HANSENS DISEASE PART 1 by Dr.

Antoinette Cabahug § Direct sunlight for 2 hours

September 17, 2020 § UV light for 30 minutes
Uy, J o Incubation period from 2-40 years *ave 3-5
years) and generation time 12 days
Leprosy is one of the oldest known disorders affecting o Highly infectious with low pathogenicity
humanity since time immemorial and it is still present today. (household contacts – 5-12% signs within 5
In fact, it is a world health problem affecting 10-15 million years)
people. It is a chronic granulomatous disease caused by o Affinity for Schwann cells and cells or R-E
the bacteria Mycobacterium leprae and is commonly system
acquired during childhood or young adulthood. Its clinical o Virulence factor – complex cell wall with M.
manifestations, natural history and prognosis are related to Leprae-specific phenolic glycolipid (PGL-1),
the host’s response and to the various types which binds to basal lamina of Schwann cells and
represent the spectra of the host’s immunologic response interaction relevant since only M.leprae can
or the cell mediated immunity. The major sites of invade peripheral nerves
involvement includes the skin, the mucous membrane of - Animal Reservoirs:
the upper respiratory tract, and the peripheral nerve. o Cultivated in mouse foot pads and
Leprosy related stigma (“leprostigma”) is defined as armadillos, chimpanzees, mangabey
ignorance, fear, and superstition on leprosy. In almost all monkeys, sphagnum moss
cultures, the predominant attitude is ?, disgust, and o Humans are the main reservoirs of
rejection towards persons suffering from this disease. In M.Leprae
fact, even in ancient times, persons with leprosy are
believed to be cursed and outcast and punished by God. Acid fast stain
The medical term for leprosy is Hansen’s disease in honor
of Dr. Gerhard Henrick Armauer Hansen from Norway who
was the first to see the leprosy germ under the microscope
in 1873. Since’s Hansen’s discovery, leprosy as a disease
became revolutionary. Theres a clear cut evidence that it is
caused by a bacteria Mycobacterium leprae and it is not
hereditary, nor from a curse or from a sin.

