undergraduate class

2. Global Project on the History of Leprosy
http://www.leprosyhistory.org/graphics/gallery/hansen.jpg

3.  Leprosy, first described in ancient Indian texts
from the sixth century B.C., is a nonfatal, chronic
infectious disease caused by Mycobacterium leprae,
whose clinical manifestations are largely confined
to the skin, peripheral nervous system, upper
respiratory tract, eyes, and testes.
 The unique tropism of M. leprae for peripheral
nerves (from large nerve trunks to microscopic
dermal nerves) and certain immunologically
mediated reactional states are the major causes of
morbidity in leprosy.

4. Skin Peripheral Nerves
http://www.nlm.nih.gov

5.  M. leprae is an obligate intracellular bacillus
(0.3–1 m wide and 1–8 m long) that is confined
to humans, armadillos in certain locales
 The organism is acid-fast, indistinguishable
microscopically from other mycobacteria, and
ideally detected in tissue sections by a
modified Fite stain.
 The morphologic index (MI), a measure of the
number of acid-fast bacilli (AFB) in skin
scrapings that stain uniformly bright, correlates
with viability.

6. Scollard, DM et al. 2006. “The continuing challenges of leprosy.”
Clinical microbiology reviews 19, no. 2: 338-81.

7.  The bacteriologic index (BI), a logarithmic-
scaled measure of the density of M. leprae in the
dermis, may be as high as 4–6+ in untreated
patients
 A rising MI or BI suggests relapse and
perhaps—if the patient is being treated—drug
resistance.

8.  The unique trisaccharide of M. leprae binds to
the basal lamina of Schwann cells;
 this interaction is probably relevant to the fact
that M. leprae is the only bacterium to invade
peripheral nerves

9.  Nasal/oral Droplets
 Dermal Inoculations
 Materno-fetal
 milk

10.  Lepromatous (low resistance)
 Tuberculoid ( high resistance)
 Polar forms: opposite poles

11.  The incubation period prior to manifestation of
clinical disease can vary between 2 and 40
years, although it is generally 5–7 years in
duration.
 Ridley and jopling s classification:
 polar tuberculoid (TT)
 borderline tuberculoid (BT)
 mid-borderline (BB, which is rarely encountered)
 Lepromatous indefinite (LI)
 borderline lepromatous (BL)
 polar lepromatous (LL)

12.  these forms of leprosy result in symptoms
confined to the skin and peripheral nerves.
 The skin lesions of tuberculoid leprosy consist
of one or a few hypopigmented macules or
plaques that are sharply demarcated and
hypesthetic, often have erythematous or raised
borders, and are devoid of the normal skin
organs (sweat glands and hair follicles) and
thus are dry, scaly, and anhidrotic.
 AFB are generally absent or few in number.

13.  Tuberculoid leprosy patients may have
asymmetric enlargement of one or a few
peripheral nerves.
 those most commonly affected are the ulnar,
posterior auricular, peroneal, and posterior
tibial nerves, with associated hypesthesia and
myopathy.

14.  In tuberculoid leprosy, T cells breach the
perineurium, and destruction of Schwann cells
and axons may be evident, resulting in fibrosis
of the epineurium, replacement of the
endoneurium with epithelial granulomas, and
occasionally caseous necrosis.
 Such invasion and destruction of nerves in the
dermis by T cells are pathognomonic for
leprosy.

15.  present with symmetrically distributed skin nodules
raised plaques, or diffuse dermal
infiltration, which, when on the face, results in leonine
facies.
 Late manifestations include loss of eyebrows (initially
the lateral margins only) and eyelashes, pendulous
earlobes, and dry scaling skin, particularly on the feet.
 In LL leprosy, bacilli are numerous in the skin (as
many as 109/g), where they are often found in large
clumps (globi), and in peripheral nerves, where they
initially invade Schwann cells, resulting in foamy
degenerative myelination and axonal degeneration and
later in Wallerian degeneration.

16.  Lepra reactions comprise several common
immunologically mediated inflammatory states
that cause considerable morbidity.


17.  Type 1 lepra reactions occur in almost half of patients with
borderline forms of leprosy but not in patients with pure
lepromatous disease.
 Manifestations include classic signs of inflammation within
previously involved macules, papules, and plaques and, on
occasion, the appearance of new skin lesions, neuritis, and
(less commonly) fever—generally low-grade.
 The nerve trunk most commonly involved in this process is
the ulnar nerve at the elbow, which may be painful and
exquisitely tender.
 If patients with affected nerves are not treated promptly
with glucocorticoids irreversible nerve damage may result
in as little as 24 h.
 The most dramatic manifestation is footdrop, which occurs
when the peroneal nerve is involved

18.  When type 1 lepra reactions precede the
initiation of appropriate antimicrobial therapy,
they are termed downgrading reactions, and the
case becomes histologically more lepromatous;
 when they occur after the initiation of therapy,
they are termed reversal reactions, and the case
becomes more tuberculoid.

