Leprosy

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 Leprosy (Hansen’s Disease)
• A chronic infectious disease caused by the bacterium
Mycobacterium leprae
• It is mainly a Granulomatous disease affecting: peripheral
nerves and mucosa of the upper-respiratory tract
• Granulomatous - refers to granulomas which are lesions of
epithelioid macrophages

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 Indonesia no 3
New leprosy cases detected in India, Indonesia, Brazil
and the rest of the world, 2012

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 A Little History …
• Gerhard Henrik Armauer
Hansen was a physician which
first identified Mycobacterium
leprae as the cause of leprosy in
1873

7/29/1841-2/12/1912
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 A little taxonomy ….

Kingdom Bacteria
Phylum Actinobacteria
Order Actinomycetales
Suborder Corynebacterineae

Family Mycobacteriaceae
Genus Mycobacterium
Species M. leprae
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 Pathology
• Gram-positive, Intracellular
• Aerobic rod-shaped bacillus
• With a waxy coating
• M. leprae is unable to grow in vitro
• Because of its inability to grow on agar, nude
mice and nine-banded armadillos are used as
animal models

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 Clinical Features
• Skin lesions, typically anaesthetic at the
tuberculoid end of the spectrum
• Thickened peripheral nerves
• Acid-fast bacilli on skin smears or biopsy
• Acid-fast is a property of Mycobacteria in which
they a resistant to decolorization by acids during
staining
• This is a helpful diagnostic tool for M.
tuberculosis and M. leprae
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 Symptoms
Tuberculoid Borderline Borderline Borderline Lepromatous
Tuberculoid Lepromatous

Skin

Infiltrated Defined plaques, Polymorphic, Papules, nodules, Diffuse Diffuse thickening

lesions irregular plaques, partially raised punched-out thickening
healing centers edges, satellites centers

Macular Single, small Several, any size Multiple, all sizes, Innumerable, Innumerable,
lesions bizarre small confluent

Peripheral Solitary, enlarged Irregular Many nerves Late neural Slow, symmetrical
Nerve nerves enlargement of involved thickening, ‘glove-and-
lesions several large symmetrical asymmetrical stocking’
nerves, patterns anaesthesia and anaesthesia
asymmetrical paresis
patterns
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 Immunology
• Tuberculoid leprosy
- Patient’s lymphocytes respond to M. leprae in vitro
- Skin tests: lepromin elicit  strong positive response
- They also have a Th1- type response producing interleukin-2 and
interferons-γ
- These strong cell-mediated responses clear antigens, but cause local
tissue destruction
• Lepromatous leprosy
- Patients do not mount a normal cell mediated response to M. leprae,
and in fact their lymphocytes do not respond to M. leprae in vitro
- The lepromin test - negative
- They have specific T cell failure and macrophage dysfunction, and
problems producing interleukin-2 and interferons-γ
- But they do produce Th2-type cytokins 12
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 Transmission
• The transmission of leprosy is thought to occur through the respiratory
track
• Infected individuals discharge bacilli through their nose and a healthy
individual breaths them in
• But it is important to note that the extract mechanism is not known
• The main reservoir is humans
• Risk group: children, people living in endemic areas, in poor
conditions, with insufficient diet, or have a disease that compromises
their immunity (ie HIV)

“In the 19th century leprosy was believed to be a hereditary ailment” 16

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INCUBATION

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Immunocompromised individuals
are more susceptible to disease
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Sensory Loss Can Lead to Secondary
Infections and Severe Deformities

International Federation of Anti-Leprosy Associations (ILEP)

http://www.ilep.org.uk/en/
 How to examine for leprosy?

