, anorexia & malaise
 Multisystem disease= conjunctivitis, neuritis, keratitis,
iritis, synovitis, nephritis, hepatosplenomegaly, orchitis
& lymphedema
 Reactional states
Erythema Nodosum Leprosum (ENL)
3. Lucio’s Reaction
 Uncommon & unusual reaction
 Presents with hemorrhagic infarcts
 Prevalent in Mexico & Caribbean regions & restricted to
patients with LATAPI’S lepromatosis
 Purplish suffusion of hands & feet with numerous telangiectatic
molts or eruptive telangiectasia & necrotic lesions in crops
 Ulceration is common
 Nasal septum perforation, total alopecia of eyebrows & lashes
& well-developed acral distal symmetric anesthesia with ocular
sparing
 Before treatment is initiated
Reactional states
Lucio’s reaction
 Early lesion before host can make a
definitive immunologic commitment to cure
or to overt granulomatous response

 Hypopigmented macule with or without

sensory deficit

 AFB if (+) very small in number or if lesions

rich in AFB, lesions are neither tuberculoid
or lepromatous in histologic response
 TREATMENT
“The diagnosis and successful treatment of Leprosy can be one of the
most rewarding and gratifying experience in clinical medicine.”
 Medical management directed at infection itself or at
reactional state if present
 General principles for the management of Leprosy:
 Eradicate infection with anti lepromatous treatment
 Prevent & treat reactions
 Reduce the risk of nerve damage
 Educate patient to deal with neuropathy & anesthesia
 Treat complications of nerve damage
 Rehabilitate patients into society
 TT or BT
a. WHO combination
 Unsupervised Dapsone 100 mg daily
 Supervised Rifampicin 600mg monthly
 Duration of 6 months

b. Other authors
 Dapsone 100mg daily 3-5 yrs. with or without
Rifampicin 600mg monthly
 Follow-up exam 1 & 2 yrs. after treatment is
discontinued
1. Dapsone
 Bacteriostatic
 Potent oxidants
 MOA: interferes with the folate biosynthesis
pathway of bacteria
 Adverse effects: Hemolysis
Methemoglobinemia

2. Rifampicin
 Bactericidal
 Adverse effects: produce reddish urine
hepatotoxic
 BB, BL & LL
a. WHO combination
 Unsupervised Dapsone100 mg daily
 Supervised Rifampicin 600 mg monthly
 Unsupervised Clofazimine 50 mg daily
 Supervised Clofazimine 200 mg monthly
 Routine duration of 2 yrs.

Rationale: Rifampicin kills susceptible organisms including

resistant to Dapsone & Dapsone eventually eliminates
all susceptible organisms including resistant to Rifampicin
 Clofazimine added to obviate the risk of 1° Dapsone
resistance
1. Clofazimine (Lamprene)
 Riminophenazine derivative
 Bacteriostatic & anti-inflammatory
 Produce red-brown to grayish-blue discoloration
of lesions when exposed to sunlight
b. Other authors
 Rifampicin 600 mg daily
 Dapsone 100 mg daily
 3 yrs. duration followed by:
 Dapsone 100 mg daily indefinitely

c. Other alternatives
 Minocycline (bactericidal) 100 mg daily
 Rifampicin 600 mg daily
 for 2-3 yrs. followed by monotherapy
1. Reversal Reactions
 Prednisone 0.5 to 1.0 mg/kg/day
 Prevent risk of permanent nerve damage
 Tapered slowly & continued for a minimum of 6 months

2. Erythema Nodosum Leprosum (ENL)

 Thalidomide 100 to 200 mg nightly but if partially effective
add:
 Prednisone 0.5 to 1.0 mg/kg/day with tapering of dose in
6-8 weeks
* Thalidomide - potent teratogen & should not be given to
women of child-bearing potential (fetal limb malformations)
MANAGEMENT OF DISABILITIES

 Prevention of minor trauma or thermal

injury is of major importance

 Wound care & prevention of secondary

infection

 Physiotherapy & reconstructive surgery

SUMMARY
CONCLUSION
THANK YOU