19.  occurs exclusively in patients near the lepromatous
end of the leprosy spectrum (BL-LL), affecting
nearly 50% of this group.
 Although ENL may precede leprosy diagnosis and
initiation of therapy (sometimes, in fact, prompting
the diagnosis), in 90% of cases it follows the
institution of chemotherapy, generally within 2
years.
 The most common features of ENL are crops of
painful erythematous papules that resolve
spontaneously in a few days to a week but may
recur; malaise; and fever that can be profound.

21.  Patients with this reaction develop recurrent crops
of large, sharply marginated, ulcerative lesions—
particularly on the lower extremities—that may be
generalized and, when so, are frequently fatal as a
result of secondary infection and consequent septic
bacteremia.
 Histologically, the lesions are characterized by
ischemic necrosis of the epidermis and superficial
dermis, heavy parasitism of endothelial cells with
AFB, and endothelial proliferation and thrombus
formation in the larger vessels of the deeper
dermis.
 Like ENL, the Lucio phenomenon is probably
mediated by immune complexes

22.  The Extremities
 consequence of neuropathy leading to
insensitivity and myopathy
 Plantar ulceration
 Foot drop
 The loss of distal digits

23.  The Nose
 In lepromatous leprosy, bacillary invasion of
the nasal mucosa can result in chronic nasal
congestion and epistaxis.
 Saline nose drops may relieve these symptoms.
 Long-untreated LL leprosy may further result
in destruction of the nasal cartilage, with
consequent saddle-nose deformity or anosmia
(more common in the preantibiotic era than at
present).

24.  The Eye
 Owing to cranial nerve palsies, lagophthalmos and
corneal insensitivity may complicate leprosy,
resulting in trauma, secondary infection, and
(without treatment) corneal ulcerations and
opacities.
 in LL leprosy, the anterior chamber of the eye is
invaded by bacilli, and ENL may result in uveitis,
with consequent cataracts and glaucoma.
 Thus leprosy is a major cause of blindness in the
developing world. Slit-lamp evaluation of LL
patients often reveals "corneal beading,"
representing globi of M. leprae

25.  The Testes
 M. leprae invades the testes, while ENL may cause
orchitis.
 Thus males with lepromatous leprosy often
manifest mild to severe testicular dysfunction,
with an elevation of luteinizing and follicle-
stimulating hormones, decreased testosterone, and
aspermia or hypospermia in 85% of LL patients
but in only 25% of BL patients. LL patients may
become impotent and infertile. Impotence is
sometimes responsive to testosterone replacement.

26.  Amyloidosis
 Secondary amyloidosis is a complication of LL leprosy and
ENL that is encountered infrequently in the antibiotic era.
This complication may result in abnormalities of hepatic and
particularly renal function.
 Nerve Abscesses
 Patients with various forms of leprosy, but particularly
those with the BT form, may develop abscesses of nerves
(most commonly the ulnar) with an adjacent cellulitic
appearance of the skin. In such conditions, the affected
nerve is swollen and exquisitely tender. Although
glucocorticoids may reduce signs of inflammation, rapid
surgical decompression is necessary to prevent irreversible
sequelae

27. Worobec, Sophie M. 2009. “Treatment of leprosy/Hansen's disease in the early
21st century.” Dermatologic therapy 22, no. 6: 518-37.

28. Ziehl Neelsen Carbol Fuchsin Stain (ZNCF)
Global Project on the History of Leprosy
http://www.leprosyhistory.org/graphics/gallery/mleprae.jpg

30. 1. Entry Through
Blood Vessels
2. Inflammatory
Response
3. Demyelination
Scollard, DM et al. 2006. “The continuing challenges of leprosy.”
Clinical microbiology reviews 19, no. 2: 338-81.

31. Outcomes of Nerve Damage
 Sensory Loss
 Paralysis
 Deformities
Leprosy: eMedicine Infectious Diseases
http://emedicine.medscape.com/article/220455-overview

32. International Federation of Anti-Leprosy Associations (ILEP)
http://www.ilep.org.uk/en/

35.  Delayed hypersensitivity reaction
 An early positive reaction appearing as an
indurated area in 24 hrs – fernandez reaction
 A delayed granulomatous lesion appearing
after 3 weeks – mitsuda reaction