LEPROSY

Question 1

Leprosy case definition

Answer 1

1 or more cardinal features

1. Hypopigmented patches with partial pr total loss of cutaneous sensation in affected areas
2. Presence of thickened nerves
3. Presence of AFB - skin or nasal smears

Question 2

Geography

Answer 2

Asia, Africa, Central/south America, Canada, Mexico

India, Brazil, Indonesia account for most cases

Question 3

Age & Gender

Answer 3

Bimodal peak
10-15yo
30-60yo

M= F except LL 2 x commoner men

Question 4

Aetiology

Answer 4

M Leprae and M lepromatosus

AFB - small curved rod, non motile, non spre forming
Obligate intracellular organisms
Like macrophage, endothelial cells, schwann cells
Grow at 27-33 degrees
Stain with Fit or Zn stain (bc acid fast)

Humans primary carrier; cannot culture
Other resevoirs - 9 banded amidillo, mokeys, mice, red squirrels.

Question 5

Hows leprosy transitted

Answer 5

Mainly dependent upon host CMI
Also depends on infectivity of other host, frequency/duration of contact
25% risk of house hold contacts aquiring the disease

IP average 3-5 years; can be 2-40!

Transmission
Primarily inhalation - resp drop (nasal/oral)
Skin contact - direct or via fomites
Other - ?tattoos, insect vectors, reports breastfeeding/vertical but not provn

Question 6

Risk factors for contracting leprosy

Answer 6

Close contact with recently diagnosed patient (esp polar lepromatous leprosy LL/multibacillary leprosy)

Exposure to armadillos

Age 5-15 and >30yo at time of exposure.
Immunosuppression, immunodeficiency
Genetic predisposition.

Question 7

Risk factors for disability

Answer 7

Male sex, LL, presence of immunologic reactions.

Question 8

Immunopathogenesis

Answer 8

Entry M leprae via nose —> invades –> multiples in lymphatics and endothelial cells of vessels –> haem spread –>invades nerves –> immune response

Question 9

Describe classficiation schemes for leprosy

Answer 9

Ridley jobling
o Combines – clinical, histo, bacteriologic index
o Spectrum - borderline lepromatous (BL), borderline-borderline (BB, in the middle), and borderline tuberculoid (BT)

WHO
o Based on number of skin lesions or bacteriologic index
o (1) paucibacillary, single-lesion leprosy (one skin lesion); (2) paucibacillary leprosy (two to five skin lesions); and (3) multibacillary leprosy (more than five skin lesions).
o OR slit skin examination where patients with 1-5 skin lesions are classified as having PB (when BI is negative at all examined sites) or MB (when BI is positive at any examined site).

Question 10

WHO/Ridley presentation of TL

Answer 10

Paucibacillary - strong CMI
Low – 1+, (0 bacilli in 100 fields)

Skin smear negative
Lepromin test - positive

Single (up to 3)
Localised

Macules and plaques
Erythematous in light skin, hypopigmented in dark skin

Well defined sharp borders

Dry and scaly
Anhidrosis – loss sweat
Anaesthetic

NERVES
Absent over plaques
Facial lesions do not have decreased sensation due to large density of facial nerves

Tender thickened nerve (preliciton for superficial nerves, cooler temperature)
Can present with neuro ONLY involvement

Question 11

WHO/Clinical Borderline tuberculoid

Answer 11

1-2+ (1-10 bacilli in 100 fileds
Single or a few lesions
Asymmetric
Infiltrative macules and plaques

Larger and more numerous than TT
Saellite lesions around larger lesion is common.

Less Well defined borders

Dry surface

Loss sensation

Diminished hair growth
Absent sensation over plaques
Peripheral nerve involvement is extensive, high risk disability.

