pathology inflammation

1. Presented by:
Dr. VAMSHIKRISHNA DUSSA

2. • Leprosy, also known as Hansen's disease (HD), is
a chronic infectious disease caused by the bacteria
Mycobacterium leprae or Mycobacterium
lepromatosis.

3. • The Mycobacterium leprae bacteria was first
discovered by Dr. Hansen and hence the disease
name is also known as HANSEN’S DISEASE.
• However the disease was first described in
ancient indian text going back to 6th century B.C

4. MYCOBACTERIUM LEPRAE
• It is an acid fast, rod shaped bacilli and an obligate
intracellular bacterium.
• It mainly affects nerves and skin. (only bacilli that can enter
the nerve schwann cell)
• Bacilli have affinity for the cooler tissues.
• Bacterium invades either dermal (cutaneous) nerves or
main peripheral nerve trunks situated superficially, in
regions that are relatively cooler (face & limbs).

5. • It has low pathogencity, only a small proportion of
infected people develop signs of the disease.
• Though infected, majority of the population do not
develop the disease.
• After entering the body, bacilli migrate towards the
neural tissue and enter the Schwann cells.

6. Incidence
• Endemic in HOT AND MOIST CLIMATES, POOR TROPICAL
COUNTRIES/POOR DEVELOPING NATIONS.
• More prevalent in countries like India, China, Nepal, Brazil,
Indonesia, Myanmar (Burma), Madagascar, nigeria.
• India accounts for one-third of all registered leprosy cases
globally.
• More commonly in states of Tamil Nadu, Bihar, Puducherry,
Andhra Pradesh, Odisha, West Bengal and Assam

7. Risk factors:
• The greatest risk factor for developing leprosy is
contact with another person infected by leprosy.
• People who are exposed (in contact) with a
person who has leprosy are 5-8 times more likely
to develop leprosy than members of the general
population.
• Leprosy also occurs more commonly among
those living in poverty.

8. • Not all people who are infected with M.
leprae develop symptoms.
• Conditions that reduce immune function, such as
malnutrition, other illnesses, or genetic mutations,
may increase the risk of developing leprosy.

9. Mode of Transmission:
• Leprosy is a slow communicable disease.
• The incubation period between first exposure and appearance
of signs of disease varies from 2 to 20 years (average about 3
years).
• The spread of leprosy is believed to be via nasal discharge
(droplets infection)
- Every 1 cc of nasal secretion contains 1-2 millions lepra
bacilli.

10. • The infectivity may be from the following sources:
1. Direct contact with untreated leprosy patients who
shed numerous bacilli from
- Damaged skin,
- Nasal secretions,
- Mucous membrane of mouth
- Hair follicles.
2. Materno-foetal transmission across the placenta.
3. Transmission from milk of leprosy affected mother to
infant.

11. 4. From infected armadillo animals (carriers).

12. IMMUNOLOGY OF LEPROSY:
• The immune response in leprosy is T-Cell Mediated (CMI)
Delayed Hypersensitivity (type IV reaction).
• Person with “GOOD” CMI response (NORMAL CD4-T
HELPER CELLS) develops milder & localized form of the
disease (Tuberculoid Leprosy) with less bacterial load.
• Whereas, in persons with WEAK OR ABSENT CMI (LOW
CD4-T HELPER CELLS), develop disseminated wide spread
disease (Lepromatous Leprosy) with high bacterial load.

13. PATHOGENESIS:
• After entering the Schwann cells /macrophage, bacilli start
multiplying slowly (about 12-14 days for one bacterium to
divide into two) within the cells, get liberated from the
destroyed cells and enter other unaffected cells.
• Till this stage person remains free from signs and symptoms
of leprosy.
• As the bacilli multiply, bacterial load increases in the body
and infection is recognized by the immunological system

14. • As the bacilli multiply, bacterial load increases in the body
and infection is recognized by the immunological system.
• Lymphocytes (CD4-Thelper cells) and histiocytes
(macrophages) invade the infected tissue.
• At this stage clinical manifestation may appear as
involvement of nerves with impairment of sensation &/ or
skin patch.
• If it is not diagnosed and treated in the early stages, further
progress of the diseases is determined by the strength of
the patient’s immune response

