Leprosy

Leprosy is a clinical condition characterized by a long variable incubation period, ranging from 3 to 5 years or even 6 ½ years, and a protracted course with lesions affecting the skin, mucosa of the upper respiratory tract, and peripheral nerves. These manifestations are a result of infections caused by M. leprae and M. lepromatosis.

The causative organisms are acid and alcohol-fast bacilli that do not grow in artificial media but do thrive and multiply in the footpad of a mouse.

Humans and armadillos are the major reservoirs of leprosy bacilli. Armadillos are known to be infected with the disease and are used in research efforts to study leprosy. They have an unusually low body temperature, around 34°C, which provides a hospitable environment for the growth of M. leprae.

M. Leprae was discovered by J.H. Armauer Hansen, a Norwegian physician in 1873.

Leprosy is from a Greek word ‘lepra’ meaning: disease which makes the skin scaly.

The first mention of leprosy in the Bible was in Leviticus 13:2-5 and thereafter in 2 Kings 5:1-3 (Naaman, captain of the host of the king of Syria).

India has the highest prevalence, followed by Brazil and Burma. Regional prevalence rates reveal the following:

• Africa – 40,850
• America – 32,904
• South East Asia – 133,422
• West Pacific – 8,646

Definition

Leprosy is a chronic granulomatous disease of humans with predilection for skin, peripheral nerves, and nasal mucosa.

It is a droplet infection in which prolonged and intimate contact of a susceptible subject with an index case shedding viable bacilli is required.

The major source is the mucoid nasal secretions of lepromatous leprosy patients, although transcutaneous implantation and ingestion of the bacilli do occur.

The fate of the bacilli depends on the immunological capacity of the individual to mount cell-mediated immunity.

At one extreme, called tuberculoid leprosy, the patient mounts a vigorous response to the pathogen that limits the spread to few lesions.

In lepromatous leprosy, no effective immunity is generated, resulting in uninhibited growth of the bacilli and systemic infection.

Incubation/Infectious Period

Incubation seems to range between 9 months to 20 years.

The infective period depends on the type of leprosy, but is doubtful if the tuberculoid form is infectious at all.

1. Early or indeterminate leprosy
2. Tuberculoid leprosy
3. Borderline-Tuberculoid leprosy
4. Mid-borderline leprosy
5. Borderline-Lepromatous leprosy
6. Lepromatous leprosy
7. Histoid leprosy
8. Diffuse leprosy of Lucio and Latapi

It manifests along a spectrum of 2 forms with the borderline manifesting features of both polar forms.

An untreated patient with borderline disease tends to shift to Lepromatous while a treated patient tends towards tuberculoid.

The immune response to the bacilli varies over a large continuum and is therefore responsible for the heterogeneous clinical picture of leprosy. The recognized clinical types are:

1. Indeterminate leprosy
2. Tuberculoid leprosy
3. Borderline or dimorphic leprosy
4. Lepromatous leprosy
5. Histoid leprosy

Indeterminate

This is characterized by:

• Hypopigmented ill-defined macule that maintains tactile,
• Sweating, and
• Hair growth function.

It may regress spontaneously, persist, or progress to the determinate type.

Tuberculoid

Well-defined asymmetric hypopigmented areas of skin, characterized by:

• Diminished sensation, sweating, and hair growth.

The edges are usually raised, hard, and craggy. Tuberculoid lesions may occur in any part of the body but tend to spare the scalp and axilla. Affected nerves are usually enlarged and palpable.

The commonly involved nerves include:

• Ulnar nerve
• Posterior tibial nerve
• Facial nerve
• Median nerve
• Radial nerve

The most commonly affected superficial nerves are the posterior auricular and the radial cutaneous nerve. Sensory and motor modalities are affected pari passu.

The insensitive tissues are readily injured with the development of neuropathic ulcers. Paresis of the facial nerve may lead to the loss of the protective eyelid reflex, corneal ulceration, and destruction of the eye, resulting in blindness.

The loss of sensation leads to serious consequences, including ulcerations, fractures, and bone resorption.

Borderline leprosy

The clinical manifestations range from near tuberculoid to near lepromatous, and lepromin reaction may indicate minimal to moderate sensitivity.

The individual lesions tend to be more raised in the center than around the edges. Nerve involvement occurs early, even before the skin lesions, with enlargement and tenderness of the nerves.

Cutaneous lesions consist of numerous, red, irregularly shaped plaques that are less well defined than those in the tuberculoid type. Their distribution may mimic those of the lepromatous type, but they are more asymmetric.

Anesthesia is only moderate, and regional adenopathy may be present. The disease may remain in this stage, improve, or worsen.

Tuberculoid & borderline leprosy

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Tuberculoid & borderline leprosy

Lepromatous leprosy

This is characterized by extensive and bilaterally symmetrical skin nodules, papules, and macules with diffuse infiltration of the face, hands, and feet. Nasal mucosa and ocular involvement may lead to breathing problems and eye inflammation.

The lepromatous macules are characterized by marked pigment loss within flat and ill-defined areas. There is no obvious sensory or thermal loss, but slit-smear usually discloses millions of M. leprae.

Nodular types of lepromatous leprosy, which are localized aggregations of lepromatous tissue, appear on the earlobes and face.

When there is diffuse infiltration and thickening of the skin, the face becomes corrugated into the leonine facies.

The mucous membrane of the nose, mouth, nasopharynx, pharynx, and larynx are commonly involved. The whole mucosa is replaced by irregularly thickened granulomas that may ulcerate. Secondary infection of these lesions causes gross destruction of various tissues (nose, testes).