Question 12

BB clinical/WHO

Answer 12

Borderline are unstable
Prone to reactions
2-3+ (1-10 in 10 fields)

Lepromin test – negative
Weak positive BT
Several
Asymmetric
Numerous 

Annular lesions with well defined inner rim but

Indistinct borders
“punched out centre = inverted saucer”

Shiny surface

Somewhat diminished
Somewhat diminished/variable

Question 13

BL

Answer 13

Multibacillary, poor CMI

-4+ (1-10 bacilli in each field)

Lepromin test negative
SS – many bacteria
Numerous lesions
Symmetric
More juicy
Numerous asymmetric macules, papules plaques  Annular lesions (infiltrative border with central clearing)

Lepromas

Less well defined borders

Shiny surface

Slightly diminished
Slightly diminished

Question 14

LL

Answer 14

Multibacillary poor CMI
4-6+ (100-1000 bacilli in each field).

Lepromin test (checks CMI) – negative)
SS – numerous AFB
Innumerable 20-100
Symmetric
Face/buttocks/LL
Widespread
Poorly defined
Numerous and symmetric

Erythematous-violaceous lesions Macules, Papules and nodules (lepromas)

Shiny surface

Classically spare warm areas of body – prefer face, scalp, fingers, toes.

Dermal infiltration Leonine facies, madarosis

Normal sensation intially
Unaffected
Not affected early on
Enlagred peripheral nerves with “stocking and glove anaesthesia”

Question 15

menmonic for leprosy complications

Answer 15

LEPROSY = Leonine facies, Eye, Papal Hand, Resorption of bone, Orchitis, Saddle nose, Y(icthYosis)

Question 16

Cutaneous complications of LL

Answer 16

Facial  due to infiltration
o	Leonine facies
o	Madarosis
o	Elongated/soft ear lobes 
o	Saddle nose deformity  destruction of nasal cartilage and bone

Question 17

Neuro complications LL

Answer 17

o Thickening of superficial peripheral nerves (both TL and LL) in colder areas
o Sensory
 First sensation to go is thermal ie cold >fine touch. Proprioception usually preserved
 Localised loss over skin patches in TL
 LL as disease progresses peripheral dorsal nerves becomes enlarged  anaesthesia of hands/feet in glove and stocking distribution  Decreased sensation pain/temperature/touch distal extremities
 Neurtrophic ulcers on plantar surface from sensory neuropathy
o Vasomotor alterations
o Secretory disturbances: dry eyes and nose
o Motor
 Muscle weakness
 Atrophy
 Neuritic pain
 Sequelae
- Ulnrar nerve most commonly involved, radial nerve least. Most common CN is trigeminal
- Facial nerve (lagopthalmos)
- Claw hand (ulnar, median)
- Papal hand (ulnar)
- Wrist drop (radial)
- Clawing of toes (posterior tibial)
- Foot drop (lateral popliteal)
- Facial droop (from Facial nerve involvement)

Question 18

Ocular complications of LL

Answer 18

Ocular (70-75%)  (BL, LL)
Direct damage of facial and ophthalmic nerve
Bacillary invasion of anterior eye chamber
o Madarosis, trichiasis  corneal vascularity and opacity
o Facial nerve palsy Lagopthalmos, ectropion
o Trigeminal nerve palsy  Exposure Keratitis, Eiscleritis, Blindness
o Lacrimal gland  dry eye, dacryocystitis

Question 19

Mucosal complication of LL

Answer 19

o Oral – palatal performation. Non sprcific – asymptomatic erythematous macules, papules, nodules  ulcerate Affects soft/hard palate, posterior tongue, gingiva. Note that clinically normal oral mucosa may show histo consistent with leprosy
o Nasal – stuffiness, crusting, epistaxis
o Hoarseness of voice form thickening of vocal cords

Question 20

What is indeterminate leprosy

Answer 20

Kids
1-2 anaesthetic hypopigmented macules (looks like pityriasis alba)
Face/limbs
Unstable; negative smears
Can spont resolve vs 30% progress to other types of leprosy

If macule/papule no longer indeterminnate

Question 21

What is histoid leprosy

Answer 21

LL > Borderline and indeterminant. Inadequate or irreg treatment. Drug resistance.

