Leprosy (also Refer CME Summary) Flashcards
Demographics
Chronic granulomatous infection
Long incubation period - lepromatous > tuberculoid
Mycobacterium Leprae
- Never grown/cultured in vitro
Source of infection/transmission —> Nasal discharge
Tuberculoid leprosy —> probably never infectious d/t M. Leprae remaining within skin and nerve compartments
Affects peripheral nerves and skin
Teens, early 20s
India Bangladesh Indonesia Brazil Nigeria Ethiopia
Predisposing factors
Living in an endemic area
Household contact
BCG vaccination —> Protective
Improved socioeconomic condition —> reduces risk
Good housing —> reduces risk
HIV and leprosy co-infection
HIV positivity does not confer increased susceptibility to leprosy
borderline types dominate clinical picture
Co-infection increases risk of leprosy reactions
Leprosy may present as an immune recomstitution syndrome (IRIS) phenomenon in HIV parient swhomrecently started HAART
Pathogenesis
LEPROMATOUS LEPROSY
Failure of cell-mediated immunity towards M. Leprae —> bacillary multiplication —> spread/accumulation of antigen in infected tissues —> absence of activated lymphocytes and macrophages —> nerve damage slow, gradual
Haematogenous spread of bacilli to cool superficial sites —> eyes, face, upper resp tract, testes, small muscles bones/hands, feet
Erthema nodosum leprosum (type 2) lepra reactions —> immune complex deposition d/t antibodies + large antigen load
TUBERCULOID LEPROSY
Cell mediated immunity —> infection restricted to 1/few skin sites and peripheral nerves —> lymphocytic infiltration —> rapid nerve damage
Bacilli not readily found
BORDERLINE TUBERCULOID/BORDERLINE/LEPROMATOUS
Immunologically unstable —> Susceptible to lepra reactions
Reversal reactions (type 1) —> delayed hypersensitivity reactions d/t increased recognition of M. Leprae antigens in skin and nerves
Erthema nodosum leprosum (type 2) —> immune complex deposition in borderline lepromatous and lepromatous leprosy patients who produce antibodies + have large antigen load
NERVE DAMAGE AND COMPLICATIONS
Develops in nerve endings of skin lesions and peripheral nerve trunks
Skin lesions —> small dermal sensory and autonomic nerve fibres supplying dermal and subcut structures damaged —> LOCAL sensory loss, loss of sweating within area of skin lesion
Peripheral nerve trunks —> vulnerable at sites where they are superficial/in firbo-osseus tunnels —> small increase in nerve diameter —> raised intraneural pressure —> neural compression, ischaemia —> DERMATOMAL sensory loss, dysfunction of muscles supplied by the nerve
Dryness, Anaesthesia, Muscle weakness/paralysis, Contracture, Autonomic dysfunction —> permit trauma, bruising, burns, cuts, tissue necrosis from prolonged repetitive trauma —> ulceration, secondary cellulitis, osteomyelitis
Clinical features
EARLY LESIONS
Area of numbness on the skin or visible skin lesion
Clasically indeterminate leprosy -
- 1 or more slightly hypopigmented or erythematous macules with poorly defined margins
- Hair growth not affected
- Nerve function not affected
- Face
- Extensor surface limbs
- Trunk
- Buttocks
- Histo —> Perineurovascular infiltrate, scanty AFB
Signs of peripheral nerve trunk damage -
- Weakness/anaesthesia
- Blister, burn, ukcer in an anesthetic hand/foot
Borderline patients —> presenting with lepra reaction Multiple new skin lesions Nerve pain Sudden palsy Eye pain Febrile illness
ESTABLISHED LEPROSY - TUBERCULOID LEPROSY
1-10 lesions
Asymmetrical, anywhere
Markedly hypopigmented, defined edge
Early, marked defined anaesthesia localised to skin lesions or major peripheral nerve
Autonomic loss early in skin and nerve lesions
Merked nerve enlargement in a few nerves
Absent mucosal and systemic symptoms
M. Leprae not detectable
ESTABLISHED LEPROSY - LEPROMATOUS LEPROSY
Hundreds, confluent skin lesions
Symmetrical, avoiding “spared areas”
Slight hypopigmentation, vague edge
Late, initially slight ill-defined anaesthesia, but extensive over cool areas of body
Autonomic loss late but extensive
Slight but widespread nerve enlargement
Common mucosal and systemic symptoms during type 2 lepra reaction (erthema nodosum leprosum)
M. Leprae numerous in all affected tissues
Clinical variants
TUBERCULOID LEPROSY
Nerves and skin only
Few solitary lesions
May be purely neural or purely skin
