2. HISTORICAL ASPECT
Oldest and most dreaded disease known to
mankind
In 600 BC: described in India as Kushtha
Roga & attributed to punishment of GOD
Word leper comes from Greek word
“Scaling”
M.Leprae was discovered by Dr.Hansen in
1873 in Norway (Hansen’s disease)
Dapsone was used for several years as
monotherapy for 5 or more years duration.
Now MDT is the main tool against leprosy
3. Introduction
Nonfatal, chronic infectious skin disease
Confined to the skin, peripheral nervous
system, upper respiratory tract, eyes, and
testes
Causative agent – Mycobacterium leprae
Acid fast obligate intracellular bacilli, slow
multiplying
Do not grow on artificial media. They multiply
in mice footpads and armadillo, which are
used to evaluate antimicrobial agents and
screen vaccines
4. Continued…
The route of transmission - nasal droplets,
contact with infected soil, and even insect
vectors have been considered
Skin-to-skin contact is not an important
route of transmission.
Social stigma is associated with the
disease
Completely curable
15. Dapsone [Diamino - Diphenyl Sulfone, DDS ]
Other Uses
■ DDS + Pyrimethamine
Chloroquine resistant malaria
Toxoplasmosis (T.gondii, asymptomatic but a
problem for immunocompromised patients)
Pneumocystis jirovecii (previously P. carinii, a yeast
like fungus)
■ Acne: used as 5% topical gel
16. Dapsone : Adverse effects
■ Hemolytic anaemia (dose related , 20%) more
in G6PD deficient individuals
■ Gastric intolerance (nausea, anorexia)
■ Meth-hemoglobinemia
■ Fixed Drug Eruption
■ Phototoxicity,
■ Agranulocytosis, aplastic anemia (rare)
■ Hepatitis
17. Sulfone reaction
Develops 4-6 weeks after starting dapsone
treatment
Fever, malaise, lymph node enlargement,
desquamation of skin, jaundice and anemia.
Temporary discontinuation of dapsone only in
severe cases.
Clofazimine is highly effective in controlling this
reaction (200mg daily)
18. ■ Severe anemia (Hb less than 7%)
■ G6PD deficiency
■ Hypersensitive individuals
Contraindications
19. CLOFAZIMINE
■ a dye with leprostatic and anti-inflammatory
■ 40-70% oral absorption, poor CSF level
■ Accumulates in macrophages, subcutaneous fat
■ Long half life – 70 days
■ Used as a component of MDT
■ Used in lepra reaction
20. CLOFAZIMINE - MOA
■ Interferes template function of DNA
■ Alteration of membrane structure
and its transport function
■ Disruption of mitochondrial electron
transport chain
21. Adverse Effects
■ Skin: produces pink to brownish skin
pigmentation in 75 – 100 % patients within few
weeks, most body fluids and secretions also,
conjunctival pigmentation
Reversible (months to years)
■ GI symptoms: Nausea, anorexia, abdominal
pain, weight loss, enteritis (early syndrome and
late syndrome - after few months of therapy due
crystal deposition)
■ Avoid – pregnancy , hepatic & renal dysfunction
22. RIFAMPICIN
■ Bactericidal
■ Kills 99.9 % in 3-7 days
■ Shortens duration of treatment
■ Low monthly dose:
non toxic, do not induce enzymes
■ NOT used in –
hepatic or renal dysfunction
ENL
reversal reaction
23. Other drugs
Fluoroquinolones:
■ Ofloxacin (400 mg/day)
■ Moxifloxacin – most potent quinolone
■ Sparfloxacin
Minocycline: lesser than R but greater than
Clarithromycin, side effect – vertigo
Clarithromycin : only macrolide active
against M. Leprae
Ethionamide – hepatotoxic (10%), used as
an alternative to clofazimine
25. For operational purpose WHO classification (1998)
■ Single lesion paucibacillary leprosy (SL PB) –
Solitary cutaneous lesion
■ Paucibacillary Leprosy (PB) – 2-5 skin lesions
Both SL PB and PB cases are smear negative
■ Multibacillary Leprosy (MB) –
More than 6 lesions as well as all smear
positive cases
Followed by NLEP from 2009
26. Single drug therapy not effective:
long duration, relapse, resistance develop
27. MULTIDRUG THERAPY
• Highly successful in both MBL & PBL
• Effective in dapsone resistant cases
• No resistance to rifampicin & clofazimine