Firm red nodule shiny
Many baccilli on smears

Question 22

What is lucio leprosy

Answer 22

Rare form of LL in Mexico

Diffuse widespread infiltration, loss body hair, widespread sensory loss

Question 23

What is lazarine leprosy

Answer 23

Diffuse ulceration seen as part of lepra reaction in undernourished or HIV pts.

Question 24

What is pure neuritic leprosy

Answer 24

Nerve only. Sensory loss.
Neuritic - tingling, heaviness, numbness, paraesthetisa, paresis, hypotonia, atrophy,claw hand, wrist drop, foot drop
Other - anhidrotic, dry glossy skin, blisters, neuropathic ulcersm decalcification, bone resorption.

Question 25

Histo TT

Answer 25

o Dermal epitheloid granulomatous infiltrate, may have linear pattern following course of nerve o Lymphocytic infiltrate surrounding adnexa and nerves o Cutaneous nerves: edematous, no organisms, fragmented nerve fibres (unlike sarcoid)

Question 26

Histo borderline

Answer 26

o Features of both LL and TL o Virchow cells (LL), granulomas (TL) o 3 patterns  some lesions with LL pattern and others with TL pattern  Virchow and tuberculoid patterns in same lesions (ie mixed patterns)  lesions have mix of foamy cells and epithelioid cells ie mixed cells

Question 27

Histo LL

Answer 27

o Grenz Zone (band of normal epidermis/dermis) o Disorganized diffuse histiocytic aggregates with Infiltrate: Virchow cells (macrophages with multi bacilli and lipid droplets in cytoplasm- appear foamy),plasma cells, L o Bacilli clump forming globi o Presence of AFB in dermal nerves pathomneumonic. o Dermal nerves well preserved early on but become fibrotic later with lamination of perineurium- onion-like appearance axis of the cell)

Question 28

How to examine a patient with leprosy

Answer 28

o Loss of sensation – touching skin lightly using cotton wool or graded monofilaments. Patient is asked to pinpoint each place touched. When patient feels cntact points on normal appearing skin but not in anesthetic patches a diagnosis of leprosy is strongyl suspected. Also heat/cold/pain o Examination of Peripheral nerves – esp ulnar and common peroneal. But all major peripheral nerve and multiple cutaneous nerve trunks may be affected. Roll between two fingers to check for cord like changes. Other nerves - supraorbital, greater auricular, ulnar, lateral popliteal, dorsal radial

Question 29

T/F - can culture leprosy

Answer 29

F

Question 30

How to perform slit skin smear (bacilloroscopy)

Answer 30

o Site: Taken from lesions which appear most active or that have been present for the longest amount of time. If no lesions take from “cooler” sites – earlobes, nasal mucosa, forehead, chin, extensor forearms, knees and dorsal fingers. o Fite stain or modified ZN stain are used to visualise AFB (M leprae is less acid fast c/w M TB). o The ridley or BI is used to interpret results. o Method  Fold of skin held firm between examiners finger and thumb  Small incision with scalpel  Liquid  smeared onto slide, allow to dry  stain with Fite> Zn method  Examine for red rods (against blue bg) at 100 x with oil immersion o Organisms will be found – 100% LL, 75% borderline, 5% TL

Question 31

Ix for leprosy

Answer 31

Examination - palpate thickened nerves, light touch sensation Slit Skin smear (bacilloroscopy) Histo + stain for AFB (Fit > Zn, gram, methamine silver) PCR on histo Screen for sequelae - Neuro - nerve conduction>EMG. Can also do biopsy and US. - Opthal review

Question 32

Treatment of leprosy

Answer 32

Paucibacillary = DR C 6 months of dapsone 100mg OD, rifampicin 600mg/mth, clofazamine 300mg/month + 50mg daily. Multibacillary as above but 12/12

Question 33

How to improve compliance

Answer 33

Educational material in easy to understand format Treatment instructions easy to understand format Schedule regular FU Build pt provider relationship Provide information about risk/spread and address misconceptions/stigma.