Purely neural —> pain and swelling of affected peripheral nerve trunk —> anaesthesia +/- weakness/muscle wasting
Skin lesions -
- Conspicuous, erythematous, copper/purple coloured plaque with raised clear cut edges sloping towards flattened and hypopigmented centre
- Less commonly macule with altered skin texture —> erythematous in light skin, hypopigmented in dark skin
- Dark skins may not show erythema
- Dry surface, sometimes scaly
- Hairless
- Insensitive
- Usually anaesthetic (face is exception due to generous supply of nerve endings)
- Thickened sensory nerve/nerve trunk may be palpated just beyomd outer edge of skin lesion or in the vicinity
LEPROMATOUS LEPROSY
Skin -
- Dermal lesions because early nerve involvement is usually asymptomatic —> unnoticed by patient
- Macules - small, multiple erythematous/faintly hypopigmented vague edges, shiny surface
- Diffuse papules - normal skin colour or erythematous
- Infiltration - normal skin colour or erythematous
- Nodules - normal skin colour or erythematous
- Bilateral, symmetrical
- Face
- Arms
- Legs
- Buttocks
- Except regions of skin with highest temp i.e. hairy scalp, axillae, groin, perineum
- Hair growth and sensation not initially impaired
Mucosal lesions -
- Papules on lips
- Nodules on palate, uvula, tongue, gums
- Nasal mucosa bleeds, ulcerates easily —> epistaxis
Peripheral nerves -
- Sensory fibres first affected —> numbnes/anaesthesia dorsal hands/feet —> extensor surfaces arms/legs —> trunk
- Affects eyes as below
Eyes-
- cLagophthalmos d/t damage to facial nerve
- Infiltration of Corneal nerves —> anasthesia —> injury, infection, blindness esp of there is also lagophhthalmos
Peripheral oedema d/t leprous dactylitis -
- Hands and feet
Bones -
- Osteoporosis of phalanges
- Osteolytic cysts
- Hairline compression fractures
- Fingers crooked/short
If untreated -
- Leonine facies d/t deeper furrows forehead as skin thickens
- Thickened ear lobes
- Thinning/loss of eyebrows, eyelashes (madorosis)
- Leprous deposits in eye —> keratitis, iridocyclitis, iris atrophy
- Nose mishapen —> collapse d/t septal perforation, loss of anterior nasal spine (saddle nose)
- Hoarse voice
- Upper incisor teeth fall out
- Skin on legs —> Ichthyosis and thick
- Ulcerating nodules
- Nerve thickening + bilateral glove and stocking anaesthesia
- Testicular atrophy —> sterility, impotence, gynaecomastia
Lucio pure diffuse subtype -
- Impaired sensation hands feet
- Gradual loss of eyebrows, eyelashes (madorosis), body hair
- Sclerodermoid (diffusely thickened, stiff, smooth)
- Alopecia
- Nasal, laryngeal involvement
- Widespread telemgiectases
- No plaques/nodules
- Shining eyes
BORDERLINE LEPROSY
borderline lepromatous leprosy commonest type
- Unstable
- If untreated —> downgrades to lepromatous leprosy
- Upgrades towards tuberculoid
- Clinical change lags behind immunological anf histo changes
Skin -
- Asymmetrical distribution
- Macules
- Plaques
- Annular lesions with well-defined central hypopigmentation (typical of middle of the spectrum)
- Bizarre-shaped bands
- Tuberculoid end —> lesions fewer, drier, more hair loss, anhidrosis, more insensitive, fewer bacilli in smears/biopsies
- Extensive disease may serioudly impair sweating and heat control
Peripheral nerves -
- 1 or more nerves likely thickened/non-functioning
- Neural symptoms may precede skin lesions
Damage to structures other than skin and nerves will not manifest clinically in birderline lepromatous (even thiugh bacilli may be present in other tissues)
PURE NEURITIC LEPROSY
Asymmetrical involvement of peripheral nerve trunks
No visible skin lesions
All types of leprosy on biopsy of cutaneous nerve
DDx Macular lesions
Birthmarks (abnormally pigmented but physiologically normal)
Vitiligo (depigmented)
Pityriasis alba
Pityriasis versicolor (central distribution on trunk, minute distinct macules)
Tinea corporis (itchy, vesicular edge)
DDx plaques, annular lesions
Tinea corporis
Other granulomatous disorders (lesions not anaesthetic) -
GA
Sarcoidosis
Cutaneous TB
DDx nodules
Cutaneous leishmaniasis (usually crust, ulcerate after weeks/months, seldom as numerous as lepromatous leprosy lesions) —> slit skin smear = leishmania; leishmanin test = positive
Post-kala-azar dermal leishmaniasis in India, East Africa similar to Lepromatous leprosy
