LEARNING OBJECTIVES

Upon completion of this lecture ;

1. Describe etiopath & epidemiology of
Leprosy
2. Describe the clin pict & diag of Leprosy
3. List condit & lesions diff diag of
Leprosy
4. State treatment recommed for Leprosy

SYNONIM
Lepra,

Morbus

Hansen,

Lionthiasis, Elephanthiasis
graecorum,

Zaraath,

Hansenosis, Lepra arabum.

Definition :
Chronic infected disease
Mycobacterium leprae (M.leprae)
Attack

neural

edge,

skin,

mucous, respiration track, eyes,

bones, testicel , EXCEPT CNS.

 Kochs postulates have never been

fulfilled with respect to leprosy
The clinical and pathological
manifestation of leprosy are
determined by spread of bacilli and
resistance of the individual to the
infection.

PREVALENCE
In 1998 1.4 million were estimated to have
leprosy.
It is a problem in 80 countries of Asia,
Africa and Latin America.
It is most common between the ages of
10-14, 30-60 years and in males.

Registered Global Leprosy

Cases
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996
miliions per year

Data from medical library CD Rom

Myc. Leprae

An obligate,
intracellular, acid-fast
bacillus.
Generation time 12-14
days.
Optimal growth
temperature 32-34C.
Principally infects
Schwann cells and the
skin.
Taken from the University of Iowa website

ETIOLOGY
M.leprae,
the first is found
G.A.Hansen (Norwegian, 1895).
Not yet in-vitro.
Could inoculated in animal mouse,
armadillo, hamster.
Regeneration periods 12-13 days.

Transmission
Inhalation of
droplets
Nasal secretions
Breast milk
Insect bites

Mycobacterium Leprae
A. Pathogenesis and clinical disease
M. Leprae is the causative agent of
Leprosy (Hansens disease)
2 Major forms of Leprosy :
1. Tuberculoid leprosy
2. Lepromatous Leprosy

Ridley-Joplings
Classification

TT-Tuberculoid leprosy
BT- Borderline tuberculoid leprosy
BB-Borderline leprosy
BL- Borderline lepromatous leprosy
LL- Lepromatous Leprosy

WHO (1981):
PB I, TT, BT with BI 2+
MB LL, BL, BB with BI 2+
WHO (1987):
PB BTA - , I, TT, BT
MB LL, BL, BB

(BTA +)

WHO 1995
PB
Lesion : Macula, papul, nodus 1-5
Hypo pigmentation
Erythematous
Distribution not symmetric
Loss of sensation is clear
Nerve : Only one branch is damage.

MB

Lesion of skin: > 5 lesions

distribution > symmetric,
loss of sensation is not
clear
Nerve : a lot of nerves branch

1. Tuberculoid leprosy
a. Lesions; erythematous edge and a dry
1. Paucibacillary
2. Patchy anesthesia
3. Giant cells and lymphocytic
infiltration
b. Delayed type hypersensitivity reaction
to lepromin

2. Lepromatous Leprosy
a. lesions; large, diffuse and
granulomatous
1. Multibacillary
2. Patchy anesthesia is common
b. facial disfigurement leonine facies
c. anergic to lepromin
3. Borderline cases

Epidemiology
1. Transmission
a. inhalation of contaminated droplets
b. incubation period is long several
months to 30 years
2. Incidence
15 and 20 million cases in the world
primarily in the tropics and subtropics

 WHO: eliminate of leprosy in

the 2000

1 / 10.000 population.
Indonesia:
eliminated of leprosy in the
2000 1,57 / 10.000.

Age distribution :
* All ages , early infancy Very old
age
3 weeks, 2.5 Peak Months
Tuberculoid.
Peak

: 10 14 and 30 60 year
Male > Female
LM:F 2 : 1
TM:F 1 : 1

Muscular paralysis and Atrophy

# Small muscles

Hands, feet,
facial

muscles.

weakness and
progressive
atrophy.

Min Incub Period Few Weeks

Max Incub Period 30 Y or Over
2.5 5.3 Y Tuberculoid
9.3 11.6 Y Lepromatous
Average 8.4 Y
Risk Infection
Contact L than T .