EPIDEMIOLOGY
- 10-15 million in the world suffering from leprosy
- studies determining susceptibility and expression of
disease:
o environmental factors
§ endemic in many areas of Asia:
• Indian subcontinent, Sub-
Saharan Africa, South and
Central America, clumps of bright pink or red slender or cigar shaped rods
Philippines, Pacific Island
§ Tropical, developing countries - mode of transmission of leprosy
§ Low economic status with o transmission by inhalation
inadequate housing § infectious droplets via respiratory
• Unsuitable sanitation; poor route
nutrition and lack of § close contact associated with
education acquiring the infection
o genetic factors o transmission by contact
§ immunologic evidence of exposure § ulverated skin lesions
in 50% or more of potentially § close contact associated with
exposed persons acquiring the infection
- Adults 2-3 fold increase in men than women o other routes
- Children gender ratio 1:1 § insect vectors eg mosquito,
bedbugs
ETIOLOGY § tattooing needs
- Mycobacterium Leprae § Newborn: breastfeeding and
o Slender, straight (cigar-shaped) or slightly transplacental infection do not
curved gram (+) acid fast rod about occur
3.0x0.5um - Predisposing factors:
o Grows best at temperature below human o Residence in an endemic area
core body temperature o Having a blood relative with leprosy
§ Viable for 9-16 days and in moist o Poverty (malnutrition)
soil for 46 days o Close contact with affected armadillos
PATHOGENESIS
- clinical spectrum depends on variable limitation of
host to develop effective CMI to M.leprae
- organism à invade and multiple peripheral nerves
à infect surviving endothelial and phagocytic cells
in organs
- sub-clinical infection common in residents of
endemic areas and handed by host CMI response
- clinical expression develop “granuloma” and
patients develops “reactional state”
- granulomatous spectrum of leprosy consists of:
o highly resistance tuberculoid response (TT)
o Low or (-) resistance lepromatous pole (LL)
o Dimorphic or borderline region (BB)
o 2 intermediary regions:
§ borderline lepromatous (BL)
§ borderline tuberculoid (BT)
- In order of decreasing resistance:
TT à BT à BB à BL à LL
DIAGNOSIS
- begins with suspicion with leprosy
- considered in patients with neurlogic or cutaneous
lesions
- suspicious if several risk factors are (+):
o birth or residence in endemic areas
o blood relative with disease reflecting
genetic make up or environmental
exposure
o armadillo exposure
- firm diagnosis requires (+) of a consistent
peripheral nerve abnormality or demonstration of
organism in tissues
- nerve changes:
o several kinds of peripheral nerve
abnormalities:
§ nerve enlargement (asymmetrical)
especially nerve close to the skin:
• ulnar (MC), great auricular,
median, superficial
peroneal, sural, posterior
tibial, radial (least
common), trigeminal (MC
CN involved
§ sensory loss in skin lesions d/t
acral distal symmetrical anesthesia
= withering away of type C fibers
involving loss of heat and cold
discrimination before loss of
perception of pinprick or light touch
sparing on acral areas then
extends centrally but spares the
palms. Hot and cold sensation
disappears first, followed by fine
touch. Proprioception is preserved
o Anhydrosis – common manifestation of
sympathetic nerve involvement
- Palpate for nerves involved in leprosy:
o Median nerve
§ Best palpated infront of wrist with
wrist joint in semiflexed
o Great auricular nerve
§ Head turned to the opposite side
and a prominent cord-like
enlargement of the greater
auricular nerve
o Lateral popliteal nerve
§ Palpated behind the neck of the
fibula with the knee joint
semiflexed
o Ulnar nerve
§ Inner aspect of elbow with elbow
joint semiflexed
o Posterior tibial nerve
§ near medial malleolus of tibia
o sural nerve
§ along midline of back of lower leg
in the mid to lower part of leg
where the calf muscles join the
Achilles tendon
- Test for sensory loss in skin lesions
o Use survival gloves for safety measures
o Explain to patient the procedure and make
sure patient’s eyes are open
o Light touch: Lightly touch the lesional skin
with a cotton wool/nylon thread/tip of pen.
Ask patient to close their eyes. Against
lightly touch the lesional skin. Alternately
touch the adjacent skin for comparison.
Ask patient to p oint with his index finger
the exact spot where he or she feels the
sensation or touch. The skin on the
contralateral side should also be examined
for comparison. In case of loss of
sensation, the patient will be able to point
where they were touched on normal skin
but not on the lesional skin
o Temperature: Test is done usning 2 test
tubes, containing hot and cold water.
Alternately test the lesional skin with these
two test tubes.
o Pain: Test is done by pinprick. You can use
the blunt end of a pin or use a toothpick
- The presence of one or more chronic skin lesions
associated with anesthesia or hyposthesia should
suggest leprosy
LABORATORIES
- identifying organism in affected tissue is important
since organism cannot be cultured
Two ways in identifying organism:
1. skin biopsies = skin and nerve lesions
- fite-faraco stain
o epitheloid cell granulomas = organism
around dermal nerves
o lepra cells or Virchow cells = macrophages
filled with M.leprae cells
- H&E stain
o Grenz zone = lepromatous leprosy;
extensive cellular infiltrate separate from
epidermis
2. Slit smears of the skin
- mall skin incisions à scrapings obtain tissue fluid
à smear and examine using Ziehl-Beelsen staining
- smears taken from cooler areas: earlobes, elbows,
and knees (they grow best in temperatures below
human core temp)
- clinicobacteriological WHO classficiation:
o organism/s is/are (+) – multibacillary
o Organism/s is/are (-) – Paucibacillary
- Organisms counted per HPF = bacillary index (BI) –
bacterial load of infection
- Morphologic index (MI) – staining characteristic of
organism
- MI changes sooner than bI “early indicator of
efficacy of treatment and detect medicine
resistance especially Dapsone
- Reporting of bacterial index (BI) using the Ridley
Logarithmic scale:
0 No bacteria in 100 fields (oil emersion)
1+ 1-10 bacteria in 100 fields
2+ 1-10 bacteria in 10 fields
3+ 1-10 bacteria in an average field
4+ 10-100 bacteria in an average field
5+ 100-1000 bacteria an average field
6+ Many clumps of bacteria (>1000) in an
average field
- mepromin skin test/Mitsuda test
o lepromin skin test reagent – from armadillo
cultivated organism
o nnot a useful test in diagnosis
o determine immunologic status of patients in
relation to bacillus = helpful classifying a
case
o test for cell mediated immunity (CMI)
§ early reading 24-48 hrs known as
Fernandez reaction
§ 4 weeks known as late reaction of
Mitsuda
o (+) in tuberculoid leprosy but (-) in
lepromatous leprosy
o TT and BT are (+) (>3 mm induration or
nodule in 21 days)
o BB to LLp are (-) (<3 mm induration)
o 1st 6 months of life, most children are
lepromin (-)
 o BCG vaccination is capable of converting
lepra reaction from (-) to (+)

