REVIEW

NEURITIS IN MORBUS HANSEN

Presentant : dr. Reni Angraini
Division : Dermatology Infection
Advisor/chairman: dr. Susanti Budiamal, SpKK

Dermatovenereology Departement
Faculty of Medicine Sriwijaya University
Dr. Mohammad Hoesin General Hospital Palembang
2011
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 INTRODUCTION
Morbus Hansen (MH) or leprosy

a chronic infectious disease caused by the intracellular

pathogen Mycobacterium leprae, particularly affected the
peripheral nerves & skin

Cause peripheral neuropathies  severe damage to nerve tissue,

deformities of the hands, feet, face, eyes, irreversible &
permanent loss of nerve function
Diagnostic criteria of MH: skin lesions with nerve
involvement, both clinically & histologically.
The involvement of peripheral nerves  morbidity & social stigma.
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 Khanolkar: Leprosy originally from the neural.

Signs and symptoms suggests that the nerves play a very large of the
overall picture of the disease.

Pain occur in the early stages and during periods of increased disease
activity

Confirmation of clinical diagnosis of neurological involvement:

thickening of peripheral nerves, local anesthetic in the skin, muscle
paralysis of the hands, feet and face.

Estimated 25% of leprosy patients have been reported disability and

50% of these cases are severe disabilities.
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 Many advances in management of leprosy, significantly reduce
prevalence of leprosy.

 Deformity arises due to disability. The main cause is neuritis.

This review will discuss:

Neuritis in MH, structure of peripheral nerve, leprous neuritis
definition, pathogenesis, risk factors and management

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 DISCUSSION
Complex pathological changes in nerve trunks would be better
assessment, if the normal nerve completely understood by studying
the structure & histology of peripheral nerve

Peripheral nervous system connect cranial nerve & peripheral area.

Each peripheral nerve consists of nerve fibers parallel, afferent

& efferent axons, myelinated & non mielinated, enveloped by the
sheath of Schwann cells (SC).
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 Blood vessel
Fat Unmyelinated fiber, Segmental
most autonom myelinated fiber,
sensoric or motoric

Figur 1. Peripheral nerve 6

 Myelin sheath
Schwann cell Axon
nucleus

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Sc covered by basal lamina, surrounded by endoneurium. Some units
axons or Sc attached to the endoneurium surrounded by perineurium
(collagen fibers)

Strong bond between the capillary endothelial cells & basal membrane
separates the endoneurium from the circulation blood/nerve barrier
 maintaining an appropriate physicochemical environment for axon
and protecting from harmful agents.

Sc elaborate a basal lamina (BL): matrix of proteoglycans & fibrillar

components, include an isoform of laminin surrounded by perineurium.

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Figure 2. Anatomy fasciculus consists of small blood vessels, Sc myelinated & non myelinated.
Ax: axon, M: myelin, Mф: macrophages, Sc: Schwann cells
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♣ Sc function is formed myelin. Formation of myelin from the membrane
cell around the axon. Membranes are fused and form a lipoprotein complex.

♣ Myelin formation by Sc wrap the axons of single large (ϕ> 1μm)

concentric, the smaller axons containing small myelin sheath.

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 Sensory nerve receptors (functionally):
♠ Mekanoreseptor
♠ Thermoreseptor
♠ Nosiseptor
♠ Electromagnetic receptors
♠ Chemoreceptors
Based on the basic structure:
♣ encapsulated & not encapsulated

♦ Peripheral nerve fasciculus bound and protected by the perineurium:

safe place to M. leprae.
♦ M. leprae multiplied in Sc and is strongly attached
♦ Perineurium and blood vessel is a barrier & destroyed during
infection

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Three target invasion M. leprae: peripheral nerve tissue (Sc),
small blood vessels (Ec & perisit) & monocyte-makrofag.

