Management of leprosy with details about etiology and pathogensis of leprosy.Special emphasis on individual drugs used in leprosy.

1. Asif Hussain
JNMCH A.M.U

2.  LEPROSY IS A CHRONIC GRANULOMATOUS INFECTION
CAUSED BY MYCOBACTRIUM LEPRAE (By G.A.Hansen 1873)
 SKIN
 PERIPHERAL NERVOUS SYSTEM
 UPPER RESPIRATORY TRACT
 EYES
 TESTES
 M.Leprae has uniqe tropism for peiphral nerves
 Reactional state responsible for morbidity &
disease if not treated leads to charecterstic deformity & profound social
stigma

3.  First bacterium to be identified as causing disease in
humans.
 Obligate intracellular bacilli
 Acid-fast
 Reductive evolution
 Cell wall contains PGL-1, Trisaccharides
 Grows in cooler tissues
 Doubling time 14 days
 Culture
 Incubation period

4. EPIDEMIOLOGY
 Disease of developing world
 Endemic among 10 to 15 million people living in poor
tropical countries.
 Prevalence rate decreased from 21 cases/ 10000
population in 1985 to <1 per 10000 in 2000.
 Leprosy has been eliminated from 119 of 122 countries
where it was considered as a public health problem.
 2005 - Elimination of Leprosy at National Level

5.  M.leprae replicates intracellularly in the skin histocytes and
nerve cells and has two forms.
 Tuberculoid, which induces a cell-mediated response that
limits its growth. M.leprae multiplies at the site of entry,
(skin), invading and colonizing Schwann cells.
 The microbe then induces T-helper lymphocytes, epitheloid
cells, and giant cell infiltration of the skin, causing infected
individuals to exhibit large flattened patches with raised and
elevated red edges on their skin.
 These patches have dry, pale, hairless centers, accompanied
by a loss of sensation on the skin.
 The loss of sensation may develop as a result of invasion of
the peripheral sensory nerves.

6.  The second form is the lepromatous form.
 This form of the microbe proliferates within the
macrophages at the site of entry.
 It also grows within the epithelial tissues of the face and
ear lobes.
 With cell mediated immunity impaired, large numbers
of M.leprae appear in the macrophages and the infected
patients develop papules at the entry site, marked by a
folding of the skin.
 Gradual destruction of cutaneous nerves lead to what is
referred to as "classic leonine facies." Extensive
penetration of this microbe may lead to severe body
damage; for example the loss of bones, fingers, and toes.

8.  Ridley Jopling
Tuberculoid (TT) Borderline tuberculoid (BT)
Borderline (BB) Borderline Lepromatous (BL)
Lepromatous (LL).
 W.H.O
Multibacillary (MB)
Paucibacillary (PB)
Single skin lesion paucibacillary

10.  Physical examination findings and skin biopsy and/or
smear.
 Lepromin test.
 Antibody against phenolic glycolipid antigen.
 PCR

11.  Early reaction: (Fernandez)
 An inflammatory response develops within 24 to 48
hrs. & tends to disappear after 3 to 4 days.
 +ve test if the diameter of red area is more than 10mm
at the end of 48 hrs.
 It indicates whether person has previously sensitized
by exposure to & infection by leprosy.

12.  Late Reaction: (Mitsuda)
This reaction becomes apparent in 7-10days and
reaching its maximum in 3 or 4 weeks. Test is read at
21 days and at the end, if nodule is more than 5mm in
diameter reaction is said to be (+)ve. The nodule may
even ulcerate & heal with scarring.

13.  Leprosy reactions are the acute episodes of
inflammation occurring during the chronic course of
disease.
 They pose a challenging problem because they
increase morbidity due to nerve damage even after the
completion of treatment.