Other laboratories
1. Polymerase chain reaction (PCR)
- PCR and recombinant DNA technology allows
development of gene probes with M. Leprae-
specific sequences
- Identifies the bacteria in biopsy samples, skin, and
nasal smears, blood and tissue sections
2. Lymphocyte migration inhibition test (LMIT)
- determines cell mediated immunity to M. Leprae
which is absent to Lepromatous leprosy but present
in tuberculoid leprosy
3. Contact of family screening for history of leprosy
Hansens Disease Part 2 - Sites of predilection = cool peripheral areas:
Dr. Antoinette Cabahug o Buttocks
September 17, 2020 o Extensor surface of the limbs
Padillo, C. o Face
o Elbows & knees
Classification of Leprosy - Peripheral nerves involve:
- Clinical manifestations correlate with level of host o Ulnar (most frequent)
CMI to pathogen o Peroneal
- Ridley system TT ← BT ↔ BB ↔BL ↔LLs x LLp o Great auricular
o 6 membered granulomatous spectrum
range from high to low resistance
(IMMUNOHISTOLOGICAL)
o Detailed spectral classification of px
combining clinical & histologic criteria =
represents outcome of host response to
M.Leprae
o TT & LLp clinically stable but between
poles, host granulomatous posture may
change
o BB is highly unstable midsection or midpoint
of infection
o BT px may upgrade to TT so unstable
o LLs patients do not downgrade to LLp nor
LLp px upgrade
o All TT px & almost all BT cases are
Paucibacillary
o BB, BL, LLs, & LLp are all Multibacillary
o Tuberculoid corresponds to TT & BT
o Borderline or dimorphic to BB & BL
o Lepromatous to LLs & LLp

Clinical Features
I. Tuberculoid Leprosy (TT)
- Strong immunity, spontaneous manifestations &
absence of downgrading to a status of less host
resistance
- Skin lesions are solitary to few, well-defines
hypopigmented macules with raised edges &
varying in size involving the entire trunk
- Lesions asymmetrical & annular with a red or
purple border and central hypopigmentation
- Surface of lesion is dry scaly, anesthetic & does
not sweat
II. Borderline Tuberculoid (BT)
- Strong immunologic resistant to restrain infection
- Limited bacillary growth partially inhibited but host
response insufficient to self cure
- Lesions similar to TT, but smaller, more numerous
(usually 3-10) & satellite lesions around large
macule or plaque characteristic
- Little or (-) scaling, less erythema, induration, &
elevation but can be larger (>10cm in diameter) &
single lesion may involve entire extremity
- Loss of sensation is the rule, nerve trunk
involvement, enlargement or palsies less than 2 &
asymmetrical
III. Borderline Leprosy (BB)
- Immunologic midpoint or midzone of
granulomatous spectra & most unstable area
- Numerous but countable & consist of red, irregular
shaped plaques surrounded by small satellite
lesions & islands of clinically normal skin with in
plaque having Swiss-cheese appearance or
classic simorphis lesions
- Generalized but asymmetrical & edges not well
defined
- Thickened & tender nerves but anesthesia
moderate
IV. Borderline Lepromatous Leprosy (BL)
- Low resistance to restrain bacillary proliferation
but sufficient to tissue destruction or inflammation
in nerves
- Symmetrical, numerous from macules, papules,
plaque & nodules
- Number of small lepromatous lesions outnumber
large borderline type
- Nerve involvement appears later & enlarged,
tender or both & symmetrical
- Hyperesthetic or anesthetic
- Sensations & sweating normal but does not show
features of full brown lepromatous leprosy
- Classic dimorphic lesion in 1/3 of px
- Lepromatous-like = numerous poorly defined
papules & nodules but accompanied by some
sharply marginated lesions elsewhere
- Lesions range from solitary to numerous to
widespread
- Nerve trunk palsies range from none to 6 or > &
involvement of median & ulnar nerves are
characteristic
 - Untreated LL can progress but can be altered by
reactional states