15. M.Leprae bacteria
Enter through respiratory tract
Schwann cells in cooler places (Cutaneous
nerves & peripheral nerve trunks of limbs and
face) Bacilli multiply in the Schwann cells
Good CMI Response Weak CMI Response
No Signs
and
Symptoms
Signs and
Symptoms:
SKIN/NERVE
LESIONS
(IL, TT, BT)
DISSEMINATED DISEASE
(BB, BL, LL)

16. Classification
RIDLEY AND JOPLING’S CLASSIFICATION
Ridley and Jopling’s classification divides leprosy
into 5 groups based on host immunity:
• TT—Tuberculoid Polar (High resistance)
• BT—Borderline Tuberculoid
• BB—Mid Borderline (dimorphic)
• BL—Borderline Lepromatous
• LL—Lepromatous Polar (Low resistance)

17. RIDLEY & JOPLING’S CLASSSIFICATION
BASED ON HOST’S IMMUNITY
LEPROSY
TUBERCULOID
(TT)
BORDERLINE
(BL)
BORDELINE
TUBERCULOID
(BT)
BORDERLINE
BORDERLINE
(BB)
BORDERLINE
LEPROMATOUS
(BL)
LEPROMATOUS
(LP)

18. Variants:
In addition, not included in Ridley-Jopling’s Classification are
following types:
”1. Indeterminate leprosy (IL): This is an initial non-specific stage of
any type of leprosy.
2. Pure neural leprosy: In these cases, skin lesions which are the
cardinal feature of leprosy are absent but instead neurologic
involvement is the main feature.
”3. Histoid leprosy: It is a variant of LL in which the skin lesions
resemble nodules of dermatofibroma and is the lesions are highly
positive for lepra bacilli

19. WHO CLASSIFICATION
BASED ON BACTERIAL LOAD
LEPROSY
NEGATIVE
PAUCIBACILLARY
(IL, TT, BT)
POSITIVE
MULTIBACILLARY
(BB, BL, LL)

20. • Paucibacillary leprosy types like IL, TT, BT are found in
people with good CMI.
• The disease remains localized producing a single or few skin
lesions with or with out peripheral nerves involvement.
• Skin lesions may be macule (flat)/ papule (slightly raised)
and plaque.
• People with strong immune response are able to destroy
large number of organisms and routine skin smears are
usually negative in most of them.

21. • Multibacillary leprosy types like BB, BL, LL are found in
people with poor CMI.
• Bacilli multiply and spread more widely resulting in a
generalized disease.
• It usually presents with widespread lesions in the skin,
nerve, and to lesser extent in other organs like eyes,
respiratory mucosa, testes and reticulo-endothelial system.
• It usually spares the central nervous system and upper
reproductive system in females

22. • In the absence of treatment, paucibacillary form of
leprosy may downgrade to multibacillary (from
tuberculoid to lepromatous) through borderline
spectrum.

23. CLINICAL CYCLE OF LEPROSY
BORDERLINE
LEPROSY
BT->BB->BL
TUBERCULOID
LEPROSY
LEPROMATOUS
LEPROSY
INDETERMINATE
LEPROSY (IL)
PEOPLE INFECTED WITH M. LEPRAE
NO DISEASE
UNSTABLE IMMUNITY

24. The salient features of major types of leprosy:
1. INDETERMINATE LEPROSY: (IL)
• Indeterminate leprosy refers to a very early form
of leprosy that consists of
- One or two hypopigmented macules with slightly
diminished sensation to touch. (maculo-anesthetic
lesions)
• It will usually progress to one of the major types
of leprosy if untreated.

26. Histopathology of Indeterminate Leprosy:
• Lymphocytic or mononuclear cell infiltrate, localised
particularly around skin adnexal structures like hair
follicles and sweat glands or around blood vessels.
• Nerve involvement, if present, is strongly supportive
of diagnosis.

27. 2. TUBERCULOID LEPROSY: (TT)
• Seen in patient with Good CMI.
• The polar tuberculoid form presents the following features:
• Lesions are:
- SINGLE OR FEW ASYMMETRICAL LESIONS (<5)
- RAISED BORDERS,
- ATROPHIC CENTRE,
- MACULAR TYPE,
- HYPOANAESTHETIC/ANAESTHETIC
- HYPOPIGMENTED/ERTHYMATOUS
• Nerves near to the lesions are thickened.

