LEPROSY

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.