Leprosy

Synonym: Hansen's disease.

This disease is notifiable in the UK under the Public Health (Infectious Diseases) Regulations 1988.

Although rarely seen in the UK, leprosy is one of the most common causes of peripheral neuropathy worldwide. The first descriptions of leprosy are from India around 600 BC. In the fourth century, the disease was imported into Europe, where its incidence peaked in the 13th century.
Armauer Hansen discovered Mycobacterium leprae in Norway in 1873. It was the first bacillus to be associated with human disease.

It is an infectious disease caused by an obligate intracellular bacillus Mycobacterium leprae.

• The intracellular Mycobacterium act on the Schwann cells producing a chronic granulomatous reaction resulting in the destruction of both myelin and the underlying nerve cells.The damage to nerves and their protective outer layers leads to permanent neurological damage.
• It is only in the last decade that progress has been made in culturing the organism, defining its genomic sequence, and understanding the important differences in the host's reaction to the organism.
• The mode of transmission of the disease is uncertain, although it is thought that droplet transmission, contact with infected soil and contact with infected blood all occur.
• The severity of disease which develops in any individual is now known to due to the immune response of that individual to the organism. Genetic susceptibility to leprosy has been observed in some races and is thought to reflect a difference in immunological response to the mycobacterium.

The reported prevalence of leprosy has declined over the past decade in part due to a World Health Assembly initiative aimed at the elimination of leprosy as a public health problem. In 2002 WHO reported a prevalence of 1 per 10,000 as opposed to 12 per 10,000 15 years earlier.¹ Although it is probable that this reported prevalence probably underestimates the true incidence of the disease, the incidence has certainly fallen. The majority of cases are now centred in only 6 countries, with 64% of all cases occuring in India.

The symptoms of leprosy may develop in a very insidious fashion due to an average incubation period of approximately 7 years.Three features are required in order to make a diagnosis of leprosy:

• Reddish patches or hypopigmented areas of skin with reduced sensation.
• Thickened peripheral nerves.
• The presence of acid-fast bacilli in skin smears or biopsies.

The initial skin lesion, often referred to as indeterminate leprosy, may resolve spontaneously. If this fails to happen, the subsequent progression of the disease will depend on the patient's immune response to the organism. A spectrum of disease activity is described from tuberculoid leprosy, in which there is a low bacterial load and few skin lesions, to lepromatous leprosy, in which there is a high bacterial load and diffuse infiltration. This can affect not only the skin, but also areas such as the respiratory tract, the eye and lymph glands.² The mycobacterium has a preference for cooler temperatures and therefore it is the superficial structures rather than deep visceral organs which are usually involved.

Other neurological disorders that share similar features to leprosy will need to be considered in the differential diagnosis such as³:

• Mononeuritis muliplex
• Syringomyelia
• Other causes of neuropathy e.g. diabetes mellitus.

• The gold standard for establishing the diagnosis of leprosy, is the finding of M. leprae in biopsies of the skin lesions or slit skin smears. The smears are made by nicking the skin with a sharp scalpel and scraping it. Obtained fluid and tissue are thickly spread on a slide, stained by using the Ziehl-Neelsen method, and partially decolourised with 1% acid alcohol.
• Important serological tests for the detection of M. leprae antibodies or antigens are fluorescent antibody absorption test (FLA-ABS) test and phenolic glycolipid-1 (PGL-1)ELISA, which have been further simplified as dot ELISA and dipstick ELISA.
• In patients with pure neural leprosy, serum levels of PGL-1 may be helpful although only 50% will be seropositive.
• Patients seropositive for PGL-1 have an increased risk of relapse, and the level of PGL-1 may be used as an indicator of bacterial load in these patients.
• Nerve conduction studies may be useful in both establishing the diagnosis, and in monitoring the disease progress or response to treatment.

There are two different classification systems for leprosy:

Multibacillary (MB) or paucibacillary (PB) leprosy⁴

• Paucibacillary (PB) leprosy, negative smears at all sites, single or only a few hypopigmented and hypoaesthetic skin lesions.
• Multibacillary (MB) leprosy - either positive smears at any site, or multiple (>5) hypopigmented, hypoanaesthetic or erythematous skin lesions (sometimes poorly defined). Lesions may also be macules, papules or nodules.

Tuberculous or lepromatous leprosy

After exposure to leprosy and the incubation period, leprosy may fluctuate between various stages depending on the individual's cell mediated immune response or in response to therapy.

Transition toward the TT end of the spectrum is referred to as upgrading (and may lead to a reversal or type I reaction) and transition toward the LL pole as downgrading

1. Indeterminate stage - single skin lesion, frequently heals spontaneously
2. Tuberculoid leprosy (TT) - few skin lesions
3. Borderline tuberculoid leprosy (BT)
4. Borderline leprosy (BB)
5. Borderline lepromatous leprosy (BL)
6. Lepromatous leprosy(LL) - most severe stage, diffuse skin lesions and high bacterial load.

See related article: management of leprosy.

• If left untreated, leprosy may result in blindness and physical deformity.
• Despite treatment with MDT, reactive states may still lead to neurological damage producing Charcot's joints and other deformities.
• Secondary amyloidosis is now rare in patients treated with MDT.

• The prognosis for patients adequately treated with MDT is very good.
• Relapse with MDT is 0.1% per year for PB and 0.06% per year for MB on average, with a low frequency of adverse effects.⁵
• Relapse may occur as late as thirteen years after treatment, however a second course of MDT is likely to produce a good response.
• Nerve damage may still occur in a few despite appropriate treatment due to a reactive state.

• There is no specific and effective vaccine against leprosy.
• Trials of bacille Calmette-Guérin (BCG) plus killed M. leprae vaccine, and International Committee of the Red Cross (ICRC) bacillus vaccine yielded 65-70% protective efficacy in trials in India. ⁶
• No vaccines provide a level of efficacy that can be considered a cost-effective intervention for a public health program.
• Early detection and treatment of the disease will minimise spread, and prophylactic treatment of close contacts of infected individuals may also help to prevent spread.