DDx peripheral nerve thickening/polyneuropathy
DDX PERIPHERAL MERVE THICKNENING
Hereditary sensory motor neuropathy
Peroneal muscular atrophy (Charcot-Marie-Tooth disease)
Amyloidosis
DDX POLYNEUROPATHY HIV Dianetes ETOH Vasculitides Heavy metal poisoning
Complications, co-morbidities
LEPRA REACTIONS
Type 1 reversal reactions (upgrading to tuberculoid leprosy d/t cell mediated immunity delayed hypersensitivity reaction)
- Skin + nerves
- Occur in borderline disease
- Acute neuritis - tender, loss of sensory and motor function
- Acutely inflamed skin lesions - existing skin lesions become erythematous/oedematous, may scale, ulcerate
- New skin lesions may appear
- Oedema of face, hands, feet (occasional)
- Constitutional symptoms unusual
- Triggers —> after starting Rx, postnatal
Type 2 erythema nodosum leprosum (downgrading to lepromatous leprosy d/t immune complex deposition + high antigen load)
- Systemic disorder
- Lepromatous leprosy, borderline lepromatous (multibacillary disease)
- Before, during, after Rx
- Acute vs prolonged vs recurrent
- Painful red nodules face, extensor limbs
- Suppurative superficial or deep
- Acute lesions crop and scale over —> fade over days
- When chronic —> Ulceration, brawny induration
- Fevers, malaise
- Uveitis
- Neuritis
- Dactylitis, arthritis, myositis
- Lymphadenitis
- Orchitis
Lucio reaction d/t infarction upon deep subcutaneous vasculitis —> may be fatal
- Only in patients with Lucio leprosy
- Irregularly shaped erythematous oatches —> dark, heal, form bullae, necrose, become painful ulcers taht are slow to heal
- D/t M. Lepromatosis
NERVE DAMAGE
Sensory component commonly first and most severely affected
Occasional pure motor lesion
Autonomic dysfunction always present in severe nerve damage —>
- loss of hair growth, sebaceous, sweat secretion
- poor pigment formation
- in limbs —> capillary stasis, cyanosis, dryness —> fissuring
- POSTERIOR TIBIAL NERVE most commonly affected —> paralysis, contracture small muscles foot, sole anaesthesia
- Ulnar nerve —> small muscle weakness, hand anaesthesia
- Median nerve —> small muscle weakness, hand anaesthesia
- Lateral popliteal nerve
- Common peroneal nerve —> affects dorsiflexion, eversion; anaesthesia outer border of foot
- Facial nerve —> lagophthalmos if affecting zygomatic + temporal branches
EYE INVOLVEMENT
D/t nerve damage + bacillary invasion
Higher risk with presemde of facial lesions
Involvement of zygomatic + temporal branches of facial nerve —> Lagophthalmos d/t paralysis of orbicularis oculi
Damage to ophthalmic branch of trigeminal nerve —> anaesthesia of cornea, conjunctiva —> drying —> reduction in blinking —> cornea at risk of trauma, ulceration
Bacillary invasion of iris, ciliary body —> susceptible to lepra reactions
Investigations
Dx usually made clinically based on —>
2 of 3 characteristic findings
- Anaesthesia of a skin lesion OR in the distribution of a peripheral nerve OR over dorsal surfaces hands/feet
- Thickened nerves esp at sites of predilection
- Typical skin lesions
OR
AFB in slit skin smears (demonstrated by wade-fite stain) of suspect lesions in common sites in LL i.e. forehead, earlobes, chin, extensor forearms, trunk, buttocks —> bacterial index
OR
Histology typical of leprosy
IX Slit skin smears Skin bx Nerve bx Serology
SLIT SKIN SMEARS
Lesion cleaned with alcohol
Fold gripped between thumb and forefinger to render it blood free (Bloody smear is useless)
Incision of 5mm long and 3mm deep made with size 15 blade
Then the blade is turned at rigt angles to the incision
Without relaxing the finger pressure, wound scraped several times in 1 direction
Fluid and pulp from dermis on 1 side of blade gently smeared on to glass slide
Smear fixed over a flame and stained woth wade fite/mpdified ZN stain
SKIN BX
Incison made down to subcut fat to include whole depth of dermis (if not, leprous changes im the deeper layers of the dermis will be missed)
NERVE BX in pure neural leprosy (where there are no skin lesions)
Neccesary to establish Dx
Purely sensory thickened nerve should be sampled -
Radial cutaneous nerve at the wrist
Superficial peroneal at the anterior ankle
Sural nerve at the ankle
SEROLOGY —> PGL-1 antibody testing
PGL-1 is a M. Leprae specific cell wall component
