Hansen’s Disease,

Leprosy
NUR SABRINA BINTI MOHD NURUL BADRI
PROVISIONALLY REGISTERED PHARMACIST
HOSPITAL KEPALA BATAS
NO PRP: 019598
 Introduction
Monitoring
CONTENTS

Epidemiology
Complication

Symptoms & Prevention

Diagnosis
Treatment
 INTRODUCTION
It can affect the
nerves, skin, eyes,
Infection caused by and nasal mucosa
slow-growing bacteria
called Mycobacterium
leprae complex.
Classified as paucibacillary
(PB) or multibacillary (MB),
based on:
-the number of skin lesions
First described by the -presence of nerve
Norwegian physician involvement
Gerhard Armauer Hansen -identification of bacilli on
slit-skin smear

1. CDC. Hansen’s Disease (Leprosy) [Internet]. CDC. 2019. Available from: https://www.cdc.gov/leprosy/index.html
2. Maymone MBC, Laughter M, Venkatesh S, Dacso MM, Rao PN, Stryjewska BM, et al. Leprosy: Clinical aspects and diagnostic techniques. Journal of the American Academy of
Dermatology. 2020 Jul;83(1):1–14.
3. WHO. Guidelines for the Diagnosis, Treatment and Prevention of Leprosy [Internet]. 2018. Available from:
https://apps.who.int/iris/bitstream/handle/10665/274127/9789290226383-eng.pdf
INTRODUCTION
The affected skin changes color and either becomes:

● lighter or darker, often dry or flaky, with loss of feeling, or

● reddish due to inflammation of the skin.

1. CDC. Hansen’s Disease (Leprosy) [Internet]. CDC. 2019. Available from: https://www.cdc.gov/leprosy/index.html
 CAUSATIVE AGENTS
M leprae
● Acid-fast, slow-growing organism
● Replicate in macrophages, endothelial cells, and Schwann cells.
● Replicate slowly
● Grow ideally in temperatures ranging from 27°C to 33°C, and cannot
be cultured in artificial media.

M lepromatosis
● More recently described mycobacterial organism that also causes leprosy
● The DNA sequences of M leprae and M lepromatosis differ enough to distinguish them
as separate species, but they share many biologic similarities

1. Maymone MBC, Laughter M, Venkatesh S, Dacso MM, Rao PN, Stryjewska BM, et al. Leprosy: Clinical aspects and diagnostic techniques. Journal of the American Academy of
Dermatology. 2020 Jul;83(1):1–14.
 TYPES OF LEPROSY
PAUCIBACILLARY/ TUBERCULOID MULTIBACILLARY/ LEPROMATOUS

● Involve 1 to 5 skin lesions ● Involve more than five skin lesion

● Absence of bacilli in a skin smear or with nerve involvement
or with the demonstrated presence of
bacilli in a slit-skin smear, irrespective of
the number of skin lesions
● Asymmetrical ● Toward symmetrical
● Definite loss of skin sensation ● No loss of sensation
● Incubation period 3-5 years ● Incubation period 9-12 years

Borderline leprosy involves symptoms of both tuberculoid and lepromatous leprosy.

Borderline leprosy is also called dimorphus leprosy.
1. WHO. Guidelines for the Diagnosis, Treatment and Prevention of Leprosy [Internet]. 2018. Available from:
https://apps.who.int/iris/bitstream/handle/10665/274127/9789290226383-eng.pdf
2. Ahmed MMH, ANURADHA, Wadhwa P. A REVIEW ON AGENTS FOR THE TREATMENT OF LEPROSY INFECTION. Asian Journal of Pharmaceutical and Clinical Research
[Internet]. 2021 Mar 7 [cited 2023 Jun 10];14(3):25–9. Available from: https://journals.innovareacademics.in/index.php/ajpcr/article/view/40373/24598
3. Leprosy (Hansen’s Disease): Causes, Symptoms & Treatment. Cleveland Clinic. 2022. Available from: https://my.clevelandclinic.org/health/diseases/23043-leprosy-hansens-disease
 Droplets from the nose and
mouth.