Question 34

Leprosy in pregnancy ?risks ?can you treat?

Answer 34

- Reduce CMI in pregnancy increases risk of contracting leprosy, spread of disease, type 2 reaction. - Type 1 reversal reaction common in post partum. - All women should be treated due to significant risk of nerve damage/other. - MDT safe during pregnancy - Breastfeeding – dapsone not recommended. Consider discontinuing or limiting breastfeeding

Question 35

Frequency of FU for PB vs MB

Answer 35

- PB – annual for 5 yrs | - MB – annual for 10 years.

Question 36

Prevention of leprosy pharmacological options

Answer 36

- Single dose rifampicin for close contacts (adults and children >/=2)  57% reduction in incidence of all type of leprosy for 2 years  Higher if bacterial load low, decrease effectiveness with time  Note dapsone/acedapsone NOT recommended - BCG vaccine  Variable protection 20-90%  High protection rares in younger population, wanes over tie.  Recommended given in countries with high leprosy burden

Question 37

Rifampicin SE

Answer 37

Hepatotoxicity, intrahepatic cholestasis ETOH avoidance, GIT sx Dec platelets RF Red-orange body fluids

Question 38

Clofazamine SE

Answer 38

Red-brown skin pigmentation and xerosis GIT symptoms

Question 39

Dapsone SE

Answer 39

Hemolytic anaemia, agranulocytosis GIT sx Headache Hypersensitivity rxns

Question 40

SCS SE

Answer 40

Bruising, skin atrophy msk weakness, bone fractures glaucoma, cataracts sleep disturbance, mood disorder insulin resistance, excess mineralocorticoid activity

Question 41

Thalidomide SE

Answer 41

Teratogenic Itch, erythematous rash on trunk Drowsy Peripheral neuropathy DVT Constipation Hepatotoxicty.

Question 42

Describe Type 1 reversal reaction Who occurs in? Presentation? Rx

Answer 42

Borderline (BT, BL > LL) But can affect any type 30-50% of leprosy pts develop this Reversal reaction with “upgrading” Enhancement of CMI with Th1 Delayed type hypersensitivity rxn Cause = Antimicrobial drugs > pregnancy, other infections, and mental distress. Timing any time during course (inc years after rx) Clinical New lesions + increase in erythema of pre-exisitng lesions Acute nerve pain or tenderness (neuritis) Nerves enlarged, tender, painful, loss of gunction Paraesthesia Sudden motor loss – wrist drop, foot drop, facial palsy DON’T tend to have organ involvement/systemic disturbance. Rx MDT continued – reassure not drug reaction. Prednisone 40-60mg (max 1mg/kg) 12 weeks (WHO CsA if recalcitrant

Question 43

T2 reaction

Answer 43

Erythema nodosum leprosum LL =50% Less commonly BL 5-10% Vasculitis (commonly EN leprosum) Excessive humoral immunity withTh2 Formation of immune complexes Typically occur when patients with lepromatous forms of leprosy undergo treatment. Commonly in first year of rx. CLINICAL Crops of new painful erythematous nodules Ulcerate and discharge purulent content Face, trunk, pextremities Bilateral, Symmetrical Resolve with hyperpigmentation and scarring. EXTRACUTANOUS Extracutaneous symptoms Nodular skin lesions Fever, myalgias, malaise Severe jt pain and swelling Iridocyclitis, Lymphadenitis, Orchitis, Hepatosplenomegaly, Glomerulonephritis Lucio phenomenon: reactional state characterised by thrombotic phenomena, necrotising cutaneous sml vessel vasculitis. Can die Rx Mild - aspirin + analegsics and rest Thalidomide 100-200mg/day Each episode lasts 1-3 weeks

Question 44

What is lucio phenomenon

Answer 44

Patients with the diffuse form of lepromatous leprosy, who are usually from Central or South America, A reactional state characterized by thrombotic phenomena in addition to necrotizing cutaneous small vessel vasculitis.