Useful in paucibacillary patients who are slit skin smear negative, but have low bacterial load and at risk of undertreatment
PREGNANCY
Relative immunosuppression + contact with health care providers —> leprosy
High risk of type 1 reversal lepra reactions in the post partum period —> may present with leprosy during this period
Rx
5 PRINCIPLES OF RX
Stop infection with multidrug therapy
Treat lepra reactions —> reduce risk of nerve damage
Educate patient to cope with existing nerve damage esp anaesthesia
Treat complications of nerve damage
Rehab patient socially and psychologically
EXPECTATIONS OF RX
Reassure patients that infection is curable as antibacterial Rx for leprosy is highly effective woth low relapse rates, but need to be taken over 6-24 months
Aim is to minimise further nerve damage
Should not develop the mutilating sequelae previously seen
Established nerve damage —> irreversible —> severely disabling
Treatment of neuritis currently unsatisfactory —> permanent nerve damage despite corticosteroids
Not possible to predict which patients will develop lepra reactions or nerve damage
If untreated, Borderline patients —>
- will downgrade towards lepromatous end of spectrum —> suffer consequences of bacillary invasion
- at risk of developing type 1 reversal lepra reactions —> devastating nerve damage
FIRST LINE RX
Multidrug Rx -
- Rifampicin —> S/Es hepatotoxicity (mild transient elevation transaminases) which is rare at the dosage/intervals for leprosy —> not imdication of stopping Rx
- Dapsone —> S/Es mild haemolysis, anaemia, psychosis, dapsone drug hypersensotivity syndrome 6 weeks after starting (exfoliative dermatitis, LN, HSM, fever, hepatitis, can be fatal)
- Clofazamine —> Anti-inflammatory effect useful in type 2 erythema nodosum leprosum lepra reactions —> S/Es skin discolouration ranging from red-purple black (degree depending on dose and amount of leprous infiltration in skin, fades within 6-12 months of stopping), pink urine/sputum/sweat, ichthyosis shins/forearms, GI upset
Paucibacillary —> 6-9 month course, 2 year monitoring upon Rx completion -
Rifampicin 600mg monthly
Dapsone 100mg daily
Multibacillary —> 12-18 month course, 5 year monitoring upon Rx completion -
Rifampicin 600mg monthly
Dapsone 100mg daily
Clofazimine 50mg daily + 300mg monthly
Relapsed multibacillary patients —>
Paucibacillary —> 2 yrs
Multibacillary —> at least 5 yrs, with monitoring after Rx
SECOND LINE RX
Fluoroquinolones (ofloxacin, perfloxacin)
Minocycline 100mg daily
Clarithromycin 500mg daily
Triple Rx of rifampicin, ofloxacin, minocycline monthly dose for 6-12 months cam be used for patients with adverse effects to one of the components of the classic MDT
Complications of Rx
LEPRA REACTIONS
Type 1 Reversal reactions —> Nerve damage/acute neuritis
Peak for reversal reactions = 6 months after starting Rx
Aim of Treating lepra reactions -
- Controlling acute inflammation
- Easing pain
- Reversing nerve damage
- Reversing eye damage
- Reassuring patient
Multidrug Rx should be continued during lepra reactions
Neuritis —> nerve tenderness, new anaesthesia, motor loss, inflamed skin lesions
From Type 1 reversal reaction
Nerve damage occurs before Dx, during Rx, after Rx, during Lepra reaction
Higher risk for multibacillary leprosy
Oral pred 40mg daily, reducing by 5mg every 2-4 weeks —> longer durations give better outcomes
Severe Type 2 Erythema nodosum leprosum reactions -
- Thalidomide 400mg daily (drug of choice for young men, needs discussion of benefits vs risks for young women d/y risk of phocomelia in 1st trimester of pregnancy) —> double contraception
OR
- High dose oral pred 80mg daily tapered rapidly
OR
- Clofazamine 300mg daily for several months
Mild chronic type 2 erythema nodosum leprosum lepra reactions (iritis, neuritis)
- Long term thalidomide
- Long term clofazamine
Acute iridocyclitis ssoc with type 2 erthema nodosum leprosum lepra reaction -
1% HCT eye drops Q4H +
1% atropine eye drops BD
Mx - patient education
Reassure patient that they will not be infectious within a few days of multidrug Rx —> can lead a normal social life
Clearly explain the disease
Refute myths about leprosy to help patients come to twems with the Dx —> improve compliance
Address anxieties re: transmission, lepra reactions
Address issues re: compliance