V. Lepromatous Leprosy (LL)

- Divided into 2
o Polar form (LLp)
o Subpolar (LLs) = clinical clue sharply
marginated region in lesion maybe residual
of BL that downgraded to LLs
- Lack CMI against bacteria permits unrestricted
bacillary replication & widely disseminated multi-
organ dse
- Lesions with numerous bacteria & (-) reaction to
lepromin test
- Poorly defined skin colored nodules up to 2cm &
symmetrically distributed = LEPROMAS
- Diffuse dermal infiltration manifested by widening
of nasal root & fusion swelling of fingers mimics
rheumatic dse
- Progressive bacillary proliferation → thickening of
the dermis → thrown into folds = LEONNE FACIES
- Eye: anterior chamber can be invaded resulting to
glaucoma & cataract formation; iritis/iridocyclitis
- Testes: may be involved resulting to
hypogonadism
- Hair loss on the eyebrows = MADAROSIS
- Severe acral distal distal symmetric anesthesia
lead to debilitating trophic changes on hands and
feet
- Nerve trunk palsies but less common than BL

Indeterminate Leprosy
- Early lesion before host makes a definitive
immunologic commitment to cure or to overt
granulomatous response
- Hypopigmented macule with or without sensory
deficit
- AFB if (+) very small in number or lesions rich in
AFB, lesions are neither tuberculoid nor
lepromatous in histologic response
- Histamine Test
o Reliable test detecting early stage of
peripheral nerve damage from leprosy
o Method: inject 0.1ml or 1:1000 histamine
phosphate into hypopigmented area or in
areas of anesthesia
o Result: normal person gives rise to a wheal
surrounded by erythematous flare (Lewis
triple response) but in leprosy, flare is lost
Reactional States
- Distinctive, tissue-destructive &
inflammatory process
- Immunologically drive – increases morbidity
of the dse
1. Delayed-type Hypersensitivity Reaction
o Jopling’s type 1 reaction
o Upgrading or Downgrading or Reversal
reaction
o Common in BL but can occur in LLs or BT
o May upgrade to resistant granulomatous
presentation, remain unchanged, or
downgrade
o Enhanced CMI response to M. leprae
o During antibiotic chemotherapy = reversal
reaction
o When borderline dse shifts towards
lepromatous pole = downgrading rxn
o Not associated with systemic s/s
o Abrupt conversion of previously torpid
plaques to tumid lesions & appearance of
new lesions in clinically normal skin with or
without abrupt onset of neuritis
 o Characteristic purplish color o Ulceration is common
o Iritis, lymphedema (elephantiasis o Nasal septum perforation, total alopecia of
greacorun), neuritis eyebrows & lashes & well-developed acral
o Can occur up to 3 years after starting tx & distal symmetric anesthesia with ocular
even after tx has stopped sparing
o Before tx is initiated

2. Erythema Nodosum Leprosum (ENL)

o Jopling’s type 2 reaction
o In LL & BL px
o Features common with Erythema nodosum
o Before, during, or after chemotherapy
o Crops of widely distributed painful & tender
bright pink dermal & subcutaneous nodules
form normal skin associated with fever,
anorexia & malaise
o Multisystem dse = conjunctivitis, neuritis,
keratitis, iritis, synovitis, nephritis,
hepatosplenomegaly, orchitis,
lymphedema
4. Lazarine Leprosy
o Bullous formations followed by eschars and
deep mutilating ulcers
o Seen in px with lepromatous lepromatous
leprosy with underlying malnutrition or other
debilitating disorder
o Rare, ulcerating form considered as an
exaggerated type 1 rxn
& o Rxn seen in association with HIV