Examine in a well-lit room

Examine the whole body
Ask since when the patch was noticed
Ask what treatments have been tried
Test for sensation
Look for any visible deformities
 How to diagnose leprosy

Examine skin
Check for patches
Test for sensation
Count the number of patches
Look for damage to nerves
 DIAGNOSIS OF LEPROSY

• Hypopigmented or reddish skin lesion(s)

with definite loss of sensation
• Damage to the peripheral nerves, as
demonstated by loss of sensation
• Weakness of the muscles of hands, feet or
face
• Positive skin smear
 FLOW CHART FOR DIAGNOSIS
AND CLASSIFICATION

SKIN LESION AND

SENSORY LOSS - LEPROSY

ONE SKIN LESION 2-5 SKIN LESION More than 5 lesions

SLPB leprosy PB LEPROSY MB LEPROSY
Leprosy - one of the few diseases which can be
eliminated

Leprosy meets the demanding criteria

for elimination
practical
and simple diagnostic tools: can
be diagnosed on clinical signs alone;
the availability of an effective intervention
to interrupt its transmission: multidrug
therapy
asingle significant reservoir of infection:
humans.
 Diagnosis
• Is clinical, by finding signs of leprosy and supported
with the use of acid-fast bacilli smear or skin biopsy
• But this is contingent on experienced histopathologist
• What doctors typically look for include: anaesthesia of
skin lesions, and peripheral nerve thickening and
tenderness

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Symptoms & Diagnosis:
(1) Skin Lesions

Worobec, Sophie M. 2009. “Treatment of leprosy/Hansen's disease in

the early 21st century.” Dermatologic therapy 22, no. 6: 518-37.
Symptoms & Diagnosis:
(2) Skin Smear Tests

Global Project on the History of Leprosy

http://www.leprosyhistory.org/graphics/gallery/mleprae.jpg
Technique of Bacteriological
Examination

•Slit Skin Smear

•Nose Blow Smear
•Nasal Scraping
 Reading of Smears
• BI – Density of Leprosy Bacilli in
smears
• MI – Percentage of living Bacilli
among total
• SFG – Percentage of solid,
fragmented & granular Bacilli
 Treatment & Management
- First line drugs are rifampicin, dapsone, and clofazimine
- The WHO recommends that if a patient test positive in an
acid-fast skin smear they should be treated for MB
- The patients bacterial load decides length of treatment (6-24
months)
- Patients tend to improve quickly with minimal side-effects
- Second line drugs are ofloxacin and minocycline
- Leprosy is combated with multidrug therapy to reduce the
chance of developing resistance
- Since in the 1960’s resistance to dapsone developed

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Multibacillary (MB or lepromatous) is a 24-month treatment of rifampicin, clofazimine, and dapsone.
Paucibacillary (PB or tuberculoid) is a six-month treatment of rifampicin and dapsone.

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1941: Discovery of Dapsone

• Targets dihydropteroate
synthase (DHPS)

• Inhibits nucleic acid

synthesis
1960’s: Rifampicin and
Clofazimine Discovered
• Rifampicin (Rifampin):
Inhibit RNA synthesis

• Clofazimine:
Anti-inflammatory
 1981: WHO Proposes Multi-
Drug Therapy (MDT)
• Combination of DAPSONE, RIFAMPICIN,
and CLOFAZIMINE

+ +
1995: WHO Distributes MDT Drugs
for Free to Worldwide Patients
 Treatment & Management
• New Nerve Damage
- Patients with motor or sensory loss of 6 moths or less should receive a 6 month
treatment of corticosteroids (a treatment for type 1 reactions)

• Patient Education
- It is very important since within a few days of starting chemotherapy since
patients will no longer be infectious and can live a normal life
- Also care of limbs is very important

• Preventing Disability
- Nerve damage produces anaesthesia, dryness and muscle weakness which in turn
causes misuse of affected limbs causing ulceration and infection, leading to
deformity, Dryness can lead to skin cracking and ultimately infection
- Treatment involves soaking and applying oil- based creams to affected areas, also
physiotherapy can help prevent contractures, muscle atrophy and over stretching
of muscles

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 Treatment & Management
• Immune-Mediated Reactions
- Type 1 reactions occur in borderline leprosy – delayed
hypersensitivity occurring at site of localized M. leprae antigens
- Skin lesions appear and are erythematous, and peripheral nerves
become tender and painful
- Loss of nerve function can be sudden (ie foot-drop)

- Type 2 reactions occur in borderline lepromatous and lepromatous

cases, – erythema nodosum leprosum (ENL) results from immune
complex deposition
- The main symptoms are malaise, fever, and crops of small, pink
nodules on face and limbs, and ENL may continue for years
- Management procedures include : control inflammation, pain, treat
neuritis, and halt eye damage
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