Download LEPROSY( HANSEN DISEASE)

LEPROSY( HANSEN DISEASE)
Microbiolgy
Mycobacterium leprae.
Gram positive, and strong acid fast bacillus.
Obligate intercellular, mainly in macrophage and schwann cells.
Grow best in low temperature.
History
Leprosy used to be known as possible heredity skin disease 2500 ago in tropical,
subtropical Africa, and southern Asia, until Hansen in 1873 discovered the rod shaped
leprosy bacillus.
Epidemiology
Endemic in part of Asia, Africa, and central South America.
WHO identified 5.5 million and incidence of 1 million new patients yearly.
Tend to occur in cluster, families, usually in new, cases there is history of long contact
with know patient with leprosy.
Human are the only known reservoir for the disease.
Respiratory tract, nasal mucus, and the skin lesion are the principal sources for the
transmission of organisms.
If the disease caught early, then with multiple drug therapy, we can make the patient
noncontagious.
Pathogenesis
Mycobacterium Leprae tend to affect peripheral structure where the temperature is
cooler, as skin, peripheral nerves ( more common in ulnar N near elbow, peroneal N near
fibula), anterior portion of the eye, respiratory tract above larynx, testes, and structure of
the hand and feet.
Clinical features
Two extremes clinical presentation 1) Lepromatous leprosy: disseminated infection with
minimal cell mediated immunity), and 2) Tuberculoid leprosy (limited infection with
marked cell mediated immunity).
Madrid classification 1953: Tuberculoid, lepromatous, intermediate..
Ridley and Jopling 1962-1966: Intermediate I, Tuberculoid TT, Borderline
tuberculoid BT, Borderline BB, Borderline lepromatous BL, Lepromatous LL
Another classification is paucibacillary, and multibacillary, according to skin smears,
Paucibacillary patients have negative skin smears for acid fast bacilli and would
encompass I, TT, and BT. Multibacillary patients have positive skin smears and are
classified as BB, BL, or LL. This grouping is used to define the WHO recommendations
for type and duration of treatment.
Intermediate leprosy (early):
Is the first sign of leprosy ,only few hypopigmented , or hyperpigmented erythematous
skin macules , often with some slight sensory loss, but the nerve are not tender or
thickened , Histopathologically there is scanty lymphocytic-histocytic infiltration around
skin appendages, nerves, and blood vessels. The lesion may clear spontaneously in a year
or two, but specific treatment is recommended.
Tuberculoid leprosy:
Often by hypopigmented which are sharply demarcated, later it enlarges by peripheral
spread and margin become elevated and circinate, the central area in turn becomes
atrophic and depressed. This also usually would be associated with sensation and loss of
normal skin structure. Lesions can be single or multiple.
Nerve involvement occur early, as the superficial nerve leading to the lesion may be
enlarged even can be visible and palpable. As ulnar, peroneal, auricular, there might be
severe neuritis pain, neural involvement might lead to muscle atrophy, and contracture.
Involvement of the facial nerve would lead to exposure keratitis.
Histology consists of noncaseating granuloma, lymphocytes, epithelioid cells, and
possible giant cells, bacilli are frequently absent or difficult to demonstrate.
Lepromatous leprosy:
Cutaneous involvement is extensive and roughly bilaterally symmetric across the midline
of the host. Individual skin lesions are highly variable and can include macules, papules,
plaques, or nodules. The border of the lesion is ill defined, and the centre of the lesion
indurated and convex (rather than concave). The sites of the predilection are the face
(cheeks, nose, brows), ears, wrists, elbows, buttocks, and knees. Loss of the lateral
portion of the eyebrows, much later the skin of the face and forehead becomes thickened
and corrugated (leonine face), and the earlobes become pendulous.
Epistaxis, obstruction of breathing, complete nasal obstruction, septal peroration, and
nasal collapse lead to saddlenose, painless inguinal and axillary lymphoadenopathy,
scarring of the testes lead to sterility. Gynecomastia is common.
Invlovement of peripheral nerves is les prominent than tuberculoid form.
Histologically there is diffuse granulomatous reactions, and many bacilli, no epithelioid,
or giant cells.
Borderline leprosy:
Spectrum lies between the tuberculoid and Lepromatous poles and usually subdivided
into borderline tuberculoid, borderline, borderline Lepromatous, skin and peripheral
nerve involvement are variable and show variety of both forms. It is unstable from and
usually progress to LL because of the gradual loss of cell mediated immunity, unless
patient received treatment then it would shift to TL.
Histologically, varies from predominant of macrophages in BT to epithelioid cells in LL.
BT as well as I and TL are paucibacillary, while BB, BL, LL are mutlibacillary.
Reactional states:
The general course of leprosy is indolent, but it may be interrupted by two types of
reaction, both forms of reaction can occur in untreated patients but more often emerge as
a complications of chemotherapy.
1. Erythema nodosum leprosum ENL type II reaction
Immune complex reaction occur in BL, and LL. As a result of immune complex
deposition in skin, Erythema nodosum would characterize by painful erythematous
nodules or plaques on the face ,arm, thighs. Fever, malaise, arthritis, orchitis,
iridocyclitis, lymphoadenopathy and proteinuria.
The reaction usually triggered by transient imbalance in the patient immune
regulatory mechanism, there is an increase in the CD4/CD6 ration resulting in release
of bacillary antigens from macrophage, which set a stage of antibody/antigen to
combine, and fix complement, and attract neutrophils.
(Lucio phenomeneon) is variant of ENL but involves vessels wall leading to
vasculitis and necrosis of the overlying skin. Occur in Mexico and central America.
2. Type I reaction (reversal reaction) : delayed hypersensitivity reaction that tend to
occur in patietbns with BB, who are on treatment, as a result of the recovery of
immune status, patient might experience fever, edema, hyperemia, infiltration of
the skin lesion, and severe peripheral neuritis.
Ocular Disease
Ocular adnexa :
 Lateral thinning of the eyebrow and subsequent total loss is common .
 Madarosis. More common in TL. Lower lid mainly.
 VII paralysis….ectropion, upper lid entropion, poor lacrimal draininage.
 V nerve palsy.
 Eye lid nodules and placoid lesions may occur in paucibacillary, reversal reaction,
and Erythema nodsum.
 Dacryoadenitis, and possibly dacryocystitis secondary to nasal mucosa
obstruction can occur in LL.
Cornea
 Exposure keratitis.
 Neurotrophic ulcer.
 KCS.
 Enlarged edematous corneal nerve. Can regress after treatment.
 Avascular keratitis, chalky white punctuate sub epithelial opacities in superior
temporal cornea near the limbus, eye usually uninflammed and it represent
macrophage with bacilli later destruction to bowman’s layer can occur with
pannus formation.
 Interstitial keratitis more severe from of avascular keratitis and might progress to
necrosis.