Close

The Diagnosis and

Classification of Leprosy
Based on:

Clinical Examination
Skin Smear
Histopathology Examination
Serologic Test
Polymerase Chain Reaction (PCR)

Ideal Diagnostic Test Would be:

Simple

Identify all cases (100%

sensitivity)
Negative in people who do not
have
leprosy (100% specificity)

Bacterial Index (BI) density of bacilli

without differentiate between solid & non
solid (grade 0-6 according to Ridley)
0 :1+ : 1 10 bacilli in 100 field
2+ : 1 10 bacilli in 100 field
3+ : 1 10 bacilli in each field
4+ : 11 100 bacilli in each field
5+ : 101 1000 bacilli in each field
6+ : > 1000 bacilli in each field

Morphology Index (MI): percentages of

solid is compared with totally solid &
non solid.
Formula :

Solid
X 100% = %

Solid + Non solid

Regulation of calculation MI:

Minimal bacilli each lesion is 100
bacilli. BI 1+ Dont make MI
BI 3+ / > Must look for MI

3 Cardinal sign for the Clinical

Diagnosis of Leprosy :
Anesthetic skin lesion
Enlarged peripheral nerve
Acid fast bacilli in the skin
smear
Now one of three signs is
Leprosy

WHO Expert Committee on Leprosy

define a case of Leprosy as
follows : A case of Leprosy is a
person having one or more of the
following features :
- hypopigmented or reddish skin
lesion with definite loss of
sensation

- involvement of the peripheral nerves

demonstrated by definite thickening
with loss of sensation
- skin smear positive for acid fast bacilli

Treatment
Multi Drug Therapy (MDT)
MDT was first recommended by : WHO
Study Group in 1981 its chief
Characteristics were the following :
1. The regiment included several drugs
acting by different mechanism :
- Dapson, clofazimine, rifampicine

2. The duration of MDT was limited

3. Rifampicin was included as a key
component
4. The recommended regimens were the
minimal effective regimens

Other regimen
3 regimens have been officially recommended
1. WHO/MDT for paucibacillary (PB)
leprosy
2. WHO/MDT for multibacillary (MB)
leprosy
3. A single dose of the combination
Rifampicin, Ofloksasin, Minocylin
(ROM) for single lesion PB Leprosy

Treatment and Prevention

Chemotherapy ReconstructivS
urgery
Multidrugs
therapy (MDT)
BCG
ROM
vaccinations
Physiotherapy

Antileprosy
vaccine

Dapsone (di-amino-di-phenyl
sulphone, DSS)

Compete with p-aminobenzoic acid for

dihydropteroate synthetase
Results in functionless Dihydrofolate
analogue
Not harmful in humans
Side effects: allergy, fever, dermatitis

Basic and Clinical Pharmacology Bertram G. Katzung 98

Rifampicin and Clofazimime

Rifampicin
Inhibits bacterial
RNA polymerase
Low host toxicity
Stains urine and
tears
Gastrointestinal side
effects

Clofazimime
A riminophenzaine dye
Unknown mechanism
Skin discoloration

Contra indication :
Rifampisin : severe liver &
kidney dysfunction
Klofazimin: Stomach pain repeatedly
DDS : only for normal Hb

Newer drug combinations

ROM
Rifampicin (600mg)

Ofloxacin (400mg)

Minocycline (100mg)

 Recommended for two categories of

leprosy:

Single skin lesion paucibacillary

leprosy with one dose of ROM.
Patients have a high tendency to
heal without specific treatment

 Multibacillary leprosy patients

who can not accept clofazimine
of MDT. Treated with 24 monthly
doses of ROM

Development into the spectrum of leprosy

NERVE DAMAGE & DEFORMITY

__________________________________________
Nerve Trunk damaged
Deformity
__________________________________________
Ulnae Nerve
Claw fingers
Median Nerve
Claw thumb
Radial nerve
Drop-wrist
Common peroneal nerve
Drop-foot
Posterior tibiae nerve
Claw toes
Facial nerve
Lagophthalmos
__________________________________________