♣ Peripheral nerves involved in MH:

1. Supra orbital.n 2. Facial.n 3. Auricular magnus.n
4. Supra clavicularis.n 5. Radial.n 6. Ulnar.n 8. Median.n
9. Femoral.n 10. Lateral popliteal.n 11. Superficial peroneal.n
12. Suralis.n 13.Tibialis posterior.n

♣ Six regular nerve examined by palpation:

1. Auricular magnus.n 2. Ulnar.n 3. Radial.n 4. Median.n
5. Lateral popliteal.n 6. Posterior tibial.n (Figure 3)
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Figur 3. The palpation sites 13
 Leprosy reactions and neuritis
Leprosy reactions: immunological phenomena occur before, during or
after treatment of multi drug therapy (MDT)

Major complication of acute inflammatory severe nerve injury, occurs

very rapidly, resulting further loss of sensation, paralysis deformity

an emergency medical condition, should to be diagnosed & treated

early to prevent permanent neurological disability

Two types: type 1 (up/downgrading) & type 2 (Erythema nodosum leprosum

/ENL).
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 1. Reversal reaction (type 1)
• Characterized: acute inflammation of skin lesions or nerves or both.
• Occur in borderline leprosy.
• Upgrading or downgrading.
• Clinically: sign of acute inflammatory reaction, tissue edema, induration at
the erythematous lesions & ulceration.
• Neuritis progressive destruction of nerve. Paralysis in the first 24 hours,
nerve granulomatous irreversible & ischemic paralysis due to an ↑
intraneural pressure. Granuloma destroy the nerve (necrosis), abscess 
sensory & motoric neuropathy.

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 2. Erythema nodosum leprosum (type 2).
• More severe inflammatory condition.
• Borderline lepromatous (BL) & lepromatous leprosy (LL).
• Skin manifestations: sudden onset of erythematous nodules, painful, on
the face, extremities & body. Ulceration, necrotic, pustular & bullous.
• Neuritisenlarged nerve, painful & NFI. Recurrent (chronic phase)
deformitas.
• Systemic symptoms: fever & malaise. Lymphadenitis, orchiitis,
iridosiklitis, bone pain, dactilitis, arthritis & proteinuria.

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 Pathogenesis
• Mycobacterium leprae is the only organism parasitic on the Sc, enter nerve through four
ways:

1. M. leprae enters the naked axons in the epidermis  centripetal spread along nerves.

2. M. leprae enters the skin, engulf by Sc in the dermis.

3. Basil eaten by macrophages in the upper dermis, gathered around adnexal structures
& nerves (perineurium).

4. Bacilli enter the bloodstream through the capillary intraneural & engulf by Sc

Destruction of Sc is a major factor in leprosy neuritis.

 Four aspects of nerve injury is involved in the pathogenesis of neuritis in MH:

localization of M. leprae into peripheral nerves, Sc infection, immunological &
inflammatory response.

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Model infection of peripheral nerves by M. leprae via blood vessels 18
 Figure 3. Model infection of peripheral nerves by M.
leprae via blood vessels

Colonization epineurium (e) the Produces accumulation of

Localization ↑ by drainage
basil (red) located in cells bacilli, ↑ bacilli carried in
lymphatic basil (green).
around blood vessels (blue) the circulation

Pathogenesis of neuritis
depends on the patient's M. leprae run into the compartment
Bacilli are engulf by Sc endoneurium along blood vessels from foci
immune response to M.
leprae. perineurium (p), spread to the nerves.

If no effective immune response, bacilli proliferate within

Immunologic cause
macrophages and Sc perineural inflammation, thickening & ↑
inflammation to eliminate the
bacterial load. bacilli are adjacent to the
epineurium, perineurium,
stimulate fibrosis& thickening
If effective cellular immunity  slow type hypersensitivity of the perineurium.
(tuberculoid leprosy), granulomatous response occurs at the
site of infection near the epineurium, endoneurium & Sc.
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 Move towards the
Binds to exposed Sc in
M. leprae adjacent to proximal ascending "like
the dermis with a strong
the surface of Sc a fish swimming up a
affinity
stream"

Potential mechanisms of binding:

♠ α-dystroglycan (alpha-DG),
M. leprae by Sc
♠Phenolic glycolipid (PGL-1) x to laminin-2 in the basal lamina,
eaten slowly.
♠Myelin P0,
♠Histone like protein x laminin ♠Erb2B

Attachment of M.
M. leprae can not M. leprae interfere
leprae to the Sc
be destroyed by normal endocytic
surface induce
the protein kinase maturation in Sc
demyelinisasi
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• Sc infected directly present antigen to CD 4+ T cells become target
of immune response Sc easily destroyed by cytotoxic T cells.
• Sc present MHC class I/ II, ICAM I & CD 80.

• These cells begin the process of presenting M. leprae antigenic

to the CD 4 + T cells efficiently destroyed by activated T cells.