Corneal or limbal leproma. Large white or yellow nodule, represent granulomata
(macrophages laden with bacilli)..
Sclera:
 Episcleritis (nodular), and scleritis can occur either due to bacillary invasion or
immune reaction as in Erythema nodum.
Anterior Uvea:
 Two form of uveitis seen in leprosy, one is an acute form with fulminant
granulomatous iritis, which occur in system Erythema nodosum, can be
associated with hypopyon. The other is chronic low grade insidious, which may
seen in LL.
 Iris pearls, chlky white paticles seen on the ris surface and near the pupil, it ,
represent , noniflammatory microleproma, can be seen in the peripheral retina.
 Miosis because of dilator muscle involvement.
 Paralysis of accommodation. nerve involvement.
IOP:
 Low IOP have been seen, which may be due to cilliary body nerve involvement.
 Glaucoma occur due to inflammation.
Lens
 Cataract due to inflammation.
Diagnosis
By skin biopsy or slit skin smear, and it is important to classify paitent to either
paucibacillary or multibacillary, for drug treatment.
Clinical diagnosis can be based on presence of 2 at least out of the following three:
 Characteristic skin lesion.
 Sensory loss.
 Enlarged peripheral nerve.
Lepromin test, not diagnostic but helps to classify patients once diagnosis been done,
Intradermal injection of Lepromatous tissue, that would be followed by :
 Fernandez reaction occur within 24 to 48 hrs.
 Mistuda reaction occurs after 3 to 4 weeks.
It will give similar possibilies as TB test, so if test positive this would suggest good
cellular immunity and possible that it is BT or TT, if negative then it could be BL or LL,
Borederline BB will have variable results.
Therapy
Primary drugs are Dapsone, rifampin, clofazimine, and ethionamide.
Secondary drugs are thiacetazone, thiambutosine, aminoglycosides.
WHO recommendations

For paucibacillary:
Dapsone 50 mg daily.
Rifampin 10 mg/kg ?month (or as much as 600 mg), monthly for minimum of 6
months.
These patients should be then observed for 3 years,

For multibacillary
Dapsone 50 mg.day
Raifampin 10mg/kg/month 9or as much as 600 mg).. monthly
Clofazimine 1 to 4 mg/kg daily
until skin smear are negative.
For reaction states, aspirin, steroid, thalidomide, clofazimine can be used
Always conti using anti Lepromatous drugs during Reactional states also
For type I use Prednisone 60 to 80 mg daily and titrate
For type II use similar treatment as in type I,,often u would need alternate treatment with
clofazimine, thalidomide can be used also..
Prognosis
Most common cause of the destruction effect of leprosy specially to nerve is during
reactional states, that necessitate appropriate diagnosis and management.
Prevention
Vaccine still in process of testing.
For now early treatment is the standard.