STAGE OF NERVE INVOLVEMENT

Stage I
INVOLVEMENT

Thickening
of nerve
Tenderness
Pain
No loss of
function

Stage II
DAMAGE

Incomplete
or recent
Complete
paralysis
Recovery
possible

Stage II
DESTRUCTION

Long-standing
paralysis
Recovery
no
possible

DIFFERENTIAL DIAGNOSIS

Macular lesions
Babies
Birthmarks
Vitiligo
Fungal infection
Seborrhoeic dermatitis
Resolving inflammatory lesions
(fungal
infection,
eczema,
impetigo, pityriasis alba)

 Plaques & rings

Ringworm
Granuloma multiforme
Sarcoidosis
Cutaneous tuberculosis (lupus
vulgaris)
Lupus eritematosus
Other common dermatoses
lichen
simplex,
psoriasis,
lichen planus

 Nodules
Cutaneous leishmaniasis
Other

neurofibromatosis,

moluscum

contagiosum,

blastomycosis, histoplasmosis

___________________________
Epidemic
___________________________
Spreads Rapidly.

____________________________
Endemic
____________________________
Slowly.

Most village and homes and no

particular foci can be identified.

Cases are often clustered

around foci of villages or
families.

Most people tuberculoid (BTTT) heals spontaneously.

Relatively
more
lepromatous disease.

All ages & sexes are equally

susceptible.

Children & young adults are

more commonly affected, and
males > females.

Contact
with
lepromatous
patients does not seem to be
important in determining the
pattern of spread.

Contact
with
lepromatous
patients greatly increases the
risk of infection & affects the
pattern of spread.

have

 Nerve lesions
Thickened
Peroneal muscular atrophy
Dejerine-Sottas disease
Refsums disease
Nerves
Anesthesia
Contractures
Plantar ulcers
neuropathy

DM,

sensory

 Eye lesions
Entropion
Iridocyclitis

ERYTHEMA NODOSUM
LEPROSUM(ENL)
Defenition : ENL is immunologically
immune complex deposition in tissue
space, blood, n lymphatic vesselsacute
inflammatory.
Occurs>>LL, BL
Triggers: pregnancy, parturition, lactation,
menstruation, trauma,pfysical or mental
stress.

 Pathogenesis :
ENL the Arthus phenomenonIg G, Ig
M, C3 n MLimmune complex formation
Physical examinationpainful red
nodules 2-5 mm, dome shaped, shiny n
tender, may ulcerate, discharging thick
yellow pus.
Distribution: the face n the limbs.

 Appear : iridocyclitis, orchitis, neuritis.

Fever, headache,insomnia
PA: infiltration of superficial dermis by
neutrophils, vasculitis, necrosis n
ulceration of skin
Diagnosisclinical features n PA

 Management ENL prednisone 40 to 60

mg/d, tapered rapidly; clofazimine 300
mg/d, thalidomide 100 to 300 mg/d

REVERSAL REACTION (RR)

Defenition : a delayed hypersensitivity
reaction (type IV hypersensitivity reaction)
occur in patients with borderline
disease (BL, BB, BT) immunological
status is unstable.

 Pathogenesis :
antigen (ML) bacilli reacts with T
lymphocytes n a rapid change in CMI in
borderline patients.
the rx is associated with a rapid increase
in specific CMI upgrading rx.
the rx is associated with a reduction in
immunity downgrading rx.

 Physical examination :
skin lesions acutely inflamed + edema;
erythema, desquamation, may ulcerate tender
or painful.
Neuritis is the most important part of a type I
reaction BT.
nerves rapidly swollen, painful and tender.
Paraesthesiae or pain. Loss of motor function
develops rapidly. Pure neural leprosy may
present in this way.

 PA :
edema the acute phase.
The inflammatory cells spread out n
disorganization of the granuloma.
increase in lymphocytes.
Langhansgiant cells may also be seen.
AFB in the lesions of BL are considerably
reduced or completely disappear,
indicating is true upgrading of the lesion
and an increase in immunity

 Diagnosis RR: based on clinical features

and histopathology.
Management RR: prednisone, 40 to 60
mg/d indications for prednisone: neuritis,
lesions that threaten to ulcerate, lesions
appearing at cosmetically important sites

MUH. DALI AMIRUDDIN

TUMOR DAN BEDAH KULIT

Bagian Ilmu Penyakit Kulit & Kelamin Fakultas

Kedokteran Universitas Hasanuddin
Makassar
2003