Prolong close contact

TRANSMISSION
Transmission stops when
patient begins treatment

Does not passed from mother to

unborn baby during pregnancy
and not spread through sexual
contact

1. WHO. Guidelines for the Diagnosis, Treatment and Prevention of Leprosy [Internet]. 2018. Available from:
https://apps.who.int/iris/bitstream/handle/10665/274127/9789290226383-eng.pdf
2. CDC. Hansen’s Disease (Leprosy) [Internet]. CDC. 2019. Available from: https://www.cdc.gov/leprosy/index.html
 EPIDEMIOLOGY
● According to WHO figures based on reports
from 159 countries, 208,619 new leprosy
cases were reported globally in 2018. The
worldwide prevalence reported at the end of
2018 was 184,212 cases
● In 2018, Brazil, India, and Indonesia
accounted for 79.6% of all new leprosy cases.
In addition, 23 priority countries accounted
for 96% of cases worldwide in 2018.
● Leprosy is endemic in Malaysia but the
incidence is low
● In 2021, leprosy cases for Malaysia was 142
● Leprosy generally is more common in males
than in females, with a male-to-female ratio
of 2:1

1. World Health Organization. Leprosy [Internet]. Who.int. World Health Organization: WHO; 2019. Available from: https://www.who.int/news-room/fact-sheets/detail/leprosy
2. Dottie. Leprosy - PORTAL MyHEALTH [Internet]. PORTAL MyHEALTH. 2011. Available from: http://www.myhealth.gov.my/en/leprosy/
3. Smith D. Leprosy: Background, Pathophysiology, Epidemiology. eMedicine [Internet]. 2023 May 1 [cited 2023 Jun 10]; Available from:
https://emedicine.medscape.com/article/220455-overview
 RISK FACTORS
Genetic predisposition
Age between 5 to 15 years and more than
30 years at the time of exposure
Immunosuppression

Close contact with a recently diagnosed patient, especially patients

with multibacillary leprosy

● The risk factors involved in higher risks of developing physical disability includes male sex
and the presence of leprosy immunologic reactions

1. Maymone MBC, Laughter M, Venkatesh S, Dacso MM, Rao PN, Stryjewska BM, et al. Leprosy: Clinical aspects and diagnostic techniques. Journal of the American Academy of
Dermatology. 2020 Jul;83(1):1–14.
 PATHOGENESIS
● In the skin, M. leprae has an affinity for keratinocytes, macrophages, and histiocytes
● In peripheral nerves, M. leprae can be found in Schwann cells
● Keratinocytes seem to play a key role in the release of the antimicrobial peptide -defensin in
response to M. leprae antigens
● Once inside the host cell, M. leprae interacts with the host cell lipid metabolism to foster
bacterial intracellular survival
● The entry of M. leprae bacilli into Schwann cells triggers cells to dedifferentiate into
immature cells through the activation of signaling of the Erk1/2 pathway.
● This transformation creates a suitable environment for the bacteria to proliferate
● The presence of bacilli in the skin produces the dermatological manifestations of the
disease, and nerve infection produces axonal dysfunction and demyelination, leading to
sensory loss and its consequences of disability and deformity

1. White C, Franco-Paredes C. Leprosy in the 21st Century. Clinical Microbiology Reviews [Internet]. 2015 Jan;28(1):80–94. Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284303/
 PATHOGENESIS
Transmission
Dysfunction or
through respiratory
tract
01 06 distortion

Bacilli migrate to the Paucibacillary/

Schwann cell 02 05 multibacillary

Bacilli divide in Cell mediated

Schwann cell 03 04 immunity

Ahmed MMH, ANURADHA, Wadhwa P. A REVIEW ON AGENTS FOR THE TREATMENT OF LEPROSY INFECTION. Asian Journal of Pharmaceutical and Clinical
Research [Internet]. 2021 Mar 7 [cited 2023 Jun 10];14(3):25–9. Available from: https://journals.innovareacademics.in/index.php/ajpcr/article/view/40373/24598
Painless skin patch Foot drop or
clawed hand

SYMPTOMS
Paresthesias
Hand or foot ulcers

Muscle wasting and

weakness
 CLINICAL MANIFESTATION & DIAGNOSIS
Leprosy should be considered if the chronic skin lesions are not responding to standard treatment with
sensory loss. Additional hints include absence of pain on skin cuts or burns and has travel history in
endemic countries.

thickened or enlarged peripheral nerve with loss of sensation

and/or weakness of the muscles supplied by that nerve

definite loss of sensation in a Physical Presence of acid fast bacilli

pale (hypopigmented) or Examination in a slit-skin smear
reddish skin patch

1. WHO. Guidelines for the Diagnosis, Treatment and Prevention of Leprosy [Internet]. 2018. Available from: https://apps.who.int/iris/bitstream/handle/10665/274127/9789290226383-eng.pdf
TREATMENT
PAUCIBACILLARY MULTIBACILLARY