• Safe and acceptable
• HIV +ve case treated same
• Reduces total duration of therapy
• Quick symptomatic relief
28. MDT regimen
MULTIBACILLARY: LL, BL, BB
■ RIFAMPICIN - 600mg once a month
■ DAPSONE - 100mg daily
■ CLOFAZIMINE
300mg once a month
50mg daily
■ 12MONTHS
30. Alternative regimens
■ Clofazimine + ANY 2 of Ofloxacin /Clarithromycin
/Minocycline daily for 6 months
followed by Clofazimine + ANY ONE for 18 months
■ R (600)+ spar (200) + Clar (500) +Mino (100 mg) -
12 weeks – 4 drug regimen
■ Solitary lesion (PBL) – Single dose ROM regimen
■ Intermitt ROM - once a month – 3-6 months for PBL
12 – 24 months – MBL
■ Intermittent RMMx: once a month, 6 for PBL,
12 for MBL
ROM: R, Ofl, Mino; RMM: R, Mino, Moxi
31. Lepra reactions
TYPE 1 LEPRA REACTION (Reversal)
delayed type IV Hypersenstivity, cell mediated
reaction, Occur suddenly even after completion
of therapy
Patients with TT and BL
Manifestations – fever, cutaneous ulceration &
multiple nerve involved (neuritis), swollen and
painful nerves
Most commonly involved - ulnar nerve. Irreversible
nerve damage may result in as little as 24 h.
Foot drop - occurs when the peroneal nerve is involved.
32. Type 1 lepra reactions – treatment
Glucocorticoids (Prednisone, initially at doses of 40 to 60
mg/d). As the inflammation subsides, the glucocorticoid dose
can be tapered, but steroid therapy must be continued for at
least 3 months lest recurrence supervene.
Strictly limited to lesions whose intense inflammation
poses a threat of ulceration. Mild to moderate lepra
reactions that do not meet these criteria should be tolerated
and glucocorticoid treatment withheld.
Thalidomide is ineffective
clofazimine (200 to 300 mg/d) is of questionable
benefit; far less efficacious than glucocorticoids.
33. TYPE 2 LEPRA REACTION
(ERYTHEMA NODOSUM LEPROTICUM, ENL)
Occurs exclusively in patients with LL
Jarisch Herxheimer (Arthus) type of reaction due to release of
antigen from killed bacilli
Usually coincides with initiation of chemotherapy and / or
intercurrent infection
Crops of painful erythematous papules, malaise, fever,
neuritis, lymphadenitis, uveitis, orchitis, and
glomerulonephritis.
May develop anemia, leukocytosis, and abnormal liver
function tests, particularly increased aminotransferase
levels. In rare instances, ENL results in death.
34. Lepra reactions – treatment
Type 2 lepra reactions
If ENL is mild: antipyretics only
In cases with many skin lesions, fever, malaise,
and other tissue involvement - Glucocorticoids
(initially 40 to 60 mg/d for 1 to 2 weeks) are often
effective.
If, despite two courses of glucocorticoid therapy,
ENL appears to be recurring and persisting,
treatment with thalidomide (100 to 300 mg nightly)
should be initiated
35. Continued…
Mechanism of thalidomide's action - reduction
of TNF levels and IgM synthesis and its slowing
of polymorphonuclear leukocyte migration.
After the reaction is controlled, lower doses of
thalidomide (50 to 200 mg at night) are effective
in preventing relapses of ENL.
Clofazimine in high doses (300 mg nightly) has
some efficacy against ENL.
36. Lepra reactions – cont…
LUCIO'S PHENOMENON
This unusual reaction is seen exclusively in patients
from the Caribbean and Mexico who have the diffuse
lepromatosis form of lepromatous leprosy.
Develop recurrent crops of large ulcerative lesions —
frequently fatal as a result of secondary infection and
septic bacteremia.
Mediated by the immune complex.
Glucocorticoids and thalidomide: Ineffective
Optimal wound care and therapy for bacteremia are
indicated.
Ulcers tend to be chronic and heal poorly. In severe
cases, exchange transfusion may prove useful.
37. Points to be remembered…….
■Mechanism of dapsone & its adverse
effects
■Mechanism of clofazimine & its
adverse effects
■Treatment regimen for multibacillary &
paucibacillary leprosy
■Types of lepra reaction & its treatment