29. i) The dermal lesions show granulomas resembling hard
tubercles composed of epithelioid cells, Langhans’
giant cells and peripheral mantle of lymphocytes.
ii) Lesions of tuberculoid leprosy have predilection for
dermal nerves which may be destroyed and infiltrated
by epithelioid cells and lymphocytes.
iii) The granulomatous infiltrate erodes the basal layer of
epidermis i.e. there is no clear zone.
iv) The lepra bacilli are few and seen in destroyed nerves.
Histopathology of Tuberculoid Leprosy:

30. 3. BORDERLINE LEPROSY: (BL)
• Skin lesions are similar to tuberculoid leprosy but the number
is >5, <10 and larger in size compared to TT.
• Characteristic feature: presence of SATELLITE LESIONS near
the main lesion.
• Spectrum of BL:
I. BT
II. BB
III. BL

32. Histopathology of BORDERLINE LEPROSY:
1. Borderline tuberculoid (BT) form shows epithelioid cells and
plentiful lymphocytes. There is a narrow clear subepidermal zone.
Lepra bacilli are scanty and found in nerves.
2. Mid-borderline (BB) or dimorphic form shows sheets of
epithelioid cells with no giant cells. Some lymphocytes are seen in
the peri-neurium. Lepra bacilli are present, mostly in nerves.
3. Borderline lepromatous (BL) form shows predominance of
histiocytes, a few epithelioid cells and some irregularly dispersed
lymphocytes. Numerous lepra bacilli are seen.

33. 4. LEPROMATOUS LEPROSY: (LL)
• Seen in patient with weak/poor CMI.
• Severe form of Leprosy.
• Greater bacterial load is seen in this stage, hence more
chances of infection to others.
• Lesions are
• BILATERAL, SYMMETRICAL,
• HYPOPIGMENTED,
• SENSORY LOSS IS LESS COMPARED TO TT.

34. • Lesions are MACULAR, PAPULAR, NODULAR TYPES
• SMALLER THAN TUBERCULOID LESIONS IN SIZE.
NODULARMACULAR PAPULAR

35. OTHER LESIONS: LEONINE FACE
• Extensive tissue destruction of NASAL CARTILAGE ->
NASAL COLLAPSE (Saddle nose deformity)
• Lost eye brows.
• Thickened ear lobes
• Lost upper incisor teeth
• Thickened Forehead skin.

36. LEONINE FACES

37. Other clinical features:
- Rhinorrhoea (with numerous bacteria)
- Glove and stocking anaesthesia (due to damage to nerves on
both side of the limbs (symmetrical).
 Loss of temperature sensation
 Loss of sensation to touch, pain, deep pain.
This result in trophic ulcers due to frequent
trauma to hands and legs.

38. • Resorption of distal phalanges (Acroosteolysis) due
to digital necrosis.

39. Contractures

40. • Renal damage
• Testicular damage
• Keratitis
• Ulceration of Hard palate.
• Nasal septum Ulceration.

41. Histopathology of LEPROMATOUS LEPROSY:
• In the dermis, there is proliferation of macrophages with
foamy change, particularly around the blood vessels, nerves
and dermal appendages. The foamy macrophages are called
‘lepra cells’ or Virchow cells.

42. • The lepra cells are heavily laden with acid-fast bacilli
demonstrated with AFB staining. The AFB may be
seen as compact globular masses (globi) or arranged
in parallel fashion like ‘cigarettes-in-pack’ .

43. LEPROMIN TEST
• It is NOT A DIAGNOSTIC TEST but is used for classifying leprosy on the
basis of immune response.
• Intradermal injection of lepromin, an antigenic extract of M. leprae,
reveals delayed hypersensitivity reaction in patients of tuberculoid
leprosy:
1) An early positive reaction appearing as an indurated area in 24-48
hours is called Fernandez reaction.
2) A delayed granulomatous lesion appearing after 3-4 weeks is called
Mitsuda reaction.

44. “PATIENTS OF LEPROMATOUS LEPROSY ARE NEGATIVE FOR
LEPROMIN TEST”
• The test indicates that cell-mediated immunity is greatly
suppressed in lepromatous leprosy while patients of tuberculoid
leprosy show good immune response.
• Delayed type of hypersensitivity is conferred by T helper cells. The
granulomas of tuberculoid leprosy have sufficient T helper cells and
fewer T suppressor cells at the periphery while the cellular
infiltrates of lepromatous leprosy lack T helper cells and more T
suppressor cells.