15.  Dapsone
 Clofazimine
 Rifampicin
 Ofloxacin
 Minocycline

16.  Diamino diphenyl sulfone.
 Structural analogs of PABA – prevents Folic acid synthesis.
 Competitive inhibitor of dihydropteroate synthase.
 Resistance - mutant genes encoding dihydropteroate
synthase
 Oral bioavailability.

18.  Hemolysis in patients with G6PD deficiency.
 nervousness, insomnia, blurred vision, paresthesias,
drug fever, pruritus, psychosis, and a variety of skin
rashes.

19.  Fat soluble Riminophenazine dye.
 MOA - Bind to DNA of M. leprae, membrane disruption,
inhibition of mycobacterial phospholipase A2, inhibition of
microbial K+ transport, generation of hydrogen peroxide,
interference with the bacterial electron transport chain.
 Variable oral bioavailability.
 Hydrolytic dehalogenation, hydrolytic deamination,
glucuronidation, and hydroxylation.

20.  AE – Acute abdominal symptoms, Skin discolouration.
 Anti-inflammatory effects via inhibition of
macrophages, T cells, neutrophils, and complement.
 Interaction

21.  Semisynthetic derivative of macrocyclic antibiotic rifamycin.
 Rapidly bactericidal against M. leprae.
 β subunit of DNA-dependent RNA polymerase - RNA transcription.
 It is readily absorbed with an elimination half-life of ~3 hours.
 Excreted mainly through liver into bile and undergoes enterohepatic
circulation.
 Enzyme inducer – Auto enzyme induction, Ocp’s, warfarin.
 Resistance

22. Adverse Effects
 Rash, fever, and nausea and vomiting. Hepatitis,
Hemolysis, hemoglobinuria,
 Flu like syndrome
 Orange-tan discoloration of skin, urine, feces, saliva,
tears.

23.  Patients with intolerance, resistance, or clinical failure
to primary therapy(rifampicin).
 Inhibits DNA gyrase - DNA replication and
transcription.
 400mg on first day followed by 200mg/day.

24.  Intolerance to Clofazimine.
 30S ribosomal subunit.
 100mg/day.
 Deposit in tooth enamel and discolor teeth.

25.  Multi drug therapy (MDT) is a key element for cure.
 MDT is available free of charge from WHO
 The drugs used in WHO-MDT are a combination of
Rifampicin,clofazimine and Dapsone for MB leprosy
patients
 Rifampicin and Dapsone for PB leprosy patients.
 Treatment of leprosy with only one anti leprosy drug
will always result in development of drug resistance.
 Treatment with Dapsone or any other anti leprosy
drug used as monotherapy should be considered as
unethical practice.

28.  Type 1 reaction: Clofazimine 200 mg daily
Corticosteroids
 Loss of sensation or other peripheral nerve symptoms,
corticosteroids should be started immediately to
prevent permanent damage.
 Type 2 reactions may not respond to corticosteroids
alone, and the addition of drugs such as thalidomide.

29.  40 mg (8 tablets) every morning for 14 days
 30 mg (6 tablets) every morning for 14 days
 20 mg (4 tablets) every morning for 14 days
 15 mg (3 tablets) every morning for 14 days
 10 mg (2 tablets) every morning for 14 days
 5 mg (1 tablets) every morning for 14 days
Aspirin or paracetamol as required
 Examine the patient every 14 days before reducing the
dose
 Continue MDT

30.  Reduce systemic concentrations of TNF-α, IL-2,
Interferon
 100–300 mg/day
 Avoided in pregnancy and during lactation.

31.  Care of hands-avoid direct skin contact with hot objects.
While working reducing pressure prevents injuries. Gentle
massage keeps fingers mobile. Exercise to keep hands
mobile. Use clothes or canvas gloves for protection.
 Care of feet-clean & soak in salt water for 15 min. Rub off
hard skin with water. Rest the swollen foot by elevation.
Regular dressing helps to heal simple ulcer. Use MCR
(micro-cellular rubber insole) footwear to prevent injuries.

32. THANK YOU!