Rifampicin 600mg PO monthly Rifampicin 600mg PO monthly

PLUS PLUS
Dapsone 100mg PO q24h Clofazimine 300mg PO monthly and 50-100mg
PO q24h
PLUS
Dapsone 100mg PO q24h

Duration: 6 months Duration: 1 year (if initial BI<4)

Completion of 6 doses within 9 2 years (if BI≥4)
months Completion of 12 doses within 18 months (BI<4)
Surveillance: 5 years Completion of 18 doses within 36 months (BI≥4)
Surveillance: 15 years

1. National Antibiotic Guideline 2019

 Rifampicin

● Reduces the quantities of M. leprae discharged in the nasal secretions of lepromatous patients
within three weeks, thus rapidly decreasing the potential infectivity of these individuals
● Treatment with rifampicin and dapsone for six months reduced the number of persisting
leprosy bacteria more than treatment with dapsone alone. Although rifampicin proved more
effective than dapsone, it is unlikely that used by itself if can significantly shorten the length of
treatment in lepromatous leprosy
● MOA: binds to the β subunit of DNA-dependent RNA polymerase leading to inhibition of
bacterial RNA synthesis.
● Side effects: Hypersensitivity reaction, anemia, thrombocytopenia, visual disturbance, headache

1. Waters R, Rees RC, Pearson H, Laing G, Helmy HS, Gelber RH. Rifampicin for lepromatous leprosy: nine years’ experience. 1978 Jan 21 [cited 2023 Jun
10];1(6106):133–6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1602838/
2. Bullock WE. Rifampin in the Treatment of Leprosy. Clinical Infectious Diseases. 1983 Jul 1;5(Supplement_3):S606–13.
3. MIMS
 Dapsone
● Dapsone is bacteriostatic against Mycobacterium leprae at concentrations of 1 to 10
mg/L. It acts via inhibition of the folic acid pathway.
● Prevents the bacteria from utilizing para-aminobenzoic acid (PABA) for the synthesis of
folic acid by competitively antagonizing PABA. It is a competitive inhibitor of
dihydropteroate synthase

Clofazimine

● Antimycobacterial agent with anti-inflammatory and immunosuppressive effects. Its exact

mechanism is not yet known; however, it appears to inhibit mycobacterial replication
and growth by binding into the DNA of Mycobacterium leprae

1. Kurien G, Jamil RT, Preuss CV. Dapsone [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2021. Available
from: https://www.ncbi.nlm.nih.gov/books/NBK470552/
2. MIMS
 TREATMENT ALTERNATIVE
● For bacterial resistance or hypersensitivity to first-line Monitoring:
● Can only be initiated by dermatologist electrocardiographic
● Can be substituted with one of the following:
monitoring, due to the risk
of QT interval
prolongation and
Ofloxacin 400mg PO Minocycline 100mg associated cardiac
q24h PO q24h arrhythmia, which is
associated with exposure
to clarithromycin as well as
Ethionamide 250mg Clarithromycin
minocycline and
PO q24h 500mg PO q24h quinolones.

1. National Antibiotic Guideline 2019

2. WHO. Guidelines for the Diagnosis, Treatment and Prevention of Leprosy [Internet]. 2018. Available from:
https://apps.who.int/iris/bitstream/handle/10665/274127/9789290226383-eng.pdf
 TREATMENT IN HIV PATIENT
PAUCIBACILLARY MULTIBACILLARY

Rifampicin 600mg PO monthly Rifampicin 600mg PO monthly

PLUS PLUS
Dapsone 100mg PO q24h Clofazimine 300mg PO monthly and 50-100mg
PO q24h
PLUS
Dapsone 100mg PO q24h

Duration: 6 months Duration: 1 year (if initial BI<4)

Completion of 6 doses within 9 2 years (if BI≥4)
months Completion of 12 doses within 18 months (BI<4)
Surveillance: 5 years Completion of 18 doses within 36 months (BI≥4)
Surveillance: 15 years

1. National Antibiotic Guideline 2019

LEPROSY TREATMENT IN CHILDREN
PAUCIBACILLARY MULTIBACILLARY

10-14 years old Rifampicin 450mg PO monthly Rifampicin 450mg PO monthly

PLUS PLUS
Dapsone 50mg PO daily Dapsone 50mg PO q24h
PLUS
Clofazimine 150mg PO monthly & 50mg q48h

<10 years old Rifampicin 10mg/kg PO monthly Rifampicin 10mg/kg PO monthly

PLUS PLUS
Dapsone 2mg/kg PO q24h Dapsone 2mg/kg PO q24h
PLUS
Clofazimine 6mg/kg PO monthly & 1mg/kg PO
q48h