3. Lucio’s Reaction
o Uncommon & unusual rxn
o Presents with hemorrhagic infarcts
o Prevalent in Mexico & Carribean regions &
restricted to px with LATAPI’s
lepromatosis
o Purplish suffusion of hands & feet with
numerous telangiectatic molts or eruptive
telangiectasia & necrotic lesions in crops
HANSENS DISEASE PART 3 by Dr. Antoinette Cabahug vomiting; abdominal discomfort;
September 17, 2020 hepatotoxic
Uy, J - MULTIBACILLARY
o BB, BL, LL
TREATMENT § WHO combination
“The diagnosis and successful treatment of Leprosy can be • Unsupervised dapsone
one of the most rewarding and gratifying experience in 100 mg daily
clinical medicine” • Supervised rifampicin 600
- medical management directed at infection itself or mg monthly
reactional state if (+) • Unsupervised clofazimine
- once tx starts à not infectious anymore but 50 mg daily
treatment duration should be continued to prevent • Supervised clofazimine
recurrence, should not be isolated 200 mg monthly
- general principles for the management of leprosy: • Duration of 2 years
o eradicate infection with anti lepromatous • Rationale: Rifampicin kills
treatment susceptible organism
o prevent and treat reactions including resistant to
o reduce risk of nerve damage dapsone and dapsone
o educate patient to deal with neuropathy eventually eliminates all
and anesthesia susceptible organisms
o treat complications of nerve damage including resistant to
o rehabilitate patients into society rifampicin. Clofazimine
- important points on MDT: added to obviate the risk of
o not contraindicated in patients with HIV 1o dapsone resistance
o safe during pregnancy § CLOFAZIMINE (LAMPRENE)
o drugs are excreted in breast milk but no • Riminophenazine
reports of adverse reaction except for mild derivative
discoloration of infant’s skin by Clofazimine
• Bacteriostatic and anti
o leprosy is exacerbated during pregnancy,
inflammatory
important that MDT is continued
• Originally synthesized for
- PAUCIBACILLARY:
tuberculosis, less effective
o TT or BT
than dapsone but
§ WHO combination:
advantage to prevent
• Unsupervised dapsone
leprae reaction
100 mg daily
• More expensive but less
• Supervised rifampicin 600
toxic producing dark, red
mg monthly
discoloration of skin,
• Duration of 6 months mucous membranes,
§ Other authors: sweat and urine
• Dapsone 100 mg daily for • Produce red-brown to
3-5 years with ot without grayish-blue disocoloration
rifampicin 600 mg monthly of lesions when exposed to
• Follow up exam 1 and 2 sunlight
years after treatment is • Alternatives if
discontinued unacceptable due to skin
o DAPSONE discoloration:
§ Bacteriostatic; weakly bactericidal o Ethionamide 250-
§ Has potent oxidants o
§ MOA: interferes with the folate o 375 mg daily
biosynthesis pathyway of bacteria o Prothionamide
accounting for its bacteriostatic (highly bactericidal
effect killing 98% of
§ Adverse effects: hemolytic anemia; viable bacilli in 3-4
methemoglobinemia; days but more
agranulocytosis; hepatitis; expensive and
neuropathy and psychosis more toxic
o RIFAMPICIN § Other authors:
§ Highly bactericidal (single 1,500mg
• Rifampicine 600 mg daily
dose kills 99% of viable organism)
• Dapsone 100 mg daily
§ Adverse effects: produce reddish
or orange discoloration of body
secretion; anorexia; nausea;
 • 3 years duration followed Treatment for reactional states
by dapsone 100 mg daily 1. Reversal reactions
indefinitely - prednisone 0.5 to 1.0 mg/k/gday
§ Other alternatives: - prevent risk of permanent nerve damage
• Minocycline (bactericidal) - tapred slowly and continue for a min of 6 mos
100 mg daily + rifampicin 2. Erythema Nodosum Leprosum (NEL)
600 mg daily for 2-3 years - thalidomide 100 to 200 mg nigthyl but if partially
followed by monotherapy effective, add: Prednisone 0.5 to 1.0 mg/kg/day
• Rifampicin 600 mg + tapering in 6-8 weeks
ofloxain 400 mg +
clarithromycin 500 mg (one Thalidomide
dose - potent teratogen and should not be given to women
of child-bearing age (fetal limb malformations)
- antipyretic action but not recommended by WHO in
leprosy since prednisolone more effective in
controlling ENL and associated neuritis
- clofazimine is the DOC of chronic, recurrent ENL
reactions
- pentoxyfylline useful also in ENL

Lepra Reactions Treatment

Prednisone regimen Add Clofazimine to ENL
(tapering doses)
400 mg daily for first 2 weeks 100 mg TID x 4 weeks
30 mg daily for week 3 and 4
20 mg daily for week 5 and 6 100 mg BID x 4 weeks
15 mg dialy for week 7 and 8
10 mg daily for week 9 and 10 100 mg OD x 4 weeks
5 mg daily for week 11 and 12
For neuritis, treatment with Should be prolonged to 4 weeks
prednisolone 20 mg onwards

Management of disabilities
- prevention of minor trauma or thermal injury is of
major importance
- wound care and prevention of secondary infection
- physiotherapy and reconstructive surgery

SUMMARY
How to diagnose leprosy:
- examine skin
- check for macules/plaques
- test for sensation
- count number of lesion
- look for damage to nerves

Diagnosis of leprosy:
- lesions hypopigmented or reddish skin
- damage to the peripheral nerves as demonstrated
by loss of sensation
- weakness of the muscle of the hands, feet, or face
- positive skin smear

CONCLUSION
- the biggest disease today (precovid) is not leprosy
or tuberculosis, but rather the feeling of being
unwanted

SAFETY REMINDERS AGAINST COVID: Keep distance,

wear mask, stay at home, wash hands