• As a consequences of long term immunological processes & other

unknown mechanisms result inflammation Sc functionally impaired
or damaged.
• Finally result neuropathy may occur accompanied by axon atrophy &
demyelinisation.

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• Another mechanism causes destruction of the nerve is trauma.
• Infected nerve segment M. leprae most often in the proximal to
the canal fibrooseous & extremity joints.
• Enlarged nerve that is inflamed, continue to get trauma during
movement of joints.
• Trauma results inflammation & affects vascular permeability.
• Enlarged nerve would increase the risk trauma.

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Peripheral nerve involvement in the pathogenesis of MH:

1. phase parasitisasi
Transition between the state of 'disease & non-disease'. M. leprae was
found inside Sc & host tissue response (-)

2. Phase response of the network

Continuous existence & multiplication of bacilli evoke a response network,
initially non-specific  specific.

3. Phase of clinical infection

Tissue response ↑, the nerve thickened & clinically not recognizable. No
visible nerve functional deficits despite sensory disorders, pain & numbness.
Can not predict clinical signs & symptoms arise from this stage.

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4. Phase of nerve damage
Neurological functional deficits become visible clinically. First, the
NFI are thermal sensibility, pain perception and sweating, followed
by loss of myelinated nerve fibers (sensibility loss  parese 
motor paralysis).

5. Phase destruction of nerve

Elements totally destroyed & had collagenisation. Can occur in
tuberculoid leprosy caseation & cold abscess formation. This is the
last stage of nerve involvement in leprosy.

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• The stages do not occur simultaneously. Timing & duration of
each stage vary in individual, nerve to nerve and on different
parts of one nerve.
• First & second stages can be identified only by a histological
examination, the last three stages can be identified clinically.

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 Risk factors neuritis

• Neuritis risk factors occur in the reaction, type 1: extensive disease,

acid-resistant bacteria (AFB) in skin smears, DNA detection of M.
leprae (PCR), age, & disability levels 1 & 2.
• Type 1 reaction is common after MDT treatment is started or during
puerperium (nifas).
• Type 2: lepromatous leprosy (LL ), BI > 4.
• Trigger factors: pregnancy, lactation, puberty, vaccinations &
psychological stress.

 Major risk factor of neuritis is: leprosy multibasiler, NFI, NFI before the
patient diagnosed.

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 Management of neuritis in Morbus hansen
• Steroids start as early as possible. Cure rate: 60-70%.
• Neuritis < 6 months: oral prednisolone 12 weeks 40-60 mg (0.5-1
mg/kg/day), tappered slowly 5 mg every 2-4 weeks based on
improvement or response to treatment.
• Clofazimin 300 mg/day (3 months) in PB prevent neuritis.

Treatment of reactions with corticosteroids in a long time is still a

problem. They have many side effects & no definite evidence about
the optimal regimen treatment is still adjusting individually.

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 Prevention of nerve damage
 Early diagnosis & treatment of leprosy
Before the nerve infected prevent nerve damage totally. Effective &
adequate therapy  MDT
 Prevention of Reaction
Many nerve damage occurs during the reaction phase risk factor of
neuritis /reaction
 Direct treatment of the infected nerve
Prevention of edema, cellular infiltration & progressive fibrosis by
administering steroids.

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• Rest of the infected nerve
• Advised to rest an infected nerve
• Awareness of patients essential to minimize nerve damage (daily
self-care) & protection to prevent trauma (special footwear).
• Ulcer take a rest reduce weight-bearing

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 CONCLUSION
• ♣Morbus hansen: a chronic infectious disease caused by
intracellular pathogens M. Leprae on peripheral nerves and skin.
• ♣Morbus hansen cause peripheral neuropathies  severe nerve
and tissue damage, irreversible, lead to deformity hands, feet,
face, eyes & permanent loss of nerve function.
• ♣The main cause of neuropathy is neuritis.
• ♣Neuritis: an acute inflammation of peripheral nerves with pain,
local edema & rapid loss of nerve function.

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♣ Neuritis may occur during leprosy reactions or without leprosy.
♣ Neuritis in MH manifests in two forms, active and silent.
♣ Risk factors neuritis associated to the reaction of type 1 & 2.
♣Treatment of neuritis is corticosteroid. Long course steroid still a
problem cause have many side effects.
♣There is no definite evidence about the optimal regimen, so the
treatment is still adjusting individually.

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Thank you
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