Duration 6 months 1 year for BI<4

treatment 2 years for BI≥4

Surveillance 5 years 15 years

1. National Antibiotic Guideline 2019

 MDT REGIMEN

1. KKM. PENGURUSAN DAN PENGENDALIAN UBAT KUSTA (MULTIDRUG THERAPY) DARI WHO UNTUK KEGUNAAN FASILITI KESIHATAN
KERAJAAN 2016 https://www.pharmacy.gov.my/v2/sites/default/files/document-upload/sop-pengurusan-pengendalian-ubat-kusta-2016.pdf
 Treatment in children

1. KKM. PENGURUSAN DAN PENGENDALIAN UBAT KUSTA (MULTIDRUG THERAPY) DARI WHO UNTUK KEGUNAAN FASILITI KESIHATAN
KERAJAAN 2016 https://www.pharmacy.gov.my/v2/sites/default/files/document-upload/sop-pengurusan-pengendalian-ubat-kusta-2016.pdf
 PREVENTION
Single-dose rifampicin
● For contacts of leprosy patients (adults and children aged 2 years and above), after
excluding leprosy and tuberculosis disease, and in the absence of other
contraindications
● This intervention shall be implemented only by programmes that can ensure:
(i) adequate management of contacts
(ii) consent of the index case to disclose his/her disease.

BCG vaccine
● BCG at birth is effective at reducing the risk of leprosy; therefore, its
use should be maintained at least in all leprosy high-burden countries
or settings

1. WHO. Guidelines for the Diagnosis, Treatment and Prevention of Leprosy [Internet]. 2018. Available from: https://apps.who.int/iris/bitstream/handle/10665/274127/9789290226383-eng.pdf
 Rifampicin dose for single-dose
rifampicin (SDR)

Age/ weight Rifampicin single dose

15 years and above 600mg

10-14 years 450mg

Children 6-9 years (weight >20kg) 300mg

Children <20kg (> 2 years) 10-15mg/kg

1. WHO. Guidelines for the Diagnosis, Treatment and Prevention of Leprosy [Internet]. 2018. Available from: https://apps.who.int/iris/bitstream/handle/10665/274127/9789290226383-eng.pdf
 COMPLICATIONS
Type 1 reaction
● Delayed hypersensitivity reaction
● Characterized by edema and erythema of existing skin lesions,
formation of new skin lesions, neuritis, and additional sensory and motor
loss.
● Likelihood 30%
● Treatment: NSAIDS and high dose steroid
● Prednisone is given at a dose of 40-60 mg/day with a decreasing taper
of 5 mg every 2-4 weeks

1. Smith D. Leprosy: Background, Pathophysiology, Epidemiology. eMedicine [Internet]. 2023 May 1 [cited 2023 Jun 10]; Available from:
https://emedicine.medscape.com/article/220455-treatment#d2
 Type 2 reaction

● Also known as erythema nodosum leprosum (ENL)

● Characterized by the development of inflamed subcutaneous
nodules accompanied at times by fever, lymphadenopathy, and
arthralgias
● Treatment includes prednisolone, clofazimine, or thalidomide
● Mild ENL: Aspirin 600-1200 mg/day in 4-6 doses per day.
● Severe ENL: Prednisone 60-80 mg/day with a slow taper, reducing
by 5-10 mg every 2-4 weeks
● Cases that involve large subcutaneous plaques, arthritis, and
temperature that exceeds 38.8°C: Thalidomide 100 mg PO 4 times
per day

1. Smith D. Leprosy: Background, Pathophysiology, Epidemiology. eMedicine [Internet]. 2023 May 1 [cited 2023 Jun 10]; Available from:
https://emedicine.medscape.com/article/220455-treatment#d2
 Lucio phenomenon

● Severe complication of multibacillary leprosy

● Marked by blue hemorrhagic plaques and necrotic
ulcerations.
● The bacilli may extend to the endothelial cells along with the
appearance of necrotic epidermis and vasculitis with
thrombus formation and endothelial proliferation.
● Treatment: systemic steroids

1. Smith D. Leprosy: Background, Pathophysiology, Epidemiology. eMedicine [Internet]. 2023 May 1 [cited 2023 Jun 10]; Available from:
https://emedicine.medscape.com/article/220455-treatment#d2
 MONITORING
Frequency ● Monthly outpatient visit
● Weekly visits may be necessary if the patient experiences a leprosy
reaction.
● Yearly skin scrapings taken from the 3 or 4 most active lesions are
recommended.