Lepromatous Leprosy

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Lepromatous Leprosy

Histoid leprosy

This is a variant of Lepromatous leprosy that presents with clusters of histiocytes and a grenz zone (an area of collagen separating the lesion from normal tissues).

• Digital loss
• Blindness
• Sterility (testicular dx)
• Gynecomastia
• Amyloidosis
• Erythema nodosum leprosum (ENL)
• Skin Ulcers
• Contractures
• Nerve Damage

Definitive diagnosis is made in the majority of cases based on history and pathognomic signs of the different types, and it is confirmed by one of the following methods:

1. Presence of M. leprae in lesions of lepromatous or borderline cases.
2. Histology of the involved tissue in tuberculoid leprosy using Fite-Faraco stain.
3. Rapid molecular assay using polymerase chain reaction to identify and quantify M. leprae/lepromatosis DNA in tissue samples.

• A slit-skin smear is prepared and examined under oil immersion lens for bacterial and/or morphological index (i.e. no per field of vision/ratio of solid & broken rods).
• Lepromin test (does not aid in diagnosis but assists in classification of the type of leprosy).
• Lepromin is a material prepared from lepromatous nodule.
• Intradermal injection of the material is read either 48-72 hours (Fernandez) or 3-4 weeks (Mitsuda reaction) in which there is erythema and edema.
• In lepromatous leprosy, Mitsuda test is negative but is invariably positive in tuberculoid leprosy.

• Duration: Two years for tuberculoid or at least one year after all signs have gone.
• Lepromatous cases for four years or two years after all signs have ceased.
• It is advised to continue treatment at half the total dose for life in cooperative LL and BL patients.
• Multidrug therapy is preferred to monotherapy because of the emergence of drug-resistant strains.
• The current therapeutic regimen divides leprosy patients into Pauci-bacillary and Multibacillary groups based on the clinical classification (Ridley and Jopling & WHO).

The WHO classification scheme is superimposed on the Ridley-Jopling scale to fit the two-drug therapy regimen.

The two broad categories are:

• Paucibacillary (Tuberculoid and Borderline-Tuberculoid)
• Multibacillary (Midborderline, Borderline leprosy, and Lepromatous leprosy)

Paucibacillary	Multibacilliary
Tuberculoid (TT)	Lepromatons (LL)
Borderline Tuberculoid (RT)	Borderline leprosis (BL)/td>
Indeterminate (1)	Mid-borderline (BB)

Despite the above classification, all patients with a bacterial index of >2 at any site are treated as part of the multibacillary group.

WHO recommends combined therapy for adults, which includes:

• Monthly supervised 600mg rifampin with 300mg clofazimine
• Daily administration of 100mg dapsone with 50mg clofazimine

For children, the recommended treatment regimen is as follows:

• Rifampicin 450mg monthly
• Clofazimine 150mg monthly
• Dapsone 50mg daily
• Clofazimine 50mg daily

The regimen for paucibacillary (PB) in adults consists of monthly rifamycin 600mg and daily dapsone 100mg. For children, the regimen includes rifampin 450mg monthly and dapsone 50mg daily.

It is recommended by the World Health Organization (WHO) that slit-skin smears and the bacteriological index be used for the purpose of grouping patients into paucibacillary (PB) and multibacillary (MB) groups.

Ridley scale of bacteriological index:

• 0 = 0/100 fields
• 1 = 1-10/100 fields
• 2 = 1-10/10 fields
• 3 = 1-10/HPF
• 4 = 10-100/HPF
• 5 = 100-1000/HPF
• 6 = > 1000/HPF

Morphological index = solid rods (live bacilli) / broken rods (dead)

The introduction of the blister calendar pack (BCP) for the PB and MB regimen has greatly improved the delivery and compliance with medications.

The real challenge in the management of leprosy is the treatment of reactionary states, and recognized interventions include:

1. Steroids to relieve inflammation and edema.
2. Clofazimine for its steroid-sparing effect.
3. Thalidomide for the management of erythema nodosum leprosum.

WHO Classification	NHDP	WHO
Single lesion paucibacillary	Dapsone 100mg daily and Rifampicin 600mg monthly for 12 months	Rifampicin 600mg, Ofloxacin 400mg and Minocycline 100mg as a single dose
Paucibacillary	Dapsone 100mg and Rifampicin 600mg for 12 months	Dapsone 100mg daily unsupervised and Rifampicin 600mg monthly supervised for 6 months
Multibacillary	Dapsone 100mg daily, Rifampicin 600mg daily and Clofazimine 50mg daily for 24 months	Dapsone 100mg daily unsupervised and Rifampicin 600mg monthly and Clofazimine 300mg monthly supervised for 24 months

Current Recommended Treatment

Paucibacillary (1-5 skin lesions):

• Treatment: Rifampicin 600mg monthly (supervised) and Dapsone 100mg daily (unsupervised).
• Duration: 6 months

Multi bacillary (greater than 5 skin lesions):

• Treatment: Rifampicin 600mg (monthly, supervised), Clofazimine 300mg (monthly, supervised), Dapsone 100mg (daily, unsupervised), Clofazimine 50mg (daily, unsupervised).
• Duration: 12 months

Treatment for Erythema Nodosum Leprosum (ENL):

• Thalidomide is the specific treatment for ENL.
• Steroids in addition to Dapsone and Clofazimine may also assist in management.
• Thalidomide use is limited due to teratogenicity.

Reconstructive Surgery:

Reconstructive surgery also plays a role in the management of deformities.