Laboratory ● Urinalyses
data ● CBC count
● Creatinine
● Liver function tests

1. Smith D. Leprosy: Background, Pathophysiology, Epidemiology. eMedicine [Internet]. 2023 May 1 [cited 2023 Jun 10]; Available from:
https://emedicine.medscape.com/article/220455-treatment#d2
 MONITORING
Response to ● Flattening and elimination of nodules, papules, and plaques, as well as
treatment improved nerve function
● Noncompliance or drug resistance should be suspected if intact
organisms are present after several months of treatment.

Once treatment is completed, the patient should be monitored for the next 5-10 years to
evaluate for signs of relapse. The WHO defines relapse as marked increase in the bacillary
index at any single site, usually accompanied by clinical deterioration.

1. Smith D. Leprosy: Background, Pathophysiology, Epidemiology. eMedicine [Internet]. 2023 May 1 [cited 2023 Jun 10]; Available from:
https://emedicine.medscape.com/article/220455-treatment#d2
CONCLUSION

Leprosy is an infectious disease caused by Mycobacterium leprae

Primarily affect skin and nerve

Leprosy is curable with multidrug therapy (MDT)

 REFERENCES
1. Ahmed MMH, ANURADHA, Wadhwa P. A REVIEW ON AGENTS FOR THE TREATMENT OF LEPROSY INFECTION. Asian
Journal of Pharmaceutical and Clinical Research [Internet]. 2021 Mar 7 [cited 2023 Jun 10];14(3):25–9. Available from:
https://journals.innovareacademics.in/index.php/ajpcr/article/view/40373/24598
2. Bullock WE. Rifampin in the Treatment of Leprosy. Clinical Infectious Diseases. 1983 Jul 1;5(Supplement_3):S606–13.
3. CDC. Hansen’s Disease (Leprosy) [Internet]. CDC. 2019. Available from: https://www.cdc.gov/leprosy/index.html
4. Dottie. Leprosy - PORTAL MyHEALTH [Internet]. PORTAL MyHEALTH. 2011. Available from:
http://www.myhealth.gov.my/en/leprosy/
5. KKM. PROSEDUR OPERASI STANDARD PENGURUSAN DAN PENGENDALIAN UBAT KUSTA (MULTIDRUG THERAPY)
DARI WHO UNTUK KEGUNAAN FASILITI KESIHATAN KERAJAAN [Internet]. 2016. Available from:
https://www.pharmacy.gov.my/v2/sites/default/files/document-upload/sop-pengurusan-pengendalian-ubat-kusta-2016.pdf
6. Kurien G, Jamil RT, Preuss CV. Dapsone [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2021. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK470552/
7. Leprosy (Hansen’s Disease): Causes, Symptoms & Treatment. Cleveland Clinic. 2022. Available from:
https://my.clevelandclinic.org/health/diseases/23043-leprosy-hansens-disease
 REFERENCES
1. Maymone MBC, Laughter M, Venkatesh S, Dacso MM, Rao PN, Stryjewska BM, et al. Leprosy: Clinical aspects and diagnostic
techniques. Journal of the American Academy of Dermatology. 2020 Jul;83(1):1–14.
2. MOH. National Antimicrobial Guideline [Internet]. 2019. Available from:
https://www.pharmacy.gov.my/v2/sites/default/files/document-upload/nag-2019-latest-9-dis-2020_0.pdF
3. Smith D. Leprosy: Background, Pathophysiology, Epidemiology. eMedicine [Internet]. 2023 May 1 [cited 2023 Jun 10]; Available from:
https://emedicine.medscape.com/article/220455-overview#
4. Waters R, Rees RC, Pearson H, Laing G, Helmy HS, Gelber RH. Rifampicin for lepromatous leprosy: nine years’ experience. 1978 Jan 21
[cited 2023 Jun 10];1(6106):133–6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1602838/
5. White C, Franco-Paredes C. Leprosy in the 21st Century. Clinical Microbiology Reviews [Internet]. 2015 Jan;28(1):80–94. Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284303/
6. WHO. Guidelines for the Diagnosis, Treatment and Prevention of Leprosy [Internet]. 2018. Available from:
https://apps.who.int/iris/bitstream/handle/10665/274127/9789290226383-eng.pdf
7. World Health Organization. Leprosy [Internet]. Who.int. World Health Organization: WHO; 2019. Available from:
https://www.who.int/news-room/fact-sheets/detail/leprosy